text
stringlengths 11
9.77k
| label
stringlengths 2
104
|
|---|---|
To understand the effect of lipid degradation on Maillard formation of meaty flavors, initial reaction intermediates in model systems of glucose-glutathione with hexanal, (E)-2-heptenal, or (E,E)-2,4-decadienal were identified by HPLC-MS and by NMR. Besides Amadori compounds, hemiacetals and thiazolidines via addition of sulfhydryl to carbonyl or to the conjugated olefinic bond were found. Concentrations of all intermediates increased with reaction time while degradation of the intermediates with a glutathione moiety helped formation of thiazolidines with cysteinylglycine. The unsaturated aldehydes (E)-2-heptenal and (E,E)-2,4-decadienal exhibited high reactivity against glucose for glutathione, yielding higher levels of intermediate compounds than from glucose. Heating prepared intermediates reversibly released the original aldehydes, which caused various compounds formed by retro-aldol, oxidation, etc. to react with H(2)S and NH(3). Among them, formation pathways including 3-nonen-2-one, 2-hexanoylfuran, and six dialkylthiophenes (e.g., 2-ethyl-5-(1-methylbutyl)thiophene) were proposed for the first time. | Maillard Reaction |
A detailed investigation of the wood, leaf, branch and root oil of Eremophila mitchellii (Benth.) was carried out by a combination of GC-FID, GC-MS and NMR. The wood oil was composed predominantly of eremophilanes, a rare class of biologically active, bicyclic sesquiterpenoids. The root oil was also found to contain the eremophilanes together with the zizaene sesquiterpene, sesquithuriferone. 9-Hydroxy-1,7(11),9-eremophilatrien-8-one and the known 1(10),11-eremophiladien-9-one (eremophilone), 9-hydroxy-7(11),9-eremophiladien-8-one (2-hydroxyeremophilone), 8-hydroxy-11-eremophilen-9-one (santalcamphor), 8-hydroxy-10,11-eremophiladien-9-one, sesquithuriferone and 8-hydroxy-1,11-eremophiladien-9-one were purified and elucidated by NMR. Three approaches to the purification of the major eremophilanes from the wood oil are described. (+) Spathulenol, alpha-pinene, globulol, viridiflorene were the major constituents of the leaf oil. All of the essential oils and the eremophilanes exhibited cytotoxicity against P388D(1) mouse lymphoblast cells in-vitro. | Myoporaceae |
Lipo-chitooligosaccharides (LCOs) are microbial symbiotic signals that also influence root growth. In Medicago truncatula, LCOs stimulate lateral root formation (LRF) synergistically with auxin. However, the molecular mechanisms of this phenomenon and whether it is restricted to legume plants are not known. We have addressed the capacity of the model monocot Brachypodium distachyon (Brachypodium) to respond to LCOs and auxin for LRF. For this, we used a combination of root phenotyping assays, live-imaging and auxin quantification, and analysed the regulation of auxin homeostasis genes. We show that LCOs and a low dose of the auxin precursor indole-3-butyric acid (IBA) stimulated LRF in Brachypodium, while a combination of LCOs and IBA led to different regulations. Both LCO and IBA treatments locally increased endogenous indole-3-acetic acid (IAA) content, whereas the combination of LCO and IBA locally increased the endogenous concentration of a conjugated form of IAA (IAA-Ala). LCOs, IBA and the combination differentially controlled expression of auxin homeostasis genes. These results demonstrate that LCOs are active on Brachypodium roots and stimulate LRF probably through regulation of auxin homeostasis. The interaction between LCO and auxin treatments observed in Brachypodium on root architecture opens interesting avenues regarding their possible combined effects during the arbuscular mycorrhizal symbiosis. | Brachypodium |
We conducted a systematic review and meta-analysis to assess all-cause mortality and heart failure (HF) hospitalization with sacubitril/valsartan (S/V) compared to standard HF therapy in patients with HF with reduced ejection fraction (HFrEF) using real-world data. We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed and Google Scholar for the observational studies published in English exploring the clinical outcomes of S/V use in HFrEF till March 14, 2022. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. The outcomes assessed were all-cause mortality and HF hospitalization associated with S/V use in comparison to standard HF therapy. A total of 9 observational studies comparing S/V to Angiotensin-converting enzyme inhibitors (ACE-I)/Angiotensin II receptor blockers (ARB) in HFrEF were included in the systematic review, with more than 32000 patients included in the final analysis. Overall, S/V use was associated with a significant reduction in all-cause mortality (Risk Ratio [RR]â¯=â¯0.70, 95% CI 0.53-0.93, I(2)â¯=â¯83%) and HF hospitalization (RRâ¯=â¯0.62; 95% CI, 0.48-0.80, I(2)= 94%). Similar to the landmark controlled evidence, real-world data of S/V use in HFrEF demonstrated a significant reduction in all-cause mortality and HF hospitalization. | Tetrazoles |
Human interleukin-15 (hIL15) exerts anticancer effects through the activities of lymphokine-activated killer (LAK) cells. However, its short half-life hinders its clinical application. Recombinant adeno-associated virus serotype 2 (rAAV2) is used for hIL15 gene transfer vectors, because of its low immunogenicity and long-term gene expression in human clinical trials. SV40 T/t antigens are related with many human epithelial cancers and are generally found in human breast cancer. In order to demonstrate the anticancer effects of hIL15 on SV40 T/t antigen-induced breast cancer, rAAV2-hIL15 was constructed and an SV40 T/t antigen-induced transgenic mouse breast cancer model was established. Our study showed that rAAV2-hIL15 could express the hIL15 protein with anticancer bioactivity. In addition, rAAV2-hIL15 could activate the cytotoxic activity of LAK cells in vivo. Furthermore, the rAAV2-hIL15 successfully delayed cancer growth and eventually led to cancer cell death in SV40 T/t antigen-induced breast cancer transgenic mice. In summary, our study indicates that rAAV2-hIL15 may be applied for cancer immunotherapy of SV40 T/t antigen-induced breast cancer. | Interleukin-15 |
INTRODUCTION: Despite playing an integral part in sexual and reproductive health care, including abortion care, nurses are rarely the focus of research regarding their attitudes about abortion. METHODS: A sample of 1,820 nurse members of the Association of Women's Health, Obstetric and Neonatal Nurses were surveyed about their demographic and professional backgrounds, religious beliefs, and abortion attitudes. Scores on the Abortion Attitudes Scale were analyzed categorically and trichotomized in multinomial regression analyses. RESULTS: Almost one-third of the sample (32%) had moderately proabortion attitudes, 29% were unsure, 16% had strongly proabortion attitudes, 13% had strongly antiabortion attitudes, and 11% had moderately antiabortion attitudes. Using trichotomized Abortion Attitudes Scale scores (proabortion, unsure, antiabortion), adjusted regression models showed that the following characteristics were associated with proabortion attitudes: being non-Christian, residence in the North or West, having no children, and having had an abortion. CONCLUSIONS: Understanding nurses' attitudes toward abortion, and what characteristics may influence their attitudes, is critical to sustaining nursing care for patients considering and seeking abortion. Additionally, because personal characteristics were associated with antiabortion attitudes, it is likely that personal experiences may influence attitudes toward abortion. A large percentage of nurses held attitudes that placed them in the unsure" category. Given the current ubiquitous polarization of abortion discourse, this finding indicates that the binary narrative of this topic is less pervasive than expected, which lends itself to an emphasis on empathetic and compassionate nursing care." | Nurses, Neonatal |
Selenium (Se) enrichment has been demonstrated to vary by several orders of magnitude among species of planktonic algae. This is a substantial source of uncertainty when modelling Se biodynamics in aquatic systems. In addition, Se bioconcentration data are largely lacking for periphytic species of algae, and for multi-species periphyton biofilms, adding to the challenge of modelling Se transfer in periphyton-based food webs. To better predict Se dynamics in periphyton dominated, freshwater ecosystems, the goal of this study was to assess the relative influence of periphyton community composition on the uptake of waterborne Se oxyanions. Naturally grown freshwater periphyton communities, sampled from five different water bodies, were exposed to environmentally relevant concentrations of selenite [Se(IV)] or selenate [Se(VI)] (nominal concentrations of 5 and 25â¯mug Se L(-1)) under similar, controlled laboratory conditions for a period of 8 days. Unique periphyton assemblages were derived from the five different field sites, as confirmed by light microscopy and targeted DNA sequencing of the plastid 23S rRNA gene in algae. Selenium accumulation demonstrated a maximum of 23.6-fold difference for Se(IV) enrichment and 2.1-fold difference for Se(VI) enrichment across the periphyton/biofilm assemblages tested. The assemblage from one field site demonstrated both high accumulation of Se(IV) and iron, and was subjected to additional experimentation to elucidate the mechanism(s) of Se accumulation. Selenite accumulation (at nominal concentrations of 5 and 25â¯mug Se L(-1) and mean pH of 7.5 across all treatment replicates) was assessed in both unaltered and heat-killed periphyton, and in periphyton from the same site grown without light to exclude phototrophic organisms. Following an exposure length of 8 days, all periphyton treatments showed similar levels of Se accumulation, indicating that much of the apparent uptake of Se(IV) was due to non-biological processes (i.e., surface adsorption). The results of this study will help reduce uncertainty in the prediction of Se dynamics and food-chain transfer in freshwater environments. Further exploration of the ecological consequences of extracellular adsorption of Se(IV) to periphyton, rather than intracellular absorption, is recommended to further refine predictions related to Se biodynamics in freshwater food webs. | Periphyton |
Capsule size of five isolates of Cryptococcus neoformans was controlled by cultivation in media containing varying amounts of sugar. High concentrations of sugar (e.g., 16%) suppressed encapsulation whereas low concentrations (e.g., 1%) allowed maximal encapsulation. Suppression of capsule size was attributed at least in part to the increased osmolarity of the medium because a medium with low sugar concentration but having high osmolarity (by virtue of added sodium chloride) also produced cells having small capsules. The extent of control was more marked with certain of the isolates than with others. Mice were intravenously inoculated with cells of a single isolate cultivated so as to have either small or large capsules, and virulence was measured by comparing death rates. Results indicate that virulence after such an inoculation is a constant characteristic of an isolate and is not affected by size of the capsule of the cells in the inoculum. | Cryptococcus |
Recently we demonstrated that neocortical pyramidal cells in visual, visual association and prefrontal cortex of the macaque monkey are characterised by different growth, branching, spinogenesis and pruning during development. Some neurons, such as those in the primary visual area, prune more spines than they grow following sensory onset, while others such as those in area TE grow more than they prune. To what extent these different neuronal growth profiles may vary among cortical areas remains to be determined. To better comprehend the nature and extent of these regional differences in pyramidal cell growth profiles we expanded the bases for comparison by studying neurons in the primary auditory cortex (A1). We found that pyramidal cells in A1 continue to grow their basal dendritic trees beyond the peak period of spinogenesis (3(1)/(2) months) up until at least 7 months of age. Likewise, the most prolific branching patterns were observed in the dendritic trees of pyramidal cells at 7 months of age. These data reveal that the basal dendritic trees of cells in A1 continue to grow for a much longer period, and attain almost double the number of spines, as compared with those in V1. Such differences in the growth profiles of neocortical pyramidal cells among cortical areas may influence therapeutic outcomes when applying new technologies such as neurotrophic delivery devices or stem cell therapy. | Pyramidal Cells |
Submicromolar zinc inhibits alpha-ketoglutarate-dependent mitochondrial respiration. This was attributed to inhibition of the alpha-ketoglutarate dehydrogenase complex (Brown, A. M., Kristal, B. S., Effron, M. S., Shestopalov, A. I., Ullucci, P. A., Sheu, K.-F. R., Blass, J. P., and Cooper, A. J. L. (2000) J. Biol. Chem. 275, 13441-13447). Lipoamide dehydrogenase, a component of the alpha-ketoglutarate dehydrogenase complex and two other mitochondrial complexes, catalyzes the transfer of reducing equivalents from the bound dihydrolipoate of the neighboring dihydrolipoamide acyltransferase subunit to NAD(+). This reversible reaction involves two reaction centers: a thiol pair, which accepts electrons from dihydrolipoate, and a non-covalently bound FAD moiety, which transfers electrons to NAD(+). The lipoamide dehydrogenase reaction catalyzed by the purified pig heart enzyme is strongly inhibited by Zn(2+) (K(i) approximately 0.15 microm) in both directions. Steady-state kinetic studies revealed that Zn(2+) competes with oxidized lipoamide for the two-electron-reduced enzyme. Interaction of Zn(2+) with the two-electron-reduced enzyme was directly detected in anaerobic stopped-flow experiments. Lipoamide dehydrogenase also catalyzes NADH oxidation by oxygen, yielding hydrogen peroxide as the major product and superoxide radical as a minor product. Zn(2+) accelerates the oxidase reaction up to 5-fold with an activation constant of 0.09 +/- 0.02 microm. Activation is a consequence of Zn(2+) binding to the reduced catalytic thiols, which prevents delocalization of the reducing equivalents between catalytic disulfide and FAD. A kinetic scheme that satisfactorily describes the observed effects has been developed and applied to determine a number of enzyme kinetic parameters in the oxidase reaction. The distinct effects of Zn(2+) on different LADH activities represent a novel example of a reversible switch in enzyme specificity that is modulated by metal ion binding. These results suggest that Zn(2+) can interfere with mitochondrial antioxidant production and may also stimulate production of reactive oxygen species by a novel mechanism." | Protein Disulfide Reductase (Glutathione) |
A variety of cellular processes, both physiological and pathophysiological, require or are governed by calcium, including exocytosis, mitochondrial function, cell death, cell metabolism and cell migration to name but a few. Cytosolic calcium is normally maintained at low nanomolar concentrations; rather it is found in high micromolar to millimolar concentrations in the endoplasmic reticulum, mitochondrial matrix and the extracellular compartment. Upon stimulation, a transient increase in cytosolic calcium serves to signal downstream events. Detecting changes in cytosolic calcium is normally performed using a live cell imaging set up with calcium binding dyes that exhibit either an increase in fluorescence intensity or a shift in the emission wavelength upon calcium binding. However, a live cell imaging set up is not freely accessible to all researchers. Alternative detection methods have been optimized for immunological cells with flow cytometry and for non-immunological adherent cells with a fluorescence microplate reader. Here, we describe an optimized, simple method for detecting changes in epithelial cells with flow cytometry using a single wavelength calcium binding dye. Adherent renal proximal tubule epithelial cells, which are normally difficult to load with dyes, were loaded with a fluorescent cell permeable calcium binding dye in the presence of probenecid, brought into suspension and calcium signals were monitored before and after addition of thapsigargin, tunicamycin and ionomycin. | Calcium Ionophores |
Prenatal exposures may have a distinct impact for long-term health. Exposure to maternal 'diabesity' during pregnancy increases offspring 'diabesity' risk, e.g. by malprogramming the central nervous regulation of body weight, food intake and metabolism. Critical mechanisms and concrete disrupting factors still remain unclear. Due to the independent development, from the mother, the chicken embryo could provide a valuable model to distinctively establish causal factors. Aim of this study was to determine effects of temporary prenatal hyperglycemia on postnatal hypothalamic neuronal glucose sensitivity in the chicken. To induce hyperglycemia in chicken embryos, 0.5 ml glucose solution (concentration 30 mmol/l) were daily administered via catheter into a vessel of the chorioallantoic egg membrane from days 14 to 17 of incubation. On day 21 of postnatal age, body weight, body fat content, blood glucose, neuroelectrophysiological glucose sensitivity as well as glucose transporter expression were determined in hypothalamic brain slices. No significant changes in morphometric and metabolic parameters were observed. However, strongly decreased neuronal glucose sensitivity and glucose transporter expression occurred, indicating prenatally acquired hypothalamic 'glucose-resistance'. In conclusion, temporary late prenatal hyperglycemia induces lasting changes in central glucose sensing. The prenatally glucose-treated chicken provides a valuable new model for investigating early central nervous origins of 'diabesity' and related disorders. | Glucose Transporter Type 3 |
Inbred strains of laboratory mice have several distinct advantages as models for examining conditions that influence the human auditory system, but the CBA/J mouse which has most often been used as a normal model has recently been found to have several disadvantages. This paper is the first report of the auditory brainstem responses (ABRs) of the F1 offspring of CBA/CaJ and AU/SsJ parents. At midlife, high-frequency ABR thresholds are lower in the F1 than in either parental genotype. Tuning curves obtained by forward masking of the ABR also display heterosis, i.e. they are narrower in the F1 than in either parental strain. | Mice, Inbred CBA |
Hypoglycemic sulfamide BZ-55 activates or inhibits germination of Raphanus sativus, depending upon the dosis. Since this drug acts upon the glycemia by increasing the secretion and action of insulin, the influence of this hormone on germination and ionic changes (Na+-K+) between seeds and culture medium, were studied. Seeds were incubated during 72 h with different concentrations of insulin in 10 ml deionized water or in 10 ml 18 mM K+ (KCl) solutions at 37 degrees C in vapor saturated atmosphere. A solution of 0.125 IU insulin/ml in water increases the germination to 110% whereas 0.175 IU insulin/ml inhibits it to 40% against controls. Further increases in insulin concentration always inhibit germination. Similar results have been obtained with K+ containing media. Germination rate changes in a small concentration range suggest that insulin might affect an enzymatic activity in the seed. | Carbutamide |
Stickler syndrome (SS) is characterized by ophthalmic, articular, orofacial, and auditory manifestations. SS is usually autosomal dominantly inherited with variants in COL2A1 or COL11A1. Recessive forms are rare but have been described with homozygous variants in COL9A1, COL9A2, and COL9A3 and compound heterozygous COL11A1 variants. This article expands phenotypic descriptions in recessive SS due to variants in genes encoding Type IX collagen. Clinical features were assessed in four families. Genomic DNA samples derived from venous blood were collected from family members. Six affected patients were identified from four pedigrees with variants in COL9A1 (one family, one patient), COL9A2 (two families, three patients), and COL9A3 (one family, two patients). Three variants were novel. All patients were highly myopic with congenital megalophthalmos and abnormal, hypoplastic vitreous gel, and all had sensorineural hearing loss. One patient had severe arthropathy. Congenital megalophthalmos and myopia are common to dominant and recessive forms of SS. Sensorineural hearing loss is more common and severe in recessive SS. We suggest that COL9A1, COL9A2, and COL9A3 be added to genetic screening panels for patients with congenital hearing loss. Although recessive SS is rare, early diagnosis would have a high impact for children with potentially dual sensory impairment, as well as identifying risk to future children. | Collagen Type IX |
The fluorescence of Green Fluorescent Protein (wtGFP) and variants has been exploited in distinct applications in cellular and analytical biology. GFPs emission depends on the population of the protonated (A-state) and deprotonated (B-state) forms of the chromophore. Whereas wtGFP is pH-independent, mutants in which Ser65 is replaced by either threonine or alanine (as in GFPmut2) are pH-dependent, with a p K(a) around 6. Given the wtGFP pH-independence, only the structure of the protonated form was determined. The deprotonated form was deduced on the basis of the crystal structure of the Ser65Thr mutant at basic pH, assuming that it corresponds to the conformation populated in solution. Here, we present an investigation where structures of the protonated and deprotonated forms of GFPmut2 were determined from crystals grown in either MPD at pH 6 or PEG at pH 8.5, and moved to either higher or lower pH. Both crystal forms of GFPmut2 were titrated monitoring the process via polarized absorption microspectrophotometry in order to precisely correlate the protonation process with the structures. We found that (i) in solution, chromophore titration is not thermodynamically coupled with any residue and Glu222 is always protonated independent of the protonation state of the chromophore; (ii) the lack of coupling is reflected in the structural behavior of the chromophore and Glu222 environments, with only the former showing variations with pH; (iii) titrations of low-pH and high-pH grown crystals exhibit a Hill coefficient of about 0.75, indicating an anticooperative behavior not observed in solution; (iv) structures where pH was changed in the crystal point to Glu222 as the ionizable group responsible for the outset of the anticooperative behavior; and (v) in GFPmut2 the canonical GFP proton wire involving the chromophore is not interrupted at the level of Ser205 and Glu222 at basic pH as in the Ser65Thr mutant. This allows proposing the structure of the deprotonated state of GFPmut2 as an alternative model for the analogous state of wtGFP. | Microspectrophotometry |
Two new C19-diterpenoid alkaloids, kongboentine A (1) and kongboentine B (3), were isolated from the roots of Aconitum kongboense Lauener and their structures were elucidated by spectral data. | Aconitum |
Plant growth-promoting rhizobacteria strains from special formulations have been used to optimize eucalyptus cutting production. To undertake quality control for the formulated products, the rhizobacterial strains should be characterized to assess their purity and authentication. In the present study, we characterized nine strains of rhizobacteria, including three Bacillus subtilis (S1, S2 and 3918), two Pseudomonas sp. (MF4 and FL2), P. putida (MF2), P. fulva (Ca), Frateuria aurantia (R1), and Stenotrophomonas maltophilia (CIIb). The strains were differentiated by colony morphology after 24h of incubation in three different solid state culture media (glucose-nutritive agar, 523 medium and yeast extract-mannitol agar), sensitivity to a panel of 28 antibiotics (expressed according to the formation of inhibition halos of bacterial growth in the presence of antibiotics), and PCR-RFLP profiles of the 16S rDNA gene produced using nine restriction enzymes. It was possible to differentiate all nine strains of rhizobacteria using their morphological characteristics and sensitivity to antibiotics. The molecular analysis allowed us to separate the strains CIIb, FL2 and R1 from the strains belonging to the genera Bacillus and Pseudomonas. By using these three methods concomitantly, we were able to determine strain purity and perform the authentication. | Eucalyptus |
This self-directed learning module highlights various cumulative trauma disorders of the upper limb that may be seen in computer users. The biomechanics and ergonomics of computer users are addressed in relationship to specific neurologic and musculoskeletal conditions within the neck and upper limbs. In addition to a general overview of these conditions, a case presentation is used to show the evaluation and treatment of a computer user who has carpal tunnel syndrome and concomitant de Quervain tenosynovitis. OVERALL ARTICLE OBJECTIVES: (a) To review the important anatomic and ergonomic basis for upper limb cumulative trauma disorders in computer users and (b) to provide an example of evaluation and treatment. | Cumulative Trauma Disorders |
Cell-based therapies are emerging as effective agents against cancer and other diseases. As autonomous living drugs," these therapies lack precise control. Chimeric antigen receptor (CAR) T cells effectively target hematologic malignancies but can proliferate rapidly and cause toxicity. We developed ON and OFF switches for CAR T cells using the clinically approved drug lenalidomide, which mediates the proteasomal degradation of several target proteins by inducing interactions between the CRL4(CRBN) E3 ubiquitin ligase and a C2H2 zinc finger degron motif. We performed a systematic screen to identify "super-degron" tags with enhanced sensitivity to lenalidomide-induced degradation and used these degradable tags to generate OFF-switch degradable CARs. To create an ON switch, we engineered a lenalidomide-inducible dimerization system and developed split CARs that required both lenalidomide and target antigen for activation. Subtherapeutic lenalidomide concentrations controlled the effector functions of ON- and OFF-switch CAR T cells. In vivo, ON-switch split CARs demonstrated lenalidomide-dependent antitumor activity, and OFF-switch degradable CARs were depleted by drug treatment to limit inflammatory cytokine production while retaining antitumor efficacy. Together, the data showed that these lenalidomide-gated switches are rapid, reversible, and clinically suitable systems to control transgene function in diverse gene- and cell-based therapies." | Jurkat Cells |
STUDY DESIGN: A prospective randomized study involving 280 consecutive cases of lumbar disc herniation managed either by an endoscopic discectomy alone or an endoscopic discectomy combined with an intradiscal injection of a low dose (1000 U) of chymopapain. OBJECTIVE: To compare outcome, complications, and reherniations of both techniques. SUMMARY OF BACKGROUND DATA: Despite a low complication rate, posterolateral endoscopic nucleotomy has made a lengthy evolution because of an assumed limited indication. Chemonucleolysis, however, proven to be safe and effective, has not continued to be accepted by the majority in the spinal community as microdiscectomy is considered to be more reliable. METHOD: A total of 280 consecutive patients with a primary herniated, including sequestrated, lumbar disc with predominant leg pain, was randomized. A clinical follow-up was performed at 3 months, and at 1 and 2 years after the index operation with an extensive questionnaire, including the visual analog scale for pain and the MacNab criteria. The cohort integrity at 3 months was 100%, at 1 year 96%, and at 2 years 92%. RESULTS: At the 3-month evaluation, only minor complications were registered. At 1-year postoperatively, group 1 (endoscopy alone) had a recurrence rate of 6.9% compared to group 2 (the combination therapy), with a recurrence rate of 1.6%, which was a statistically significant difference in favor of the combination therapy (P = 0045). At the 2-year follow-up, group 1 reported that 85.4% had an excellent or good result, 6.9% a fair result, and 7.7% were not satisfied. At the 2-year follow-up, group 2 reported that 93.3% had an excellent or good result, 2.5% a fair result, and 4.2% were not satisfied. This outcome was statistically significant in favor of the group including chymopapain. There were no infections or patients with any form of permanent iatrogenic nerve damage, and no patients had a major complication. CONCLUSIONS: A high percentage of patient satisfaction could be obtained with a posterior lateral endoscopic discectomy for lumbar disc herniation, and a statistically significant improvement of the results was obtained when an intradiscal injection of 1000 U of chymopapain was added. There was a low recurrence rate with no major complications. The method can be applied in any type of lumbar disc herniation, including the L5-S1 level. | Chymopapain |
Social projection is the tendency to expect similarities between oneself and others. A review of the literature and a meta-analysis reveal that projection is stronger when people make judgments about ingroups than when they make judgments about outgroups. Analysis of moderator variables further reveals that ingroup projection is stronger for laboratory groups than for real social categories. The mode of analysis (i.e., nomothetic vs. idiographic) and the order of judgments (i.e., self or group judged first) have no discernable effects. Outgroup projection is positive, but small in size. Together, these findings support the view that projection can serve as an egocentric heuristic for inductive reasoning. The greater strength of ingroup projection can contribute to ingroup-favoritism, perceptions of ingroup homogeneity, and cooperation with ingroup members. | Social Desirability |
We describe a patient with Kleine-Levin syndrome who was initially misdiagnosed as having epilepsy and who achieved complete remission on carbamazepine treatment. A drug effect was established when symptoms recurred after carbamazepine taper and disappeared after reintroduction of the drug. Carbamazepine, a safer drug than lithium, can be a highly effective treatment in some patients with Kleine-Levin syndrome. This syndrome can sometimes be confused with epilepsy because of the episodic nature of the symptoms and the occasional response to anticonvulsants. | Kleine-Levin Syndrome |
Although extra-pulmonary manifestations of Mycoplasma pneumoniae are well described, immune thrombocytopenia associated with M. pneumoniae is rarely reported. We describe a woman who developed immune thrombocytopenic purpura during an acute mycoplasma infection. The clinical features and outcomes of all previously reported cases are reviewed, and possible mechanisms underlying this association are discussed. Immune thrombocytopenic purpura should be considered early in patients with thrombocytopenia and mycoplasma infections, with the institution of usual therapy for immune thrombocytopenic purpura." | Purpura, Thrombocytopenic, Idiopathic |
Neonatal brachial plexus palsy is a complex disorder that requires evaluation of the primary nerve injury and associated sequelae. There is no standardized approach to management, and many treatment options are available. We present a case of Erb palsy with a unique multidisciplinary approach to nonsurgical and surgical management. Inherent in the case is the complexity of decision-making, and we review the literature on treatment options and the rationale for the approach, which resulted in near normal functional recovery." | Neonatal Brachial Plexus Palsy |
Since agonists and temperature affect receptor affinity, and since these factors may influence the actual determination of receptor affinity, we assessed the in vitro effects of temperature and isoproterenol on the high and low affinity states of beta-adrenergic receptors in rat membrane preparations. There was a temperature-dependent decrease in beta-adrenergic receptor agonist affinity which was further promoted by the presence of isoproterenol. The decrease in receptor agonist affinity was reflected by a decrease in the number of receptors in the high affinity state. These data suggest that receptor desensitization may occur in membrane preparations in vitro and that the present methodology used to assess agonist affinity in vitro may itself alter the very properties being measured. | Dihydroalprenolol |
Oxide-supported transition-metal clusters and nanoparticles have attracted significant attention owing to their important role as components of model catalysts, sensors, solar cells and magnetic recording devices. For small clusters, functionality and structure are closely interrelated. However, knowledge of the structure of the bare cluster is insufficient as the interaction with the chemical environment might cause drastic structural changes. Here we show by ab initio simulations based on the density functional theory that the reaction with molecular oxygen transforms small, non-crystalline, magnesia-supported Pd-clusters to crystalline Pd(x)O(y) nano-oxide clusters that are in epitaxy with the underlying support. Restructuring of the Pd backbone is controlled by the electrostatic interaction with magnesia leading to a strong reduction of the O2 dissociation barrier. The supported Pd(x)O(y) clusters are likely to serve as Mars-van Krevelen oxygen reservoirs in catalytic oxidation reactions as observed for PdO overlayers and demonstrated here for the oxidation of CO molecules. | Magnesium Oxide |
Older adults are at increased risk of malnutrition, for a variety of physiological and psychological reasons. This has implications for health, quality of life, independence and economic circumstances. Improvements in nutrition are known to bring tangible benefits to older people and many age-related diseases and conditions can be prevented, modulated or ameliorated by good nutrition. However, practical and realistic approaches are required to optimize diet and food intake in older adults. One area where improvements can be made relates to appetite. Encouraging older adults to prepare meals can increase appetite and food intake, and providing opportunities for older adults to eat a wide variety of foods, in company, is a simple strategy to increase food intake. The protein requirement of older adults is subject to controversy and although considered the most satiating macronutrient, it appears that protein does not elicit as great a satiating effect in older adults as it does in younger individuals. This indicates that there is potential to increase protein intake without impacting on overall energy intake. Other areas where simple practical improvements can be made include both packaging of foods that are easy to prepare and the education of older adults on the safe storage and preparation of food. Research into improving the diets and nutritional status of older adults has indicated that many of the strategies can be easily and cost-effectively undertaken." | Nutritional Physiological Phenomena |
BACKGROUND: The purpose of this study was to identify pretreatment factors associated with the stability of early class III treatment, since most orthodontists start the treatment with their uncertain hypotheses and/or predictions. Subjects consisted of 75 patients with a class III skeletal relationship (ANB < 2 degrees and overjet < 0 mm) who had been consecutively treated with rapid maxillary expansion and facemask and followed until their second phase treatment. The patients were divided into two groups according to whether they showed relapse in follow-up. The stable group maintained their positive overjet (n = 55), and the unstable group experienced relapse with a zero or negative overjet (n = 20). Two general, three dental, and 13 cephalometric pretreatment factors were investigated to determine which factors were associated with stability. RESULTS: Sex, pretreatment age, and anteroposterior functional shift, which were hypothesized as associated factors, were not related to the stability of early class III treatment. Significant differences were detected between the two groups in the horizontal distance between the maxillary and mandibular molars in centric relation. Cephalometric variables, such as the mandibular length (Ar-Me), Wits appraisal, SN to ramus plane angle (SN-Rm), gonial angle, incisor mandibular plane angle (IMPA), and Frankfort plane to mandibular incisor angle (FMIA) showed significant differences between the groups. The horizontal distance was the most influential factor by logistic regression analysis. CONCLUSIONS: Hypothesis (related to sex, age, functional shift) were rejected. Several cephalometric factors related to the mandible were associated with stability. The horizontal distance between the maxillary and mandibular molars in centric relation was the best predictor of early class III treatment relapse. | Malocclusion, Angle Class III |
OBJECTIVE: Late-life hoarding is a serious psychiatric condition with significant implications in health and functioning. Geriatric hoarding patients show greater impairment in activities of daily living and have a greater number of medical conditions compared with same-aged nonhoarders. This study examined the relationship between geriatric hoarding severity and functional disability severity. METHODS: Sixty-five subjects age 60 or older with hoarding disorder (HD) participated in the current study. Participants were assessed with measures of hoarding severity, psychiatric symptoms, and general disability. Hierarchical regression was used to test the unique association of hoarding symptoms with functional disability beyond the effects of demographic factors, anxiety, and depression. RESULTS: When controlling for demographics (age and gender) and psychiatric symptoms (anxiety and depression), hoarding severity predicts functional disability severity. Analyses also show that clinician-administered measures of hoarding are stronger predictors of disability than patient self-report measures. CONCLUSIONS: When treating older adults with HD, clinicians must consider symptom impact on daily life. A multidisciplinary team must be utilized to address the wide-ranging consequences of hoarding symptoms. Future work should examine how psychiatric treatment of HD affects functional disability. | Hoarding Disorder |
Synthesis of a potent inhibitor of bacterial protein synthesis, pleuromutilin, is described. Assembly of the critical cyclooctane fragment relies on an oxidative ring-expansion, and complete stereochemical relay in the synthetic sequence is enabled by the judicious choice of tactics. The requisite connectivity pattern of the perhydroindanone motif is rapidly established in a sequence of cycloaddition and radical cyclization events. Application of this strategy allows for preparation of the target natural product in 16 steps from commercially available material. | Cyclization |
In the human isolated arm preparation Org NC 45 had a significantly faster rate of recovery and a shorter duration of action (end of injection to 90% recovery of control twitch height) than pancuronium. The isolated arm preparation is suitable for the qualitative comparison of the neuromuscular blocking activities of new and established drugs. | Androstanes |
This article presents a reflection on the meaning of the terms citizenship and health, addressing the Theory of Social Representations as a strategy for implementing and evaluating health care models in Brazil. First, a brief history about the concept of citizenship is presented; then the article addresses the principles of freedom and equality according to Kant; the third section of the article shows that health is as a right of the citizen and a duty of the state. Finally, the Theory of Social Representations is emphasized as a strategy to evaluate and implement the health services provided to citizens by the current health care models in Brazil. | Constitution and Bylaws |
From 1980 to 1986, head computed tomographic scans were performed in 49 women with eclampsia managed according to the standardized regimen used at Parkland Memorial Hospital. Abnormal radiographic findings were seen in 14 (29%). Although this incidence may have been affected by the temporal relationship of the scan to the seizure, it was greatly impacted by technical resolution obtained with succeeding improved equipment. In the last 3 years of the study more than a third of these scans showed some abnormality, and in 1986, using fourth-generation" equipment, half were abnormal. These areas of radiographic hypodensity correspond to those with petechial hemorrhages and local edema that have been described at autopsy in women who died after eclamptic episodes. All women recovered fully despite ominous findings in some. We conclude that the clinical utility of tomography in women with otherwise "uncomplicated eclampsia" is limited because these findings seldom alter management." | Eclampsia |
Vocal production is a sensory-motor process in which auditory self-monitoring is used to ensure accurate communication. During vocal production, the auditory cortex of both humans and animals is suppressed, a phenomenon that plays an important role in self-monitoring and vocal motor control. However, the underlying neural mechanisms of this vocalization-induced suppression are unknown. gamma-band oscillations (>25 Hz) have been implicated a variety of cortical functions and are thought to arise from activity of local inhibitory interneurons, but have not been studied during vocal production. We therefore examined gamma-band activity in the auditory cortex of vocalizing marmoset monkeys, of either sex, and found that gamma responses increased during vocal production. This increase in gamma contrasts with simultaneously recorded suppression of single-unit and multiunit responses. Recorded vocal gamma oscillations exhibited two separable components: a vocalization-specific nonsynchronized (induced") response correlating with vocal suppression, and a synchronized ("evoked") response that was also present during passive sound playback. These results provide evidence for the role of cortical gamma oscillations during inhibitory processing. Furthermore, the two distinct components of the gamma response suggest possible mechanisms for vocalization-induced suppression, and may correspond to the sensory-motor integration of top-down and bottom-up inputs to the auditory cortex during vocal production.SIGNIFICANCE STATEMENT Vocal communication is important to both humans and animals. In order to ensure accurate information transmission, we must monitor our own vocal output. Surprisingly, spiking activity in the auditory cortex is suppressed during vocal production yet maintains sensitivity to the sound of our own voice ("feedback"). The mechanisms of this vocalization-induced suppression are unknown. Here we show that auditory cortical gamma oscillations, which reflect interneuron activity, are actually increased during vocal production, the opposite response of that seen in spiking units. We discuss these results with proposed functions of gamma activity during inhibitory sensory processing and coordination of different brain regions, suggesting a role in sensory-motor integration." | Gamma Rhythm |
WHAT IS KNOWN AND OBJECTIVE: Linezolid, a member of the oxazolidinone class of antibacterial drugs, is approved by the US Food and Drug Administration (FDA) for the treatment of vancomycin-resistant Enterococcus faecium infections, nosocomial and community-acquired pneumonia, as a part of anti tubercular regimen and complicated and uncomplicated skin and soft tissue infections, including diabetic foot infections. Linezolid has potential adverse effects like bone marrow suppression, peripheral neuropathy and hyponatremia. One of the extremely rare reported adverse effects of the drug is hypoglycaemia. We present a case of Linezolid toxicity presenting as resistant hypoglycemia, bone marrow suppression and severe hyponatremia all together in a single patient. CASE DESCRIPTION: We present a case of an 82 years old gentleman with no known chronic co-morbidities. He was started on Linezolid 600 mg twice a day for 10 days by a local doctor possibly for some minor infection post hip surgery. He was in respiratory distress on arrival. Blood sugars showed severe hypoglycemia of 36 mg/dL (2.0 mmol/L). He was admitted in intensive care unit and started on injectable antibiotics and 5% dextrose infusion and sugars were strictly monitored. His blood tests revealed severe hyponatremia with sodium level of 119 mEq/L and haemoglobin (Hb) of 8.8 gm/dL, leucocytes of 6500/microL, platelets of 82 000/microL. The infection markers were normal throughout. The platelet count went progressively down from 82 000/microL on admission to 20 000/microL 2 days later; before it started rising back. Similarly there was drop in Hemoglobin and white cell counts. He required vasopressors to maintain mean arterial pressures. The blood sugar levels stabilized after the same. However patient had suffered acute lung injury secondary to aspiration and became NIV dependent and eventually passed away. WHAT IS NEW AND CONCLUSION: Our case was unique in a way that our patient had adverse effects of linezolid like myelosuppression as well as the rare side effects of hypoglycemia at the same time. This combination of adverse events has never been described in the past to our knowledge. All the adverse effects responded to antibiotic de-challenge in our case. We had ruled out the possibility of other causes of Hypoglycemia such as sepsis, insulinoma, alcohol excess, malnutrition or hypoadrenalism. We searched the PubMed database and found four case reports out of which two were diabetics and other two were non diabetics. Out of 15 cases described by Vishwanathan et al only three cases were non diabetics. Our patient was non diabetic as well. Therefore our case is only the sixth reported case of hypoglycemia in non diabetic receiving Linezolid to our knowledge. | Linezolid |
Peripheral nerve damage initiates a complex series of structural and cellular processes that culminate in chronic neuropathic pain. The recent success of a type 2 angiotensin II (Ang II) receptor (AT2R) antagonist in a phase II clinical trial for the treatment of postherpetic neuralgia suggests angiotensin signaling is involved in neuropathic pain. However, transcriptome analysis indicates a lack of AT2R gene (Agtr2) expression in human and rodent sensory ganglia, raising questions regarding the tissue/cell target underlying the analgesic effect of AT2R antagonism. We show that selective antagonism of AT2R attenuates neuropathic but not inflammatory mechanical and cold pain hypersensitivity behaviors in mice. Agtr2-expressing macrophages (MPhis) constitute the predominant immune cells that infiltrate the site of nerve injury. Interestingly, neuropathic mechanical and cold pain hypersensitivity can be attenuated by chemogenetic depletion of peripheral MPhis and AT2R-null hematopoietic cell transplantation. Our study identifies AT2R on peripheral MPhis as a critical trigger for pain sensitization at the site of nerve injury, and therefore proposes a translatable peripheral mechanism underlying chronic neuropathic pain. | Receptor, Angiotensin, Type 2 |
PURPOSE: This pilot study compared the clinical endpoints of the magnetostrictive and piezoelectric ultrasonic instruments on calculus removal. The null hypothesis stated that there is no statistically significant difference in calculus removal between the 2 instruments. METHODS: A quasi-experimental pre- and post-test design was used. Eighteen participants were included. The magnetostrictive and piezoelectric ultrasonic instruments were used in 2 assigned contra-lateral quadrants on each participant. A data collector, blind to treatment assignment, assessed the calculus on 6 predetermined tooth sites before and after ultrasonic instrumentation. Calculus size was evaluated using ordinal measurements on a 4 point scale (0, 1, 2, 3). Subjects were required to have size 2 or 3 calculus deposit on the 6 predetermined sites. One clinician instrumented the pre-assigned quadrants. A maximum time of 20 minutes of instrumentation was allowed with each technology. Immediately after instrumentation, the data collector then conducted the post-test calculus evaluation. RESULTS: The repeated analysis of variance (ANOVA) was used to analyze the pre- and post-test calculus data (p</=0.05). The null hypothesis was accepted indicating that there is no statistically significant difference in calculus removal when comparing technologies (p</=0.05). Therefore, under similar conditions, both technologies removed the same amount of calculus. CONCLUSION: This research design could be used as a foundation for continued research in this field. Future studies include implementing this study design with a larger sample size and/or modifying the study design to include multiple clinicians who are data collectors. Also, deposit removal with periodontal maintenance patients could be explored. | Dental Calculus |
Peripheral blood lymphocytes were cultured for 5 days with allogeneic tumor cells (allogeneic mixed lymphocyte/tumor cell culture), and subsequently cultured with recombinant interleukin-2 for 12 days. These cultured cells were found to be cytotoxic to autologous tumor cells. Results of two-color analysis using monoclonal antibodies to cell markers showed that more than 80% of their cultured cells were CD3+ cells, and CD4+ cells showed a higher distribution than CD8+ cells. However, CD8+ cells had a much higher killing activity with autologous tumor than did CD4+ cells, when estimated by an elimination study using monoclonal antibodies to T cell phenotypes and complement. The "cold-target" inhibition test showed that the cytotoxicity of these cells for autologous tumor cells was inhibited by unlabeled autologous tumor cells but not by unlabeled stimulator cells. Furthermore, about 40% of the cytotoxicity was suppressed by blocking of HLA class I antigen with a monoclonal antibody on autologous tumor cells. Thus, cytotoxic activity of lymphocytes to autologous tumor restricted by target cell HLA class I antigen is possibly induced by allogeneic tumor-stimulation." | Killer Cells, Lymphokine-Activated |
OBJECTIVE: This study aimed to evaluate the impact of intra-operative neuromonitoring of the recurrent laryngeal nerve during total thyroidectomy for benign goitre. METHODS: A single-centre retrospective study using historical controls was conducted for a 10-year period, comprising a series of 767 patients treated by total thyroidectomy for benign goitre. Of these, 306 had intra-operative neuromonitoring of the recurrent laryngeal nerve and 461 did not. Post-operative laryngeal mobility was assessed in all patients by direct laryngoscopy before hospital discharge and at post-operative follow-up visits. RESULTS: In all, 6 out of 461 patients (1.30 per cent) in the control group and 6 out of 306 patients (1.96 per cent) in the intra-operative neuromonitoring group developed permanent recurrent laryngeal nerve palsy. No statistically significant difference was observed between the two patient groups. CONCLUSION: Intra-operative neuromonitoring does not appear to affect the post-operative recurrent laryngeal nerve palsy rate or to reliably predict post-operative recurrent laryngeal nerve palsy. However, it can accurately predict good nerve function after thyroidectomy." | Recurrent Laryngeal Nerve Injuries |
OBJECTIVES: Neutrophils and their granular enzymes such as neutrophil elastase (NE) and myeloperoxidase (MPO) play important roles in inflammatory diseases, and might be utilized as biomarkers for disease severity and progression. The aim of this study was to determine reference intervals for NE and MPO activity in healthy volunteers comparing two methods of neutrophil isolation. METHODS: Neutrophils were isolated using ficoll density gradient centrifugation or immunomagnetic negative selection in two separate volunteers' cohorts. Subsequently, cells were lysed and incubated with chromogens for NE and MPO activity measurements, then measured with a microplate reader at 415 or 450 nm respectively. RESULTS: The enzymatic activity of NE and MPO depended on the neutrophil isolation technique. Both enzymatic activities were significantly higher (P < 0.001) after isolating neutrophils with ficoll density gradient centrifugation than using the immunomagnetic negative selection. CONCLUSIONS: We demonstrated that neutrophil isolation is an important factor that influences the outcome of enzymatic activity measurements. Techniques based on immunomagnetic negative selection are favorable, specifically for investigations related to NE and MPO activity. When using NE and MPO activity measurements in clinical practice, care must be taken to interpret the data depending on the applied cell isolation technique. | Ficoll |
Starting from the words of Paracelsus, 'allein und fremd und anders'--alone and foreign and different--the influence of this important Swiss physician for the balneology of his time is outlined. Up to our days Paracelsus is honored as the real father of balneology, whereas other authors saw and probably still see hypotheses and in part utopias in his specific ideas. Paracelsus has described quite a number of thermal springs in Switzerland, Austria and southern Germany, some of them rather in detail. It is certainly questionable that he visited all of them personally. Bad Pfafers, however, definitely belongs to them, since undoubted testimonies exist that emerged during his life time. His famous 'Baderbuchlin', though, has been printed after his death in 1562. His theoretical ideas about the effects of bathing are in part very modern, others originate from medieval alchemistic sources. He used this theory of 'Separatio' of the three basal elements sulphur, mercurius and sal, as well as the idea of the 'light of Nature', but beyond that he discussed also influences of personified forces, which he assumed in nymphs, melusins and others. Furthermore, in his balneology he expressed clearly his doctrine about the macro- and microcosmic relation, and he used in his balneotherapy vegetable and mineral compounds up to precious stones. Time, too, had a special importance for the effectiveness of the bath in his eyes.(ABSTRACT TRUNCATED AT 250 WORDS) | Balneology |
Feeding is a fundamental process for basic survival and is influenced by genetics and environmental stressors. Recent advances in our understanding of behavioral genetics have provided a profound insight on several components regulating eating patterns. However, our understanding of eating disorders, such as anorexia nervosa, bulimia nervosa, and binge eating, is still poor. The animal model is an essential tool in the investigation of eating behaviors and their pathological forms, yet development of an appropriate animal model for eating disorders still remains challenging due to our limited knowledge and some of the more ambiguous clinical diagnostic measures. Therefore, this review will serve to focus on the basic clinical features of eating disorders and the current advances in animal models of eating disorders. | Feeding and Eating Disorders |
CONTEXT: Schistosomiasis is a major health problem worldwide. Thus, the search for new schistosomicidal agents from natural sources can provide prototypes for drug discovery. OBJECTIVE: The present study investigated the chemical composition of the EtOAc fractions of Styrax pohlii Pohl (Styracaceae) (EF-SP) aerial parts and S. camporum A. DC. leaves (EF-SC), as well as schistosomicidal activities against Schistosoma mansoni adult worms, which have not yet been studied. MATERIALS AND METHODS: The crude ethanol extracts of S. camporum leaves and S. pohlii aerial parts (EE-SC and EE-SP) were partitioned with n-hexane, EtOAc, and n-BuOH. The EtOAc fractions were purified by preparative HPLC. The crude extracts, EtOAc fractions and pure compounds were tested against S. mansoni adult worms in vitro. RESULTS: The purification procedure resulted in the isolation of kaempferol-3-O-(2'',4''-di-O-(E)-p-coumaroyl)-beta-d-glucopyranoside (1), kaempferol-3-O-(2'',6''-di-O-(E)-p-coumaroyl)-beta-d-glucopyranoside (2), quercetin (3), and kaempferol (4). The bioassay results indicated that EE-SC, EF-SC, EF-SP, and compounds 2 and 4 are able to separate coupled S. mansoni adult worms. Additionally, EE-SC, EF-SP, and compound 4 killed the adult schistosomes in vitro at 100 microg/mL and 100 microM. DISCUSSION AND CONCLUSION: This is the first time that the presence of compounds 1-2 in S. pohlii and 3-4 in S. camporum has been reported. Additionally, biological results indicated that S. pohlii and S. camporum have great potential as a source of active compounds. | Styrax |
Plant organs arise through complex interactions between biological and physical factors that control morphogenesis. While there has been tremendous progress in the understanding of the genetics behind development, we know much less about how mechanical forces control growth in plants. In recent years, new multidisciplinary research combining genetics, live-imaging, physics, and computational modeling has begun to fill this gap by revealing the crucial role of biomechanics in the establishment of plant organs. In this review, we provide an overview of our current understanding of growth during initiation, patterning, and expansion of shoot lateral organs. We discuss how growth is controlled by physical forces, and how mechanical stresses generated during growth can control morphogenesis at the level of both cells and tissues. Understanding the mechanical basis of growth and morphogenesis in plants is in its early days, and many puzzling facts are yet to be deciphered. | Plant Shoots |
We present a physiologically based pharmacokinetic (PBPK) model simulating systemic drug concentrations following administration to the human rectum. Rectum physiology is parameterized based on literature data. The model utilizes in vitro release (IVRT) profiles from which drug mass transfer through the rectal fluid and tissue and into the systemic circulation are predicted. Due to a lack of data, rectal fluid and tissue absorption parameters are predicted either from colon absorption, with modifications relevant to rectal physiology, or optimized. The PBPK model is evaluated by simulating 29 clinical studies for 10 drugs. For 8 drugs (diazepam, diclofenac, indomethacin, naproxen, paracetamol, pentobarbital, phenobarbital and theophylline) the bias (average fold error, AFE) and precision (absolute average fold error, AAFE) of C(max), AUC(0-t) and AUC(0-inf) simulations range from 0.87 to 2.22, indicating good agreement with observed values. For prochlorperazine and promethazine, the AFEs and AAFEs of C(max) predictions are 1.30 and 2.52, respectively. TheAUC(0-t) and AUC(0-inf) are overpredicted for both compounds(AFEs and AAFEs from 2.66 to 4.90). This results from a lack of reliable elimination data for prochlorperazine and the relevance of the IVRT profiles used in the promethazine model. The model paves the way for more mechanistic rectal drug absorption studies and virtual bioequivalence methods for rectal drug products. | Rectal Absorption |
OBJECTIVE: To promote monthly interpersonal skill communication role-play and coaching for front-office staff. METHOD: For 15 min a month, during staff meetings, healthcare staff such as receptionists and medical assistants should participate in communication skill coaching. Participants should discuss a recurring communication challenge (e.g., patients irritated by repeated requests for health histories), role-play options for communication, and receive feedback. RESULT: Interpersonal communication skills such as acknowledging the concerns of others are acquired slowly. Repeated practice and supportive feedback increase the likelihood that these skills will be valued and mastered. CONCLUSION: Research shows communication skills develop when they are modeled and role-played frequently and are less likely to develop with occasional interventions. PRACTICE IMPLICATION: Health care professionals should devote time to role-playing interaction with patients for brief intervals at least monthly. Staff should give one another feedback on the best options for managing challenging communication situations. | Medical Receptionists |
Our aim was to define seminal plasma proteome signatures of infertile patients categorized according to their seminal parameters using TMT-LC-MS/MS. To that extent, quantitative proteomic data was analyzed following two complementary strategies: (1) the conventional approach based on standard statistical analyses of relative protein quantification values; and (2) a novel strategy focused on establishing stable-protein pairs. By conventional analyses, the abundance of some seminal plasma proteins was found to be positively correlated with sperm concentration. However, this correlation was not found for all the peptides within a specific protein, bringing to light the high heterogeneity existing in the seminal plasma proteome because of both the proteolytic fragments and/or the post-translational modifications. This issue was overcome by conducting the novel stable-protein pairs analysis proposed herein. A total of 182 correlations comprising 24 different proteins were identified in the normozoospermic-control population, whereas this proportion was drastically reduced in infertile patients with altered seminal parameters (18 in patients with reduced sperm motility, 0 in patients with low sperm concentration and 3 in patients with no sperm in the ejaculate). These results suggest the existence of multiple etiologies causing the same alteration in seminal parameters. Additionally, the repetition of the stable-protein pair analysis in the control group by adding the data from a single patient at a time enabled to identify alterations in the stable-protein pairs profile of individual patients with altered seminal parameters. These results suggest potential underlying pathogenic mechanisms in individual infertile patients, and might open up a window to its application in the personalized diagnostic of male infertility. | Seminal Plasma Proteins |
Dissection of the extracranial carotid and vertebral arteries is increasingly recognized as a cause of transient ischemic attacks and stroke. The annual incidence of spontaneous carotid artery dissection is 2.5 to 3 per 100,000, while the annual incidence of spontaneous vertebral artery dissection is 1 to 1.5 per 100,000. Traumatic dissection occurs in approximately 1% of all patients with blunt injury mechanisms, and is frequently initially unrecognized. Overall, dissections are estimated to account for only 2% of all ischemic strokes, but they are an important factor in the young, and account for approximately 20% of strokes in patients less than 45 years of age. Arterial dissection can cause ischemic stroke either by thromboemboli forming at the site of injury or as a result of hemodynamic insufficiency due to severe stenosis or occlusion. Available evidence strongly favors embolism as the most common cause. Both anticoagulation and antiplatelet agents have been advocated as treatment methods, but there is limited evidence on which to base these recommendations. A Cochrane review on the topic of antithrombotic drugs for carotid dissection did not identify any randomized trials, and did not find that anticoagulants were superior to antiplatelet agents for the primary outcomes of death and disability. Healing of arterial dissections occurs within three to six months, with resolution of stenosis seen in 90%, and recanalization of occlusions in as many as 50%. Dissecting aneurysms resolve on follow-up imaging in 5-40%,decrease in size in 15-30%, and remain unchanged in 50-65%. Resolution is more common in vertebral dissections than in carotid dissections. Aneurysm enlargement occurs rarely. The uncommon patient presenting with acute hemodynamic insufficiency should be managed with measures to increase cerebral blood flow, and in this setting emergency stent placement to restore cerebral perfusion may be considered, provided that irreversible infarction has not already occurred." | Carotid Artery, Internal, Dissection |
Hydrophobic drugs loaded nanogels were always associated with low encapsulation efficiency and immature burst release. In this work, dopamine grafted hyaluronate nanogels were designed for bortezomib (BTZ), a hydrophobic anticancer drug and a proteasome inhibitor. It was found that there was a more efficient loading and pH-controlled release of BTZ due to the presence of dopamine groups on the skeleton of the nanogels. The drug loading content (DLC) were up to 8.58% as the nanogels modified with 29% dopamine, compared to the DLC of less than 1% for nanogels without dopamine modification. It was the pH-sensitive nature of the borated bonds between BTZ and catechol groups that endowed the pH-responsive release behavior of BTZ in vitro. In vitro study proved good biocompatibility and efficient cell uptake of the nanogels. In vivo anti-tumor experiments demonstrated that bortezomib loading into the nanogel significantly enhanced the therapeutic effect of the drug. After 14-day treatment, the average tumor volume of BTZ loaded nanogel group was reduced by 200% more than that of free BTZ group. Combined with CD44 receptor targeting ability of hyaluronate and the merits of nanogel, the catechol modified hyaluronate nanogel exhibited as an efficient chemotherapeutic formulation of BTZ for cancer treatment. | Bortezomib |
The recent discussions about alternative sources of human embryonic stem cells (White Paper of the US President's Council on Bioethics, 2005), while stirring new interest in the developmental potential of the various abnormal embryos or constructs proposed as such sources, also raise questions about the potential of the derived embryonic stem cells. The data on the developmental potential of embryonic stem cells that seem relevant for ethical considerations and aspects of patentability are discussed. Particular attention is paid to the meaning of totipotency, omnipotency and pluripotency" as illustrated by a comparison of the developmental potential of three-dimensional clusters of blastomeres (morula), embryonic stem cells, somatic or (adult) stem cells or other somatic (non-stem) cells. This paper focuses on embryoid bodies and on direct cloning by tetraploid complementation. Usage and patenting of these cells cannot be considered to be ethically sound as long as totipotency and tetraploid complementability of embryonic stem cells are not excluded for the specific cell line in question. Testing this poses an ethical problem in itself and needs to be discussed in the future." | Totipotent Stem Cells |
BACKGROUND: Tyrosinemia type II, also known as Richner-Hanhart Syndrome, is an extremely rare autosomal recessive disorder, caused by mutations in the gene encoding hepatic cytosolic tyrosine aminotransferase, leading to the accumulation of tyrosine and its metabolites which cause ocular and skin lesions, that may be accompanied by neurological manifestations, mostly intellectual disability. AIMS: To update disease-causing mutations and current clinical knowledge of the disease. MATERIALS AND METHODS: Genetic and clinical information were obtained from a collection of both unreported and previously reported cases. RESULTS: We report 106 families, represented by 143 individuals, carrying a total of 36 genetic variants, 11 of them not previously known to be associated with the disease. Variants include 3 large deletions, 21 non-synonymous and 5 nonsense amino-acid changes, 5 frameshifts and 2 splice variants. We also report 5 patients from Gran Canaria, representing the largest known group of unrelated families sharing the same P406L mutation. CONCLUSIONS: Data analysis did not reveal a genotype-phenotype correlation, but stressed the need of early diagnosis: All patients improved the oculocutaneous lesions after dietary treatment but neurological symptoms prevailed. The discovery of founder mutations in isolated populations, and the benefits of early intervention, should increase diagnostic awareness in newborns. | Tyrosinemias |
The effects of the convertogenic ('first-stage') tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA), the non-convertogenic ('second stage') tumor promoter 12-O-retinoyl-phorbol-13-acetate (RPA) and the non-promoting phorbol esters 4-O-MeTPA and 4-alpha-PDD on the chromosomes of mouse keratinocytes in primary cultures were investigated. In these target cells of tumor promotion TPA caused severe numerical and structural chromosomal aberrations, which were evident after two cell cycles and accumulated after multiple applications. Numerical aberrations were visible as hypo- and hyperdiploidy, with non-random loss or gain of specific chromosomes. The clastogenic effects were evident as simple alterations such as gaps and breaks, but more severe alterations such as tri- and quadriradial chromatid interchanges and ring chromosomes, as well as translocations could be observed. The structural aberrations were nonrandomly distributed in the genome and chromosomes no. 1, 2, 5, 6 and 18 were preferentially involved in rearrangements. In addition to the aneuploidogenic, clastogenic and recombinogenic effects induced by TPA, short treatment with this tumor promoter was efficient in producing cytogenetic equivalents of gene amplification, i.e. double minute chromosomes. The cytogenetic effects were not merely due to cytotoxicity since they occurred after a low TPA dose (10(-8) M) and did not considerably increase with a higher dose (10(-6) M). Moreover, at both dose levels cell cycle traverse of mouse keratinocytes was not drastically altered. In contrast, the non-convertogenic tumor promoter RPA and the non-promoting phorbol esters 4-alpha-PDD and 4-O-MeTPA (at the same dose level) did not cause any substantial chromosomal alterations. This discrepancy between the action of TPA and RPA suggests that effects which result in chromosomal alterations in the target cells may be critical for the conversion stage of skin tumor promotion. This conclusion is supported by experiments with substances such as antipain and eicosa-5,8,11,14-tetraynoic acid which inhibit both tumor induction in initiated skin and the cytogenetic alterations induced by TPA in cultured keratinocytes. These studies provide for the first time the possibility of differentiating between convertogenic and non-convertogenic tumor promoters in an in vitro assay using the target cells of mouse skin carcinogenesis." | 5,8,11,14-Eicosatetraynoic Acid |
BACKGROUND: Parenteral opioids are used in more than 50% of emergency department (ED) visits for migraine. Use of opioids for migraine has been associated with subsequent ED visits, perhaps because of opioid-induced euphoria. In this study, we quantify the extent to which nontherapeutic effects of opioids influence migraine outcomes. We hypothesized that feeling good" and medication likeability would in fact be associated with receipt of opioids (rather than relief of migraine pain) and that receipt of opioids (rather than relief of migraine pain) would be associated with return visits to the ED. METHODS: During an ED-based clinical trial, migraine patients were randomized to receive hydromorphone 1 mg or prochlorperazine 10 mg + diphenhydramine 25 mg IV. Thirty minutes after medication administration, we asked, (1) How much did you like the medication you received? and (2) How good did the medication make you feel? Participants were asked to provide answers on a 0-10 scale. We also determined 0-10 pain scores at baseline and 1 hour and number of return visits for headache during the subsequent month. RESULTS: Sixty-three patients received prochlorperazine and 64 hydromorphone. Prochlorperazine pain scores improved by 6.8 (SD: 2.6), hydromorphone by 4.7 (SD: 3.3) (95%CI for difference of 2.1: 1.0, 3.2). On the 0-10 likeability scale, prochlorperazine patients reported a mean of 7.2 (SD: 2.8), hydromorphone 6.9 (SD: 2.9) (95% CI for difference of 0.3: -0.7, 1.3). On the 0-10 feeling good scale, prochlorperazine patients reported a mean of 7.5 (SD: 2.3), hydromorphone 6.8 (SD: 2.8) (95%CI: for difference of 0.7: -0.2, 1.6). In the hydromorphone group, 8/57 (14%, 95%CI: 7, 26%) returned to the ED vs 5/63 (8%, 95%CI: 3,18%) in the prochlorperazine group. In regression modeling, feeling good was independently associated with pain relief (P < .01) but not with medication received (P = .67) or return visits (P = .12). Similarly, medication likeability was independently associated with pain relief (P < .01) but not medication received (P = .12) or return visits (P = .16). CONCLUSION: We did not detect an association between hydromorphone and medication likeability, feeling good, or return visits to the ED. Headache relief was associated with medication likeability and feeling good." | Hydromorphone |
Medical audit in general consists of seven steps like choosing topic, setting criterion and standard, collecting first data, comparing data with standard, introducing change, collecting second data and reflecting. Its three basic premise are improvement of patient care by using existing knowledge, team work with ongoing educational process and change management and promotion of blame-free culture maintaining confidentiality. Audit mostly relates to a particular practice and is therefore not generalisable. An audit of residents' late evening routine notes of organophosphate poisoning patients is reported here, as the change introduced appears relevant to the situation of developing countries. Organophosphate poisoning patients should be managed in intensive care unit with close monitoring, as inadvertent stoppage or slowing of atropine infusion may occur, particularly at night, leading to reappearance of poisoning manifestations, which may cause respiratory failure and death. If they are managed in wards, residents-on-duty can check the clinical and intravenous drip status in the late evening and communicate with nurses and relatives to be particularly vigilant. In the audit done, such regular ten pm notes of organophosphate poisoning about the clinical and drip status and communication by residents were increased from 15.5% in the first to 81.7% in the second data collection (p < 0.01) after the introduction of the change. The ten pm note is being continued for about two years now. Implementation of ten pm note of organophosphate poisoning patients admitted in medical wards is feasible and appears useful to improve the quality of health care delivery and learning of residents. | Medical Audit |
There is an interest in the application of ionic liquids as additives into the separation media to improve achiral and chiral separations in electrokinetic chromatography (EKC). This review will critically discuss the developments on the use of ionic liquids in the different modes of EKC during the last five years (2015-mid 2020). A healthy number of 48 research articles searched through Scopus were categorised into two: ionic liquids as sole pseudophase (micelles, microemulsions, ligand exchange pseudophase or molecular pseudophase) and ionic liquids with pseudophase (achiral or chiral). More than half of the papers dealt with chiral separations that were mostly facilitated by another additive or pseudophase. The role of ionic liquids for improvement of separations were analysed, and we provided some recommendations for further investigations. Finally, the use of ionic liquids in different on-line sample concentration or stacking methods (i.e., field enhancement and sweeping) was briefly discussed." | Chromatography, Micellar Electrokinetic Capillary |
There are approximately 250 species of Eryngium L. distributed throughout the world, with North America and South America being centers of diversity on this continent. In the central-western region of Mexico there may be around 28 species of this genus. Some Eryngium species are cultivated as leafy vegetables, ornamental, and medicinal plants. In traditional medicine they are used to treat respiratory and gastrointestinal conditions, diabetes, and dyslipidemia, among others. This review addresses the phytochemistry and biological activities, as well as traditional uses, distribution, and characteristics of the eight species of Eryngium reported as medicinal in the central-western region of Mexico: E. cymosum, E. longifolium, E. fluitans (or mexicanum), E. beecheyanum, E. carlinae, E. comosum, E. heterophyllum, and E. nasturtiifolium. The extracts of the different Eryngium spp. have shown biological activities such as hypoglycemic, hypocholesterolemic, renoprotective, anti-inflammatory, antibacterial, and antioxidant, among others. E. carlinae is the most studied species, and phytochemical analyses, performed mainly by high-performance liquid chromatography (HPLC) and gas chromatography coupled with mass spectrometry (GC-MS), have shown its content of terpenoids, fatty acids, organic acids, phenolic acids, flavonoids, sterols, saccharides, polyalcohols, and aromatic and aliphatic aldehydes. According to the results of this review on Eryngium spp., they constitute a relevant alternative as a source of bioactive compounds for pharmaceutical, food, and other industries. However, there is a lot of research to be conducted regarding phytochemistry, biological activities, cultivation, and propagation, in those species with few or no reports. | Eryngium |
Steroid degradation genes of Comamonas testosteroni TA441 are encoded in at least two gene clusters: one containing the meta-cleavage enzyme gene tesB; and another consisting of ORF18, 17, tesI, H, ORF11, 12, and tesDEFG. TesH and I are, respectively, the Delta(1)- and Delta(4)(5alpha)-dehydrogenase of the 3-ketosteroid, TesD is the hydrolase for the product of meta-cleavage reaction, and TesEFG degrade one of the product of TesD. In this report, we describe the identification of the function of ORF11 (tesA2) and 12 (tesA1). The TesA1- and TesA2-disrupted mutant accumulated two characteristic intermediate compounds, which were identified as 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (3-HSA) and its hydroxylated derivative, 3,17-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione by MS and NMR analysis. A complementation experiment using a broad-host range plasmid showed that both TesA1 and A2 are necessary for hydroxylation of 3-HSA to 3,4-dihydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (3,4-DHSA). | Steroid Hydroxylases |
Recent discoveries of basal extracellular Rickettsiales have illuminated divergent evolutionary paths to host dependency in later-evolving lineages. Family Rickettsiaceae, primarily comprised of numerous protist- and invertebrate-associated species, also includes human pathogens from two genera, Orientia and Rickettsia. Once considered sister taxa, these bacteria form distinct lineages with newly appreciated lifestyles and morphological traits. Contrasting other rickettsial human pathogens in Family Anaplasmataceae, Orientia and Rickettsia species do not reside in host-derived vacuoles and lack glycolytic potential. With only a few described mechanisms, strategies for commandeering host glycolysis to support cytosolic growth remain to be discovered. While regulatory systems for this unique mode of intracellular parasitism are unclear, conjugative transposons unique to Orientia and Rickettsia species provide insights that are critical for determining how these obligate intracellular pathogens overtake eukaryotic cytosol. | Rickettsieae |
PURPOSE: As paid work is the occupation that people spend the most amount of their time doing, it is an important provider of personal meaning in their lives. This meaning has been shown to vary from person to person and to be important to health and well being. When a person is unable to work due to a disabling condition, it is unclear whether this meaning remains or is replaced by other meanings. The purpose of this scoping review was to explore what was known in the existing literature on what work means to those with work disability. METHODS: The review involved identifying and selecting relevant studies, charting the data and collating and summarizing the results. RESULTS: Fifty-two studies explored the meaning of work for those with cancer, mental illness, musculoskeletal disorders, brain injuries, paraplegia, and AIDS. The studies revealed that, for most, work continued to be meaningful and important. Common themes across all types of disability included work being a source of identity, feelings of normality, financial support, and socialization. These meanings were found to be both motivating for return to work and health promoting. Conversely, a small number of studies found that the meanings and values ascribed to work changed following disability. New meanings, found either at home or in modified work, replaced the old and contributed to new identities. CONCLUSIONS: The exploration of the meaning of work has been shown to provide important understanding of the experience of work and disability. This understanding can guide rehabilitation professionals in their interventions with the work disabled. | Return to Work |
OBJECTIVE: This study describes access and barriers to intrauterine device (IUD) removal appointments in 10 mid-sized cities in the United States. STUDY DESIGN: This mystery caller study utilized a sampling frame of health centers in 10 mid-sized cities gathered from 3 search engines. We gathered data about the timing of the next available appointment, the requirements for additional appointments prior to IUD removal, and the out-of-pocket cost. We used descriptive statistics to describe the availability and cost of IUD removal visits, and compared results between primary care clinics and family planning or gynecology clinics. Any additional information regarding why a visit was not available or other requirements for IUD removal that was provided to the researcher was also recorded. RESULTS: Of 229 clinics included for analysis, 60.7% could offer an IUD removal appointment to the mystery caller, and the majority of these could provide an initial appointment within 2â¯weeks (61.2%), with a median of 10â¯days. Of clinics offering IUD removal, 17.3% required more than one visit before removing the IUD, and 43.2% confirmed that IUD removal would occur at the first visit. Five clinics (5.6%) reported that they would not remove an IUD that was not placed at their clinic. Sliding scale fees were offered at 16.3% of clinics. For the clinics that cited an out-of-pocket cost and did not offer sliding scale fees, the median cost of the IUD removal was $262, with a range of $50 to over $1000. Neither appointment availability nor cost differed between primary care and family planning or gynecology clinics. CONCLUSIONS: Overall, timely IUD removal appointments were available at the clinics we sampled, but both financial and clinic policy barriers to IUD removal were documented, including the need for multiple appointments and the total out-of-pocket costs. IMPLICATIONS: In our current climate focused on improving access to IUDs, it is essential to address and reduce barriers to IUD removal when desired, in order to preserve reproductive autonomy. | Device Removal |
Rubber elongation factor (REF) is considered as one of the major allergens present in latex. An extraction and purification protocol for preparation of REF standards has been modified. A protein fraction was extracted from ammoniated latex sap and purified by gel filtration chromatography. The purified and concentrated proteins were separated by sodium dodecylsulfate-polyacrylamide gel electrophoresis into two major bands. These bands were further characterised by matrix-assisted laser desorption/ionisation time-of-flight and nano-electrospray ionization mass spectrometry. REF and a truncated form could be ascertained by the mass and fragmentation pattern of the tryptic peptides. In the faster migrating band an additional peptide could be identified. This peptide is also present in Hevb3 and a Mr 27000 latex allergen. Our findings indicate that conventional REF preparations as standards may contain additional allergenic proteins. | Antigens |
The distribution of galanin mRNA-expressing cells and galanin-immunoreactive (IR) cell bodies and processes was studied in the brain of mice overexpressing galanin under the PDGF-B promoter (GalOE mice) and of wild type (WT) mice, both in colchicine-treated and non-treated animals. In this abstract, we only describe the results in GalOE mouse. A widespread ectopic expression of galanin (both mRNA and peptide) was found, that is a situation when neither transcript nor peptide could be seen in WT mice, not even after colchicine treatment. However, in some regions, such as claustrum, basolateral amygdala, thalamus, CA1 pyramidal cells, and Purkinje cells only galanin mRNA could be detected. In the forebrain galanin was seen in the mitral cells of the olfactory bulb, throughout the cortex, in the basolateral amygdaloid nucleus, claustrum, granular and pyramidal cell layers of the hippocampus, subiculum and presubiculum. In the thalamus, the anterodorsal, mediodorsal, intermediodorsal and mediodorsal lateral nuclei, the reuniens and reticular nuclei showed ectopic expression of galanin. Within the hypothalamus, neurons of the suprachiasmatic nucleus contained galanin. In the mesencephalon, the geniculate nucleus, nucleus ruber, the mesencephalic trigeminal and reticulotegmental nuclei ectopically expressed galanin. In the cerebellum, galanin was observed in the Purkinje cells and in the lateral and interposed cerebellar nuclei. In the pons, sensory and motor nuclei of the trigeminal nerve, the laterodorsal and dorsal tegmental nuclei, the pontine, reticulotegmental and gigantocellular reticular nuclei expressed galanin. Within the medulla oblongata, labeled cells were detected in the facial, ambiguus, prepositus, lateral paragigantocellular and lateral reticular nuclei, and spinal trigeminal nucleus. High densities of galanin-IR fibers were found in the axonal terminals of the lateral olfactory tract, the hippocampal and presumably the cerebellar mossy fibers system, in several thalamic and hypothalamic regions and the lower brain stem. Possible functional consequences of galanin overexpression are discussed. | Galanin |
OBJECTIVE: The diagnosis and management for juvenile psammomatoid ossifying fibroma (JPOF) of the skull base are challenging, and clinical data are limited. METHODS: A retrospective review of JPOF was performed, and the clinical characteristics, treatment strategy, and prognosis were analyzed. RESULTS: There were 23 patients pathologically confirmed with JPOF, most with JPOF located in the skull base area (19/23, 82.6%). Of those tumors, 43.5% presented with dura matter breakthrough. Most of the chief complaints were headache (n = 8, 34.8%) and visual impairment (n = 5, 21.7%). Most of the tumors were solid tumors with spherical appearance, frequently accompanied by cysts of various size (n = 14, 60.9%). Craniotomy, mostly via the frontal approach, was the most common approach in the present series, comprising 73.6% (17/23) of all cases. The endoscopic endonasal approach was performed in 6 cases (26.1%). In total, 62.5% of patients (15/23) underwent gross total resection, 8.7% of patients (2/23) underwent subtotal resection, and 26.1% of patients (6/23) underwent partial resection. After a mean follow up of 66.1 +/- 36.1 months (range, 3-124), 3 patients (13.6%) suffered from tumor recurrence with a mean recurrence time of 13 months. CONCLUSIONS: The present series of skull base JPOFs showed that radical surgery combined with skull base reconstruction contributed to overall good prognosis. Further studies are needed to evaluate the long-term outcomes and to characterize its pathologic characteristics. | Fibroma, Ossifying |
The Fas death receptor-activated death-inducing signaling complex (DISC) regulates apoptosis in many normal and cancer cells. Qualitative biochemical experiments demonstrate that calmodulin (CaM) binds to the death domain of Fas. The interaction between CaM and Fas regulates Fas-mediated DISC formation. A quantitative understanding of the interaction between CaM and Fas is important for the optimal design of antagonists for CaM or Fas to regulate the CaM-Fas interaction, thus modulating Fas-mediated DISC formation and apoptosis. The V254N mutation of the Fas death domain (Fas DD) is analogous to an identified mutant allele of Fas in lpr-cg mice that have a deficiency in Fas-mediated apoptosis. In this study, the interactions of CaM with the Fas DD wild type (Fas DD WT) and with the Fas DD V254N mutant were characterized using isothermal titration calorimetry (ITC), circular dichroism spectroscopy (CD), and molecular dynamics (MD) simulations. ITC results reveal an endothermic binding characteristic and an entropy-driven interaction of CaM with Fas DD WT or with Fas DD V254N. The Fas DD V254N mutation decreased the association constant (Ka) for CaM-Fas DD binding from (1.79 +/- 0.20) x 10(6) to (0.88 +/- 0.14) x 10(6) M(-1) and slightly increased a standard state Gibbs free energy (DeltaG degrees ) for CaM-Fas DD binding from -8.87 +/- 0.07 to -8.43 +/- 0.10 kcal/mol. CD secondary structure analysis and MD simulation results did not show significant secondary structural changes of the Fas DD caused by the V254N mutation. The conformational and dynamical motion analyses, the analyses of hydrogen bond formation within the CaM binding region, the contact numbers of each residue, and the electrostatic potential for the CaM binding region based on MD simulations demonstrated changes caused by the Fas DD V254N mutation. These changes caused by the Fas DD V254N mutation could affect the van der Waals interactions and electrostatic interactions between CaM and Fas DD, thereby affecting CaM-Fas DD interactions. Results from this study characterize CaM-Fas DD interactions in a quantitative way, providing structural and thermodynamic evidence of the role of the Fas DD V254N mutation in the CaM-Fas DD interaction. Furthermore, the results could help to identify novel strategies for regulating CaM-Fas DD interactions and Fas DD conformation and thus to modulate Fas-mediated DISC formation and thus Fas-mediated apoptosis. | fas Receptor |
Focal nodular hyperplasia (FNH) is a benign hepatic tumor characterized by hepatocyte hyperplasia and a central stellate scar. The association of FNH with other hepatic lesions, such as adenomas, hemangiomas and hepatocellular carcinoma, has been previously reported, but FNH associated with another hepatic tumor is rare in infants. Here we report a case of FNH coexistent with hepatoblastoma in a 36-d-old girl. Computed tomography (CT) imaging showed an ill-delineated, inhomogeneous enhanced mass with a central star-like scar in the right lobe of the liver. The tumor showed early mild enhancement at the arterial phase (from 40HU without contrast to 52HU at the arterial phase), intense enhancement at the portal phase (87.7HU) and 98.1HU in the 3-min delay scan. A central scar in the tumor presented as low density on non-contrast CT and slightly enhanced at delayed contrast-enhanced scanning. This infant underwent surgical resection of the tumor. Histopathology demonstrated typical FNH coexistent with a focal hepatoblastoma, which showed epithelioid tumor cells separated by proliferated fibrous tissue. | Focal Nodular Hyperplasia |
Infectious salmon anemia virus (ISAV) infection is a constant major threat to farmed and wild Atlantic salmon worldwide. Many epidemics have recently been reported in the most important salmon farming regions of the world, including Chile (2007-2009), where ISAV generated the most important disease and economic crisis in history of the salmon industry of the country. The spread of ISAV within a region is most likely by local or neighborhood spread from an infected farm; however, there is evidence that anthropogenic activities, such as movement of live or harvested fish or their byproduct, may have played a more important role than environmental or passive transmission in the 2007-2009 outbreak. Atlantic salmon farms (n=421) were retrospectively followed from stocking to harvesting in southern Chile at the time of the ISAV epidemic (2007-2009). The effect of husbandry and spatial risk factors, in addition to contact-network risk factors, which were obtained from the social network analyses, on time to first ISAV infection was estimated using a multivariable Cox proportional hazards model. Five variables were retained in the final fitted model: co-existing multiple generations on a farm (hazard ratio [HR]=2.585), mean smolt weight at stocking greater than 120g (HR=1.165), farm area (perkm(2)) (HR=1.005), and increased number of shipments entering a farm, i.e. the farm input degree (HR=1.876) were associated with reduced time to infection; whereas time-to-infection was longer for farms located farther from an ongoing ISAV outbreak (HR=0.943). It was demonstrated that movements of latently infected fish resulted in approximately 7 outbreaks, and potentially explain about 6% of the total number of cases during the epidemic. Results from this study provide new information about the mechanisms of spread of ISAV in one the largest documented ISAV epidemics in the world. Findings may be used to support the design and implementation of risk-based surveillance and control programs that may help to prevent, detect and control future ISAV outbreaks. | Orthomyxoviridae Infections |
This article discusses a quality improvement project in the context of paediatric inter-hospital transportation. The project was set in a large university teaching hospital in Ireland. Risk assessment on the clinical site revealed a gap in the application of best national and international standards in inter-hospital transportation practice. A project was undertaken to explore current paediatric transport services and respond to a clinical service deficit. Consequently, the proposed quality improvement initiative proposes a universal Paediatric Advanced Life Support Programme (PALS) to upskill and enhance the required clinical standards and competencies of neonatal nurses. This intervention was underpinned by attention to change management principles and organisational culture in health care. As a clinical practice development, it demonstrates how benchmarking against best practice can advance the quality and safety agenda in paediatric practice. Education initiatives are recommended to ensure that clinical standards in paediatric transportation are monitored and reviewed with the potential to improve clinical outcomes. | Clinical Governance |
Genetic engineering of eggplant using fruit-specific EEF48 promoter-driven bacterial PSY gene, crtB, confers beta-carotene accumulation in fruit. Eggplant (Solanum melongena L.) is globally cultivated especially in Asia and is an important source of nutrients in the diets of low-income consumers in developing countries. Since fruits of eggplant have low provitamin A carotenoid content, it is expected to develop eggplant with high carotenoid content for combatting vitamin A deficiency. To achieve this, the present study implemented a metabolic engineering strategy to modify the carotenoid biosynthetic pathway in eggplant. Expression analysis of carotenogenic genes in eggplant tissues showed that the expression of the endogenous phytoene synthase (PSY) was low in fruit and callus. Orange-colored calluses were generated from ectopic expression of crtB gene, which encodes bacterial PSY, in eggplant cells. The orange calluses accumulated > 20 mug g(-1) FW of beta-carotene, which was approximately 150-fold higher than that of the untransformed calluses. These observations suggest that the PSY expression is the rate-limiting step for beta-carotene production in callus and fruit. Since the orange calluses did not regenerate plants, we chose eggplant EEF48 gene, which is presumably expressed in fruit. We amplified its promoter region by TAIL-PCR and showed that the EEF48 promoter is indeed active in eggplant fruit. Subsequently, transgenic eggplant lines having EEF48 promoter-driven crtB were produced. Among the transgenic lines produced, one line set fruit containing 1.50 mug g(-1) FW of beta-carotene, which was 30-fold higher than that of the untransformed fruits (0.05 mug g(-1) FW). The self-pollinated progenies showed a 3:1 segregation ratio for the presence and absence of the transgene, which was linked to the beta-carotene accumulation in fruit. These results provide a strategy for improvement of carotenoid content in eggplant fruit. | Solanum melongena |
Selective tryptic proteolysis of the mammalian alpha-ketoglutarate dehydrogenase complex (OGDC) leads to its rapid inactivation as a result of a single cleavage within the N-terminal region of its alpha-ketoglutarate dehydrogenase (E1) component, which promotes the dissociation of the dihydrolipoamide dehydrogenase (E3) enzyme and also a fully active E1' fragment. Similarities between the N-terminal region of E1 and the dihydrolipoamide acetyltransferase (E2) and E3-binding components (E3BP) of the pyruvate dehydrogenase complex are highlighted by the specific cross-reactivities of subunit-specific antisera. Analysis of the pattern of release of E1 and E1' polypeptides from the OGDC during tryptic inactivation suggests that both polypeptide chains of individual E1 homodimers must be cleaved to permit the dissociation of the E1 and E3 components. A new protocol has been devised that promotes E1 dissociation from the oligomeric dihydrolipoamide succinyltransferase (E2) core in an active state. Significant levels of overall OGDC reconstitution could also be achieved by re-mixing the constituent enzymes in stoichiometric amounts. Moreover, a high affinity interaction has been demonstrated between the homodimeric E1 and E3 components, which form a stable subcomplex comprising single copies of these two enzymes." | Ketoglutarate Dehydrogenase Complex |
A computational intelligence drug discovery platform is introduced as an innovative technology designed to accelerate high-throughput drug screening for generalized protein-targeted drug discovery. This technology results in collections of novel small molecule compounds that bind to protein targets as well as details on predicted binding modes and molecular interactions. The approach was tested on dihydrofolate reductase (DHFR) for novel antimalarial drug discovery; however, the methods developed can be applied broadly in early stage drug discovery and development. For this purpose, an initial fragment library was defined, and an automated fragment assembly algorithm was generated. These were combined with a computational intelligence screening tool for prescreening of compounds relative to DHFR inhibition. The entire method was assayed relative to spaces of known DHFR inhibitors and with chemical feasibility in mind, leading to experimental validation in future studies. | Folic Acid Antagonists |
The effects of two nonsteroidal anti-inflammatory drugs on the gastroduodenal mucosa were evaluated by endoscopy and direct photography in 36 healthy men who were randomly assigned to receive 150 mg of diclofenac, 1,200 mg of etodolac, or 600 mg of etodolac daily for seven days. Endoscopy was performed on days 1 and 8. Mild gastric lesions were observed in six subjects. The mean (+/- SD) endoscopy scores on a five-point scale were 0.08 +/- 0.27 after 600 mg of etodolac, 0.25 +/- 0.53 after 1,200 mg of etodolac, and 0.33 +/- 0.62 after diclofenac. No between-group differences were statistically significant. No duodenal lesions were seen. A strong correlation was found between endoscopy scores and photographic reviews. The results indicate that both etodolac and diclofenac cause minimal changes on the gastric mucosa. | Etodolac |
Application of Stewart-Hamilton's formula to the activity-time curve recorded over a left ventricular region of interest following an intravenous bolus injection of a radioactive indicator in gamma camera hepatography has resulted in a new method for determination of the clearance rate constant of the indicator (i.e. the ratio of the clearance to the plasma volume). In a group of 19 normal subjects the clearance rate constant was 0.116 +/- 0.036 min-1 (means +/- 1 S.D.) with 99mTc-diethyl-IDA (SOLCO HIDA) and 0.184 +/- 0.037 min-1 (means +/- 1 S.D.) with 99mTc-diethyl-iodo-IDA (SOLCO IODIDA) in 15 normal subjects. The clearance rate constant is assumed to represent mainly hepatic clearance of the radioactive indicator and to a much smaller extent renal clearance. The literature shows diverging results as to the clearance of 99mTc-diethyl-IDA and the reasons for this are discussed. The correlations between the clearance rate constant of 99mTc-diethyl-IDA and a number of laboratory variables with relation to liver function were moderate to non-existent in a group of 16 subjects with abnormal values of at least one of these variables. The rate constant for clearance as described in the paper represents a non-invasive method for rapid evaluation of the uptake capacity of the liver and, in particular, with regard to the polygonal cells of the liver parenchyma when IDA derivatives are employed. The clinical usefulness of the clearance rate constant is probably superior to the group of routine laboratory variables which also describe other functions than liver uptake." | Technetium Tc 99m Diethyl-iminodiacetic Acid |
Traumatic neuroma is a well-known disorder that occurs after trauma or surgery involving the peripheral nerve and develops from a nonneoplastic proliferation of the proximal end of a severed, partially transected, or injured nerve. We present a case of traumatic neuroma around the celiac trunk after gastrectomy in a 56-year-old man, which was confirmed by pathology. CT demonstrated the presence of a lobulated, homogeneous, hypoattenuating mass around the celiac trunk, mimicking a nodal metastasis. | Neoplasms, Post-Traumatic |
The regio olfactoria of the mole, Talpa europaea, was studied by scanning and transmission electron microscopy. Peculiar structural differentiations, i.e. ovoid-shaped, balloon-like protuberances were found on the surface of the supporting cells. The apical portion of these protuberances contained finely dispersed granular material, whereas in their central part vesicular extensions of the smooth endoplasmic reticulum were observed. | Eulipotyphla |
Human chromosome 14q32.2 carries a cluster of imprinted genes including paternally expressed genes (PEGs) such as DLK1 and RTL1, and maternally expressed genes (MEGs) such as GTL2 (alias, MEG3), RTL1as (RTL1 antisense) and MEG8. Consistent with this, paternal and maternal uniparental disomies for chromosome 14 (upd(14)pat and upd(14)mat) cause distinct phenotypes. In this report, we review the current knowledge about the underlying factors for the development of clinical features in upd(14)pat and upd(14)mat. The data available suggest that the DLK1-GTL2 IG-DMR functions as a regulator for the maternally inherited imprinted region, and that excessive RTL1 expression and decreased DLK1 and RTL1 expression play a major role in the development of upd(14)pat-like and upd(14)mat-like phenotypes, respectively. | Chromosomes, Human, Pair 14 |
OBJECTIVE: Surgical site infection is an important concern due to its association with morbidity and mortality after paediatric cardiac surgery. The aim of this study was to present our approach and experience in the utilisation of a modified care bundle in a recently established paediatric cardiac surgical unit in the low-income region of Turkey. METHODS: Between 2019 and 2021, we identified children who underwent cardiac surgical procedures and retrospectively collected relevant demographic data, disease characteristics, operational data, Risk Adjustment For Congenital Heart Surgery (RACHS-1) scores, and post-operative factors such as morbidities, mortality, critical care, and in-hospital stay lengths. Surgical site infections and late infections were scanned. RESULTS: Ninety-six patients (49 males, 47 females) underwent a total of 127 surgical procedures during the study period. Overall adherence to the protocol was 94%, 100%, and 96% in the pre-operative, intra-operative, and post-operative periods, respectively. There was no reported surgical site infection, and no late infection was encountered throughout the follow-up period. CONCLUSIONS: We conclude that a low rate of surgical site infection, or even a rate of nil, is attainable through the utilisation of locally standardised guidelines for its prevention. | Resource-Limited Settings |
This case report describes a 16-year-old patient, who presented with multiple personalities. A diagnosis of dissociative identity disorder (DID) was considered, but rejected, based on the patient's presenting psychopathology and a lack of confidence in the current scientific literature describing the diagnosis. DID is a rare diagnosis in Danish clinical practice and there is much dissent concerning its validity." | Dissociative Identity Disorder |
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are related neurodegenerative diseases that belong to a common disease spectrum based on overlapping clinical, pathological and genetic evidence. Early pathological changes to the morphology and synapses of affected neuron populations in ALS/FTD suggest a common underlying mechanism of disease that requires further investigation. Fused in sarcoma (FUS) is a DNA/RNA-binding protein with known genetic and pathological links to ALS/FTD. Expression of ALS-linked FUS mutants in mice causes cognitive and motor defects, which correlate with loss of motor neuron dendritic branching and synapses, in addition to other pathological features of ALS/FTD. The role of ALS-linked FUS mutants in causing ALS/FTD-associated disease phenotypes is well established, but there are significant gaps in our understanding of the cell-autonomous role of FUS in promoting structural changes to motor neurons, and how these changes relate to disease progression. Here we generated a neuron-specific FUS-transgenic mouse model expressing the ALS-linked human FUSR521G variant, hFUS(R521G/Syn1), to investigate the cell-autonomous role of FUSR521G in causing loss of dendritic branching and synapses of motor neurons, and to understand how these changes relate to ALS-associated phenotypes. Longitudinal analysis of mice revealed that cognitive impairments in juvenile hFUS(R521G/Syn1) mice coincide with reduced dendritic branching of cortical motor neurons in the absence of motor impairments or changes in the neuromorphology of spinal motor neurons. Motor impairments and dendritic attrition of spinal motor neurons developed later in aged hFUS(R521G/Syn1) mice, along with FUS cytoplasmic mislocalisation, mitochondrial abnormalities and glial activation. Neuroinflammation promotes neuronal dysfunction and drives disease progression in ALS/FTD. The therapeutic effects of inhibiting the pro-inflammatory nuclear factor kappa B (NF-kappaB) pathway with an analog of Withaferin A, IMS-088, were assessed in symptomatic hFUS(R521G/Syn1) mice and were found to improve cognitive and motor function, increase dendritic branches and synapses of motor neurons, and attenuate other ALS/FTD-associated pathological features. Treatment of primary cortical neurons expressing FUSR521G with IMS-088 promoted the restoration of dendritic mitochondrial numbers and mitochondrial activity to wild-type levels, suggesting that inhibition of NF-kappaB permits the restoration of mitochondrial stasis in our models. Collectively, this work demonstrates that FUSR521G has a cell-autonomous role in causing early pathological changes to dendritic and synaptic structures of motor neurons, and that these changes precede motor defects and other well-known pathological features of ALS/FTD. Finally, these findings provide further support that modulation of the NF-kappaB pathway in ALS/FTD is an important therapeutic approach to attenuate disease. | RNA-Binding Protein FUS |
The anaphase-promoting complex (APC) or cyclosome is a multi-subunit ubiquitin ligase that controls progression through mitosis and the G1-phase of the cell cycle. The APC ubiquitinates regulatory proteins such as securin and cyclin B and thereby targets them for destruction by the 26S proteasome. Activation of the APC depends on the activator proteins Cdc20 and Cdh1, which are thought to recruit substrates to the APC. In vitro, APC's RING finger subunit Apc11 alone can also function as a ubiquitin ligase. Here, we review different methods that have been used to measure the ubiquitination activity of the APC in vitro and to analyze APC-mediated degradation reactions either in vitro or in vivo. We describe procedures to isolate the APC from human cells or from Xenopus eggs, to activate purified APC with recombinant Cdc20 or Cdh1 and to measure the ubiquitination activity of the resulting APC(Cdc20) and APC(Cdh1) complexes. We also describe procedures to analyze the ubiquitination activity associated with recombinant Apc11." | Apc11 Subunit, Anaphase-Promoting Complex-Cyclosome |
Urban sewer networks (SNs) are increasingly facing water quality issues as a result of many challenges, such as population growth, urbanization and climate change. A promising way to addressing these issues is by developing and using water quality models. Many of these models have been developed in recent years to facilitate the management of SNs. Given the proliferation of different water quality models and the promise they have shown, it is timely to assess the state-of-the-art in this field, to identify potential challenges and suggest future research directions. In this review, model types, modeled quality parameters, modeling purpose, data availability, type of case studies and model performance evaluation are critically analyzed and discussed based on a review of 110 papers published between 2010 and 2019. The review identified that applications of empirical and kinetic models dominate those of data-driven models for addressing water quality issues. The majority of models are developed for prediction and process understanding using experimental or field sampled data. While many models have been applied to real problems, the corresponding prediction accuracies are overall moderate or, in some cases, low, especially when dealing with larger SNs. The review also identified the most common issues associated with water quality modeling of SNs and based on these proposed several future research directions. These include the identification of appropriate data resolutions for the development of different SN models, the need and opportunity to develop hybrid SN models and the improvement of SN model transferability. | Water Quality |
OBJECTIVE: Blood flow restriction (BFR) training utilizes a tourniquet applied to the upper or lower extremities (UE or LE) to occlude blood flow while exercising. BFR training may help augment strength in muscles that are proximal to BFR cuff application. However, prior studies have failed to demonstrate augmented strength gains in the rotator cuff when the tourniquet is applied to the UE. The purpose of this study was to evaluate if a protocol consisting of LE exercises, performed with BFR, followed by rotator cuff exercises was superior in augmenting strength, and cross-sectional area (CSA) of the rectus femoris, in untrained subjects when compared to a non-BFR training group. DESIGN: Randomized controlled trial. SETTING: University. PARTICIPANTS: Thirty-five subjects (mean age 25.8 +/- 1.6 y) randomized to a BFR or non-BFR group. MAIN OUTCOME MEASURES: Muscular strength measured via hand held dynamometer and the CSA of the dominant rectus femoris was measured by diagnostic ultrasound. RESULTS: Both groups experienced significant gains in LE and rotator cuff strength. Strength increased in the BFR group by 11.6% for the supraspinatus, 34.1% for shoulder ER, 23.4% for the quadriceps, and 17.1% for the hamstrings. Strength increased in the non-BFR group by 7.3% for the supraspinatus, 20% for shoulder ER, 12.8% for the quadriceps, and 10.7% for the hamstrings. However, there were no differences in strength gains between groups. Neither group experienced a significant increase in CSA for the rectus femoris. CONCLUSION: The BFR protocol used in this study did not augment strength for the rotator cuff in subjects who also performed LE exercises under occlusion." | Blood Flow Restriction Therapy |
The objectives of this work were to evaluate the in vitro release and in vivo pharmacokinetics and local tolerability of a novel, segmented ethylene-vinyl acetate (EVA) intravaginal ring (IVR) delivering progesterone (P) in drug-naive ovariectomized female Dorset crossbred sheep. Following preparation and assessment of in vitro release of P, animals were randomized into one of six treatment groups: group 1 Crinone(R) 8% gel (90 mg); group 2 Prometrium(R) 200-mg capsules; group 3 placebo IVR; group 4 progesterone (P) IVR 4 mg/day; group 5 P IVR 8 mg/day; or group 6 P IVR 12 mg/day. Crinone 8% gel and Prometrium capsules were administered once daily for 28 days. IVRs were inserted vaginally on day 1 and remained in place through day 14; a new ring was administered on day 15 and was removed at day 28. Animals underwent daily examinations to confirm ring placement, and vaginal irritation was scored from 0 (none) to 4 (severe). Blood samples were taken at scheduled times for pharmacokinetic analysis. Postmortem examinations performed on all IVR groups included vaginal irritation, macroscopic, and microscopic evaluations, including irritation scoring and histopathology. Intravaginal rings were retained over 28 days in all animals. Clinical observations showed no significant abnormal findings in any group. Pharmacokinetic analysis in animals showed sustained release of P over from days 0 through 14 of ring use. Irritation scores and microscopic assessments were consistent with the IVRs being well tolerated. These results will guide future human clinical studies to ultimately develop an IVR for use in women for the prevention of preterm birth. | Corpus Luteum Hormones |
The porous surface of the MCCL prosthesis macroscopically resembles spongy bone, with a porous depth of up to 10 mm, the width of the pores measuring 1-2 mm, with reticular spaces forming an intercommunicating system. The superficial porous surface and the implant stem are combined in a single structure. The standard prosthesis is made up of four components; an acetabulum in cobalt-chrome-molybdenum alloy, an interposed layer of polyethylene, a ceramic head and a stem in cobalt-chrome-molybdenum alloy, the shape of which is anatomically matched to the proximal femur. What emerges from the present study is the possibility of using right and left stems, each available in six sizes. The ceramic head may be attached to the neck of the femoral stem, which may be long, average, or short. An extra-long" metal head is also available." | Hip Prosthesis |
We have found that Arabidopsis thaliana is susceptible to infection with a crucifer strain of tobacco mosaic virus (TMV-Cg); the coat protein of TMV-Cg accumulated to a high level in uninoculated rosette leaves several days after inoculation. As a first step in the search for host-coded factors that are involved in virus multiplication, we isolated mutants of A. thaliana in which the accumulation of TMV-Cg coat protein was reduced to low levels. Of 6000 M2 plants descended from ethyl methanesulfonate-treated seeds, two such lines (PD114 and PD378) were isolated. Genetic analyses suggested that the PD114 phenotype was caused by a single nuclear recessive mutation, and that PD114 and PD378 belonged to the same complementation group. The coat protein accumulation of a tomato strain of TMV (TMV-L) was also reduced in PD114 plants compared to that in the wild-type plants. In contrast, PD114 plants infected with turnip crinkle or turnip yellow mosaic viruses, which belong to taxonomic groups other than Tobamovirus, expressed similar levels of these coat proteins as did infected wild-type plants. | Tobacco Mosaic Virus |
Prolonged Intermittent Renal Replacement Therapy (PIRRT) is the term used to define 'hybrid' forms of renal replacement therapy. PIRRT can be provided using an intermittent hemodialysis machine or a continuous renal replacement therapy (CRRT) machine. Treatments are provided for a longer duration than typical intermittent hemodialysis treatments (6-12 h vs. 3-4 h, respectively) but not 24 h per day as is done for continuous renal replacement therapy (CRRT). Usually, PIRRT treatments are provided 4 to 7 times per week. PIRRT is a cost-effective and flexible modality with which to safely provide RRT for critically ill patients. We present a brief review on the use of PIRRT in the ICU with a focus on how we prescribe it in that setting." | Intermittent Renal Replacement Therapy |
Tubers of six accessions of ahipa (Pachyrhizus ahipa) contained between 0.77 and 1.34% nitrogen on a dry weight basis. This corresponds to 4.8 to 8.4% crude protein based on a nitrogen to protein conversion factor of 6.25; but detailed analysis of AC230 showed that although 93% of the total N was extracted with buffer containing 1.0 M NaCl, about a third of this was lost on dialysis. It was calculated, therefore, that salt-soluble proteins comprise about 60% of the total tuber nitrogen, with low-molecular-mass nitrogenous components comprising a further 30%. Electophoretic analysis of the salt-soluble proteins showed similar patterns of components in the six accessions, with none being present in amounts sufficiently high to suggest a role as storage proteins. Furthermore, light microscopy failed to show significant deposits of protein within the tuber cells. Five major" protein bands, which together accounted for about 19% of the total salt-soluble protein fraction were purified and subjected to N-terminal amino acid sequencing. Comparison of these with sequences in protein databases revealed similarities to alpha-amylases, chitinases and chitin binding proteins, cysteine proteinases (including major components from P. erosus tubers), a tuberization-specific protein from potato, and proteins induced in soybean and pea by stress or the plant hormone abscisic acid, respectively. It was concluded that the primary roles of these proteins are probably in aspects of tuber metabolism and development and/or conferring protection to pests and pathogens, and that true storage proteins are not present. The absence of storage proteins is consistent with the biological role of the tubers as storage organs for carbohydrates (cf cassava tuberous roots) rather than as propagules (cf yam and potato tubers)." | Pachyrhizus |
Oxygen pressure declines from normoxic air-level to the microenvironment of mitochondria where cytochrome c oxidase (COX) reduces oxygen to water at oxygen levels as low as 0.3 kPa (2 Torr; 3 microM; 1.5 % air saturation). Intracellular hypoxia is defined as (1) local oxygen pressure below normoxic reference states, or (2) limitation of mitochondrial respiration by oxygen levels below kinetic saturation, resulting in oxyconformance. High-resolution respirometry provides the methodology to measure mitochondrial and cellular oxygen kinetics in the relevant low oxygen range < 1 kPa (7.5 mmHg; 9-10 microM; 5% air saturation). Respiration of isolated heart mitochondria follows hyperbolic oxygen kinetics with half-saturating oxygen pressure, p50, of 0.04 kPa (0.3 Torr; 0.4 microM) in ADP-stimulated state 3. Thus mitochondrial respiration proceeds at 90% of its hyperbolic maximum at the p50 of myoglobin, suggesting the possibility of a small but significant oxygen limitation even under normoxia in active muscle. Any impairment of oxygen delivery, therefore, induces oxyconformance. In addition, a shift of mitochondrial oxygen kinetics to the right, particularly by competitive inhibition of COX by NO, causes a further depression of respiration and a compensatory increase of local oxygen pressure. Above 1 kPa, mitochondrial oxygen uptake increases above hyperbolic saturation, which is probably due to oxygen radical production rather than the kinetics of COX. In cultured cells, the pronounced oxygen uptake above mitochondrial saturation at air-level oxygen pressure cannot be inhibited by rotenone and antimycin A, amounting to > 20 % of routine respiration in fibroblasts. Biochemical models of oxyconformance of COX are evaluated relative to patterns of intracellular oxygen distribution in the tissue and enzyme turnover in vivo, considering the kinetic effects of COX excess capacity on flux through the mitochondrial electron transport chain. | Cell Respiration |
The relationship between protein molecular weight (MW) distribution, quality characteristics and muffin making properties amongst Indian wheat varieties were evaluated. Flours from varieties with higher grain weight showed lower proportion of fine particles. Lactic acid solvent retention capacity (LASRC), sedimentation value (SV) and dough stability (DS) correlated with the proportion of 0-55 mum size particles. Paste peak viscosity and breakdown viscosity showed positive correlation with polymeric protein and negatively with monomeric protein, alpha-amylase activity and sodium carbonate solvent retention capacity (NaSRC). Gluten strength indicators such as DS, dough development time (DDT), LASRC and gluten index (GI) were positively related to polymeric protein and negatively to monomeric protein. Both G' and G'' were correlated significantly with GI, LASRC, DS and DDT. The varieties that possesses high MW glutenin subunits combinations of 91 kDa + 84 kDa + 78 kDa + 74 kDa showed lower G' and G''. Muffin volume was positively correlated with gluten content and LASRC. | Triticum |
BACKGROUND: Chronic Kidney Diseases (CKD) of all etiologies are usually associated with Insulin Resistance (IR). Resistin is also a protein associated with IR. Some studies conducted abroad have shown that resistin level is higher among CKD patients. OBJECTIVE: To test if serum resistin level is significantly higher in CKD patients compared to normal individuals. PATIENTS AND METHODS: 96 CKD patients and 97 normal individuals were included in the study. Written informed consent was obtained from every individual. RESULTS: Serum resistin level was higher in CKD patients compared to control subjects. The difference in serum resistin level between two groups was statistically significant. CONCLUSION: Our study is probably the first study in India comparing serum resistin levels of CKD patients vis-a-vis control subjects. Further cellular research may be needed to explore this relation. | Resistin |
BACKGROUND: Balantidium coli, a ciliated protozoan parasite that infects primates and pigs, and is the largest protozoan to infect humans, is a well-known cause of diarrhoea and dysentery in humans. Extra-intestinal disease is uncommon, however. OBJECTIVE: We describe a case of lung involvement, with severe pulmonary haemorrhage resulting in iron deficiency anaemia and respiratory failure, of a 20-year-old, immune-competent man. RESULTS: Diagnosis was made by bronchial biopsy and lavage, which showed numerous trophozoites compatible with B. coli with a background of acute inflammatory cells. The origin of infection was not clear, but inhalation of pig manure was postulated as there was no history of intestinal disease. The patient was treated with oxytetracyline and metronidazole, kept in an ICU, improved within 48 hours, and was discharged within 4 days. CONCLUSION: B. coli infection should be considered as part of the differential diagnosis of pulmonary haemorrhage. | Balantidiasis |
BACKGROUND: The development of conveniently sprayed, tissue-adherent, inert hydrogel films has made possible the creation of novel products that can serve a dual function, as a surgical sealant to achieve immediate hemostasis, and as a barrier to prevent adhesion formation over time. METHODS: A sprayable, in situ formed absorbable hydrogel film was evaluated as a tissue sealant in a heparinized canine carotid artery graft model. PTFE grafts with leaking end-to-side anastomoses were treated with the synthetic sealant, and hemostasis was evaluated upon restoration of blood flow. Also, the hydrogel films were evaluated as an adhesion barrier in a rabbit pericardial abrasion model. RESULTS: The sprayable, in situ forming hydrogel film was shown to immediately seal carotid-PTFE anastomoses in six of six applications. Hydrogel application in a rabbit pericardial abrasion model resulted in a statistically significant reduction in the number and tenacity of adhesions. CONCLUSIONS: This novel in situ formed sprayable hydrogel film has demonstrated a dual function as an effective tissue sealant and as an adhesion barrier in cardiovascular preclinical models. These next generation synthetic biomaterials are currently undergoing clinical investigations. | Methylgalactosides |
The etiology of congenital hypothyroidism (CH) is important in determining its severity, prognosis, genetic counseling and clinical management. AIMS: investigate the causes of CH and their severity using serum levels of FreeT4 and TSH. PATIENTS AND METHODS: 243 neonates with CH (61% were girls) diagnosed by the Neonatal Screening Program of Minas Gerais between 1996 and 2003. The thyroid function was assessed through serum FreeT4 and TSH by chemilumiscence. CH etiology was evaluated by ultrasonography, scintigraphy, potassium perchlorate discharge test and serum thyroglobulin levels. RESULTS: Out of 243 patients, dysgenesis was found in 114 (47%): 3.3% had athyreosis; 0.4% eutopic dysgenetic gland due to maternal use of 131I; 22% ectopic glands (8.6% an isolated ectopic gland and 13% also an eutopic dysgenetic thyroid); 9% eutopic dysgenesis, 8.6% hypoplasia and 3.7% hemiagenesis. Thyroid in situ was found in 129 (52%): 23.5% had iodide organification defect; 3.7% thyroglobulin synthesis defect; 6.2% other 0.4% dyshomonogenesis; iodide transport defect; 1.2% transient CH and 18% a normal gland. Patients with dysgenesis had a more severe CH than those with thyroid in situ (TSH 248.08 vs. 18.17 microIU/mL and FT4 0.32 vs. 0.95 ng/dL, p < 0.001). CONCLUSIONS: Some cases had more complex dysgenesis, presenting ectopia associated to a dysgenetic eutopic gland. The ultrasound was the best tool to detect the dysgenetic tissue, but the scintigraphy was the most effective in identifying the functioning tissue. The thyroid hormone synthesis defects were found more frequently than expected, but in some cases they could not be defined. | Congenital Hypothyroidism |
A significant number of patients in general hospitals suffer from psychiatric distress or illness, but not all receive psychiatric consultation. This study examined several potential predictors of such consultation. These included patient characteristics (age, sex, race, insurance, disease stage, and number of medical diagnoses), characteristics of hospital stay (number of procedures, other consultations, length of stay, discharge destination), hospital characteristics (size, percent occupancy, teaching status, presence of a psychiatric unit, type of control), and community characteristics (region, urban/rural setting). Data were derived from a national sample of 327 hospitals. Parallel analyses using stepwise logistic regression were carried out across four samples: patients determined at discharge to have been hospitalized for diabetes, hip fracture, chronic obstructive pulmonary disease, and coronary artery bypass surgery. Results show a wide variation in the use of psychiatric consultations across different subgroups. Longer lengths of stay, urban setting. Northeast region, younger patient age, and other consultations were the most consistent predictors of the probability of psychiatric consultation. These variations may reflect differences in the need for consultation, differential recognition of these needs by providers, or differential availability of psychiatric consultation services. Moreover, they may have implications for equity and/or quality of hospital care." | Psychiatric Department, Hospital |
Heparin was separated into fractions with high and low anticoagulant activities by selective barium precipitation, gel filtration and ion exchange chromatography methods. Enrichment in the anticoagulant activities were observed in fractions with high molecular weight or high degree of sulfation. The combination of selective barium precipitation and ion exchange chromatography led to the preparation of heparins with very high anticoagulant activities (300 IU/mg). These heparins have a high affinity for antithrombin III (greater than 80%) and were undistinguishable from those prepared by antithrombin III affinity chromatography regarding molecular weight, sulfate/hexosamine ratio, degree of binding to antithrombin III, electrofocusing pattern and anticoagulant activity. These methods allow now the preparation in industrial scale of heparins with high anticoagulant activities for in vivo studies. | Fractional Precipitation |
It was the aim of this study to identify cow/calf, herd and management risk factors on perinatal mortality (PM) in dairy herds from the German federal state of Thuringia. Perinatal mortality was defined as cases of stillborn calves or calves having died within 24 h after birth. From a representative sample of 53 herds (breeds: Holstein Friesian and crossbreedings between Holstein Friesian and Blackpied Dairy Cow), dairy herd improvement (DHI) records were obtained providing information about number of calvings, frequency of PM, parity, calving ease, gender, twin calvings and herd milk yield. Management practices (farm organisation, breeding policies, calving management, hygienic measures, feeding, status of infectious diseases) were recorded using a questionnaire filled in whilst interviewing the herd owner. Data of one year from 46 herds with 13 158 calvings were analysed using logistic regression models applying generalised estimation equations (GEE). The overall frequency of PM was 9.3%. The odds ratio for PM was 5.89, 1.73, 1.68 and 1.67 in cases of dystocia, heifer calving, twin and male calves, respectively. None of the management factors examined in this study remained as significant effects for PM in the final logistic regression model. In conclusion, the results of this study suggest that cow/calf related factors reported as risk factors for PM in many studies in the past such as dystocia, number of lactation, gender and twins were also major determinants of PM in commercial dairy herds in Thuringia. Besides applying appropriate breeding policies herd owners should primarily consider ways of further improving calving management with proper calving supervision and correct calving assistance in order to reduce the risk of PM. | Perinatal Mortality |
Zooplankton are major consumers of phytoplankton primary production in marine ecosystems. As such, they represent a critical link for energy and matter transfer between phytoplankton and bacterioplankton to higher trophic levels and play an important role in global biogeochemical cycles. In this Review, we discuss key responses of zooplankton to ocean warming, including shifts in phenology, range, and body size, and assess the implications to the biological carbon pump and interactions with higher trophic levels. Our synthesis highlights key knowledge gaps and geographic gaps in monitoring coverage that need to be urgently addressed. We also discuss an integrated sampling approach that combines traditional and novel techniques to improve zooplankton observation for the benefit of monitoring zooplankton populations and modelling future scenarios under global changes. | Zooplankton |
Liver cancer is the third most common cancer, with increasing morbidity and mortality rates worldwide. Despite the increasing occurrence of liver cancer, it has a poor prognosis and potential treatment options are still lacking. The current study aimed to explore the anticancer potential of arbutin against diethylnitrosamine (DEN)-triggered liver carcinogenesis in rats. Liver cancer was initiated in rats via the administration of DEN (200 mg/kg) and then treated with 30 mg/kg of arbutin. Albumin, globulin, and total protein were quantified using kits. Antioxidant, liver injury marker, and tumor biomarker contents were quantified using marker-specific assay kits. The inflammatory markers c-JNK, TRAIL, caspase-8, and p53 contents were also detected using kits. Reverse transcription PCR analysis was used to study the expression of chaperones GRP78, GRP94, and PDIA4 as well as ERDJ4, ATF4, and GADD34. Liver histology was studied microscopically. The arbutin treatment effectively improved body weight and reduced liver weight in animals with DEN-provoked liver cancer. The treatment also improved the albumin, globulin, and total protein contents and antioxidants. In addition, arbutin reduced liver injury marker enzyme function and improved c-JNK, TRAIL, caspase-8, and p53 contents. Arbutin supplementation also decreased the expression of GRP78, PDIA4, GRP94, ERDJ4, ATF4, and GADD34 in the liver tissues of DEN-provoked animals. Arbutin effectively ameliorated the DEN-provoked histological alterations. Altogether, our findings show that arbutin has anti-inflammatory, antioxidant, and anticarcinogenic activities against DEN-provoked liver cancer in rats. | Diethylnitrosamine |
The final step of carbohydrate digestion in the intestine is performed by 2 major alpha-glucosidases of the intestinal mucosa, sucrase-isomaltase (SI) and maltase-glucoamylase. Both of these enzymes are type II membrane glycoproteins, which share a significant level of homology in gene and protein structures and yet have differences in the posttranslational processing, substrate specificity and functional capacity. Insufficient activity of these disaccharidases particularly SI as a result of genetic mutations or secondary intestinal pathologies is associated with carbohydrate maldigestion and gastrointestinal intolerances. This review will discuss the maturation profiles of SI and maltase-glucoamylase relative to their functional capacities and deficiencies. | Sucrase-Isomaltase Complex |
In today's extremely competitive economic environment, the quality management processes used by industrial companies have become commonplace at hospitals and are proving successful in improving quality and controlling costs. Continuous quality improvement (CQI) methods provide a relatively new way, compared with quality assurance (QA) and quality control (QC) methods, to improve the quality of health care. Continuous quality improvement should be considered a philosophy rather than simply a methodology; it assumes no endpoints in improvement efforts and does not attempt to replace the older concepts of QA and QC but rather to reap their benefits and take them to a higher conceptual level. Continuous quality improvement has 4 foci: (1) to determine and meet the needs of patients and customers, (2) to approach quality improvement holistically on the basis of the identification of the underlying cause of poor performance, (3) to apply fact-based management and scientific methodology, and (4) to empower its practitioners to improve quality on a daily basis. Health care institutions and radiology departments use a variety of CQI systems or models, including the model of the Joint Commission on Accreditation of Healthcare Organizations, the Six Sigma model, and the Model for Business Excellence of the European Foundation for Quality Management. The International Organization for Standardization 9000, which creates a suitable organizational environment for the implementation of a CQI system, can be considered an effective QA and QC method. | Total Quality Management |
Subsets and Splits