Good death from cancer-the patient view: systematic review of qualitative studies.

BACKGROUND AND OBJECTIVE: An in-depth understanding of what constitutes a good death among patients with cancer is vital to providing patient-centred palliative care. This review aimed to synthesise evidence on the perceptions of a good death among patients with cancer. METHODS: This systematic review involved a synthesis of qualitative data. A three-step process suggested by the Joanna Briggs Institute was used to synthesise the data. RESULTS: A total of 1432 records were identified, and five articles met the inclusion criteria. Seven synthesised findings emerged: (1) being aware of cancer, (2) pain and symptom management, (3) dying well, (4) being remembered after death, (5) individual perspectives of a good death, (6) individual behaviours leading to a good death, and (7) culture and religions. A structural framework was developed to elicit two layers that could be regarded as determinants of a good death. One layer suggested how multiple external issues impact a good death, whereas the other layer involves patients' internal attributes that shape their experiences of a good death. The elements in the two layers were inter-related to exert a crossover effect on good death in specific cultural and religious contexts. CONCLUSION: A good death is a process initiated from the time of awareness of cancer and extends beyond demise. Holistic approaches encompassing the management of physical and psychological distress along with psychosocial behavioural interventions to enhance patients' positive perspectives and behaviours are recommended to improve their quality of life and death.

Genetic Toxicology and Safety Pharmacological Evaluation of Forsythin.

INTRODUCTION: Forsythin is the main ingredient of Forsythia suspensa and is widely used in treatment of fever, viral cold, gonorrhea, and ulcers clinically. This study aimed to evaluate the potential genetic toxicity of forsythin and its safety for human use. METHODS: Based on the Good Laboratory Practice regulations and test guidelines, the genetic toxicity of forsythin was assessed by the Ames test, chromosome aberration (CA) test, and bone marrow micronucleus (MN) test in vivo. In the Ames test, five strains of Salmonella typhimurium were exposed to different concentrations of forsythin in the presence or absence of the S9 mixture, and then, the number of His + revertant colonies was counted. In the CA test, Chinese hamster lung (CHL) fibroblast cells were treated with different concentrations of forsythin, mitomycin C, or cyclophosphamide in the presence or absence of the S9 mixture, and the chromosomal aberrations were determined. In the MN test, bone marrow was isolated from the mice with different treatments, and the ratios of polychromatic erythrocytes (PCE) and erythrocytes (PCE/(PCE + NCE)) were measured. Finally, beagle dogs were divided into four groups (negative control, low dose, medium dose, and high dose groups), and then, a telemetry system was used to evaluate the safe use of forsythin. RESULTS: Ames test results showed that the number of colonies in all test strains with different treatments showed no significantly dose-dependent increase in the presence or absence of the S9 mixture (p > 0.05). In the CA test, the number of cells with aberrations in the CHL fibroblast cells treated with low, medium, and high doses of forsythin for 24/48 h in the absence of the S9 mixture was, respectively, 5.0/2.5, 4.5/1.5, and 5.0/5.0, and in the presence of the S9 mixture, the number was, respectively, 5.0, 5.0, and 4.5. These results showed that there was no significant difference compared to the negative control group either in the presence (2.0) or in the absence (4.0/2.5 for 24/48 h) of the S9 mixture (p > 0.05). The MN test showed that the values of PCE/(PCE + NCE) in the negative, positive controls, and forsythin treatment groups were all more than 20%, which indicated that forsythin had no cytotoxicity. Additionally, no significant toxicological effects of forsythin on blood pressure, respiration, temperature, electrocardiogram, and other physiological indicators in the conscious beagle dogs of different groups were observed by the telemetry method. CONCLUSION: Our findings showed that forsythin has low probability of genetic toxicity and no significant toxicological effects, which implied that forsythin is suitable for further development and potential application.

Preparation, Structure and Properties of Acid Aqueous Solution Plasticized Thermoplastic Chitosan.

This work provides a simple method for the preparation of thermoplastic chitosan using the most common dilute inorganic and organic acids in aqueous solutions, namely hydrochloric acid (HCl) and acetic acid (HAc). The melting plasticization behavior of chitosan under different concentrations and types of acid solution was investigated. By means of infrared spectra (IR), scanning electron microscope (SEM), X-ray diffraction (XRD), and other characterization methods, as well as a mechanical property test, it was found that as the acid solution concentration increased, the protonation effect was stronger and the plasticization performance showed a better trend. The structure and performance of the modified chitosan were optimal when the concentration of HCl was around 8 wt %. In addition, it was found that HCl had a better effect on the plasticization of chitosan than HAc, which was because the protonation ability of HCl was stronger than that of HAc. Unlike the casting method, the structure and properties of chitosan sheets prepared by thermoplastic processing were directly affected by protonation, however not by the interaction of anionic-cationic electrostatic attractions between the -NH3+ groups of chitosan chains and the carboxyl groups of acetic acids or the chloridoid groups of hydrochloric acid.

Magnetic impurity in topological nodal loop semimetals.

We investigate the Kondo effect of a spin-1/2 magnetic impurity in a topological nodal loop semimetal, in which band touchings form a nodal loop. The Fermi surface of a nodal loop semimetal is a torus or a drum-like structure, which is determined by chemical potential. When the chemical potential µ lies at the nodal loop ([Formula: see text]), the magnetic impurity and the conduction electrons form bound states only if their coupling exceeds a critical value. As the chemical potential is tuned away from the nodal loop, the Fermi surface becomes a torus or drum-like structure and the impurity and the host material always favor a bound state due to the finite density of state. Due to the anisotropic dispersion relationship in the energy band, the spatial spin-spin correlations [Formula: see text]([Formula: see text]) are of power-law decay with the decay rates proportional to [Formula: see text] and [Formula: see text] in different directions, respectively. The product [Formula: see text] and [Formula: see text] oscillates in coordinate space and the period is enhanced gradually as the Fermi surface evolves from a torus surface into a drum-like structure.

Modest Decreases in Endogenous All-trans-Retinoic Acid Produced by a Mouse Rdh10 Heterozygote Provoke Major Abnormalities in Adipogenesis and Lipid Metabolism.

Pharmacological dosing of all-trans-retinoic acid (atRA) controls adiposity in rodents by inhibiting adipogenesis and inducing fatty acid oxidation. Retinol dehydrogenases (Rdh) catalyze the first reaction that activates retinol into atRA. This study examined postnatal contributions of Rdh10 to atRA biosynthesis and physiological functions of endogenous atRA. Embryonic fibroblasts from Rdh10 heterozygote hypomorphs or with a total Rdh10 knockout exhibit decreased atRA biosynthesis and escalated adipogenesis. atRA or a retinoic acid receptor (RAR) pan-agonist reversed the phenotype. Eliminating one Rdh10 copy in vivo (Rdh10+/- ) yielded a modest decrease (≤25%) in the atRA concentration of liver and adipose but increased adiposity in male and female mice fed a high-fat diet (HFD); increased liver steatosis, glucose intolerance, and insulin resistance in males fed an HFD; and activated bone marrow adipocyte formation in females, regardless of dietary fat. Chronic dosing with low-dose atRA corrected the metabolic defects. These data resolve physiological actions of endogenous atRA, reveal sex-specific effects of atRA in vivo, and establish the importance of Rdh10 to metabolic control by atRA. The consequences of a modest decrease in tissue atRA suggest that impaired retinol activation may contribute to diabesity, and low-dose atRA therapy may ameliorate adiposity and its sequelae of glucose intolerance and insulin resistance.

Raldh1 promotes adiposity during adolescence independently of retinal signaling.

All-trans-retinoic acid (RA) inhibits adipogenesis in established preadipocyte cell lines. Dosing pharmacological amounts of RA reduces weight gain in mice fed a high-fat diet, i.e. counteracts diet-induced obesity (DIO). The aldehyde dehydrogenase Raldh1 (Aldh1a1) functions as one of three enzymes that converts the retinol metabolite retinal into RA, and one of many proteins that contribute to RA homeostasis. Female Raldh1-ablated mice resist DIO. This phenotype contrasts with ablations of other enzymes and binding-proteins that maintain RA homeostasis, which gain adiposity. The phenotype observed prompted the conclusion that loss of Raldh1 causes an increase in adipose tissue retinal, and therefore, retinal functions independently of RA to prevent DIO. A second deduction proposed that low nM concentrations of RA stimulate adipogenesis, in contrast to higher concentrations. Using peer-reviewed LC/MS/MS assays developed and validated for quantifying tissue RA and retinal, we show that endogenous retinal and RA concentrations in adipose tissues from Raldh1-null mice do not correlate with the phenotype. Moreover, male Raldh1-null mice resist weight gain regardless of dietary fat content. Resistance to weight gain occurs during adolescence in both sexes. We show that RA concentrations as low as 1 nM, i.e. in the sub-physiological range, impair adipogenesis of embryonic fibroblasts from wild-type mice. Embryonic fibroblasts from Raldh1-null mice resist differentiating into adipocytes, but retain ability to generate RA. These fibroblasts remain sensitive to an RA receptor pan-agonist, and are not affected by an RA receptor pan-antagonist. Thus, the data do not support the hypothesis that retinal itself represses weight gain and adipogenesis independently of RA. Instead, the data indicate that Raldh1 functions as a retinal and atRA-independent promoter of adiposity during adolescence, and enhances adiposity through pre-adipocyte cell autonomous actions.

Flexible and Highly Photosensitive Electrolyte-Gated Organic Transistors with Ionogel/Silver Nanowire Membranes.

Flexible and low-voltage photosensors with high near-infrared (NIR) sensitivity are critical for realization of interacting humans with robots and environments by thermal imaging or night vision techniques. In this work, we for the first time develop an easy and cost-effective process to fabricate flexible and ultrathin electrolyte-gated organic phototransistors (EGOPTs) with high transparent nanocomposite membranes of high-conductivity silver nanowire (AgNW) networks and large-capacitance iontronic films. A high responsivity of 1.5 × 103 A·W1-, high sensitivity of 7.5 × 105, and 3 dB bandwidth of ∼100 Hz can be achieved at very low operational voltages. Experimental studies in temporal photoresponse characteristics reveal the device has a shorter photoresponse time at lower light intensity since strong interactions between photoexcited hole carriers and anions induce extra long-lived trap states. The devices, benefiting from fast and air-stable operations, provide the possibility of the organic photosensors for constructing cost-effective and smart optoelectronic systems in the future.

Determination of Histamine by High-Performance Liquid Chromatography After Precolumn Derivatization with o-Phthalaldehyde-Sulfite.

A fast and sensitive method was developed for in vivo determination of histamine in the brain microdialysate by reverse ion pair chromatography with electrochemical detection. The microdialysates were derivatized with o-phthalaldehyde and sodium sulfite, and separation was achieved using isocratic elution within 10 min. The separation was performed in an Agilent Eclipse Plus C18 column (3.0 × 150 mm, particle size 3.5 µm), and the mobile phase consisted of 100 mM monosodium phosphate (pH 6.0), 500 mg L(-1) OSA and 20% methanol (v/v). The linearity (R(2)) was found to be >0.999, with a range from 2 to 50 nM and excellent repeatability (relative standard deviation, 2.29-6.04%), and the limit of detection was 0.4 nM. This method was successfully applied to analyze the extracellular concentration of histamine in the hypothalamus of rats, with probe recovery calculated in vivo.

Development of an N-hydroxysuccinimidyl fluorescein-O-acetate-labeled probe for competitive capillary electrophoretic immunoassay of bovine serum albumin.

A highly fluorescent reagent, N-hydroxysuccinimidyl fluorescein-O-acetate (SIFA) has been labeled on bovine serum albumin (BSA) to construct a new immunofluorescent probe, SIFA-BSA, for the competitive immunoassay of BSA with capillary electrophoresis. Labeling conditions of SIFA with BSA such as the reaction molar ratio and reaction time, as well as separation conditions for free and antibody-bound SIFA-BSA including the pH and concentration of buffer were systematically investigated. Under the optimized conditions, SIFA-labeled BSA and free BSA competitively reacted with a limited amount of anti-BSA antibody. Free and antibody-bound SIFA-BSA could be well separated within 5min using 100mM boric acid buffer (pH 9.3) for background electrolyte, 28kV for the separation voltage, and 25 degrees C for the column temperature. With the proposed method, a much lower detection limit (S/N=3) of 0.1microg/mL was obtained compared with the competitive capillary electrophoresis immunoassay of BSA with fluorescein isothiocyanate (FITC) labeled BSA probe, in which the detection limit (S/N=3) is 0.0031mg/mL.

Trace determination of short-chain aliphatic amines in biological samples by micellar electrokinetic capillary chromatography with laser-induced fluorescence detection.

In this study, a new capillary electrophoresis (CE) method is described originally for the sensitive and selective determination of short-chain aliphatic amines in biological samples. These amines were converted into their N-hydroxysuccinimidyl fluorescein-O-acetate (SIFA) derivatives and measured by micellar electrokinetic capillary chromatography with laser-induced fluorescence detection. The derivatization conditions and separation parameters for the aliphatic amines were optimized in detail. The SIFA-labeled amines were fully separated within 8.5 min using 25 mM pH 9.6 boric acid electrolyte containing 60mM sodium dodecyl sulfate (SDS). The parameters of validation such as linearity of response, precision and detection limits were determined. The detection limits were obtained in the range from 0.02 to 0.1 nM, which was the lowest value reported by CE methods. The developed method was successfully employed to monitor aliphatic amines in serum and cells samples. After comparison of other CE methods using different fluorescent probes, the present method represents a powerful tool for the trace determination of aliphatic amines in complex biological samples.

Determination of amino acid neurotransmitters in human cerebrospinal fluid and saliva by capillary electrophoresis with laser-induced fluorescence detection.

A CE-LIF detection method has been developed to identify and quantitate six amino acid neurotransmitters including glutamic acid, aspartic acid, gamma-aminobutyric acid, glycine, taurine, and glutamine. N-hydroxysuccinimidyl fluorescein-O-acetate, a fluorescein-based dye, was employed for the derivatization of these neurotransmitters prior to CE-LIF analysis. Different parameters which influenced separation and derivatization were optimized in detail. Under optimum conditions, linearity was achieved within concentration ranges of up to three orders of magnitudes for those analytes with correlation coefficients from 0.9989 to 0.9998. The LODs ranged from 0.06 nM to 0.1 nM, and are thus superior or equivalent to those previously reported in the literature using CE-LIF detection. The proposed method has been successfully applied to the determination of amino acid neurotransmitters in biological samples such as human cerebrospinal fluid and saliva with satisfactory recoveries.

Sensitive determination of biogenic amines by capillary electrophoresis with a new fluorogenic reagent 3-(4-fluorobenzoyl)-2-quinolinecarboxaldehyde.

An effective approach was proposed to the derivatization of seven biogenic amines using 3-(4-fluorobenzoyl)-2-quinolinecarboxaldehyde (FBQCA) as a fluorogenic reagent. The sensitive determinations of these derivatives were achieved by micellar electrokinetic capillary chromatography (MEKC) with laser-induced fluorescence (LIF) detection. The derivatization and electrophoretic conditions have been optimized. A running buffer was composed of mixtures of 25 mM pH 9.5 boric acid, 25 mM SDS, and 27% ACN. At 25 degrees C and 22.5 kV, the baseline separation of the derivatives was accomplished in 13 min. The detection limit (S/N=3) was found as low as 0.4 nM. The proposed method was validated by the linearity of two orders magnitude and correlation coefficient in the range 0.9969-0.9998. Also, the procedure was successfully applied to the determination of biogenic amines in soy sauce, fish and wine samples.

Rapid and sensitive determination of phosphoamino acids in phosvitin by N-hydroxysuccinimidyl fluorescein-O-acetate derivatization and capillary zone electrophoresis with laser-induced fluorescence detection.

A method was developed for the determination of phosphoamino acids by capillary zone electrophoresis-laser-induced fluorescence detection (argon ion laser, excitation at 488 nm and emission at 520 nm) using derivatization with N-hydroxysuccinimidyl fluorescein-O-acetate (SIFA). Different variables affecting the derivatization (SIFA concentration, derivatization pH, reaction temperature and reaction time) and the separation (type, pH and concentration of buffer, applied voltage and injection mode) were investigated in detail. The optimized separation conditions were 40 mM boric acid buffer (pH 9.2) for background electrolyte, 25 kV for the separation voltage, 25 degrees C for the capillary temperature and 5 s at 0.5 psi for the sample injection. Under the optimal conditions, the SIFA-labeled phosphoamino acids were fully separated within 7 min. The detection limits ranged from 0.1 to 0.3 nM, which are the lowest values reported for capillary electrophoresis (CE) methods. The proposed methodology allowed the rapid, sensitive and selective determination of phosphoamino acids in hen egg yolk phosvitin by the standard addition method. The recovery of these compounds in real sample was 94.0-103.5%. The developed method surpasses previously published CE methods in terms of detection limit, separation time, stability and simplicity of the electrophoretic procedure.

6-Oxy-(acetyl ethylenediamine) fluorescein, a novel fluorescent derivatization reagent for carboxylic acids and its application in HPLC.

A novel fluorescent derivatization reagent for carboxylic acids, 6-oxy-(acetyl ethylenediamine) fluorescein (AEF), was well designed, synthesized, and applied to HPLC. The derivatization reaction with 12 fatty acids, including n-valeric acid (C5), n-hexanoic acid (C6), n-heptanoic acid (C7), n-octanoic acid (C8), n-nonanoic acid (C9), n-decanoic acid (C10), lauric acid (C12), myristic acid (C14), palmitic acid (C16), stearic acid (C18), oleic acid (C18:1), and linoleic acid (C18:2), was completed at 55 degrees C within 40 min. The derivatives of fatty acids were separated on a C18 RP column and detected by fluorescence detection. The LODs attained were 0.4-1.2 nM (S/N of 3). It has been demonstrated that AEF is a prominent derivatization reagent for carboxylic acids which is suitable for HPLC.

Quantification of biogenic amines in human plasma based on the derivatization with N-hydroxy-succinimidyl fluorescein-O-acetate by high-performance liquid chromatography.

An HPLC method for the determination of biogenic amines based on the precolumn derivatization with N-hydroxysuccinimidyl fluorescein-O-acetate (SIFA) has been developed. The derivatization was performed at 45 degrees C for 30 min in borate buffer (pH 8.0). The derivatives were separated on a ZORBAX Eclipse XDB-C8 column (150 mm x 4.6 mm id; 5 mum) and monitored by fluorescence detection (excitation, 469 nm; emission, 512 nm). The LODs (S/N = 3) for spermine, spermidine, putrescine, cadaverine, and phenethylamine were 0.4, 0.2, 0.3, 0.5, and 0.4 nM, respectively. The developed method has been successfully applied to the determination of biogenic amines in human plasma of three healthy volunteers and four cancer patients. Average recoveries for plasma samples ranged from 94 to 106% and coefficients of variation ranged from 1.8 to 4.6%. Deproteinization of plasma was accomplished with ACN to precipitate interfering substances and the centrifuged supernatant was used directly for analysis.

Design and synthesis of a novel fluorescent reagent, 6-oxy-(ethylpiperazine)-9-(2'-methoxycarbonyl) fluorescein, for carboxylic acids and its application in food samples using high-performance liquid chromatography.

A novel derivatization reagent for carboxylic acids, 6-oxy-(ethylpiperazine)-9-(2'-methoxycarbonyl)fluorescein (EPMF) has been well designed and synthesized. It was used to label 13 fatty acids, n-butyric acid (C4), n-valeric acid (C5), n-hexanoic acid (C6), n-heptanoic acid (C7), n-octanoic acid (C8), n-nonanoic acid (C9), n-decanoic acid (C10), lauric acid (C12), myristic acid (C14), palmitic acid (C16), stearic acid (C18), oleic acid (C18:1) and linoleic acid (C18:2), successfully. The derivatization reaction with fatty acids was completed at 50 degrees C, 50 min. The derivatives of fatty acids were separated on a C18 reversed-phase column with gradient elution and fluorescence detection at lambda(ex)/lambda(em)=469/518 nm. The detection limits obtained were 0.4-2 nmol L(-1) (signal-to-noise ratio of 3). The proposed method has been applied to the quantification of fatty acids in edible oil with recoveries over 93%. It has been demonstrated that EPMF is a prominent derivatization reagent for fatty acids and is suitable for HPLC.

Liquid chromatographic analysis of phosphoamino acids at femtomole level using chemical derivatization with N-hydroxysuccinimidyl fluorescein-O-acetate.

Phosphorylation of amino acid residues in proteins plays a major role in biological systems. In this paper, a reversed-phase high performance liquid chromatographic (HPLC) method based on chemical derivatization has been described for the separation and quantification of phosphoamino acids at femtomole level, using fluorimetric detection (FLD). The protocol involved pre-column derivatization of phosphoamino acids with N-hydroxysuccinimidyl fluorescein-O-acetate (SIFA) and subsequent separation on ZORBAX Eclipse XDB-C8 column. Several experimental factors that influenced derivatization and separation were carefully investigated. The derivatization was performed at 40 degrees C for 40 min in borate buffer (pH 8.5). Under the optimum conditions, phosphoserine (P-Ser), phosphothreonine (P-Thr) and phosphotyrosine (P-Tyr) were satisfactorily separated in 8 min. The detection limits (signal-to-noise ratio=3) for the phosphoamino acids could reach 10-20 fmol, which was the lowest value reported for HPLC methods and comparable to those obtained by capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection methods. The proposed method has been validated and used to characterize the phosphoamino acids in the hydrolyzed phosphorylated protein samples. The results clearly demonstrated the potential of this technique to study phosphoamino acids as well as provided a new analytical methodology that should be applicable to the study of phosphorylation of protein in biological system.

6-oxy-(acetyl piperazine) fluorescein as a new fluorescent labeling reagent for free fatty acids in serum using high-performance liquid chromatography.

A new fluorescein-based fluorescent derivatizating reagent, 6-oxy-(acetyl piperazine) fluorescein (APF), has been designed, synthesized and developed for carboxylic acid labeling. It was used as a pre-column derivatizing reagent for the determination of seven free fatty acids (lauric acid, myristic acid, arachidonic acid, linoleic acid, palmitic acid, oleic acid, and stearic acid) with high-performance liquid chromatography (HPLC). The derivatization reaction of APF with seven fatty acids was completed at 60 degrees C for 1 h using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) as the condensing reagent. On a C18 column, the derivatives of APF with seven free fatty acids could be separated completely in 22 min using a mobile phase of methanol-water (88:12, v/v) containing 7 mmol L(-1) pH 6.5 Na2HPO4-H3Cit3 buffer with fluorescence detection at lambdaex/lambdaem=467/512 nm. The detection limits could reach 0.1-6.4 nmol L(-1) (signal-to-noise=3). This reagent was applied to the determination of the free fatty acids in human serum samples with satisfying recovery efficiencies varying from 93 to 105%.