In vitro and in vivo activity evaluation and mode of action of broxaldine on Toxoplasma gondii.

Toxoplasma gondii (T. gondii) is a highly successful global parasite, infecting about one-third of the world's population and significantly affecting human life and the economy. However, current drugs for toxoplasmosis treatment have considerable side effects, and there is no specific drug to meet current needs. This study aims to evaluate the anti-T. gondii activity of broxaldine (BRO) in vitro and in vivo and explore its mechanism of action. Our results showed that compared to the control group, the invasion rate of tachyzoites in the 4 µg/mL BRO group was only 14.31%, and the proliferation rate of tachyzoites in host cells was only 1.23%. Furthermore, BRO disrupted the lytic cycle of T. gondii and reduced the size and number of cysts in vitro. A mouse model of acute toxoplasmosis reported a 41.5% survival rate after BRO treatment, with reduced parasite load in tissues and blood. The subcellular structure of T. gondii was observed, including disintegration of T. gondii, mitochondrial swelling, increased liposomes, and the presence of autophagic lysosomes. Further investigation revealed enhanced autophagy, increased neutral lipids, and decreased mitochondrial membrane potential in T. gondii treated with BRO. The results also showed a significant decrease in ATP levels. Overall, BRO demonstrates good anti-T. gondii activity in vitro and in vivo; therefore, it has the potential to be used as a lead compound for anti-T. gondii treatment.

Electric properties of the twelve-fold vortex structure in hexagonal manganites.

Hexagonal manganites, as a functional ferroelectric (FE) material, receive considerable attention due to their improper ferroelectricity and topological vortex structures. This family exhibits three low-symmetry states accompanied by distinct vortex domain structures. In addition to the FEP63cmand anti-FE (AFE)P-3c1 states accompanied by dual six-fold vortex structures, there is another FEP3c1 state accompanied by a twelve-fold vortex structure. The responses of FE materials to external stimuli, such as external electric fields, are the core ingredients in the physics of FEs and are significant for technological applications. Under external electric fields, the responses of FE materials are determined by special FE domain structures. The electric properties of the FEP63cmand AFEP-3c1 states are very different. However, the electric properties of the FEP3c1 state, which only stabilizes in Ga-substituted In(Mn, Ga)O3, are unclear. The present work studies the electric properties of the FEP3c1 state. The electric-field-driven transition of the FEP3c1 state is found to follow two sequences, i.e. (1) twelve-foldP3c1 → nine-foldP3c1 +P63cm→ three-foldP63cm, and (2) twelve-foldP3c1 → six-foldP3c1 → three-foldP63cm. The variation of average polarization withEfor the FEP3c1 state with the second transition sequence manifests as an unusual triple-hysteresis loop, different from the usual single-hysteresis loop of FE materials. The results are related to the coexistence of the FE and non-FE domain walls in the FEP3c1 state. Furthermore, it is found that the FEP3c1 state at substitution concentration 0.39 exhibits the highest dielectric response. The results advance our understanding of topological vortex structures in hexagonal manganites.

Development of magnetic molecularly imprinted polymers for selective extraction of Benzoxazolinone-type alkaloids from acanthus plants.

Benzoxazolinone-type alkaloids found in Acanthus ebracteatus and Acanthus ilicifolius Linnaeus possess various beneficial properties, such as antileishmanial, antipyretic, analgesic, antibacterial, and antioxidant effects. In this study, we employed a surface imprinting technique on nanomaterials. We utilized functionalized Fe3O4@SiO2NH2 as a scaffold, with 2-benzoxazolinone and 2H-1,4-benzoxazin-3(4H)-one serving as dual templates, methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a crosslinker, and 2,2-azodiisobutyric nitrile (AIBN) as the initiator. Prior to polymerization, we screened functional monomers using ultraviolet (UV) spectroscopy. The resulting magnetic surface molecular imprinting polymer (Fe3O4@SiO2@MIP) was thoroughly characterized using Fourier transform infrared spectrometry (FT-IR), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). We also conducted assessments of its adsorption isotherms, dynamics, and selective binding capabilities. Our findings indicate that the MIPs exhibited exceptional selective recognition performance. Through meticulous screening and optimization of extraction and separation conditions, we established an LC‒MS/MS method based on magnetic solid-phase extraction technology. The method exhibited a recovery range of 78.80-106.99 % (RSD, 0.46-3.31 %) for 2-benzoxazolinone, with a limit of detection (LOD) and limit of quantification (LOQ) of 2.85 and 9.00 µg L-1, respectively. For 2H-1,4-benzoxazin-3(4H)-one, the method yielded a recovery range of 84.75-103.53 % (RSD, 0.07-5.96 %), with an LOD and LOQ of 3.60 and 12.60 µg L-1, respectively, in real samples. The resulting Fe3O4@SiO2@MIP demonstrated a high capacity for class-specific adsorption.

Development of an Fe3O4 Surface-Grafted Carboxymethyl Chitosan Molecularly Imprinted Polymer for Specific Recognition and Sustained Release of Salidroside.

The choice of carrier material is critical in the study of natural drug release preparations and glycosylated magnetic molecularly imprinted materials. The stiffness and softness of the carrier material affect the efficiency of drug release and the specificity of recognition. The dual adjustable aperture-ligand in molecularly imprinted polymers (MIPs) provides the possibility of individualized design for sustained release studies. In this study, a combination of paramagnetic Fe3O4 and carboxymethyl chitosan (CC) was used to enhance the imprinting effect and improve drug delivery. A combination of tetrahydrofuran and ethylene glycol was used as a binary porogen to prepare MIP-doped Fe3O4-grafted CC (SMCMIP). Salidroside serves as the template, methacrylic acid acts as the functional monomer, and ethylene glycol dimethacrylate (EGDMA) serves as the crosslinker. Scanning and transmission electron microscopy were used to observe the micromorphology of the microspheres. The structural and morphological parameters of the SMCMIP composites were measured, including the surface area and pore diameter distribution. In an in vitro study, we found that the SMCMIP composite had a sustained release property of 50% after 6 h of release time in comparison to the control SMCNIP. The total amounts of SMCMIP released at 25 °C and 37 °C were 77% and 86%, respectively. In vitro results showed that the release of SMCMIP followed Fickian kinetics, meaning that the rate of release is dependent on the concentration gradient, with diffusion coefficients ranging from 3.07 × 10-2 cm2/s to 5.66 × 10-3 cm2/s. The results of cytotoxicity experiments showed that the SMCMIP composite did not have any harmful effects on cell growth. The survival rates of intestinal epithelial cells (IPEC-J2) were found to be above 98%. By using the SMCMIP composite, drugs may be delivered in a sustained manner, potentially leading to improved therapeutic outcomes and reduced side effects.

Risk factors for recurrent pressure ulcers after reconstructive surgery: A retrospective study in a single medical centre.

Recurrence of pressure ulcers following reconstructive surgery occurs frequently, causing a significant burden on the patient and the public health care system. We assessed risk factors for the recurrence of pressure ulcers based on the experience of a single surgeon at our medical centre. We retrospectively analysed patients admitted to our medical centre with stage III and IV pressure ulcers who underwent reconstructive surgery. The hospital database was searched for patients diagnosed with pressure ulcers who underwent reconstructive surgery. Patient characteristics analysed included age, sex, cause and location of defect, comorbidities, lesion size, wound reconstruction methods, operation time, debridement times, duration of hospital stay, and wound complications. Recurrence and mortality rates were retrospectively examined. One hundred and eighty-nine patients were enrolled, and 166 patients with 176 pressure ulcers met our inclusion criteria. All 14 recurrences (7.95%) were followed for at least 1 year. Logistic regression analysis indicated that recurrence was associated with albumin levels (P = 0.001) and wound size (P = 0.043); however, no association was found for body mass index, bacterial profile, comorbidities, localisation, previous surgery, operation time, or time to admission for reconstruction. In conclusion, higher albumin levels were associated with lower recurrence rates in patients who underwent reconstructive surgery.

Molecularly imprinted polymer-specific solid-phase extraction for the determination of 4-hydroxy-2(3H)benzoxazolone isolated from Acanthus ilicifolius Linnaeus using high-performance liquid chromatography-tandem mass spectrometry.

The minor constituent found in Acanthus ilicifolius Linnaeus, 4-hydroxy-2 (3H) benzoxazolone alkaloid (HBOA), has a range of versatile applications. Herein, a quick and straightforward method for extracting HBOA from A. ilicifolius Linnaeus was proposed. HBOA was used as a template, whereas methacrylic acid, ethylene glycol dimethacrylate, and acetonitrile were used as functional monomers, cross-linkers, and porogens, respectively. Molecularly imprinted polymers (MIPs) were synthesized by precipitation polymerization, and their adsorption isotherms, dynamics, and selective binding ability were characterized and analyzed. The results showed that the adsorption amount of the template was 90.18 mg/g. The MIPs were used as solid-phase extraction fillers and actual sample extraction columns, with a linear range of 0-100 µg/L, average recovery of 78.50-101.12%, and a relative standard deviation of 1.20-3.26%. The HBOA concentrations in the roots, stems, and leaves were 1,226, 557, and 205 µg/g, respectively. In addition, MIP-SPE was successfully used in isolating and purifying HBOA from different parts of A. ilicifolius Linnaeus, indicating its effectiveness in extracting and determining HBOA in other herbs.

Restricted use of copy and paste in electronic health records potentially improves healthcare quality.

ABSTRACT: The copy-and-paste feature is commonly used for clinical documentation, and a policy is needed to reduce overdocumentation. We aimed to determine if the restricted use of copy and paste by doctors could improve inpatient healthcare quality.Clinical documentation in an inpatient dataset compiled from 2016 to 2018 was used. Copied-and-pasted text was detected in word templates using natural language programming with a threshold of 70%. The prevalence of copying and pasting after the policy introduction was accessed by segmented regression for trend analysis. The rate of readmission for the same disease within 14 days was assessed to evaluate inpatient healthcare quality, and the completion of discharge summary notes within 3 days was assessed to determine the timeliness of note completion. The relationships between these factors were used cross-correlation to detect lag effect. Poisson regression was performed to identify the relative effect of the copy and paste restriction policy on the 14-day readmission rate or the discharge note completion rate within 3 days.The prevalence of copying and pasting initially decreased, then increased, and then flatly decreased. The cross-correlation results showed a significant correlation between the prevalence of copied-and-pasted text and the 14-day readmission rate (P < .001) and a relative risk of 1.105 (P < .005), with a one-month lag. The discharge note completion rate initially decreased and not affected long term after restriction policy.Appropriate policies to restrict the use of copying and pasting can lead to improvements in inpatient healthcare quality. Prospective research with cost analysis is needed.

Improvement the Healthcare Quality of Emergency Department after the Cloud-Based System of Medical Information-Exchange Implementation.

BACKGROUND: The National Health Insurance has been implemented in Taiwan since 1995. The government established a medical information-exchange system to reduce duplicate medications and examinations, which have inhibited healthcare expenditures. The potential benefit of medical information exchange about healthcare quality in emergency departments (ED) was worthy of evaluating; Methods: The inquiry rate of cloud data for patients' information in Taiwanese National Health Insurance Administration was defined as a factor, and the healthcare quality included the ratio of staying more than 48 h in the ED and the hospitalization rate within 8 h from ED by triage levels of 1, 2, and 3 in different levels of hospitals from 2013 to 2019. Poisson regression analysis was used to quantify time trends of the query rate of the MediCloud system, the rate of staying more than 48 h in ED, admission rate within 8 h in ED, and the effect of healthcare quality in ED after MediCloud system implementation; Results: The health information exchange decreased the rate of staying over 48 h in the ED of medical centers. It also improved the early hospitalization of urgent ED patients in regional hospitals; Conclusions: Through medical information exchange to understand patients' current conditions, we can reduce crowding in the ED of medical centers and facilitate rapid hospitalization of urgent patients in regional hospitals. According to these findings, the government should establish medical information exchange to improve the healthcare quality of ED.

Association between Electronic Medical Records and Healthcare Quality.

The implementation of electronic medical records (EMRs) has generally been thought to improve medical efficiency and safety, but consistent evidence of improved healthcare quality due to EMRs in population-based studies is lacking. We assessed the relationship between the degree of EMR adoption and patient outcomes.We performed an observational study using discharge data from Tri-service General Hospital from 2013 to 2018. The levels of EMR utilization were divided into no EMRs, partial EMRs and full EMRs. The primary healthcare quality indicators were inpatient mortality, readmission within 14 days, and 48-hour postoperative mortality. We performed a Cox proportional hazards regression analysis to evaluate the relationship between the EMR utilization level and healthcare quality.In total, 262,569 patients were included in this study. Compared with no EMRs, full EMR implementation led to lower inpatient mortality [adjusted hazard ratio (HR) 0.947, 95% confidence interval (CI): 0.897-0.999, P = ..049] and a lower risk of readmission within 14 days (adjusted HR 0.627, 95% CI: 0.577-0.681, P < .001). Full EMR implementation was associated was a lower risk of 48-hour postoperative mortality (adjusted HR 0.372, 95% CI: 0.208-0.665, P = .001) than no EMRs. Partial EMR implementation was associated with a higher risk of readmission within 14 days than no EMRs (HR 1.387, 95% CI: 1.298-1.485, P < .001).Full EMR adoption improves healthcare quality in medical institutions treating severely ill patients. A prospective study is needed to confirm this finding.

Magnetic molecularly imprinted specific solid-phase extraction for determination of dihydroquercetin from Larix griffithiana using HPLC.

The naturally occurring quercetin flavonoid, dihydroquercetin, is widely distributed in plant tissues and has a variety of biological activities. Herein, a magnetic molecularly imprinted solid-phase extraction was tailor made for selective determination of dihydroquercetin in Larix griffithiana using high-performance liquid chromatography. Amino-functionalized core-shell magnetic nanoparticles were prepared and characterized using scanning electron microscopy, transmission electron microscopy, vibrating sample magnetometry, and infrared spectroscopy. The polymer had an average diameter of 250 ± 2.56 nm and exhibited good stability and adsorption for template molecule, which is enriched by hydrogen bonding interaction. Multiple factors for extraction, including loading, washing, elution solvents, and extraction time, were optimized. The limit of detection was 1.23 µg/g. The precision determined at various concentration of dihydroquercetin was less than 4% and the mean recovery was between 74.64 and 101.80%. It has therefore been shown that this protocol can be used as an alternative extraction to quantify dihydroquercetin in L. griffithiana and purify quercetin flavonoid from other complex matrices.

Information System Implementation Optimizes Medical Coding.

Diagnosis Related Groups (DRGs) and the Tenth Revision of the International Statistical Classification of Disease and Related Health Problems (ICD-10) were implemented to Taiwan in 2010 and 2016 respectively. New rules related to the medical costs reimbursement were great challenges facing medical institutions. One of the medical centers in north Taiwan introduced an ICD e-dictionary, DRGs cloud computing system, and integrated them into the hospital information system. Further, developing a medical coder specialization work model optimized the workflow, coding quality, and efficiency, which defeated the adverse effects of DRGs and ICD-10 implementation successfully.

Magnetic molecularly imprinted polymers doped with graphene oxide for the selective recognition and extraction of four flavonoids from Rhododendron species.

Herein, a novel magnetic molecularly imprinted polymer doped with reticular graphene oxide (Fe3O4@SiO2-GO@MIPs) was synthesized for the selective recognition and extraction of 4 flavonoids (farrerol, taxifolin, kaempferol, and hyperin) from Rhododendrons species. The Fe3O4@SiO2-GO@MIPs with lamellar membranes showed outstanding adsorption capacity. The 3D cavities complementary to the "shape" of farrerol were "imprinted" on the polymer framework after removal of farrerol template. Competitive binding assays showed that the polymer has a higher selectivity for farrerol compared with other analogues and references. The Fe3O4@SiO2-GO@MIPs as solid-phase extraction adsorbents combined with liquid chromatography-tandem quadrupole mass spectrometry (LC-MS/MS) was used for selective determination of four flavonoids from Rhododendrons samples. The limits of detection (LOD) were 0.07, 0.08, 0.06, and 0.08 µg L-1 for farrerol, taxifolin, kaempferol, and hyperin, respectively. These results suggest that the prepared Fe3O4@SiO2-GO@MIPs have the potential applicability to extract, purify, and enrich flavonoids from herbs, supplements, and other natural products.

Extraction and identification of matrine-type alkaloids from Sophora moorcroftiana using double-templated molecularly imprinted polymers with HPLC-MS/MS.

Double-templated molecularly imprinted polymers with specific recognition of three matrine-type alkaloids were prepared using matrine and oxymatrine as the template molecules. An approach based on double-templated molecularly imprinted solid-phase extraction coupled with high-performance liquid chromatography and tandem mass spectrometry was then developed to extract and purify matrine, oxymatrine, and sophocarpine from Sophora moorcroftiana in the Tibetan plateau herbs. The polymers were characterized by Fourier-transform infrared spectroscopy and scanning electron microscopy. Their adsorption characteristics were evaluated using adsorption kinetics, isotherms, selectivity, and recycling experiments. This polymer exhibited excellent molecular recognition ability and good selectivity. The obtained polymers as adsorbent was further used for the determination of three matrine-type alkaloids coupled to high-performance liquid chromatography with tandem mass spectrometry, the recoveries of three matrines spiked at three concentration levels in samples were 73.25-98.42% (n = 5) with a relative standard deviation less than 6.82%. The limits of detection for the method were 9.23-15.42 µg/kg (S/N = 3). This proposed method was assessed to be an effective method for simultaneous extraction, isolation, and identification of matrine, oxymatrine, and sophocarpine from Sophora moorcroftiana.

Pulmonary exposure to metal fume particulate matter cause sleep disturbances in shipyard welders.

Sleep disorders may pose a risk to workers in the workplace. We aimed to investigate the associations between metal fume fine particulate matter (PM2.5) and sleep quality in workers. We assessed the effects of personal exposure to metal fume PM2.5 on lung functions, urinary biomarkers, and sleep quality in shipyard welding workers. In total, 96 welding workers and 54 office workers were recruited in the present study; office workers were exposed to 82.1 ± 94.1 µg/m3 PM2.5 and welding workers were exposed to 2166.5 ± 3149.1 µg/m3. Welding workers had significantly lower levels of FEV25-75 than office workers (p < 0.05). An increase in 1 µg/m3 PM2.5 was associated with a decrease of 0.003 ng/mL in urinary serotonin (95% CI = -0.007-0.000, p < 0.05) in all workers and with a decrease of 0.001 ng/mL in serotonin (95% CI = -0.004-0.002, p < 0.05) in welding workers, but these were not observed in office workers. There was no significant association of PM2.5 with urinary cortisol observed in any workers. Urinary serotonin was associated with urinary Cu, Mn, Co, Ni, Cd, and Pb. Urinary cortisol was associated with Cu, Mn, Co, Ni, Cd, and Pb. Sixteen subjects were randomly selected from each of the office and welding workers for personal monitoring of sleep quality using a wearable device. We observed that welding workers had greater awake times than did office workers (p < 0.05). Our study observed that exposure to heavy metals in metal fume PM2.5 may disrupt sleep quality in welding workers.

Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism and Susceptibility to Osteoarthritis of the Knee: A Case-Control Study and Meta-Analysis.

BACKGROUND: Studies of angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and the risks of knee osteoarthritis (OA) have yielded conflicting results. OBJECTIVE: To determine the association between ACE I/D and knee OA, we conducted a combined case-control study and meta-analysis. METHODS: For the case-control study, 447 knee OA cases and 423 healthy controls were recruited between March 2010 and July 2011. Knee OA cases were defined using the Kellgren-Lawrence grading system, and the ACE I/D genotype was determined using a standard polymerase chain reaction. The association between ACE I/D and knee OA was detected using allele, genotype, dominant, and recessive models. For the meta-analysis, PubMed and Embase databases were systematically searched for prospective observational studies published up until August 2015. Studies of ACE I/D and knee OA with sufficient data were selected. Pooled results were expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for the D versus I allele with regard to knee OA risk. RESULTS: We found no significant association between the D allele and knee OA [OR: 1.09 (95% CI: 0.76-1.89)] in the present case-control study, and the results of other genetic models were also nonsignificant. Five current studies were included, and there were a total of six study populations after including our case-control study (1165 cases and 1029 controls). In the meta-analysis, the allele model also yielded nonsignificant results [OR: 1.37 (95% CI: 0.95-1.99)] and a high heterogeneity (I2: 87.2%). CONCLUSIONS: The association between ACE I/D and knee OA tended to yield negative results. High heterogeneity suggests a complex, multifactorial mechanism, and an epistasis analysis of ACE I/D and knee OA should therefore be conducted.