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Melanoma-associated peptides recognized by cytolytic T lymphocytes (CTL) in the context of several histocompatibility leukocyte antigens (HLA) are required for the development of specific immunotherapies. Using a transient transfection assay into COS-7 cells, we identified the gp100/pMel17 melanosomal protein as the shared antigen recognized by three independent CD8+ CTL clones in HLA-A*6801-restricted fashion. This finding was confirmed by the correlation between lack of gp100/pMel17 protein in a number of HLA-A*6801-positive melanomas and their resistance to lysis/cytokine production by the specific effectors. The gp100/pMel17 antigenic epitope was identified based on recognition of subfragments and on a computer-based prediction algorithm. Among a panel of gp100/pMel17-derived synthetic peptides only the 10-mer HTMEVTVYHR (gp100/pMel17182-191) induced tumor necrosis factor (TNF) release by CTL clones when pulsed on suitable target cells whereas both the 10-mer and the shorter 9-mer gp100/pMel17183-191 sensitized the same antigen-pulsed cells to lysis. In conclusion, the identification of the HTMEVTVYHR peptide will extend to HLA-A*6801 melanoma patients the possibility to exploit gp100/pMel17 melanosomal protein for experimental and clinical studies. | gp100 Melanoma Antigen |
Understanding of intracellular polymerization of sickle hemoglobin (HbS) and subsequent interaction with the membrane of a red blood cell (RBC) is important to predict the altered morphologies and mechanical properties of sickle RBCs in sickle cell anemia. However, modeling the integrated processes of HbS nucleation, polymerization, HbS fiber interaction, and subsequent distortion of RBCs is challenging as they occur at multispatial scales, ranging from nanometers to micrometers. To make progress toward simulating the integrated processes, we propose a hybrid HbS fiber model, which couples fine-grained and coarse-grained HbS fiber models through a mesoscopic adaptive resolution scheme (MARS). To this end, we apply a microscopic model to capture the dynamic process of polymerization of HbS fibers, while maintaining the mechanical properties of polymerized HbS fibers by the mesoscopic model, thus providing a means of bridging the subcellular and cellular phenomena in sickle cell disease. At the subcellular level, this model can simulate HbS polymerization with preexisting HbS nuclei. At the cellular level, if combined with RBC models, the generated HbS fibers could be applied to study the morphologies and membrane stiffening of sickle RBCs. One important feature of the MARS is that it can be easily employed in other particle-based multiscale simulations where a dynamic coarse-graining and force-blending method is required. As demonstrations, we first apply the hybrid HbS fiber model to simulate the interactions of two growing fibers and find that their final configurations depend on the orientation and interaction distance between two fibers, in good agreement with experimental observations. We also model the formation of fiber bundles and domains so that we explore the mechanism that causes fiber branching. | Hemoglobin, Sickle |
Halovirus PH1 infects Haloarcula hispanica and was isolated from an Australian salt lake. The burst size in single-step growth conditions was 50-100 PFU/cell, but cell density did not decrease until well after the rise (4-6 hr p.i.), indicating that the virus could exit without cell lysis. Virions were round, 51 nm in diameter, displayed a layered capsid structure, and were sensitive to chloroform and lowered salt concentration. The genome is linear dsDNA, 28,064 bp in length, with 337 bp terminal repeats and terminal proteins, and could transfect haloarchaeal species belonging to five different genera. The genome is predicted to carry 49 ORFs, including those for structural proteins, several of which were identified by mass spectroscopy. The close similarity of PH1 to SH1 (74% nucleotide identity) allowed a detailed description and analysis of the differences (divergent regions) between the two genomes, including the detection of repeat-mediated deletions. The relationship of SH1-like and pleolipoviruses to previously described genomic loci of virus and plasmid-related elements (ViPREs) of haloarchaea revealed an extensive level of recombination between the known haloviruses. PH1 is a member of the same virus group as SH1 and HHIV-2, and we propose the name halosphaerovirus to accommodate these viruses. | Haloarcula |
OBJECTIVES: This study is aimed to report a case of SV-related gastritis and the results of a systematic literature review of SV infections. METHODS: Following a case presentation, we systematically searched different databases (MEDLINE, PubMed, Scopus, Web of Science, EMBASE, google scholar) for the items sarcina," "ventriculi," "clostridium" with AND/OR. RESULTS: A total of 55 articles reporting 65 cases of Sarcina Ventriculi were found. Thus, 66 patients, including our case, were reviewed. The median age was 51 years (IQR: 0-87 years). Females accounted for 51% of cases. 68% of patients had one or more comorbidities. SV was isolated in the gastrointestinal tract (88%), respiratory (5%), urine (4%), and bloodstream (3%) systems. Upper endoscopy was performed in 52 patients (79%). Biopsies were obtained in all 52 cases and were normal in 23%. Surgery was warranted in 15 patients (23%), and specific antimicrobial therapy was delivered in 34 (52%) patients. Mortality was 14%. At follow-up, 88% of patients showed complete eradication of the SV infection. CONCLUSIONS: Upper gastrointestinal biopsy positive for SV should prompt an evaluation of the clinical conditions, considering the risk of gastric perforation is not negligible. Antibiotic therapy may eradicate the infection and prevent complications. Emergency surgery is required in case of source control." | Sarcina |
Mouse lines have been genetically selected to be alcohol Withdrawal Seizure Prone (WSP) or Resistant (WSR). The selection index is the severity of withdrawal handling-induced convulsions seen after removal of mice from chronic exposure to ethanol vapor. Behavioral, pharmacological, and neurochemical results from a replicated bidirectional selection project are reviewed. In reciprocal F1 crosses of the WSP and WSR lines, substantial dominance for resistance to withdrawal was found in both replicated sets of lines. WSP and WSR mice differ principally, and markedly, in traits related to the severity of withdrawal from alcohols and other drugs with depressant properties. This suggests that genes influencing severity of withdrawal from chronic ethanol exposure also pleiotropically influence genetic susceptibility to dependence on other drugs of abuse. However, the results of WSP vs. WSR comparisons for traits related to ethanol sensitivity and tolerance development suggest control in large part by genes different from those influencing withdrawal severity. | Alcohol Withdrawal Delirium |
Restorative dental procedures are ever developing; one reason for this can be attributed to newer materials with better handling properties and our ability to manipulate them more effectively. As a result various techniques have been described to aid clinicians in obtaining predictable results in restorative dental procedures. This article aims to review the use of plumber's tape to assist in adhesive, endodontic and implant related dental procedures, when compared to other available materials. | Fluorocarbon Polymers |
BACKGROUND: The aging of the population is likely to increase the number of osteoporosis-related fractures, such as hip fractures, and hence the economic burden for society. Therefore, strategies to identify women at increased risk are of major interest. OBJECTIVE: The aim of this study was to determine the cost effectiveness of preventive services for osteoporosis, comparing secondary plus tertiary prevention (SP/TP) versus tertiary prevention (TP) alone in post-menopausal women in Germany. METHODS: A cost-utility analysis and a budget-impact analysis were performed from the perspective of the German statutory health insurance (SHI). A Markov model simulated costs and benefits discounted at 3% over a lifetime horizon. RESULTS: Cost effectiveness of TP compared with no screening was 669 Euros, 477 Euros and 385 Euros per QALY for women aged 60, 70 and 80 years, respectively (year 2010 values). In women aged 50 years, TP dominated no prevention. Cost effectiveness of SP/TP compared with TP was 4543 Euros, 19791 Euros, 8670 Euros and 3368 Euros for women aged 50, 60, 70 and 80 years, respectively. SP/TP resulted in additional costs of 109 million Euros or 0.10% of the SHI's annual budget (TP alone = 8 million Euros). CONCLUSION: Compared with TP, a strategy based on SP/TP appears to be more expensive but more effective in each age group. Given that cost effectiveness seems acceptable, allocation of resources to SP/TP to decrease post-menopausal osteoporotic fracture risk may be justified. | Tertiary Prevention |
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used medications due to their prescription and nonprescription availability, various dosage formulations, and therapeutic efficacy. Although NSAIDs have many known benefits, their effects on gastrointestinal, cardiovascular, bone, and renal physiology limit their widespread and long-term use. This article provides an update on dosage formulations, product availability, and pertinent adverse effects and warnings regarding the use of NSAIDs, with an emphasis on nonaspirin NSAIDs." | Anti-Inflammatory Agents, Non-Steroidal |
Interleukin-6 upregulation leads to various acute phase reactions such as local inflammation and systemic inflammation in many diseases like cancer, multiple sclerosis, rheumatoid arthritis, anemia, and Alzheimer's disease stimulating JAK/STAT3, Ras/MAPK, PI3K-PKB/Akt pathogenic pathways. Since no small molecules are available in the market against IL-6 till now, we have designed a class of small bioactive 1,3 - indanedione (IDC) molecules for inhibiting IL-6 using a decagonal approach computational studies. The IL-6 mutations were mapped in the IL-6 protein (PDB ID: 1ALU) from thorough pharmacogenomic and proteomics studies. The protein-drug interaction networking analysis for 2637 FFDA-approved drugs with IL-6 protein using Cytoscape software showed that 14 drugs have prominent interactions with IL-6. Molecular docking studies showed that the designed compound IDC-24 (-11.8 kcal/mol) and methotrexate (-5.20) bound most strongly to the 1ALU south asian population mutated protein. MMGBSA results indicated that IDC-24 (-41.78 kcal/mol) and methotrexate (-36.81 kcal/mol) had the highest binding energy when compared to the standard molecules LMT-28 (-35.87 kcal/mol) and MDL-A (-26.18 kcal/mol). These results we substantiated by the molecular dynamic studies in which the compound IDC-24 and the methotrexate had the highest stability. Further, the MMPBSA computations produced energies of -28 kcal/mol and -14.69 kcal/mol for IDC-24 and LMT-28. KDeep absolute binding affinity computations revealed energies of -5.81 kcal/mol and -4.74 kcal/mol for IDC-24 and LMT-28 respectively. Finally, our decagonal approach established the compound IDC-24 from the designed 1,3-indanedione library and methotrexate from protein drug interaction networking as suitable HITs against IL-6. | Interleukin-6 Inhibitors |
Nuclear oncogene products have the potential to induce alterations in gene regulation leading to the genesis of cancer. The biochemical mechanisms by which nuclear oncoproteins act remain unknown. Recently, an oncogene, v-jun, was found to share homology with the DNA binding domain of a yeast transcription factor, GCN4. Furthermore, GCN4 and the phorbol ester-inducible enhancer binding protein, AP-1, recognize very similar DNA sequences. The human proto-oncogene c-jun has now been isolated, and the deduced amino acid sequence indicates more than 80 percent identity with v-jun. Expression of cloned c-jun in bacteria produced a protein with sequence-specific DNA binding properties identical to AP-1. Antibodies raised against two distinct peptides derived from v-jun reacted specifically with human AP-1. In addition, partial amino acid sequence of purified AP-1 revealed tryptic peptides in common with the c-jun protein. The structural and functional similarities between the c-jun product and the enhancer binding protein suggest that AP-1 may be encoded by c-jun. These findings demonstrate that the proto-oncogene product of c-jun interacts directly with specific target DNA sequences to regulate gene expression, and therefore it may now be possible to identify genes under the control of c-jun that affect cell growth and neoplasia. | Fusion Proteins, gag-onc |
AIM: The purpose of this article is to examine research studies that compared outcome measures of students/graduates of traditional and accelerated BSN programs. BACKGROUND: Accelerated postgraduate baccalaureate nursing programs are popular. It is important to compare outcome measures and explore equivalence between traditional and accelerated programs. METHOD: Peer-reviewed research articles published within the last six years were identified in ERIC, CINAHL, and MEDLINE. RESULTS: Seven research studies involving 1,159 traditional students and 576 accelerated students were included in this review. CONCLUSION: Findings indicate that although there were some statistically significant differences in outcomes between groups, research methodologies used in several of the studies were not ideal. Future research needs to be geared toward practice pattern differences between the two groups as well as research exploring evaluation methods. | Nursing Evaluation Research |
This study was designed to determine the most efficient dentin-cement-restorative material system to minimize temperature changes from either a hot (58 degrees C) or cold (4 degrees C) source. Extracted human molar teeth were used to conduct the experiment utilizing a standard Class I occlusal preparation 3.5 mm in diameter with a remaining dentin thickness of 0.5 or 1.0 mm and a control dentin thickness of 2.0 mm. A bi-electrode thermocouple was utilized with one thermocouple mounted on the roof of the pulp chamber and the other on the occlusal surface of the specimen. The cements investigated were zinc oxide and eugenol (ZOE), zinc phosphate (ZP), glass ionomer (GI), and zinc polycarboxylate (ZPC) with a thickness of either 0.5 mm or 1.5 mm. Statistical analysis consisted of a one-way analysis of variance followed by a multiple means comparison test. For heated specimens consisting of cement and dentin only, ZOE was the least effective in limiting temperature change. When cold was applied, ZOE was the most effective. Statistically for cold application, the other three cements, ZP, GI and ZPC, and 2.0 mm of dentin were the same for limiting temperature change. When amalgam was used to restore the tooth, ZOE and GI were most effective in limiting temperature change for cooled teeth. For heated teeth, all the cements were identical except for ZOE, which was the least effective. For composite restored teeth, all cements and dentin were identical in limiting temperature changes for either heating or cooling. | Zinc Phosphate Cement |
This review covers the isolation and structure determination of triterpenoids including squalene derivatives, lanostanes, cycloartanes, dammaranes, euphanes, tirucallanes, tetranortriterpenoids, quassinoids, lupanes, oleananes, friedelanes, ursanes, hopanes, isomalabicanes and saponins. The literature from January to December 2000 is reviewed and 277 references are cited. | Squalene |
Cell-cell fusion is a fundamental process that facilitates a wide variety of biological events in organisms ranging from yeast to humans. However, relatively little is actually understood with respect to fusion mechanisms. In the model organism Saccharomyces cerevisiae, mating of opposite-type cells is triggered by pheromone activation of the G protein-coupled receptors, alpha-factor receptor (Ste2p) and a-factor receptor (Ste3p), leading to mitogen-activated protein kinase signaling, growth arrest, and cellular fusion events. Herein we now provide evidence of a role for these receptors in the later cell fusion stage of mating. In vitro assays demonstrated the ability of the receptors to promote mixing of proteoliposomes containing phosphatidylserine, potentially based on a pheromone-dependent interaction between Ste2p and Ste3p that was confirmed by tandem affinity purification and cellular pull-down assays. The cellular mating activity of Ste2p was subsequently probed in vivo. Notably, a receptor-null yeast strain expressing N-terminally truncated Ste2p yielded a phenotype demonstrating wild-type signaling but arrested mating. The arrested prezygotes showed evidence of some cell wall erosion but no membrane juxtaposition at the fusion site. Further, in vitro analyses correlated this mutation with loss of the interaction between Ste2p and Ste3p and inhibition of related lipid mixing. Overall, these results support a role for a complex between activated yeast pheromone receptors in later cell fusion stages of mating, possibly mediating events at the level of cell wall digestion and membrane juxtaposition before membrane fusion. | Receptors, Mating Factor |
Germ cell and Sertoli cell numbers were estimated in six normal adult monkeys (Macaca fascicularis) using a contemporary unbiased and efficient stereological method--the optical disector. The data was used to assess the efficiency of spermatogenesis from type B spermatogonia to elongated spermatids. Animals underwent orchidectomy, and the right testis (volume 17.5 +/- 1.7 cm3 [mean +/- SEM], range 13.2-25.1 cm3) was fixed in Bouin's fluid. Blocks were embedded in methacrylate resin and germ cells were counted in thick (25 microm) sections using the optical disector in conjunction with a systematic uniform random-sampling protocol. The total numbers of Sertoli cells and all germ cells per testis were 566 +/- 43 (419-683) million and 12.8 +/- 1.6 (9.0-20.2) billion, respectively. On average, one Sertoli cell supported 12.4 +/- 1.9 (range 8.2-18.4) step 1-12 spermatids, 3.1 +/- 0.4 (2.3-4.5) pachytene spermatocytes, and 23.7 +/- 4.1 (15.0-39.0) total germ cells. Sertoli cell number correlated poorly with both testicular size (correlation coefficient r = -0.12) and germ cell numbers (r = -0.35 with total germ cell number). However, testicular size had a consistent and significant correlation with germ cell numbers (r = 0.97 with total germ cell number). The conversion ratio of pachytene spermatocytes to step 1-12 spermatids was 3.94 +/- 0.19, which is close to the theoretical maximum of 4. Similarly, the conversion between other cell types was consistently close to the maximum theoretical value. We conclude that the efficiency of spermatogenesis in the adult monkey is high, with stepwise conversion being consistently close to the maximal values. The capacity of Sertoli cells to support a cohort of germ cells varies widely between monkeys. Although absolute number of cells per testis is always the preferred parameter, it cannot always be obtained in an experimental situation where cost and ethical constraints mean that biopsies, rather than whole testes, are collected. Thus, if absolute data on germ cell numbers are not available, experimental outcomes impacting on cells beyond preleptonene spermatocytes may be best expressed in terms of changes in germ cell conversion rather than the traditional germ cell: Sertoli cell ratio. | Sertoli Cells |
BACKGROUND AND AIMS: Video capsule endoscopy (VCE) has become a major diagnostic tool for small-bowel evaluation. However, retention of the video capsule endoscope remains a major concern. METHODS: We performed a systematic review of VCE retention rates by using Pubmed and SCOPUS (1995-2015). We included studies that enrolled at least 10 patients, included VCE retention rates, and separated retention rates by indication. We used Comprehensive Meta-Analysis (Version 3.0) to calculate pooled prevalence rates with 95% confidence intervals (CIs) and assessed heterogeneity by using the Cochran Q statistic. RESULTS: We included 25 studies (N = 5876) for patients undergoing VCE for evaluation of potential small-bowel bleeding, 9 studies (N = 968) for patients with suspected inflammatory bowel disease (IBD), 11 studies (N = 558) for patients with established IBD, and 8 studies for patients (N = 111) undergoing VCE for evaluation of abdominal pain and/or diarrhea. We used a random effects model and found that the pooled retention rate was 2.1% for patients with suspected small-bowel bleeding (95% CI, 1.5%-2.8%). Retention rates were 3.6% (95% CI, 1.7%-8.6%) for suspected IBD, 8.2% (95% CI, 6.0%-11.0%) for established IBD, and 2.2% (95% CI, 0.9%-5.0%) for abdominal pain and/or diarrhea. Based on subgroup analysis, subsequent VCE completion rates after performance of a patency capsule or CT enterography in patients with IBD to exclude retentions due to strictures was 2.7% (95% CI, 1.1%-6.4%). Reasons for retention were provided in 60 (77%) studies. The most common reasons for retention were small-bowel strictures, although etiology was not provided in all studies. CONCLUSION: VCE retention occurs in approximately 2% of patients undergoing evaluation for small-bowel bleeding and is most likely due to small-bowel strictures. Retention rates in patients with suspected or known IBD were approximately 4% and 8%, based on our meta-analysis. These rates decreased by half in those studies that used either a patency capsule or CT enterography to assess patency before performing VCE. | Capsule Endoscopes |
The present study was to evaluate the effects of Ardipusilloside I isolated from Ardisia pusilla on the growth, vascular endothelial growth factor receptor (VEGFR) expression and apoptosis of NCI-H460 cell line by MTT, ELISA and flow cytometer, respectively. The docking assay between Ardipusilloside I and VEGFR was studied by Sybyl/Sketch module. The change of microstructure was observed by transmission electron microscope (TEM). DNA fragmentation was visualized by agarose gel electrophoresis. The protein expression of Bax and Bcl-2 was detected by immunohistochemistry (IHC). A series of changes were observed in NCI-H460 cell treated by Ardipusilloside I, including microstructure, DNA fragmentation, protein expression of VEGFR, Bax and Bcl-2. The results showed Ardipusilloside I had a good docking with VEGFR and could inhibit growth and induce apoptosis of NCI-H460 cell in a dose-dependent manner. Cell cycle was significantly stopped at the G(1) phase. Under electronic microscope, the morphology of NCI-H460 cell treated with Ardipusilloside I showed nuclear karyopycnosis, chromatin agglutination and typical apoptotic body. VEGFR and Bcl-2 expression were decreased and Bax expression was increased. In conclusion, all these results demonstrate that Ardipusilloside I has a good docking with VEGFR and has an inhibitory effect on growth of NCI-H460 cell and can induce its apoptosis. | Ardisia |
Tick paralysis is a preventable cause of morbidity and death that, when diagnosed promptly, requires a simple low-cost intervention. The key to success is to consider tick paralysis in the differential diagnosis of ascending weakness, particularly in children, in geographic areas where this disease predominates. | Tick Toxicoses |
Machine perfusion of marginal grafts might be a possible solution to organ shortage and a promising tool for reducing waiting list morbidity and mortality. In recent years, optimizing the circumstances of organ preservation prior to implantation via machine perfusion has become a hot topic of research. Machine perfusion offers a platform for organ reconditioning, assessment of cell viability and function, pharmacological preconditioning, prolongation of preservation time (ischemia time) and finally reducing graft injury. The objective of the new technology is to increase the pool of transplantable organs safely. Multicentric prospective studies have been evaluating the short and long term outcomes of different methods, however, several questions still remain unanswered. This review summarizes the recent advances in the field of machine perfusion, focusing on preclinical and clinical results. Machine perfusion seems to be a new milestone in the modern era of solid organ transplantation. Orv Hetil. 2018; 159(46): 1882-1890. | Transplantation |
Among termites, lower termites need symbiotic microorganisms in the digestive tract for digestion and cellulose metabolism. In this symbiotic relationship, the decomposition of cellulose is initiated by endoglucanase in termite salivary glands and completed by beta-glycosidase of symbiotic microorganisms in the hindgut. The expression of beta-glycosidase in lower termites has been reported in recent studies. The expression of two endoglucanases and one beta-glycosidase gene related to cellulose degradation was identified in Reticulitermes speratus, a lower termite, through transcriptomic analysis. The proposed enzyme activities of three identified cellulose degradation genes were confirmed by heterologous expression in Escherichia coli. In addition to the endoglucanase expressed in the salivary gland, additional endoglucanase and beta-glycosidase genes suggest that R. speratus performs the overall cellulose digestion using its own enzymes at all stages. | Cellulases |
A horse with colitis from Manitoba referred to the Veterinary Medical Centre, Western College of Veterinary Medicine, was diagnosed with Potomac horse fever (PHF). Polymerase chain reaction analysis of the feces confirmed Neorickettsia risticii infection. This is the first reported case of PHF in Manitoba. | Neorickettsia risticii |
KIAA2022 is an X-linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with KIAA2022 variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense KIAA2022 pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19-years-old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, cafe-au-lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10-years-old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified KIAA2022 variant c.652C > T(p.Arg218*) in Patient 1, and a novel nonsense de novo variant c.2707G > T(p.Glu903*) in Patient 2. We also summarized features of all reported males with KIAA2022 variants to date. This report not only adds knowledge of a novel pathogenic variant to the KIAA2022 variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, cafe-au-lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together. | Agonistic Behavior |
On the steep surfaces that are common in arboreal environments, many types of animals without claws or adhesive structures must use muscular force to generate sufficient normal force to prevent slipping and climb successfully. Unlike many limbed arboreal animals that have discrete gripping regions on the feet, the elongate bodies of snakes allow for considerable modulation of both the size and orientation of the gripping region. We quantified the gripping forces of snakes climbing a vertical cylinder to determine the extent to which their force production favoured economy or safety. Our sample included four boid species and one colubrid. Nearly all of the gripping forces that we observed for each snake exceeded our estimate of the minimum required, and snakes commonly produced more than three times the normal force required to support their body weight. This suggests that a large safety factor to avoid slipping and falling is more important than locomotor economy. | Boidae |
Factor (F) XIII deficiency is a congenital rare bleeding disorder (RBD), with an estimated prevalence of 1 in 1 to 2 million individuals, and more than 1,200 patients have been diagnosed to date. In newborns, umbilical cord bleeding is typical, and later in life during trauma, surgery and even spontaneously prolonged bleeds, reproduction, and delivery complications occur frequently without appropriate replacement therapy. Also, an acquired form of FXIII deficiency may occur via massive bleeds or neutralizing antibodies. In the inherited form of FXIII deficiency, prophylaxis with FXIII concentrate is administered to prevent the very high risk of intracranial bleeds, the incidence being close to 30%. Laboratory diagnosis of FXIII deficiency is based on measuring plasma FXIII antigen and activity, and it is claimed that FXIII activity of around 5 IU/dL would suffice to protect from bleeds. However, at the low levels of detection, most FXIII methods are inaccurate, and quality controls and collaboration with reference laboratories are important to improve the accuracy of low-level FXIII measurements. The trough target for prophylaxis should be set to 10 to 20 IU/dL, which is achievable by administration of 25 to 35 IU/kg every 4 to 6 weeks. However, general risk factors influencing hemostasis should be carefully evaluated, including anemia and hypertension. Fibrin cross-linking by FXIII is of major importance and red cells bind to fibrin partially via platelets and FXIII to promote clot strength. Physiologically, platelets and macrophages contain FXIII providing cellular support; thus, the patients may benefit from platelet transfusion during problematic bleeds. Plasma-derived and recently a recombinant FXIII concentrate are available; however, the latter has mainly anecdotal data regarding management of bleeds and surgery, and its access is limited due to the high cost. The international registry RBD database, (RBDD) continues to gain cumulative knowledge, and registration of all FXIII deficient patients, both inherited and acquired, is highly recommended. | Factor XIII |
Currently, no specific therapeutics are available for foodborne Shiga toxin-producing Escherichia coli (STEC) infections that cause severe gastroenteritis and life-threatening complications of hemolytic uremic syndrome (HUS). As STEC attachment to intestinal epithelium might increase the host absorption of Shiga toxins and severity of the disease, we were inspired to develop a bispecific neutralizer capable of blocking its Shiga toxin and adhesin intimin simultaneously. Two nanobodies against the B subunit of Shiga toxin 2 (Stx2B) and the C terminus of Intimin (IntC280) were genetically fused together as the bispecific neutralizer, and it can be efficiently produced in a conventional E. coli expression system. We demonstrated that each of the nanobody modules in the bispecific format showed increased antigen binding capability and was able to functionally neutralize the binding of Stx2B or IntC280 to the respective host receptors even in the presence of the two virulence factors together. Moreover, the bispecific neutralizer was relatively stable to harsh storage conditions and gastrointestinal pH extremes. Taking into account its easy and economical production and superior pharmaceutical properties, we believe that a nanobody-based bispecific neutralizer would be more favorable and practical to be developed as a therapeutic to fight STEC in the developing world." | Ribosome Inactivating Proteins |
In the presence study we demonstrated that hycanthone and chlorophenoxamine can modulate the resistance of multidrug resistant (MDR) murine L1210 leukemia tumor lines in vitro and in vivo. The circumvention of MDR by hycanthone and chlorophenoxamine in vitro was demonstrated by a short-term test using tritiated nucleic acid precursors and by flow cytometrical measurement of accumulation of rhodamine 123. Furthermore, we treated mice bearing resistant L1210 ascites cells with doxorubicin and hycanthone or chlorophenoxamine. Hycanthone in combination with doxorubicin significantly inhibited tumor growth. We also found an improved therapeutic effect of doxorubicin plus chlorophenoxamine. Our results in vitro and in vivo indicate that hycanthone and chlorophenoxamine might be appropriate tools for the circumvention of MDR in human tumors. | Hycanthone |
This study gathered data from U.S. and international needle exchange programs (NEPs). Of particular interest were outcome measures of dependent variables related to behaviors within social contexts of injection drug users (IDUs), an area not well understood. Thirty-one studies, with a total of 86 separate measures of 36 dependent variables were included. Because combining all results into a single meta-analysis would be inappropriate, dependent variables were placed into five categories for five separate meta-analyses: risky contexts, injection frequency, sharing drug paraphernalia, drug preparation, and syringe use. NEP attendance was inversely related to declines in all categorical behaviors except for risky context." NEP attenders are slightly more likely to be in a risky circumstance when injecting drugs than non-attenders. While injection frequency declined only slightly among NEP attenders, that result may be interpreted as a positive outcome, given the often-stated criticism that providing clean needles encourages increased drug use. NEP use was weakly associated with a decrease in the sharing of drug paraphernalia. Clean needles alone do not appear to be sufficient motivation to motivate major changes in contextual risk behaviors analyzed herein. Research is needed to assess the impact of interpersonal IDU relationships with other stakeholders (clinic employees, van drivers, medical personnel, nutritionists, sexual partners, etc.) on IDU drug-using behaviors at many levels." | Needle-Exchange Programs |
The ovine maedi-visna virus (MVV) was the first lentivirus to be isolated and characterized 1957 in Iceland. MVV leads to a life-long, persistent infection with slow development of lesions in the lung and the central nervous system (CNS). The main target cells of MVV are of the monocyte/macrophage lineage and it does not infect T-lymphocytes or cause immune suppression like human immune deficiency virus (HIV). In spite of a fairly good immune response, including both neutralizing antibodies and cytotoxic T lymphocytes, the virus persists in the host and establishes a life-long infection. There are strong indications that the pathological lesions are immune-mediated and vaccination attempts have not only failed to induce sterile immunity but have occasionally caused increased viremia and more severe disease. | Visna-maedi virus |
OBJECTIVE: 5-Oxoprolinuria is a rare inherited metabolic disorder caused by a defective gamma-glutamyl cycle resulting from mutations in the genes encoding 5-oxoprolinase (OPLAH) and glutathione synthetase (GSS). No inherited 5-oxoprolinuria case has been reported in mainland China until now. In this study, clinical, biochemical, and genetic aspects of five Chinese 5-oxoprolinuria patients with OPLAH or GSS gene mutations were investigated. METHODS: Three boys and two girls from five unrelated Chinese families with symptomatic 5-oxoprolinuria were identified within the past 3years in Peking University First Hospital. OPLAH and GSS genes were analyzed. RESULTS: Patients were hospitalized between the age of 13days to 1year and 3months for hypersomnia, developmental retardation, feeding deficiency, vomiting, icterus and recurrent pneumonia. All patients had significantly elevated urine 5-oxoproline. Three novel mutations (c.1904G>A and c.2813_2815delGGG in Patient 1, c.2978G>T in Patient 2) on OPLAH, on GSS, one novel mutation (c.1252C>T in Patient 3) and a reported mutation (c.491G>A in Patients 3-5) were detected. Patient 4 has homozygous mutation c.491G>A, the others are heterozygous. After treatment by l-carnitine, vitamin E, B1, B2 and coenzyme Q10, three patients with GSS deficiency improved, but the two 5-oxoprolinase-deficient patients did not respond to treatment. CONCLUSIONS: 5-Oxoprolinase deficiency and GSS deficiency share some clinical and biochemical features. Genetic analysis is important for the deferential diagnosis. In this study, five Chinese patients had severe central nervous system damage. Antioxidant treatments were proved effective for the three patients with GSS deficiency but not for the two patients with 5-oxoprolinase deficiency. | Pyroglutamate Hydrolase |
Transstadial and transovarial transmission of Anaplasma marginale by Dermacentor variabilis were attempted with with ticks exposed to the organism once by feeding as larvae or nymphs, and twice by feeding as larvae and nymphs. Typical colonies of A marginale were in gut tissues of adults that were infected as larvae, larvae and nymphs, and as nymphs; repeated exposure of ticks did not appear to result in an increase in the number of colonies in the gut of subsequently molted adults nor did it affect severity of the clinical disease that developed in cattle they fed on. In contrast, colonies of A marginale were not found in the midgut epithelium of unfed nymphs exposed as larvae, even though companion nymphs transmitted the parasite, causing severe clinical anaplasmosis in susceptible calves. The organism was not transmitted transovarially by F1 larvae or nymphs from the groups exposed as parent larvae, nymphs, larvae and nymphs, and as adults. Some of the calves fed on by F1 progeny had a few erythrocytic marginale bodies that looked suspiciously like A marginale, as well as postchallenge exposure prepatent periods that were longer than other calves in the transovarial transmission study. Sera from these calves were tested for antibody to A marginale, using a highly sensitive immunoblot technique. Antibodies were not detected in any of the sera. | Arachnid Vectors |
Shiitake dermatitis is a rare cutaneous reaction to lentinan, a polysaccharide component in the cell walls of shiitake mushrooms (Lentinula edodes). Herein, we systematically review the case report and case series English-language literature on shiitake dermatitis, which refers to a total of 50 patients (38 males, 12 females; mean age: 44.58 years). The majority of cases occurred after the consumption of raw mushrooms, whereas 22% of cases were caused by the eating of lightly or undercooked mushrooms. The most common clinical presentations, localized symptoms, and systemic findings include linear flagellated dermatitis (98%), pruritus (78%), and fever, diarrhea, and mucosal ulcers, respectively. The diagnosis of this entity continues to be based on clinical findings as laboratory abnormalities, and the findings of skin biopsies and patch/prick tests are nonspecific and inconsistent. The condition is self-limiting, resolving in approximately 12.5 d without treatment. Based on the included case reports, it appears that medical treatment may slightly shorten the course of disease (to 9-11 d, varying by therapy) but should be considered on an individual patient basis. However, the treatment of symptoms, reassurance, and the avoidance of re-exposure are sufficient treatment recommendations for this condition. | Mycotoxicosis |
A grossly obese woman was wrongly diagnosed throughout her adult life of having lymphoedema. Her condition was subsequently confirmed as lipoedema, an entirely different condition, which is noted in medical text books but is seldom taught to medical students or to general practitioners. The condition is caused by abnormal deposition of adipose tissue in the extremities (usually the lower limbs) and almost exclusively affects women. It often starts at puberty or may occur after pregnancy. The exact aetiology is not yet understood but genetic and hormonal factors may be implicated. The problem is that misdiagnosis leads to inappropriate tests and improper treatment to the patient. When recognised it is often too late to do anything for the patient and they become highly dependent on social care. This case describes how the diagnosis can be confirmed through an ultrasound image and illustrates the need for early recognition to facilitate specialist care. | Leg |
A best evidence topic was written according to a structured protocol. The question addressed was regarding the indication and timing of the use of cardiopulmonary bypass (CPB), following severe hypothermic cardiac arrest. A total of 284 papers were found using the reported searches, of which nine represented the best evidence to answer the clinical question. The authors, date, journal, study type, population, main outcome measures and results are tabulated. Reported measures were survival, rewarming speed, incidence of arrhythmia during rewarming, resolution of full neurological function, long-term neurological function, evidence of damage on neurological imaging and venous metabolic parameters in hypothermic patients. The most recent of the best evidence studies, a retrospective comparative study of 68 patients, demonstrated CPB rewarming to be far superior to conventional methods of rewarming, with mortality rates of 15.8 and 53.3%, respectively. Another study of similar size, comparing CPB with extracorporeal membrane oxygenation (ECMO) for rewarming, revealed superior survival rates with ECMO, 75 vs 34%. A systematic review of 68 patients demonstrated an overall survival of 60%, and 80% of survivors returning to a previous level of activity. Two smaller observational studies reported survival rates of 73.1 and 45.5%, respectively. A retrospective study analysing long-term neurological outcomes of survivors reported normal history and physical examination in 93.3%, normal neurovascular ultrasound in 100%, normal neuropsychological findings in 93.3% and normal brain magnetic resonance imaging in 86.7%. A small comparative study demonstrated a significant survival benefit when CPB was preceded with emergency thoracotomy, internal cardiac massage and warm mediastinal irrigation compared with CPB alone. We conclude that, following deep hypothermic circulatory arrest, the urgent use of cardiopulmonary bypass is widely indicated for rewarming where it has been shown to provide good survival and neurological outcomes far superior in comparison with conventional methods of rewarming." | Circulatory Arrest, Deep Hypothermia Induced |
INTRODUCTION: CD70 and CD27 constitute a ligand-receptor pair of the TNF ligand and receptor family which is of major importance for T-cell costimulation. In healthy individuals CD70 expression is restricted to activated T-cells, certain subsets of immune cells and to epithelial cells of the thymic medulla. CD27 is expressed by naive and memory T-cells and certain types of immune cells. Strikingly, CD70 is also often highly expressed on T- and B-cell lymphomas and on a considerable fraction of solid tumors. AREAS COVERED: Based on a brief description of the signaling mechanisms and immune regulatory activities of CD70 and CD27, this review is focused on strategies and concepts that exploit the function and expression pattern of these molecules for therapeutic purposes. EXPERT OPINION: Therapeutic strategies have been developed that either aim to trigger or inhibit CD27 activity or solely use CD70 as a tumor marker. Some of these strategies are currently under consideration in clinical trials and have shown a good safety profile. The identification of biomarkers and stratification concepts is now important to ensure that a chosen CD70/CD27 targeting strategy fits optimally to the dominant function(s) of CD70 and CD27 in the corresponding individual case. | CD27 Ligand |
We present a male patient born at 38-wk gestation with rhizomelic shortening of extremities, hepatomegaly, ventriculomegaly, heart failure, severely depressed left ventricular function, biventricular hypertrophy, and biatrial enlargement. Additional physical findings included anteriorly displaced anus, vertebral anomalies, and brachydactyly. The patient's cardiac malformations led to persistent hypotension, sinus tachycardia, and multiorgan failure in the absence of arrhythmias. Rapid whole-exome sequencing was ordered on day of life (DOL) 8. The patient's family elected to withdraw supportive care, and he passed away that evening. Whole-exome sequencing returned posthumously and identified a variant in NAA10, E100K. The genotype-phenotype was closest to Ogden syndrome or amino-terminal acetyltransferase deficiency. Typical features of this rare X-linked syndrome include progeroid appearance, failure to thrive, developmental delays, hypotonia, and cardiac arrhythmias. Other family members were tested and the patient's mother, who has a history of mild intellectual disability, as well as a daughter born later, were identified as carriers. All carriers showed no cardiac findings. The carrier sister has manifested developmental delay and cortical atrophy. Protein modeling, evolution, dynamics, population variant assessments, and immunoprecipitation depict the deleterious nature of the variant on the interactions of NAA10 with NAA15 These findings had subsequent implications for posthumous diagnosis of the index patient, for female carriers, and regarding family planning. We highlight how these rapid genetic tests and variant characterization can potentially lead to informed decision-making between health-care providers and family members of patients with critical or lethal conditions when treatment options are limited." | N-Terminal Acetyltransferase A |
Periprosthetic femur fractures after total knee arthroplasty are a rising concern; however, when properly diagnosed, they can be managed nonoperatively or operatively in the form of locking plate fixation, intramedullary nailing, and arthroplasty. The degree of osteoporosis, stability of the femoral implant, and goals of the patient are a few critical variables in determining the ideal treatment. Despite excellent outcomes from each of these operative choices, the risk of nonunion, malunion, instability, and refracture cannot be ignored. | Periprosthetic Fractures |
During the evolution of the different species classified within the Saccharomyces genus, each one has adapted to live in different environments. One of the most important parameters that have influenced the evolution of Saccharomyces species is the temperature. Here we have focused on the study of the ability of certain species as Saccharomyces kudriavzevii to grow at low temperatures, in contrast to Saccharomyces cerevisiae. We observed that S. kudriavzevii strains isolated from several regions are able to synthesize higher amounts of glycerol, a molecule that has been shown to accumulate in response to freeze and cold stress. To explain this observation at the molecular level we studied the expression of glycerol biosynthetic pathway genes and we observed a higher expression of GPD1 gene in S. kudriavzevii compared to S. cerevisiae in micro-vinification conditions. We observed higher enzymatic activity of Gpd1p in S. kudriavzevii in response to osmotic and cold stress. Also, we determined that S. kudriavzevii Gpd1p enzyme presents increased catalytic properties that will contribute to increase glycerol production. Finally, we evaluated the glycerol production with S. cerevisiae, S. kudriavzevii or a recombinant Gpd1p variant in the same background and observed that the S. kudriavzevii enzyme produced increased glycerol levels at 12 or 28 degrees C. This suggests that glycerol is increased in S. kudriavzevii mainly due to increased V max of the Gpd1p enzyme. All these differences indicate that S. kudriavzevii has changed the metabolism to promote the branch of the glycolytic pathway involved in glycerol production to adapt to low temperature environments and maintain the NAD(+)/NADH ratio in alcoholic fermentations. This knowledge is industrially relevant due to the potential use, for example, of S. cerevisiae-S. kudriavzevii hybrids in the wine industry where glycerol content is an important quality parameter." | Glycerolphosphate Dehydrogenase |
Although fibrates was a medicine with a long history, at the clinical spot, the profitability had not permeated as compared with statin. However, many-sided effects, such as a fall of a cardiovascular event and control of arteriosclerosis prevention and a diabetic microangiopathy, were reported as a result of the large-scale clinical test in recent years. Accumulation of the further clinical evidence of a fibrates is expected. | Fibric Acids |
A hyperthermophilic, autotrophic iron and nitrate reducer, strain Su06T, was isolated from an active deep-sea hydrothermal vent chimney on the Endeavour Segment in the north-eastern Pacific Ocean. It was obligately anaerobic, hydrogenotrophic and reduced Fe(III) oxide to magnetite and NO3- to N2. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain was more than 97 % similar to other species of the genera Pyrodictium and Hyperthermus. Therefore, overall genome relatedness index analyses were performed to establish whether strain Su06T represents a novel species. For each analysis, strain Su06T was most similar to Pyrodictium occultum PL-19T. Relative to this strain, the average nucleotide identity score for strain Su06T was 72 %, the genome-to-genome direct comparison score was 13-19 % and the species identification score at the protein level was 89 %. For each analysis, strain Su06T was below the species delineation cutoff. Based on its whole genome sequence and its unique phenotypic characteristics, strain Su06T is suggested to represent a novel species of the genus Pyrodictium, for which the name Pyrodictium delaneyi is proposed. The type strain is Su06T (=DSM 28599T=ATCC BAA-2559T). | Pyrodictiaceae |
Disulfiram (DSF) is nontoxic and exerts anticancer activity by forming highly toxic chelates via its metabolite diethyldithiocarbamate with transition metal ions. However, there are not enough such ions in the human body to maintain the therapeutic effect. Herein, we report nanogels that complex copper ions or cis-platinum (CDDP) for tumor metal delivery to potentiate DSF's antitumor efficacy. We synthesized zwitterionic poly[N-(3-(methacryloyloxy-2-hydroxy)propyl)]-N-methyl glycine (PGMA-SAR) capable of chelating copper ions or CDDP and formed nanogels with suitable size and zeta potential. The intravenously injected nanogels circulated long in the blood compartment and delivered a high concentration of metal ions to the tumor. Separately administered DSF could sequester the metal ions from the nanogels and form highly cytotoxic complexes with potent in vitro and in vivo anticancer activity. This study provides a new strategy to potentiate DSF in anticancer treatment. | Ditiocarb |
Orthostatic hypotension is the most incapacitating symptom of autonomic failure. This disorder occurs with both central autonomic neurodegenerative disorders, such as multiple system atrophy and Parkinson's disease, and peripheral autonomic disorders, such as the autonomic peripheral neuropathies and pure autonomic failure. The hallmark of both central and peripheral causes of neurogenic orthostatic hypotension is the failure to release norepinephrine appropriately upon standing. Patient education is the cornerstone of management. There are several measures that can be implemented to improve orthostatic tolerance prior to pharmacological intervention. Plasma volume expansion is essential to improve orthostatic tolerance, and fluid and sodium chloride intake should be increased. Most patients can be treated successfully with volume expansion or fludrocortisone or both in combination with a sympathomimetic agent. Desmopressin acetate and erythropoietin are useful supplementary agents in patients with more refractory symptoms. There are rare patients who will require additional agents to treat their symptoms. A small group of patients remain refractory to all therapeutic modalities. | Sympathomimetics |
As an educational concept based on learning output, OBE (Outcome-Based Education) is student-centered and emphasizes students' personal progress and learning achievement. Based on BD (big data) analysis, this paper proposes a new talent training mode for the electronic information science and technology specialty. This model employs BD analysis technology to examine the correlation index between social demand and talent cultivation, based on the employment situation of students in the country in previous years. The teaching reform was carried out under the OBE concept, and a new training scheme was formed. Training objectives, graduation requirements, curriculum system, and continuous improvement mechanism were all determined. This paper proposes an algorithm for determining the degree of similarity between the knowledge required by the organization and the knowledge held by its employees. The person with the highest similarity is identified as the training candidate by the algorithm, and the training candidate is then trained according to the knowledge that the organization requires. Talent training in the field of electronic information science and technology has yielded positive results. | Data Analysis |
Captopril was the first oral angiotensin-converting enzyme (ACE) inhibitor available and, as such, has been extensively studied and in clinical use for many years. Several studies have defined captopril's efficacy in the treatment of congestive heart failure (CHF) as well as determined its safety profile. The most common adverse hematologic reactions associated with captopril use include neutropenia and agranulocytosis. This paper describes an uncommon and a potentially serious hematologic side effect associated with captopril-hemolytic anemia. | Anemia, Hemolytic |
Methylated L-arginine analogs are involved in nitric oxide synthase activity regulation. Methods based on high-performance liquid chromatography with fluorescence, capillary electrophoresis, or ion exchange chromatography with absorbance detection were first applied for the quantitative determination of N-monomethyl-L-arginine (NMMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in human blood and urine. These assays revealed elevated circulating levels of ADMA in various diseases and gave accumulating evidence of the usefulness of ADMA as a cardiovascular risk factor. However, the methods used are hampered by the fact that NMMA, ADMA and SDMA can be distinguished from L-arginine only by means of chromatographic separation. This has promoted the development of alternatives that involve mass spectrometry (MS) technology. Today, various MS-based approaches such as liquid chromatography (LC)-MS, LC-MS/MS, gas chromatography (GC)-MS, and GC-MS/MS are available. L-arginine and its analogs have been subjected to LC-MS analysis with and without further derivatization to their o-phthaldialdehyde derivatives. For these methods, labelled L-arginine was used as the internal standard. The first MS-based method that distinguishes NMMA, ADMA, SDMA and L-arginine by mass-to-charge (m/z)-ratio has been reported by Tsikas et al. This GC-MS approach has been further improved by Albsmeier et al by introducing labelled ADMA as an internal standard. As an alternative to existing methods, a commercially available ELISA kit has recently been developed and validated. | omega-N-Methylarginine |
Fear of flying, its nature, prevalence, etiology and treatment, has been the subject of a substantial quantity of research over the past 30 years. With the exception of a dated review of treatment methods however, there has been no evaluation of this expanding body of evidence, its contribution to theory and influence on clinical practice. Published research has also generally failed to apply developments in the understanding and treatment of anxiety disorders generally to fear of flying. This review provides a critical evaluation of the existing literature and what it reveals about theory and practice. It does this from the perspective of Cognitive Behavioural Therapy. The evidence reviewed demonstrates that fear of flying is a heterogeneous phenomenon which is acquired under the influence of complex psychological, social and physiological factors unique to each affected individual. Effective psychological interventions must therefore be founded on a comprehensive functional assessment of each individual, a finding which is considered in detail in the second part of this review. | Phobic Disorders |
Mentalization-based treatment (MBT) has demonstrated robust effectiveness in the treatment of borderline personality disorder (BPD) in both day-hospital (MBT-DH) and intensive outpatient MBT (MBT-IOP) programs. Given the large differences in intensity and associated treatment costs, there is a need for studies comparing their cost-effectiveness. A health economic evaluation of MBT-DH versus MBT-IOP was performed alongside a multicenter randomized controlled trial with a 36-month follow-up. In three mental health-care institutions in the Netherlands, 114 patients were randomly allocated to MBT-DH (n = 70) or MBT-IOP (n = 44) and assessed every 6 months. Societal costs were compared with quality-adjusted life years (QALYs) gained and the number of months in remission over 36 months. The QALY gains over 36 months were 1.96 (SD = .58) for MBT-DH and 1.83 (SD = .56) for MBT-IOP; the respective number of months in remission were 16.0 (SD = 11.5) and 11.1 (SD = 10.7). Societal costs were euro106,038 for MBT-DH and euro91,368 for MBT-IOP. The incremental cost for one additional QALY with MBT-DH compared with MBT-IOP was euro107,000. The incremental cost for 1 month in remission was almost euro3000. Assuming a willingness-to-pay threshold of euro50,000 for a QALY, there was a 33% likelihood that MBT-DH is more cost-effective than MBT-IOP in terms of costs per QALY. Although MBT-DH leads to slightly more QALYs and remission months, it is probably not cost-effective when compared with MBT-IOP for BPD patients, as the small additional health benefits in MBT-DH did not outweigh the substantially higher societal costs. (PsycInfo Database Record (c) 2023 APA, all rights reserved). | Mentalization-Based Therapy |
Purpose: Fear of movement, or kinesiophobia, is a risk factor for developing chronic post-surgical pain (CPSP) and may impede recovery. Identifying people with kinesiophobia peri-operatively is potentially valuable to intervene to optimize rehabilitation and prevent CPSP. This narrative review aims to describe and critically appraise the sensibility and measurement properties of the Tampa Scale of Kinesiophobia (TSK) in the surgical setting in both pediatric and adult populations.Material and methods: PubMed was searched for relevant articles using search terms related to the TSK and measurement properties; the search was restricted to articles published in English. COSMIN guidelines were used to rate measurement property sufficiency and study quality.Results: Four articles examined the measurement properties of the TSK-17 in the surgical setting. Included studies demonstrated sufficient internal consistency, structural validity, construct validity, but insufficient predictive validity. Study quality was variable. Although the TSK was not originally intended for the surgical setting, with minor modification, it appears sensible to use in this population.Conclusions: The TSK is a sensible tool to measure fear of movement in children and adults undergoing, or who underwent, surgery. Future studies are needed to test content validity, test-retest reliability, measurement error, and responsiveness in the surgical setting.IMPLICATIONS FOR REHABILITATIONFear of movement is a predictor of developing chronic post-surgical pain in children and adults.Rehabilitation interventions can address fear of movement in hopes to optimize surgical outcomes and prevent chronic post-surgical pain.The Tampa Scale of Kinesiophobia (TSK), with minor modification, is a sensible tool to measure fear of movement in surgical settings.There is some evidence that the TSK is reliable and valid to use with older children, adolescents, and adults who are undergoing or underwent surgery. | Kinesiophobia |
Aspiration of a foreign body is common in children and can cause upper airway obstruction, leading to significant morbidity or mortality. We report 3 cases of aspiration of a popular fruit-flavored gel snack that led to cardiopulmonary arrest and death in 1 case and respiratory failure in 2 other cases. There is increasing concern about the safety of this gel snack and its risk of aspiration, even in older children. Pediatricians should advise parents and children about the dangers of eating this candy during their health maintenance visits. | Candy |
The decades-long ultrafast examination of nearly a dozen microbial retinal proteins, ion pumps, and sensory photoreceptors has not identified structure-function indicators which predict photoisomerization dynamics, whether it will be sub-picosecond and ballistic or drawn out with complex curve-crossing kinetics. Herein, we report the emergence of such an indicator. Using pH control over retinal isomer ratios, photoinduced transient absorption is recorded in an inward proton pumping Antarctic microbial rhodopsin (AntR) for 13-cis and all-trans retinal resting states. The all-trans fluorescent state decays with 1 ps exponential kinetics. In contrast, in 13-cis it decays within approximately 300 fs accompanied by continuous spectral evolution, indicating ballistic internal conversion. The coherent wave packet nature of 13-cis isomerization in AntR matches published results for bacteriorhodopsin (BR) and Anabaena sensory rhodopsin (ASR), which also accommodate both all-trans and 13-cis retinal resting states, marking the emergence of a first structure-photodynamics indicator which holds for all three tested pigments. | Photoreceptors, Microbial |
In this report, we present comprehensive recommendations for the diagnosis and treatment of large hemispheric infarction (LHI). A systematic literature search was conducted until June 30, 2010. The American Heart Association Stroke Council's Levels of Evidence grading algorithm was used to grade each recommendation (Table 1). The guideline was revised after several official meetings with local experts, and was reviewed by 3 expert reviewers. Early diagnosis of malignant large hemispheric infarction (MLHI) is critical. Studies have shown that using computed tomography (CT) or transcranial sonography to track midline shifting of the cerebrum and applying diffusion-weighted magnetic resonance imaging might contribute to the early recognition of MLHI. Glycerol and mannitol should be administered only when a patient shows evidence of brain edema or mass effect. The effect of barbiturate coma on improving prognosis is inconclusive and requires close monitoring of the patient. Meanwhile, using steroids on patients with stroke is not recommended. The effect of hyperventilation on reducing intracranial pressure is rapid but short-lived, and is used only in emergency situations. The target levels of PaCO2 are 30-35 mmHg. Moderate hypothermia (32-34 degrees C) may be effective in controlling intracranial hypertension, but should be used cautiously along with rigorous monitoring. Timely decompressive craniectomy can probably offer patients a better chance of survival and quality of life. Usually, surgery for MLHI is indicated in patients with clinical deterioration associated with a significant mass effect, as observed on neuroimaging. However, with a reliable indicator of MLHI, early decompressive craniectomy before clinical deterioration may further reduce mortality and lead to a better functional outcome. | Brain Infarction |
BACKGROUND: Persistent formal thought disorder (FTD) is a core feature of schizophrenia. Recent cognitive and neuroimaging studies indicate a distinct mechanistic pathway underlying the persistent positive FTD (pFTD or disorganized thinking), though its structural determinants are still elusive. Using network-based cortical thickness estimates from ultra-high field 7-Tesla Magnetic Resonance Imaging (7T MRI), we investigated the structural correlates of pFTD. METHODS: We obtained speech samples and 7T MRI anatomical scans from medicated clinically stable patients with schizophrenia (n = 19) and healthy controls (n = 20). Network-based morphometry was used to estimate the mean cortical thickness of 17 functional networks covering the entire cortical surface from each subject. We also quantified the vertexwise variability of thickness within each network to quantify the spatial coherence of the 17 networks, estimated patients vs. controls differences, and related the thickness of the affected networks to the severity of pFTD. RESULTS: Patients had reduced thickness of the frontoparietal and default mode networks, and reduced spatial coherence affecting the salience and the frontoparietal control network. A higher burden of positive FTD related to reduced frontoparietal thickness and reduced spatial coherence of the salience network. The presence of positive FTD, but not its severity, related to the reduced thickness of the language network comprising of the superior temporal cortex. CONCLUSIONS: These results suggest that cortical thickness of both cognitive control and language networks underlie the positive FTD in schizophrenia. The structural integrity of cognitive control networks is a critical determinant of the expressed severity of persistent FTD in schizophrenia. | Brain Cortical Thickness |
The array of results discussed in this paper is assembled by stage of gestation in the following table (Table 1). We must allow some uncertainty for some outcomes as to the precise stages of gestation in which they originate. For instance, with obesity, the effects of famine exposure may extend beyond the first trimester into the second. Yet, the table is perhaps sufficient in itself to support the point with which the paper opened, namely, that stage of development is crucial to the appreciation of the effects of prenatal nutrition. | Starvation |
We are providing an update to our previously published review paper on inhaled nanoparticles, thus updating with the most recent reports in the literature. The field of nanotechnology may hold the promise of significant improvements in the health and well-being of patients, as well as in manufacturing technologies. The knowledge of the impact of nanomaterials on public health is limited so far. This paper reviews the unique size-controlled properties of nanomaterials, their disposition in the body after inhalation, and the factors influencing the fate of inhaled nanomaterials. The physiology of the lungs makes it an ideal target organ for non-invasive local and systemic drug delivery, especially for protein and poorly water-soluble drugs that have low oral bioavailability via oral administration. More recently, inhaled nanoparticles have been reported to improve therapeutic efficacies and decrease undesirable side effects via pulmonary delivery. The potential application of pulmonary drug delivery of nanoparticles to the lungs, specifically in context of published results reported on nanomaterials in environmental epidemiology and toxicology is reviewed in this paper. This article presents updated delivery systems, process technologies, and potential of inhaled nanoparticles for local and systemic therapies administered to the lungs. The authors acknowledge the contributions of Wei Yang in our 2008 paper published in this journal. | Administration, Inhalation |
Intraocular liquids tamponade agents, such as perfluorocarbon liquids (PFCLs), semifluorinated alkanes (SFAs), silicone oils (SOs) and heavy silicone oils (HSOs), are a crucial intraoperative and/or postoperative tool in vitreoretinal surgery, in particular for the management of complex vitreoretinal diseases. However, their use is not without complications, which are potentially severe. Consequently, a growing interest has been devoted to the biocompatibility of these compounds and the adequacy of current regulations that should guarantee their safety. Obviously, an updated knowledge on research findings and potential risks associated to the use of intraocular liquid compounds is essential, not only for vitreoretinal surgeons, but also for any ophthalmologist involved in the management of patients receiving intraocular liquid tamponades. In light of this, the review provides a comprehensive characterisation of intraocular liquid tamponades, in terms of physical and chemical properties, current clinical use and possible complications. Moreover, this review focuses on the safety profile of these compounds, summarising the existing regulation and the available evidence on their biocompatibility. | Vitreoretinal Surgery |
Nimodipine is a 1,4-Dihydropyridine type calcium antagonist routinely used to control blood pressure and reduce the risk of secondary ischemia after aneurismal subarachnoid hemorrhage. Additionally, Nimodipine has unique neuroprotective properties. With respect to brain related applications, the full potential of the desired local effect can often not be realized after systemic administration due to systemic side effects. Therefore, it was our aim to develop a biodegradable drug delivery system for the local controlled release of the drug inside the brain. As a suitable and biodegradable system we successfully electrospun PLGA fibers containing 1 and 10% drug. The results of DSC and X-Ray diffractometry measurements indicate that Nimodipine was incorporated in the polymer matrix in the amorphous state. No drug recrystallization was detected for up to 6 months. Electron-beam sterilization was tried but reduced the drug content of the fiber mats considerably. A sustained drug release over 4-8 days was observed, highly depended on release conditions. The Nimodipine fiber mats exhibited no cell toxicity. In contrast, the electrospun fibers were able to significantly reduce cell death in in vitro cell models of oxidative, osmotic and heat-induced cell stress in Schwann cells, neuronal cells as well as immortalized and primary astrocytes. Therefore, electrospun Nimodipine loaded PLGA fibers represent a promising drug delivery system to realize the drugs benefits for its intracranial use. | Nimodipine |
'Simple' hunter-gatherer populations adopt the social norm of 'demand sharing', an example of human hyper-cooperation whereby food brought into camps is claimed and divided by group members. Explaining how demand sharing evolved without punishment to free riders, who rarely hunt but receive resources from active hunters, has been a long-standing problem. Here we show through a simulation model that demand-sharing families that continuously move between camps in response to their energy income are able to survive in unpredictable environments typical of hunter-gatherers, while non-sharing families and sedentary families perish. Our model also predicts that non-producers (free riders, pre-adults and post-productive adults) can be sustained in relatively high numbers. As most of hominin pre-history evolved in hunter-gatherer settings, demand sharing may be an ancestral manifestation of hyper-cooperation and inequality aversion, allowing exploration of high-quality, hard-to-acquire resources, the evolution of fluid co-residence patterns and egalitarian resource distribution in the absence of punishment or warfare. | Diet, Paleolithic |
To investigate the biogeographical history of ashes species of the Eurasian section Fraxinus and to test the hypothesis of ancient reticulations, we sequenced nuclear DNA (nETS and nITS, 1075 bp) for 533 samples and scored AFLP for 63 samples of Eurasian ashes within the section Fraxinus. The nITS phylogeny retrieved the classical view of the evolution of the section, whereas nETS phylogeny indicated an unexpected separation of F. angustifolia in two paraphyletic groups, respectively found in southeastern Europe and in the other parts of the Mediterranean basin. In the nETS phylogeny, the former group was closely related to F. excelsior, whereas the later was closely related to F. mandshurica, a species which is restricted nowadays to northeastern Asia. This topological incongruence between the two loci indicated the occurrence of an ancient reticulation between European and Asian ash species. Several other ancient reticulation events between the two European species and the other species of the section were supported by the posterior predictive checking method. Some of these reticulation events would have occurred during the Miocene, when climatic variations may have lead these species to expand their distribution range and come into contact. The recurrent reticulations observed among Eurasian ash species indicate that they should be considered as conspecific taxa, with subspecific status for some groups. Altogether, the results of the present study provide a rare documented evidence for the occurrence of multiple ancient reticulations within a group of temperate tree taxa with modern disjunct distributions in Eurasia. These ancient reticulation events indicate that the speciation process is slow in ashes, necessitating long periods of geographical isolation. The implications for speciation processes in temperate trees with similar life history and reproductive biology are discussed. | Fraxinus |
The 3' end of the human T-cell leukemia/lymphoma virus type-1 (HTLV-1) genome contains four overlapping open reading frames (ORF) that encode regulatory proteins. Here, we review current knowledge of HTLV-1 orf-I and orf-II protein products. Singly spliced mRNA from orf-I encodes p12, which can be proteolytically cleaved to generate p8, while differential splicing of mRNA from orf-II results in production of p13 and p30. These proteins have been demonstrated to modulate transcription, apoptosis, host cell activation and proliferation, virus infectivity and transmission, and host immune responses. Though these proteins are not essential for virus replication in vitro, p8, p12, p13, and p30 have an important role in the establishment and maintenance of HTLV-1 infection in vivo. | Human T-lymphotropic virus 1 |
With the bluetongue virus serotype 8 (BTV-8) outbreak in 2006, vector monitoring programmes (according to EU regulation 1266/2007) were implemented by European countries to obtain information on the spatial distribution of vectors and the vector-free period. This study investigates the vector monitoring programmes in Austria and Switzerland by performing a retrospective cost analysis for the period 2006-2010. Two types of costs were distinguished: costs financed directly via the national bluetongue programmes and costs contributed in-kind by the responsible institutions and agricultural holdings. The total net costs of the monitoring programme in Austria amounted to euro1,415,000, whereby in Switzerland the costs were valued at euro94,000. Both countries followed the legislation complying with requirements, but differed in regard to sampling frequency, number of trap sites and sampling strategy. Furthermore, the surface area of Austria is twice the area of Switzerland although the number of ruminants is almost the same in both countries. Thus, for comparison, the costs were normalised with regard to the sampling frequency and the number of trap sites. Resulting costs per trap sample comprised euro164 for Austria and euro48 for Switzerland. In both countries, around 50 per cent of the total costs can be attributed to payments in-kind. The benefit of this study is twofold: first, veterinary authorities may use the results to improve the economic efficiency of future vector monitoring programmes. Second, the analysis of the payment in-kind contribution is of great importance to public authorities as it makes the available resources visible and demonstrates how they have been used. | Bluetongue |
The effect of sublethal concentrations of antibiotics on the serum sensitivity of Pseudomonas aeruginosa was examined. Cefepime, ceftazidime, and imipenem but not amikacin nor ciprofloxacin increased the serum bactericidal activity of pooled normal human serum. Killing was both serum- and antibiotic dose-dependent. Increased sensitivity to the bactericidal action of serum in the presence of cefepime was observed for several different clinical isolates. With the use of C8-deficient sera, the late components of the complement pathway were shown to be essential for bacterial killing. A significant increase in the amount of [125I]C9 based on bacterial mass was observed with bacteria incubated with cefepime compared with non-antibiotic- or amikacin-treated controls. No major change in the amount of type of lipopolysaccharide was observed when cefepime-treated and control bacteria were compared. The data show that cefepime and other cephalosporins at sublethal concentrations increase the complement-mediated bactericidal activity of serum against P. aeruginosa. | Serum Bactericidal Test |
Myasthenia gravis, focal to the larynx, should be considered in the differential diagnosis of intermittent breathy dysphonia and aponia. A 20-year-old woman had intermittent breathy dysphonia and aphonia as the sole manifestation of myasthenia gravis. The vocal cords were flaccid, and adducted to the paramedian position for phonation. Improvement of laryngeal function was demonstrated with edrophonium and neostigmine bromide. Therapy with pyridostigmine bromide (Mestinon) maintained normal phonation. | Phenylammonium Compounds |
BACKGROUND: Protamine is commonly used in cardiac surgery to reverse the anticoagulant effects of heparin. We investigated the role of different nitric oxide synthase pathways in the response of the human internal thoracic artery to protamine and evaluated whether heparin could prevent this effect. METHODS: A tension-recording method was used to obtain baseline measurements of contractions of human internal thoracic artery rings achieved with norepinephrine. Isolated internal thoracic artery rings were suspended in two organ chambers. One contained Krebs-Henseleit solution and served as control. The other contained a heparin or Nomega-Nitro-L-arginine (L-NAM, an inhibitor of both endothelial and inducible nitric oxide synthase) or a specific inhibitor of inducible nitric oxide synthase, aminoguanidine. Increasing doses of protamine were added to both chambers and dose-response curves were obtained. RESULTS: Protamine was found to relax contracted internal thoracic arteries 56% +/- 4.7% of baseline measurements in a concentration-dependent manner. When L-NAM was added, protamine caused only a slight decrease of tension. There were no differences in the relaxing effect of protamine in the presence of aminoguanidine or heparin. CONCLUSIONS: Protamine induces nitric oxide-dependent relaxation of the internal thoracic artery by activation of endothelial nitric oxide synthase pathway. Heparin could not prevent this relaxing effect of protamine. | Thoracic Arteries |
OBJECTIVES: Despite the progress in the diagnosis and treatment of breast cancer, it remains a major health problem in women. Natural flavones along with chemotherapeutic agents enhance therapeutic response and minimize toxicity of chemical agents. Centchroman (CC) colloquially called as ormeloxifene, is a nonsteroidal oral contraceptive categorized as selective estrogen receptor modulator with anti-breast cancer activity. Genistein (GN), an isoflavone found mainly in soy products possesses anti-cancerous potential against a number of cancers including breast. The present study aims at investigating the combination of CC and GN in human breast cancer cell lines (HBCCs). MATERIALS AND METHODS: Cytotoxic effect of CC and GN separately and in combination were assessed by sulforhodamine B (SRB) assay in MDA MB-231, MDA MB-468, MCF-7, T-47D HBCCs, and nontumorigenic human mammary epithelial cell (HMEC) MCF-10A. The drug interaction was analyzed using CompuSyn software through which combination index and dose reduction index were generated. RESULTS: Combination of CC plus GN exerts significantly higher cytotoxicity compared to each drug per se in HBCCs, whereas HMEC-MCF-10A remains unaffected. CONCLUSION: On an overall basis, the drugs in combination enhanced cell killing in malignant cells. Therefore, the combination of CC with GN may offer a novel approach for the breast cancer. | Centchroman |
Lysozyme acts as an innate immunity molecule against pathogen infection. In this study, a new G-type lysozyme gene with a typical G-type lysozyme domain (designated as Ec-lysG) was cloned and characterized from the orange-spotted grouper, Epinephelus coioides. The full-length Ec-lysG cDNA contains 1419 bp and encodes a 256-residue protein containing a 25-residue signal peptide at the N-terminus. BLAST analysis reveals Ec-lysG shares 64% identity with Siniperca chuatsi, but 63% to another reported G-type lysozyme from orange-spotted grouper (OSG-lysG). The genomic DNA of Ec-lysG contains four exons and three introns, with a total length of 2062 bp. An amino acid sequence alignment showed that Ec-lysG shares the fundamental structural features of G-type lysozyme, including the catalytic residues, substrate binding sites, and soluble lytic transglycosylase domain. Quantitative PCR showed that Ec-lysG transcript is most abundant in the head kidney, and less abundant in the heart. The expression of Ec-lysG was differentially upregulated in the head kidney after stimulation with lipopolysaccharide, Vibrio alginolyticus, and Singapore grouper iridovirus (SGIV). A subcellular localization analysis showed that Ec-lysG is distributed predominantly in the cytoplasm. Recombinant Ec-lysG (rEc-lysG) has optimal activity at pH 7.5 and 35 degrees C. rEc-lysG showed lytic activities against Gram-positive bacterium Streptococcus iniae, Staphylococcus aureus, and Micrococcus lysodeikticus, and the Gram-negative bacterium V. alginolyticus. Scanning electron microscopy (SEM) showed that rEc-lysG acts on M. lysodeikticus cell walls. The overexpression of Ec-lysG in grouper cells did not significantly delay the occurrence of the cytopathic effect (CPE) induced by SGIV, and did not inhibit viral gene transcription. In conclusion, Ec-lysG might be a potent antibacterial protein, with a role in innate immunity. | Head Kidney |
Using indirect immunofluorescence we have examined the effects of reagents which inhibit the function of ras-related rab small GTP-binding proteins and heterotrimeric G alpha beta gamma proteins in ER to Golgi transport. Export from the ER was inhibited by an antibody towards rab1B and an NH2-terminal peptide which inhibits ARF function (Balch, W. E., R. A. Kahn, and R. Schwaninger. 1992. J. Biol. Chem. 267:13053-13061), suggesting that both of these small GTP-binding proteins are essential for the transport vesicle formation. Export from the ER was also potently inhibited by mastoparan, a peptide which mimics G protein binding regions of seven transmembrane spanning receptors activating and uncoupling heterotrimeric G proteins from their cognate receptors. Consistent with this result, purified beta gamma subunits inhibited the export of VSV-G from the ER suggesting an initial event in transport vesicle assembly was regulated by a heterotrimeric G protein. In contrast, incubation in the presence of GTP gamma S or AIF(3-5) resulted in the accumulation of transported protein in different populations of punctate pre-Golgi intermediates distributed throughout the cytoplasm of the cell. Finally, a peptide which is believed to antagonize the interaction of rab proteins with putative downstream effector molecules inhibited transport at a later step preceding delivery to the cis Golgi compartment, similar to the site of accumulation of transported protein in the absence of NSF or calcium (Plutner, H., H. W. Davidson, J. Saraste, and W. E. Balch. 1992. J. Cell Biol. 119:1097-1116). These results are consistent with the hypothesis that multiple GTP-binding proteins including a heterotrimeric G protein(s), ARF and rab1 differentially regulate steps in the transport of protein between early compartments of the secretory pathway. The concept that G protein-coupled receptors gate the export of protein from the ER is discussed. | rab1 GTP-Binding Proteins |
This opinion article aims to raise awareness of a fundamental issue which governs sustainable production of biofuels and bio-chemicals from photosynthetic cyanobacteria. Discussed is the plasticity of carbon metabolism, by which the cyanobacterial cells flexibly distribute intracellular carbon fluxes towards target products and adapt to environmental/genetic alterations. This intrinsic feature in cyanobacterial metabolism is being understood through recent identification of new biochemical reactions and engineering on low-throughput pathways. We focus our discussion on new insights into the nature of metabolic plasticity in cyanobacteria and its impact on hydrocarbons (e.g. ethylene and isoprene) production. We discuss approaches that need to be developed to rationally rewire photosynthetic carbon fluxes throughout primary metabolism. We outline open questions about the regulatory mechanisms of the metabolic network that remain to be answered, which might shed light on photosynthetic carbon metabolism and help optimize design principles in order to improve the production of fuels and chemicals in cyanobacteria." | Gram-Negative Oxygenic Photosynthetic Bacteria |
Smoking is creating a burden on the healthcare budgets all over the world. Management of nicotine dependence is difficult due to the so-called pleasurable effects experienced by smokers. Among the various treatment approaches, nicotine replacement therapy, where nicotine from cigarettes is replaced with nicotine from a relatively safer delivery vehicle, has been successful. Transdermal delivery of nicotine is an effective type of nicotine replacement therapy due to inherent pharmacokinetic advantages over other routes of delivery. Several nicotine transdermal delivery systems are available to suit the varying needs of smokers and have been found to be clinically patient friendly and well tolerated. This review focuses on the various clinical and pharmaceutical aspects of nicotine with special emphasis on transdermal delivery systems. | Cholinergic Agonists |
Diseases that affect the eye, including photoreceptor degeneration, diabetic retinopathy, and glaucoma, affect 11.8 million people in the US, resulting in vision loss and blindness. Loss of sight affects patient quality of life and puts an economic burden both on individuals and the greater healthcare system. Despite the urgent need for treatments, few effective options currently exist in the clinic. Here, we review research on promising neuroprotective strategies that promote neuronal survival with the potential to protect against vision loss and retinal cell death. Due to the large number of neuroprotective strategies, we restricted our review to approaches that we had direct experience with in the laboratory. We focus on drugs that target survival pathways, including bile acids like UDCA and TUDCA, steroid hormones like progesterone, therapies that target retinal dopamine, and neurotrophic factors. In addition, we review rehabilitative methods that increase endogenous repair mechanisms, including exercise and electrical stimulation therapies. For each approach, we provide background on the neuroprotective strategy, including history of use in other diseases; describe potential mechanisms of action; review the body of research performed in the retina thus far, both in animals and in humans; and discuss considerations when translating each treatment to the clinic and to the retina, including which therapies show the most promise for each retinal disease. Despite the high incidence of retinal diseases and the complexity of mechanisms involved, several promising neuroprotective treatments provide hope to prevent blindness. We discuss attractive candidates here with the goal of furthering retinal research in critical areas to rapidly translate neuroprotective strategies into the clinic. | Ursodeoxycholic Acid |
OBJECTIVE: To describe a case of leukoplakia and underlying intraepithelial squamous cell neoplasia of the palpebral conjunctiva presenting in a patient wearing an ocular prosthesis. METHODS: The clinical presentation, histopathological findings and surgical outcome are described in a 62-year-old man in whom leukoplakic lesions of the palpebral conjunctiva in a socket fitted with an ocular prosthesis were noted in addition to squamous cell carcinoma of the lower lid skin. RESULTS: Histopathological examination revealed islands of squamous cell carcinoma in the skin lesion and squamous cell carcinoma-in-situ in the leukoplakic conjunctival specimen. Successful tumour excision and lid reconstruction were performed. CONCLUSION: This report highlights the successful treatment of long-standing conjunctival squamous cell carcinoma-in-situ associated with an ocular prosthesis and a general tendency to pre-neoplastic lesions of the skin. Regular examination of the sockets of patients wearing long-standing ocular prostheses is recommended. | Leukoplakia |
Most gastrointestinal (GI) subepithelial tumors (SETs) are identified incidentally during endoscopic examination and are located in the stomach. Some SETs are malignant or have the potential to become malignant. Tumors originating from deeper layers, such as the muscularis propria or serosa, are not easy to diagnose and resect. Current guidelines recommend yearly endoscopic surveillance of SETs smaller than 2 cm. This recommendation may not be cost-effective in managing GI SETs. Endoscopic resection results not only in obtaining sufficient tissue for pathological diagnosis but also in resection and curing the tumor. Many different endoscopic methods for resection of GI SETs have been published in the literature. To avoid confusion, we have divided these methods into standard endoscopic submucosal dissection, modified endoscopic submucosal dissection, submucosal tunneling endoscopic resection, and nonexposed and exposed endoscopic full-thickness resection. These procedures offer less invasive approaches than surgery for resection of GI SETs and may be the most cost-effective in taking care of patients with GI SETs. | Endoscopic Mucosal Resection |
Pulmonary complications caused by rheumatoid arthritis are a clinically relevant aspect of this chronic arthropathy. Those complications can involve all parts of the thorax, including the lung parenchyma, the pleura, and the thoracic cage. The most common complications are necrobiotic nodules, pleural abnormalities, Caplan's syndrome, parenchymal fibrosis, bronchiolitis obliterans, and iatrogenic damage of lung the parenchyma. This article reviews pulmonary abnormalities induced by rheumatoid arthritis and their clinical and radiological findings. In addition, the role of different imaging modalities in the diagnostic work-up of pulmonary complications caused by rheumatoid arthritis is discussed. | Caplan Syndrome |
An inpatient on a secure unit with a history of bipolar affective disorder and physical complaints including pain was prescribed carbamazepine, quetiapine, dihydrocodeine, nefopam, paracetamol and various aperients. A benzodiazepine urine test by immunoassay was positive. Initial literature searches did not suggest a candidate drug for positive interference. Other explanations were excluded. Positive results continued, despite room searches and other disruptive security measures. Further literature searches revealed one experimental series demonstrating positive interference of nefopam in the relevant assay. Benzodiazepine assays were negative after cessation of nefopam. This is the first such clinical case to our knowledge. | Oxazocines |
The knowledge of the distribution of sleep and wake over a 24-h day is essential for a comprehensive image of sleep-wake rhythms. Current sleep-wake scoring algorithms for wrist-worn actigraphy suffer from low specificities, which leads to an underestimation of the time staying awake. The goal of this study (ClinicalTrials.gov Identifier: NCT03356938) was to develop a sleep-wake classifier with increased specificity. By artificially balancing the training dataset to contain as much wake as sleep epochs from day- and nighttime measurements from 12 subjects, we optimized the classification parameters to an optimal trade-off between sensitivity and specificity. The resulting sleep-wake classifier achieved high specificity of 80.4% and sensitivity of 88.6% on the balanced dataset containing 3079.9 h of actimeter data. In the validation on night sleep of separate adaptation recordings from 19 healthy subjects, the sleep-wake classifier achieved 89.4% sensitivity and 64.6% specificity and estimated accurately total sleep time and sleep efficiency with a mean difference of 12.16 min and 2.83%, respectively. This new, device-independent method allows to rid sleep-wake classifiers from their bias towards sleep detection and lay a foundation for more accurate assessments in everyday life, which could be applied to monitor patients with fragmented sleep-wake rhythms. | Actigraphy |
Most malpractice litigation in obstetrics could be replaced with an alternative insurance system based on accelerated-compensation events," which are classes of medical injuries determined in advance by medical experts to be readily identifiable, normally preventable with good care, and nondistorting of medical decision making. This professionally derived system would help prevent injury and improve the resolution of injuries. Prior work on accelerated-compensation events was largely conceptual, so to study the likely effects of accelerated-compensation events, we applied the events to a large database of obstetrical malpractice claims. Results refute prior criticisms. Accelerated-compensation events (1) are definitely feasible to develop and apply, (2) would probably cover two thirds of currently paid claims and three quarters of indemnity dollars, (3) would likely involve substantial savings in time and expense per case, and (4) would probably not introduce an unmanageable number of large new claims." | Malpractice |
The woodchuck hepatitis virus (WHV) and its host, the eastern woodchuck, is a very valuable model system for hepatitis B virus infection. Many aspects of WHV replication and pathogenesis resemble acute and chronic hepatitis B infection in patients. Since the establishment of immunological tools, woodchucks were used to develop new therapeutic vaccines and immunomodulatory approaches to treat chronic hepadnaviral infections. Combination therapy of nucleos(t)ide analogs, with prime-boost vaccination and triple therapy, including immunomodulatory strategies by blocking the interaction of the programmed death-1 (PD-1) receptor with its ligand inducing a potent T-cell response in chronic WHV carrier woodchucks, suppression of viral replication, and complete elimination of the virus in 30% of the animals. Both strategies may be used for future therapies in patients with chronic hepatitis B. | Hepatitis B Virus, Woodchuck |
For the last 20 years, researchers have focused their intention on the impact of gut microbiota in healthy and pathological conditions. This year (2021), more than 25,000 articles can be retrieved from PubMed with the keywords gut microbiota and physiology", showing the constant progress and impact of gut microbes in scientific life. As a result, numerous therapeutic perspectives have been proposed to modulate the gut microbiota composition and/or bioactive factors released from microbes to restore our body functions. Currently, the gut is considered a primary site for the development of pathologies that modify brain functions such as neurodegenerative (Parkinson's, Alzheimer's, etc.) and metabolic (type 2 diabetes, obesity, etc.) disorders. Deciphering the mode of interaction between microbiota and the brain is a real original option to prevent (and maybe treat in the future) the establishment of gut-brain pathologies. The objective of this review is to describe recent scientific elements that explore the communication between gut microbiota and the brain by focusing our interest on the enteric nervous system (ENS) as an intermediate partner. The ENS, which is known as the "second brain", could be under the direct or indirect influence of the gut microbiota and its released factors (short-chain fatty acids, neurotransmitters, gaseous factors, etc.). Thus, in addition to their actions on tissue (adipose tissue, liver, brain, etc.), microbes can have an impact on local ENS activity. This potential modification of ENS function has global repercussions in the whole body via the gut-brain axis and represents a new therapeutic strategy. This article is part of the special Issue on 'Cross Talk between Periphery and the Brain'." | Enteric Nervous System |
1. The lipids from a variety of keratinized tissues from terrestrial vertebrates were extracted with chloroform:methanol and the nonpolar and saponifiable lipids were removed. The composition of the remaining polar lipids was examined by thin layer chromatography and color reactions. 2. The tissues studied included: hair from a monkey (Macacca fascicularis), dog (Canis familiaris), raccoon (Procyon lotor) and cow (Bos taurus); full-thickness epidermis from a pig (Sus scrofa) and pilot whale (Globicephala melaena); epidermal scales and feathers from a fowl (Gallus gallus); scales, feathers, beaks and claws from a turkey (Meleagris gallopavo); hoof and horn from cattle (Bos taurus); and cast skins from a Columbian boa (Boa constrictor) and a Ball python (Python regius). 3. All of the tissues contained both simple ceramides and highly polar glycolipids (presumably gangliosides). 4. Glycolipids of intermediate polarity were present in all of the tissues from birds and snakes and in the mammalian tissues which contained unkeratinized epidermal cells, but were absent from fully keratinized mammalian tissues such as hair, hoof and horn. 5. The presence of the highly polar gangliosides provides for the formation of the multiple intercellular lipid lamellae which have been observed in the epidermal horny layer of mammals, birds and reptiles and which are believed to constitute the epidermal barrier to water diffusion. | Vertebrates |
BACKGROUND: With the rapidly growing population and expanding vehicle density on the roads, there has been an upsurge in road accidents in developing countries. Knowledge about the causes and patterns of trauma-related amputations helps in the formulation of strategies for limb savage, timely management, and effective rehabilitation. OBJECTIVE: To study the epidemiology, demographic profile, and outcomes of post-trauma amputations at a level I tertiary care centre in North India. METHODS: Retrospective evaluation of the amputee data from 1st January 2018 to 31st December 2019, focusing on demographic details, injury mechanisms, surgical delays, hospital stay, and complications. RESULTS: A total of 17,445 trauma cases were seen in our trauma centre during the study period. Of these, 442 patients (2.5%) underwent major limb amputation. The hospital-based prevalence of traumatic limb amputation was 2.5%. The mean age of the amputees was 35.6years (range 1-75), and the majority were males (n = 369, 83.5%). The lower to upper limb involvement ratio was 3:1 (n = 338:105). A road traffic accident was the most common mode of injury (77.4%), followed by machine-cut injuries (16.1%). On-site traumatic amputation was seen in 23.1% (n = 102), while 43.5% had a mangled limb amputated in the hospital (mean MESS score 9.53). Overall, 27% of cases had a vascular injury after trauma, ultimately ending in limb amputation. The in-hospital mortality was 2% (n = 9/442). 43.7% of patients with a single limb amputation were discharged within 48 h. Extended hospital stay was noted in cases with associated fractures in the other limbs (28.5%), head or facial injury (9.9%), and with or without a combination of chest, abdomen, pelvic, or spine injury (7.2%). CONCLUSION: A 2.5% incidence of post-trauma amputation reflects on the severity of injury related to road and industrial accidents which predominantly affect the lower limbs at the peak of productive work life. In the absence of national amputation registries, the results underscore the need to focus on road safety protocols, patient transfer methods, and the up-gradation of local hospitals. | Amputation, Traumatic |
This paper describes a method for measuring electrically elicited auditory reflex thresholds (EARTs) in young children who use the CLARION Multi-Strategy Cochlear Implant. The EART is an objective measure that can guide the fitting of a cochlear implant in individuals who are unable to perform behavioral tasks required to program the device. Reflexes were obtained in 11 of 17 pediatric Clarion users. The EART current level indicated a point at which an auditory percept was present and the sound was loud, but not uncomfortable. The EART then was used as a basis for conditioning behavioral responses, and as a guideline for setting most comfortable loudness levels." | Evoked Potentials, Auditory, Brain Stem |
Anaplastic large-cell lymphoma, T-/null-cell type (ALCL), is a rare disease that has only been well characterized for two decades. Despite this, the biology of ALCL is better understood than that of many other more common variants of lymphoma. This review focuses on the pathophysiology, clinical presentation, and therapy of ALCL, including stem cell transplantation. In particular, the text emphasizes how novel prognostic features and the evolving understanding of the biology of this disease will influence treatment selection and drug development." | Lymphoma, Large-Cell, Anaplastic |
Kluyvera Spp is an enterobacterium rarely isolated in medical microbiology, an opportunistic pathogen the clinical significance of which remains unclear. Four strains of Kluyvera Spp were isolated for the first time in the Ibn Rochd Teaching Hospital microbiology laboratory. These strains were isolated in hemocultures of four patients hospitalized in the same medical ward, at the same time, and presenting with bacteriemia. An antibiotic susceptibility study allowed identifying the wild phenotype in the first isolate, the three next isolates had acquired resistance to trimethoprim-sulfamethoxazole, gentamycin, tobramycin, and ciprofloxacin, and produced broad-spectrum betalactamase. The epidemiological investigation in the patients' environment made after isolating the fourth strain was negative. The four patients evolved uneventfully without antibiotic treatment. This raises the question of the real pathogenic capacity of these strains, their epidemic power, and their ability to acquire resistance. | Kluyvera |
OBJECTIVE: To assess the efficacy of butorphanol-azaperone-medetomidine (BAM) and butorphanol-midazolam-medetomidine (BMM) protocols for immobilization of wild common palm civets (Paradoxurus musangus) with subsequent antagonization with atipamezole. STUDY DESIGN: Prospective, randomized, blinded clinical trial. ANIMALS: A total of 40 adult wild common palm civets, 24 female and 16 male, weighing 1.5-3.4 kg. METHODS: The civets were randomly assigned for anesthesia with butorphanol, azaperone and medetomidine (0.6, 0.6 and 0.2 mg kg(-1), respectively; group BAM) or with butorphanol, midazolam and medetomidine (0.3, 0.4 and 0.1 mg kg(-1), respectively; group BMM) intramuscularly (IM) in a squeeze cage. When adequately relaxed, the trachea was intubated for oxygen administration. Physiological variables were recorded every 5 minutes after intubation. Following morphometric measurements, sampling, microchipping and parasite treatment, medetomidine was reversed with atipamezole at 1.0 or 0.5 mg kg(-1) IM to groups BAM and BMM, respectively. Physiological variables and times to reach the different stages of anesthesia were compared between groups. RESULTS: Onset time of sedation and recumbency was similar in both groups; time to achieve complete relaxation and tracheal intubation was longer in group BAM. Supplementation with isoflurane was required to enable intubation in five civets in group BAM and one civet in group BMM. All civets in group BAM required topical lidocaine to facilitate intubation. End-tidal carbon dioxide partial pressure was lower in group BAM, but heart rate, respiratory rate, rectal temperature, peripheral hemoglobin oxygen saturation and mean arterial blood pressure were not different. All civets in both groups recovered well following administration of atipamezole. CONCLUSIONS AND CLINICAL RELEVANCE: Both BAM and BMM combinations were effective for immobilizing wild common palm civets. The BMM combination had the advantage of producing complete relaxation that allowed intubation more rapidly. | Azaperone |
The Golgi may be considered a principal organizer of macromolecular traffic in the cell because many molecules, such as secreted proteins, glycoproteins, glycolipids, and plasma membrane glycoproteins, pass through the Golgi during their maturation. The fluorescent probes used to tag the Golgi make use of this function for labeling by using a fluorescent ceramide. In this protocol, two probes for labeling the Golgi are presented: a classic NBD-ceramide and a BODIPY-ceramide probe that is more resistant to photobleaching. | 4-Chloro-7-nitrobenzofurazan |
A review of the clinical pharmacokinetics of lidocaine is presented. Available evidence suggests that antiarrhythmic effects are reasonably well correlated wih plasma concentration. Adverse effects also covary with plasma concentration, but available evidence suggests that the correlation is not strong. A simple, multiple-bolus loading schedule appears to be superior to techniques using loading infusions; most of the multiple-bolus protocols mandate that only enough drug be given to attain the desired pharmacologic effect. In contrast, the loading infusion protocols almost invariably require the administration of a fixed dose, regardless of what fraction of the dose has been given when arrhythmia suppression is achieved. Since multiple-bolus and constant-rate infusion techniques have been shown to reduce substantially the incidence of primary ventricular fibrillation, they should be considered appropriate prophylactic and treatment regimens for acute myocardial infarction patients. | Lidocaine |
We present a particular case of TRAP (twin reversed arterial perfusion) syndrome, which has a very rarely association of the simultaneous existence of a rudimentary malformed heart and brain, and also other malformations like abdominal wall abnormality, absent bladder with present kidneys, and absence of the lungs, which appear only in a few cases on the receptor twin from this sequence, malformations incompatible with life. A Caucasian 26-year-old pregnant woman, at the first pregnancy, with a monochorionic-diamniotic pregnancy, 26 weeks of gestation was referred to our hospital, for polyhydramnios. The patient delivered a living female newborn, weighing 950 g, with an Apgar score of 2 at one minute - the donor fetus and a second female newborn with multiple malformations, no signs of life and who weighed 2300 g - the receptor fetus. The anatomopathological examination confirmed the TRAP sequence associated with severe facial dysmorphism, bilateral phocomelia and cardiac malformations (rudimentary hypoplastic, univentricular) and a vascular anastomosis between the two umbilical cords. Anemia and cardiac complications which can lead to cardiac failure, appear early during pregnancy and caused the death of the pumping twin. We emphasize that in our case of TRAP sequence, the ultrasound examination established the diagnosis of the syndrome with high accuracy. Therefore, we can conclude that the existence of a rudimentary heart and a vascular anastomosis between the two umbilical cords supports the apparition of TRAP sequence. The early diagnosis of this pathology, the observation of the pregnancy with the help of weekly ultrasounds and the intrauterine interventions can increase the survival chances of the donor fetus from the TRAP sequence. | Fetofetal Transfusion |
We describe the synthesis and results of biological evaluation of newly designed 2,4,6-trisubstituted symmetrical 1,3,5-triazine (TAZ) derivatives. Among the tested trisubstituted TAZ derivatives, some CS-symmetrical alkoxy-amino-substituted TAZ derivatives, including 7ggp and 6dpp, showed significant antiviral activity against herpes simplex virus type 1 (HSV-1). The compound with the highest level of antiviral activity was C3-symmetrical trialkoxy-TAZ derivative 4bbb, which showed a considerably high selectivity index (IC50/EC50=256.6). The structure-activity relationships for anti-HSV-1 activity of the tested 2,4,6-trisubstituted TAZ derivatives are also described. | Triazines |
Twelve undescribed limonoids, meliazedarines J-U (1-12), along with a known one, were isolated from the roots of Melia azedarach. Their structures were elucidated by extensive spectroscopic investigations, X-ray diffraction analyses, and ECD calculations. Compounds 1-8 were identified as ring intact limonoids, while compounds 9-12 were established as ring C-seco ones. The anti-inflammatory potential of compounds 1-4, 6, 8, 9, and 11-13 was evaluated on macrophages. Compounds 1, 3, 4, 6, and 9 significantly suppressed nitric oxide production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, among them compound 3 showed the best inhibitory effect with an IC(50) value of 7.07 +/- 0.48 muMu. Furthermore, compound 3 effectively reduced interleukin-1beta secretion in LPS plus nigericin-induced THP-1 macrophages by inhibiting NLRP3 inflammasome activation. The results strongly suggested that limonoids from the roots of M. azedarach might be candidates for treating inflammation-related diseases. | Melia azedarach |
Flatbed scanner densitometers can be operated under various illumination and recording exposure levels. In this work, we show that optical density measurement accuracy, sensitivity, and stability of stained polyacrylamide electrophoresis gel densitometry are crucially dependent on these two factors (brightness and exposure level), notwithstanding that the source is monochromatic, spatially uniform, and the measurements are made using an accurately calibrated step wedge in tandem. We further outline a method to accommodate the intensity deviations over a range of illumination and exposure levels in order to maintain sensitivity and repeatability in the computed optical densities. Comparisons were also made with results from a commercial densitometer. | Densitometry |
Viscoelastic hemostasis analyses (VHA) are a complement in the evaluation of hemostasis in patients with major bleeding. The analysis measures viscoelastic changes in whole blood and the results give an overview of several components of hemostasis. VHA can be used to optimize fibrinogen levels, platelet and plasma substitution. The main clinical evidence supporting this strategy is in trauma, obstetric bleeding, heart and liver surgery, where algorithms based on VHA results facilitate individualized therapy. VHA measurement is of limited value to exclude treatment with anticoagulants and platelet inhibitors. Quality control aspects are also more cumbersome since whole blood with limited sustainability is used. Newer, more automated versions of the instruments have increased the reproducibility. The main advantage of VHA is the fast turn-around time and their role in guiding treatment in an emergency situation with bleeding. | Thrombelastography |
AIM: Testing the ability of the alternative ethanol production yeast Dekkera bruxellensis to produce ethanol from lignocellulose hydrolysate and comparing it to Saccharomyces cerevisiae. METHODS AND RESULTS: Industrial isolates of D. bruxellensis and S. cerevisiae were cultivated in small-scale batch fermentations of enzymatically hydrolysed steam exploded aspen sawdust. Different dilutions of hydrolysate were tested. None of the yeasts grew in undiluted or 1:2 diluted hydrolysate [final glucose concentration always adjusted to 40 g l(-)(1) (0.22 mol l(-)(1))]. This was most likely due to the presence of inhibitors such as acetate or furfural. In 1:5 hydrolysate, S. cerevisiae grew, but not D. bruxellensis, and in 1:10 hydrolysate, both yeasts grew. An external vitamin source (e.g. yeast extract) was essential for growth of D. bruxellensis in this lignocellulosic hydrolysate and strongly stimulated S. cerevisiae growth and ethanol production. Ethanol yields of 0.42 +/- 0.01 g ethanol (g glucose)(-)(1) were observed for both yeasts in 1:10 hydrolysate. In small-scale continuous cultures with cell recirculation, with a gradual increase in the hydrolysate concentration, D. bruxellensis was able to grow in 1:5 hydrolysate. In bioreactor experiments with cell recirculation, hydrolysate contents were increased up to 1:2 hydrolysate, without significant losses in ethanol yields for both yeasts and only slight differences in viable cell counts, indicating an ability of both yeasts to adapt to toxic compounds in the hydrolysate. CONCLUSIONS: Dekkera bruxellensis and S. cerevisiae have a similar potential to ferment lignocellulose hydrolysate to ethanol and to adapt to fermentation inhibitors in the hydrolysate. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study investigating the potential of D. bruxellensis to ferment lignocellulosic hydrolysate. Its high competitiveness in industrial fermentations makes D. bruxellensis an interesting alternative for ethanol production from those substrates. | Dekkera |
Liang gave an extension of the Mantel-Haenszel estimating procedure for a common odds ratio to logistic regression models. It is applicable to case-control studies with multiple exposure levels, which yield K 2 x J tables. This paper provides variance and covariance estimators, which are consistent in both sparse-data and large-strata, for Liang's estimating functions in the K 2 x J tables case, and proposes an approximate confidence interval method for the common odds ratios. | Regression Analysis |
Acute basilar artery (BA) occlusion is associated with an extremely high mortality. The pathogenesis in younger patients is usually embolism form cardiac sources or less frequently from vertebral artery dissection. Local atherothrombosis is more common in elderly patients. Differently to the carotid territory, for the vertebrobasilar territory there are no placebo controlled studies proving efficacy of thrombolytic treatment. Furthermore, neither the best route of administration nor the best fibrinolytic agent have been evaluated. Several uncontrolled series, however, indicate that intraarterial thrombolysis reduces mortality of patients with BA occlusion. Recanalization rates average 60% and are associated with occlusions of embolic etiology. Mortality with an average rate of 40-60% is significantly lower in the recanalization group in most series. Other independent variables affecting mortality are identified as length of obstruction, proximal BA occlusion, collateralization, high age, and initial poor clinical state. Time from onset of symptoms to start of intraarterial thrombolysis, however, is not associated with recanalization or mortality rate. This indicates that differently from thrombolytic treatment in the anterior circulation there is no fixed time window in BA thrombosis. Rate ofparenchymal hemorrhage seems to be lower with an average of 6% compared with systemic thrombolytic therapy in hemispheric stroke. Recanalization of the BA is clinically beneficial under certain circumstances only: (1) BA occlusion should affect only one segment; (2) an effective collateral supply is essential; and (3) the patient should not already be tetraplegic or comatose for a longer period of time. Clinical outcome and assessment of quality of life on follow-up of survivors with successful recanalization encourage thrombolysis in acute BA occlusions of embolic origin. | Vertebrobasilar Insufficiency |
We evaluated the potential effects of the organophosphate insecticide azinphosmethyl (AZP) in a combined microcosm and field approach. The upper regions of the Lourens River, South Africa, are free of contamination (control site), whereas the subsequent stretches flowing through a 400-ha orchard area receive transient insecticide pollution (e.g.. 0.82 microg/L AZP, 344 microg/kg chlorpyrifos) following spray drift and runoff (contaminated site). Stones taken from the control site were transferred to outdoor microcosms (1.5 x 0.2 x 0.2 m), providing 12 core species and approximately 350 individuals per microcosm. Microcosms were contaminated for 1 h with AZP (control, 0.2, 1, 5, and 20 microg/L; three replicates each), and acute effects on survival were evaluated 6 d following exposure. The two strongest treatments (measured concentrations: 19.2 +/- 1.0 and 4.9 +/- 0.3 microg/L, respectively) resulted in a significantly (analysis of variance) reduced invertebrate density, attributed mainly to various insect taxa, such as Demoreptus sp., Castanophlebia sp., Simuliidae, and Chironomidae. In contrast, Aeshna sp., Dugesia sp., Ceratopogonidae, and Cheumatopsyche sp. were unaffected. In parallel, we conducted a quantitative macroinvertebrate survey at the control site and the contaminated site of the Lourens River after the seasonal pesticide application period. The two sites contained a similar number of species but differed considerably in their species composition and abundances. Five of the eight species that were affected by AZP in the microcosm study occurred in the field at significantly lower densities at the contaminated than at the control site or were absent at the contaminated site. All of the four species that were unaffected in the microcosm occurred at significantly higher densities at the contaminated field site. Only 3 of the 12 species reacted differently in the microcosm and the field study. We conclude that microcosm studies employing a field-relevant design could be linked successfully to field studies and our results suggest that transient pesticide contamination affects the aquatic communities of the Lourens River. | Azinphosmethyl |
OBJECTIVE: The aim of this study was to compare the incidence of airway haemorrhage between participants who received manual cardiopulmonary resuscitation (CPR) and those who had received mechanical CPR using the LUCAS device. METHODS: A retrospective cohort study was conducted by means of a medical chart review. All non-traumatic cardiac arrest patients that presented to the ED, from May 2014 to February 2018, were recruited. The groups were stratified according to those who had the majority of CPR performed using the LUCAS and those who had the majority of CPR performed manually. The primary outcome was the proportion of participants with airway haemorrhage, defined as blood observed in the endotracheal tube, pharynx, trachea or mouth, and documented in the doctor or nursing notes. Logistic regression analysis was performed to adjust for confounders. RESULTS: 12 of 54 (22%) participants in the majority LUCAS CPR group had airway haemorrhage, compared with 20 of 215 (9%) participants in the majority manual CPR group, a difference of 13% (95% CI 3% to 26%, p=0.02). The unadjusted odds for developing airway haemorrhage in the majority LUCAS CPR group was 2.8 (95% CI 1.3 to 6.1). After adjusting for confounders, the odds for developing airway haemorrhage in the majority LUCAS CPR group was 2.5 (95% CI 1.1 to 5.7). CONCLUSIONS: The LUCAS mechanical CPR device is associated with a higher incidence of airway haemorrhage compared with manual CPR. Limitations in the study design mean this conclusion is not robust. | Oral Hemorrhage |
Otomycosis is frequently seen in Shanghai and is a challenging problem due to recurrence and resistance to therapy. The aims of this study were to determine the pattern of fungal agents, sex distribution, clinical presentation, predisposing factors, complications and treatment outcomes of otomycosis. Retrospective review of 108 patients with a clinical diagnosis of otomycosis treated from September 2009 to September 2010 in otolaryngology outpatient department. It has been found to be more prevalent in female patients than male patients with a sex ratio (F : M) of 2 : 1. Aspergillus niger (54.78%) followed by Candida albicans (16.52%) were the dominant fungi. Pruritus and otorrhea were the most common presenting complaints. The predisposing factors included frequent scratching of the external ear canal (79.63%), taking ototopical and/or oral antimicrobials (24.07%), diabetes (11.11%) and otologic procedures (7.41%). Residual disease was observed in 9.26% and recurrence in 8.89% of the subjects. Topical Fluconazole ear drops and mechanical debridement of visible fungal elements in the external auditory canal were all relatively effective with 83.33% resolution rate on initial application. The diagnosis of otomycosis requires vigilance from clinicians given its non-specific symptoms. Sometimes mycological examinations are necessary. Treatment regimens such as topical fluconazole coupled with mechanical debridement are generally effective. However, recurrence is not uncommon and eradication of disease can be particularly difficult in patients with diabetes and a mastoid cavity. | Otomycosis |
AIM: Nocturia is such a commonplace occurrence in the lives of many older adults that it is frequently overlooked as a potential cause of sleep disturbance. The aim of the present study was to evaluate the prevalence of nocturia among elderly men living in a rural area in Egypt, and its impact on sleep quality and health-related quality of life (HRQoL). METHOD: This was a cross-sectional study. A total of 1200 elderly men participated in the survey. The Pittsburgh Sleep Quality Index (PSQI) Arabic version and the short form-36 (SF-36) were used in this survey. RESULTS: The prevalence of nocturia in the studied participants (>/= 1 void/night) was 63.5%. With the criterion (>/= 2 voids/night) the prevalence was 46.0%. Multivariate logistic regression analysis showed that nocturia is an independent risk factor of poor sleep quality (OR 5.08), and poor sleep is an independent risk factor of the poor physical component of QoL (OR 17.6) and the mental component of QoL (OR 3.2). CONCLUSION: Nocturia is widely prevalent among elderly men living in a rural area in Egypt. The adverse effect of nocturia on QoL is related to poor sleep. | Nocturia |
People will often rationalize the status quo, reconstruing it in an exaggeratedly positive light. They will even rationalize the status quo they anticipate, emphasizing the upsides and minimizing the downsides of sociopolitical realities they expect to take effect. Drawing on recent findings on the psychological triggers of rationalization, I present results from three field studies, one of which was preregistered, testing the hypothesis that an anticipated reality becoming current triggers an observable boost in people's rationalizations. San Franciscans rationalized a ban on plastic water bottles, Ontarians rationalized a targeted smoking ban, and Americans rationalized the presidency of Donald Trump, more in the days immediately after these realities became current compared with the days immediately before. Additional findings show evidence for a mechanism underlying these behaviors and rule out alternative accounts. These findings carry implications for scholarship on rationalization, for understanding protest behavior, and for policymakers. | Rationalization |
BACKGROUND: Recent studies have shown dysregulation in TJ structure of several cancers including breast. Claudin-5 is a protein member of the TJ structure expressed in both endothelial and epithelial cells. This study examined the level of expression and distribution of Claudin-5 in human breast cancer tissues and the effect of knockdown and forced expression of Claudin-5 in the MDA-MB-231 breast cancer cell line. METHODS: Immunohistochemistry and quantitative-PCR were used to analyse patient tissue samples. The Claudin-5 gene was cloned and overexpressed or knocked down using ribozyme technology in human breast cancer cells. Changes in function were assessed using in vitro assays for invasion, growth, adhesion, wounding, motility, transepithelial resistance and electric cell-substrate impedance sensing. Changes in cell behaviour were achieved through the use of Hepatocyte Growth factor (HGF) which we have shown to affect TJ function and expression of TJ proteins. In addition, an in vivo model was used for tumour growth assays. Results data was analyzed using a Students two sample t-test and by Two-way Anova test when the data was found to be normalized and have equal variances. In all cases 95% confidence intervals were used. RESULTS: Patients whose tumours expressed high levels of Claudin-5 had shorter survival than those with low levels (p = 0.004). Investigating in vitro the effect of altering levels of expression of Claudin-5 in MDA-MB-231 cells revealed that the insertion of Claudin-5 gene resulted in significantly more motile cells (p < 0.005). Low levels of Claudin-5 resulted in a decrease in adhesion to matrix (p < 0.001). Furthermore, a possible link between Claudin-5 and N-WASP, and Claudin-5 and ROCK was demonstrated when interactions between these proteins were seen in the cells. Moreover, followed by treatment of N-WASP inhibitor (Wiskostatin) and ROCK inhibitor (Y-27632) cell motility was assessed in response to the inhibitors. Results showed that the knockdown of Claudin-5 in MDA-MB-231 masked their response after treatment with N-WASP inhibitor; however treatment with ROCK inhibitor did not reveal any differences in motility in this cell line. CONCLUSIONS: This study portrays a very new and interesting role for Claudin-5 in cell motility involving the N-WASP signalling cascade indicating a possible role for Claudin-5 in the metastasis of human breast cancer. | Claudin-5 |
The role of mechanosensitive (MS) Ca(2+)-permeable ion channels in platelets is unclear, despite the importance of shear stress in platelet function and life-threatening thrombus formation. We therefore sought to investigate the expression and functional relevance of MS channels in human platelets. The effect of shear stress on Ca(2+) entry in human platelets and Meg-01 megakaryocytic cells loaded with Fluo-3 was examined by confocal microscopy. Cells were attached to glass coverslips within flow chambers that allowed applications of physiological and pathological shear stress. Arterial shear (1002.6 s(-1)) induced a sustained increase in [Ca(2+)] (i) in Meg-01 cells and enhanced the frequency of repetitive Ca(2+) transients by 80% in platelets. These Ca(2+) increases were abrogated by the MS channel inhibitor Grammostola spatulata mechanotoxin 4 (GsMTx-4) or by chelation of extracellular Ca(2+) Thrombus formation was studied on collagen-coated surfaces using DiOC(6)-stained platelets. In addition, [Ca(2+)] (i) and functional responses of washed platelet suspensions were studied with Fura-2 and light transmission aggregometry, respectively. Thrombus size was reduced 50% by GsMTx-4, independently of P2X1 receptors. In contrast, GsMTx-4 had no effect on collagen-induced aggregation or on Ca(2+) influx via TRPC6 or Orai1 channels and caused only a minor inhibition of P2X1-dependent Ca(2+) entry. The Piezo1 agonist, Yoda1, potentiated shear-dependent platelet Ca(2+) transients by 170%. Piezo1 mRNA transcripts and protein were detected with quantitative RT-PCR and Western blotting, respectively, in both platelets and Meg-01 cells. We conclude that platelets and Meg-01 cells express the MS cation channel Piezo1, which may contribute to Ca(2+) entry and thrombus formation under arterial shear. | Receptors, Purinergic P2X1 |
This symposium includes 12 very brave and intimate narratives about the challenges associated with becoming a surgeon and practicing surgery as a woman. This symposium also includes three commentaries on the narratives written by 1) Patricia Dawson, MD, Ph.D., FACS, 2) Kelsey Medeiros, Ph.D, and Jennifer Griffith, Ph.D, and 3) Peter Angelos, MD, Ph.D., FACS. This narrative collection offers diverse female perspective on the impact of surgical training and practice, yet common themes emerge related to gender in the field of surgery. This symposium provides insight on surgical culture and traditions that are detrimental to surgeons in general, and woman surgeons in particular. It addresses how leadership and institutional changes must be made to equitably and successfully recruit, support, promote, and retain women training and practicing surgery. There is hope for the future of gender equity, diversity, and inclusion in the surgical workforce but only if its leaders adopt a zero tolerance policy against the range of gender-disparities identified and prioritize a culture of safety, dignity and equity. | Physicians, Women |
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