[Cross-sectional survey between schistosomiasis liver fibrosis and health-related quality of life among agricultural workers].

Objective: To assess the health-related quality of life in the agricultural workers with schistosomiasis liver fibrosis using Europe Health-Related Quality of Life Questionnaire 5 Dimensions (EQ-5D) . Methods: From January to December 2019, a cross sectional study was applied to 3507 agricultural workers at a township, Kaihua County, Zhejiang Province, of which 424 agricultural workers with schistosomiasis liver fibrosis as objective group and of which 3083 agricultural workers without schistosomiasis liver fibrosis as the control group whom were respectively evaluated by the EQ-5D scale. At the same time, aspartate aminotransferase (AST) and platelet (PLT) ratio index (APRI) was calculated, and B-type ultrasound was used to test the degree of liver fibrosis among two groups. Results: There were 424 patients in the objective group, aged (66.29±7.21) years, and 3083 person in the control group, aged (65.98±14.81) years. The APRI scores between the control group and the objective group were (0.74±0.51) points and (1.04±0.53) points, respectively (P<0.01) . The total score of 5 items of EQ-5D was (6.86±2.21) points and (7.88±2.71) points, respectively, in the objective group had 375 cases of liver fibrosis grade I and 49 cases of liver fibrosis grade Ⅱ, which were significantly higher than that of the control group[ (5.50±1.17) points] (P<0.01) . Among the respondents, EQ-VAS score was negative correlated with EQ-5D scores (r=-0.616, P<0.01) . Conclusion: The health-related quality of life of agricultural workers with schistosomiasis liver fibrosis at a township, Quzhou City Kaihua County decreased compared with the control group.

Construction of multifunctional porcine acellular dermal matrix hydrogel blended with vancomycin for hemorrhage control, antibacterial action, and tissue repair in infected trauma wounds.

Prevention of bacterial infection and reduction of hemorrhage, the primary challenges posed by trauma before hospitalization, are essential steps in prolonging the patient's life until they have been transported to a trauma center. Extracellular matrix (ECM) hydrogel is a promising biocompatible material for accelerating wound closure. However, due to the lack of antibacterial properties, this hydrogel is difficult to be applied to acute contaminated wounds. This study formulates an injectable dermal extracellular matrix hydrogel (porcine acellular dermal matrix (ADM)) as a scaffold for skin defect repair. The hydrogel combines vancomycin, an antimicrobial agent for inducing hemostasis, expediting antimicrobial activity, and promoting tissue repair. The hydrogel possesses a porous structure beneficial for the adsorption of vancomycin. The antimicrobial agent can be timely released from the hydrogel within an hour, which is less than the time taken by bacteria to infest an injury, with a cumulative release rate of approximately 80%, and thus enables a relatively fast bactericidal effect. The cytotoxicity investigation demonstrates the biocompatibility of the ADM hydrogel. Dynamic coagulation experiments reveal accelerated blood coagulation by the hydrogel. In vivo antibacterial and hemostatic experiments on a rat model indicate the healing of infected tissue and effective control of hemorrhaging by the hydrogel. Therefore, the vancomycin-loaded ADM hydrogel will be a viable biomaterial for controlling hemorrhage and preventing bacterial infections in trauma patients.

Amido-3-hydroxypyridin-4-ones as iron(III) ligands.

The synthesis and physicochemical properties of a range of 2- and 6-amido-3-hydroxypyridin-4-ones are described. All the amido-substituted 3-hydroxypyridin-4-ones have lower pK(a) values than 1,2-dimethyl-3-hydroxypyridin-4-one (deferiprone). This is due to the inductive effect of the amido group. Furthermore, the pK(a) values of the 3-hydroxy group in 1-nonsubstituted pyridinones are dramatically lower than those of the corresponding 1-alkyl analogues, indicating that a strong hydrogen bond exists between the 2-amido function and the 3-oxygen anion, which stabilises the anion. As a result of the decreased competition with protons, the pFe(3+) values of this group of molecules are higher than that of deferiprone. The distribution coefficients of these molecules are also increased despite the lack of a hydrophobic 1-alkyl substituent and this is ascribed to the intramolecular hydrogen bond. X-ray diffraction studies confirm the existence of the intramolecular hydrogen bond.

Effects of Visual Aids for End-of-Life Care on Decisional Capacity of People With Dementia.

Purpose This study evaluated the decision-making capacity of persons with mild and moderate dementia on end-of-life care when using visual aids. A secondary purpose was to learn whether the judges naive to the experimental conditions would rate participants' decisional abilities as better when augmented by visual aids, thereby validating the behavioral changes due to the use of these external support. Method Twenty older adults with mild and moderate dementia demonstrated Understanding, Expressing a Choice, Reasoning, and Appreciation of 2 medical vignettes under 2 counterbalanced conditions: verbal alone or verbal with visual aids. Transcripts were analyzed and scored to measure decisional skills. Twelve judges rated participants' decisional abilities using a 7-point Likert scale. Results Participants demonstrated significantly better overall decisional capacity in Understanding, Reasoning, and Appreciation when supported by visual aids during the decision-making process. No significant differences between conditions were found in Expressing a Choice, the decisional skill Logical Sequence under Reasoning, and Acknowledgment under Appreciation. Overall, the judges' ratings validated these outcomes; the judges' ratings reflected greater agreement in the visual condition than in the verbal condition. Conclusions Findings indicated that visual aids (a) improved the decision-making capacity of individuals with dementia in comprehending medical information, employing supportive reasons, and relating this information to his or her own situation and (b) contain the potential for judges who majored or are majoring in speech-language pathology to reach a stronger consensus when determining the decision-making capacity of individuals with dementia.

Basic 3-hydroxypyridin-4-ones: potential antimalarial agents.

3-Hydroxypyridin-4-ones selectively bind iron under biological conditions and one such compound has found application in the treatment of thalassaemia-linked iron overload. Related molecules have also been demonstrated to possess an antimalarial effect at levels which are non-toxic to mammalian cells. In an attempt to improve the efficiency of such molecules we have investigated the effect of introducing basic nitrogen centres into 3-hydroxypyridin-4-ones in an attempt to achieve targeting to lysosomes and other intracellular acidic vacuoles. Several of the compounds reported in this communication possess enhanced antimalarial activity over that of the simple hydroxypyridinone class.

Structural characterization of chelator-terminated dendrimers and their synthetic intermediates by mass spectrometry.

Herein, we report the structural analysis of a novel family of iron-chelating dendrimers and their synthetic intermediates utilizing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and electrospray ionization ion trap (ESI IT) MS. These dendrimers share a benzene tricarbonyl core moiety attached to three tripodal branching units, each linking to three terminal groups, ranging from carboxyl, catechol and 3-hydroxy-6-methyl-pyran-4-one moieties and their protected analogs. In order to monitor the progression of dendrimer synthesis, all intermediates and final products were mass analyzed by conventional MALDI-TOF MS with and without alkali metal spiking. For structural characterization, interpretable post-source decay (PSD) and electrospray ionization ion trap MS/MS spectra were obtained from proton, sodium and potassium adducts of the dendrimers. One major route of dendrimer fragmentation was at or adjacent to the amide bonds either of the terminal chelating groups or near the core moiety. Fragmentation in the latter case was primarily at the N-terminal side of the amide bond and was directed by the proximity of a tertiary carbon of the branching unit. Furthermore, it was found that terminal ester, ether and amide linkages to the protecting and chelating groups could be sequentially broken in a single MS/MS spectrum through multiple cleavages resulting in product ions of decreasing intensity. Moreover, such cleavages could also be induced in a stepwise manner in a multistage ion trap MS(n) experiment.

Emerging understanding of the advantage of small molecules such as hydroxypyridinones in the treatment of iron overload.

Deferiprone, a hydroxypyridin-4-one, is effective at facilitating iron removal from iron overloaded patients, when administered orally. Some problems associated with deferiprone are discussed. Hydroxypyridinone analogues with improved distribution, metabolism and affinity for iron are described. In particular the "high pFe(3+)" hydroxypyridin-4-ones possess considerable clinical potential.

Oral iron chelators--development and application.

Iron chelation therapy is the only therapeutic approach that leads to enhanced iron excretion in beta-thalassaemia major and other transfusion-dependent patients. Although desferrioxamine has been used in such treatment over the last three decades, it is not an ideal drug due to its poor oral availability. Consequently extensive research effort has been directed towards the identification of non-toxic, orally active iron chelators. An ideal candidate must possess a range of critical physicochemical and biological properties, such as high selectivity and affinity for iron(III), tightly controlled distribution and metabolic profiles and low toxicity. Unfortunately, hexadentate ligands are generally associated with poor oral bioavailability, whereas many tridentate and bidentate molecules are orally active. The tridentate triazoles have been investigated for clinical potential; they are readily absorbed from the gastrointestinal tract and promote iron excretion with high efficacy. In similar fashion, several bidentate hydroxypyridinones have been demonstrated to possess potential as oral chelating agents.

Design, synthesis, and evaluation of novel 2-substituted 3-hydroxypyridin-4-ones: structure-activity investigation of metalloenzyme inhibition by iron chelators.

A range of novel 3-hydroxypyridin-4-ones with different R(2) substitutents has been synthesized for the investigation of the structure-activity relationship between the chemical nature of the ligand and the inhibitory activity of the iron-containing metalloenzyme 5-lipoxygenase. Results indicate that the molecular dimensions, together with the lipophilicity, have a critical impact on the ability of this class of chelator to inhibit 5-lipoxygenase. Hydrophilic ligands with a bulky R(2) substitutent tend to be weak inhibitors; thus 1,6-dimethyl-2-(4'-N-n-propylsuccinamido)methyl-3-hydroxypyridin-4(1H)-one (22b) which has the largest R(2) substitutent only caused 2% inhibition of the enzyme activity after 30 min incubation at 110 microM IBE (iron-binding equivalents), as compared with deferiprone which caused 40% inhibition of the enzyme activity, under the same conditions.

Design, synthesis and properties of novel iron(III)-specific fluorescent probes.

Bidentate chelators such as hydroxypyridinones and hydroxypyranones are highly iron selective. The synthesis of two novel fluorescent probes N-[2-(3-hydroxy-2-methyl-4-oxopyridin-1(4H)-yl)ethyl]-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide (CP600) and N-[(3-hydroxy-6-methyl-4-oxo-4H-pyran-2-yl)methyl]-2-(7-methoxy-2-oxo-2H-chromen-4-yl)acetamide (CP610) is reported. The method involves coupling the bidentate ligands, 3-hydroxypyridin-4-one and 3-hydroxypyran-4-one, with the well-characterised fluorescent probe methoxycoumarin. Fluorescence emission of both probes at 380 nm is readily quenched by Fe(3+). The fluorescence was quenched to a greater extent by Fe(3+) than by Mn(2+), Co(2+), Zn(2+), Ca(2+), Mg(2+), Na(+) and K(+) and to approximately the same extent as Cu(2+). Comparison of the fluorescence-quenching ability by a range of metal ions on CP600 and CP610 and the hexadentate chelator, calcein, under in-vitro conditions, demonstrated advantages of the two novel fluorescent probes with respect to both iron(III) sensitivity and selectivity. Chelation of iron(III) by CP600 and CP610 leads to the formation of a complex with a metal-to-ligand ratio of 1:3. Fluorescence is quenched on formation of such complexes. These probes possess a molecular weight less than 400 and thus they are predicted to permeate biological membranes by passive diffusion, and have potential for reporting intracellular organelle labile iron levels.

Design of clinically useful iron(III)-selective chelators.

Iron overload is a serious clinical condition which can be largely prevented by the use of iron-specific chelating agents. Desferrioxamine-B, the most widely used iron chelator in haematology over the past 30 years, has a major disadvantage of being orally inactive. Consequently, the successful design of an orally active, nontoxic, selective iron chelator has become a much sought after goal. In order to identify an ideal iron chelator for clinical use, a range of specifications must be considered such as metal selectivity and affinity, kinetic stability of the complex, bioavailability and toxicity. A wide range of chelator types bind iron(III) and of these, hexa-, tri-, and bidentate are capable of providing iron(III) with the favoured octahedral environment. In this review, the comparative properties of such ligands are discussed, examples being selected from hydroxamates, aminocarboxylates, hydroxypyridinones, orthosubstituted phenols and triazoles.

Analysis of related factors in complications of stereotactic radiosurgery in intracranial tumors.

OBJECT: To investigate the related factors in complications of stereotactic radiosurgery for intracranial tumors. METHODS: A retrospective review of 146 patients with intracranial tumors treated with stereotactic radiosurgery was conducted. Sixty-five patients received single-dose treatment and the rest received fractionated stereotactic radiosurgery. Ninety-five patients received conventional radiotherapy in the meantime. RESULTS: Follow-up period was 18-54 months. Follow-up rate was 92.5% and 39 patients (26.7%) had different complications. The Cox statistics showed that target volume, target peripheral dose, target maximal dose, and ratio of maximal dose to peripheral dose are related to the complications. Conversely, neither type of tumor disease, gender, radiation schedule with or without conventional radiotherapy, target minimal dose, nor ratio of target peripheral isodose volume to target volume were found to be related to complications. CONCLUSION: Target volume and dose are the major factors causing complications, and the optimization of the therapeutic planning can play a significant role in reducing them.