11-Azaartemisinin derivatives bearing halogenated aromatic moieties: Potent anticancer agents with high tumor selectivity.

While artemisinin and its derivatives, including 11-azaartemisinin-based compounds, have shown promising anticancer activity, the integration of halogens into aromatic structures can amplify drug potency, metabolic stability, and selectivity. Herein, we present the synthesis of new novel 11-azaartemisinin derivatives bearing halogenated aromatic moieties connected via 1,2,3-triazole bridges and evaluate their anticancer activities against three human tumor cell lines: epidermoid carcinoma (KB), hepatocellular carcinoma (HepG2), and human lung adenocarcinoma (A549). Among the synthesized compounds, six of them (8c-h) displayed good to excellent antiproliferative activity in the low micromolar range across all three human cancer cell lines. In general, the m-bromide (8c) and m-iodide (8d) compounds exhibited superior anticancer activities compared to their o- and p-analogs, as well as the m-chloride and m-fluoride compounds. The most promising m-Br compound (8c) displayed 50 % inhibition of KB, HepG2, and A549 cell growth at concentrations of 7.7, 42.5, and 15.5 µM, respectively. Notably, the m-Br compound (8c) exhibited approximately 32-, 6-, and 16-fold lower activity in normal cells (Hek293) compared to KB, HepG2, and A549 tumor cells, respectively, indicating a significant tumor-selectivity.

Ecotoxicological assessment of sanitary sewer overflows and rainfall dynamics offers insights into conditions for potential adverse ecological outcomes.

Sewer overflows are an environmental concern due to their potential to introduce contaminants that can adversely affect downstream aquatic ecosystems. As these overflows can occur during rainfall events, the influence of rainwater ingress from inflow and infiltration on raw untreated wastewater (influent) within the sewer is a critical factor influencing the dilution and toxicity of the contaminants. The Vineyard sewer carrier in the greater city of Sydney, Australia, was selected for an ecotoxicological investigation of a sanitary (separate from stormwater) sewerage system and a wet-weather overflow (WWO). Three influent samples were collected representing dry-weather (DW), intermediate wet-weather (IWW) and wet-weather (WW). In addition, a receiving water sample was also collected downstream in Vineyard Creek (WW-DS) coinciding with a WWO. We employed direct toxicity assessment (DTA) and toxicity identification evaluation (TIE) approaches to gain comprehensive insights into the nature and magnitude of the impact on influent from rainwater ingress into the sewer. Three standard ecotoxicological model species, a microalga, Chlorella vulgaris, the water flea, Ceriodaphnia dubia and the midge larva, Chironomus tepperi were used for both acute and chronic tests. The study revealed variable toxicity responses, with the sample of influent collected in wet-weather displaying lower toxicity compared to the dry-weather sample of influent. Ammonia, and metals, were identified in dry weather as contributors to the observed toxicity, however, this risk was alleviated through rainwater ingress in wet-weather with further dilution within the receiving water. Based on toxicity data, dilutions of influent to minimise effects on C. vulgaris and C. dubia ranged from 1 in 12 in DW to 1 in 2.8 in WW, and further diminished in the receiving water to 1 in 1.8. The successful application of ecotoxicological approaches enabled the assessment of cumulative effects of contaminants in influent, offering valuable insights into the sanitary sewer system under rainwater ingress.

Determination of Site-Specific Phosphorylation Occupancy Using Targeted Mass Spectrometry Reveals the Regulation of Human Apical Bile Acid Transporter, ASBT.

The human apical bile acid transporter (hASBT, SLC10A2) reabsorbs bile acids in the distal ileum, facilitating their recycling to the liver and resecretion. Its activity has been implicated in various disease states, including Crohn's disease, hypercholesterolemia, cholestasis, and type-2 diabetes. Post-translational modifications such as N-glycosylation, ubiquitination, and S-acylation regulate ASBT function by controlling its translocation and stability. However, the precise role of phosphorylation and its relationship with activity remains unknown. Here, we employed parallel reaction monitoring targeted mass spectrometry to investigate ASBT phosphorylation in the presence of various kinase inhibitors and activators. Our study ascertains phosphorylation at multiple sites (Thr330, Ser334, and Ser335), with Ser335 being the predominant phosphosite. We further demonstrate the critical involvement of PKC in regulating ASBT activity by phosphorylation at Ser335. Importantly, we establish a proportional relationship between the phosphorylation level of Ser335 and ASBT bile acid uptake activity. Collectively, our findings shed light on the molecular mechanisms underlying phosphorylation-mediated regulation of ASBT.

Biodegradation of DDT using multi-species mixtures: From genome-mining prediction to practical assessment.

DDT (dichlorodiphenyltrichloroethane) is a commonly used insecticide that is recalcitrant and highly stable in the environment. Currently, DDT residue contamination, especially in agricultural soil, is still a concern in many countries, threatening human health and the environment. Among the approaches to resolve such an issue, novel biodegradation-based methods are now preferred to physicochemical methods, due to the sustainability and the effectiveness of the former. In this study, we explored the possibility of building mixed microbial cultures that can offer improved DDT-degrading efficiencies and be more environmentally transilient, based on genome annotation using the KEGG database and prediction of interactions between single strains using the obtained metabolic maps. We then proposed 10 potential DDT-degrading mixed cultures of different strain combinations and evaluated their DDT degradation performances in liquid, semi-solid and solid media. The results demonstrated the superiority of the mixtures over the single strains in terms of degrading DDT, particularly in a semi-solid medium, with up to 40-50% more efficiency. Not only did the mixed cultures degrade DDT more efficiently, but they also adapted to broader spectra of environmental conditions. The three best DDT-degrading and transilient mixtures were selected, and it turned out that their component strains seemed to have more metabolic interactions than those in the other mixtures. Thus, our study demonstrates the effectiveness of exploiting genome-mining techniques and the use of constructed mixed cultures in improving biodegradation.

Epigenetic tuning of PD-1 expression improves exhausted T cell function and viral control.

PD-1 is a key negative regulator of CD8+ T cell activation and is highly expressed by exhausted T cells in cancer and chronic viral infection. Although PD-1 blockade can improve viral and tumor control, physiological PD-1 expression prevents immunopathology and improves memory formation. The mechanisms driving high PD-1 expression in exhaustion are not well understood and could be critical to disentangling its beneficial and detrimental effects. Here, we functionally interrogated the epigenetic regulation of PD-1 using a mouse model with deletion of an exhaustion-specific PD-1 enhancer. Enhancer deletion exclusively alters PD-1 expression in CD8+ T cells in chronic infection, creating a 'sweet spot' of intermediate expression where T cell function is optimized compared to wild-type and Pdcd1-knockout cells. This permits improved control of chronic infection without additional immunopathology. Together, these results demonstrate that tuning PD-1 via epigenetic editing can reduce CD8+ T cell dysfunction while avoiding excess immunopathology.

Age-associated contraction of tumor-specific T cells impairs antitumor immunity.

Progressive decline of the adaptive immune system with increasing age coincides with a sharp increase in cancer incidence. In this study, we set out to understand whether deficits in antitumor immunity with advanced age promote tumor progression and/or drive resistance to immunotherapy. We found that multiple syngeneic cancers grew more rapidly in aged versus young adult mice, driven by dysfunctional CD8+ T-cell responses. By systematically mapping immune cell profiles within tumors, we identified loss of tumor antigen-specific CD8+ T cells as a primary feature accelerating the growth of tumors in aged mice and driving resistance to immunotherapy. When antigen-specific T cells from young adult mice were administered to aged mice, tumor outgrowth was delayed and the aged animals became sensitive to PD-1 blockade. These studies reveal how age-associated CD8+ T-cell dysfunction may license tumorigenesis in elderly patients and have important implications for the use of aged mice as pre-clinical models of aging and cancer.

Manganese catalysed dehydrocoupling of silanes and siloxanes with ammonia to prepare oligosilazanes and polysiloxazanes.

The halogen-free synthesis of oligosilazanes has been observed upon dehydrocoupling silanes with ammonia at 25 °C using [(2,6-iPr2PhBDI)Mn(µ-H)]2. Extending this methodology to polymethylhydrosiloxanes afforded thermally robust polysiloxazane solids, and the dehydrocoupling of 1,3,5,7-tetramethylcyclotetrasiloxane with ammonia afforded a polysiloxazane having a weight-average molecular weight of 4300 g mol-1. A representative oligosilazane has been applied to a copper surface and found to afford a 20 µm thick coating that resists corrosion after 24 h under water. Addition of ammonia to [(2,6-iPr2PhBDI)Mn(µ-H)]2 allowed for characterization of the catalyst resting state, [(2,6-iPr2PhBDI)Mn(µ-NH2)]2, which has been found to mediate Si-N dehydrocoupling.

Factors Associated With Mosaicism in Human Embryos: A Retrospective Study.

Objective This study aims to identify factors associated with mosaicism in human embryos at Hung Vuong Hospital. Methods We performed a retrospective analysis of data from 2018 to 2022, approved by the Hung Vuong Hospital Ethics Committee (CS/HV/23/15). We analyzed variables such as demographic characteristics, clinical measurements, and in-vitro fertilization (IVF) cycle outcomes to investigate their relationship with embryo mosaicism. Results A total of 73 couples undergoing IVF with preimplantation genetic testing (PGT) were included in the analysis. Among 308 embryos, 98 (31.8%) were mosaic, 124 (40.3%) were euploid, and 86 (27.9%) were aneuploid. Univariable analysis revealed that female age was significantly associated with increased odds of mosaicism (odd ratio (OR) = 1.11, 95% confidence interval (CI): 1.04 - 1.19, p = 0.003). Male age demonstrated a marginal association with mosaicism (OR = 1.05, 95% CI: 1.00 - 1.11, p = 0.07). Other factors, including body mass index (BMI), anti-Mullerian hormone (AMH) levels, blood types, and sperm quality, were not significantly associated with mosaicism. In the multivariable analysis, controlling for both female and male age, female age showed a trend toward significance (OR = 1.12, 95% CI: 1.02 - 1.23, p = 0.02), while male age showed no significant effect (OR = 0.99, 95% CI: 0.92 - 1.06, p = 0.75). Conclusions The findings suggest that female age is a critical factor influencing the occurrence of mosaicism in embryos. Further research is needed to fully understand the mechanisms underlying mosaicism in human embryos.

Associations of COVID-19-related fear with kidney disease quality of life and its subscales among hemodialysis patients as modified by health literacy: a multi-hospital survey.

Background: Receiving hemodialysis treatment makes end-stage renal disease (ESRD) patients highly vulnerable amidst the COVID-19 pandemic. Hence, their kidney disease quality of life (KDQOL) is affected. We aimed to examine the association between fear of COVID-19 (FCoV-19) and KDQOL, and the effect modification of Health literacy (HL) on this association. Material and Methods: A survey was conducted at 8 hospitals from July 2020 to March 2021 on 972 patients. Data collection includes socio-demographic factors, clinical parameters, HL, digital healthy diet literacy (DDL), hemodialysis diet knowledge (HDK), FCoV-19, suspected COVID-19 symptoms (S-COVID-19-S), and KDQOL. Results: Higher HL scores B = 0.13 (95% CI = 0.06-0.21, p = 0.001) and HDK scores B = 0.58 (95% CI = 0.31-0.85, p = 0.001) were associated with higher KDQOL scores. Whereas, S-COVID-19-S B = -6.12 (95% CI = -7.66 to - 4.58, p = 0.001) and FCoV-19 B = -0.91 (95% CI = -1.03 to - 0.80, p = 0.001) were associated with lower KDQOL scores. Notably, higher HL scores significantly attenuate the negative impact of FCoV-19 on overall KDQOL and the kidney disease component summary. Conclusions: In hemodialysis patients, FCoV-19 and S-COVID-19-S were associated with a lower KDQOL. Health literacy significantly mitigates the negative impact of FCoV-19 on KDQOL. Strategic public health interventions to improve HL are suggested to protect patient's KDQOL during the pandemic.

Outcomes After Implantation of a Trifocal Toric Intraocular Lens Using Intraoperative Aberrometry, Digital Image Tracking, and Femtosecond Laser.

Purpose: To evaluate the refractive and visual acuity outcomes when using trifocal toric intraocular lenses (IOLs), femtosecond laser assisted cataract surgery (FLACS), swept-source optical coherence tomography (SS-OCT) biometry, digital image tracking (DT) and intraoperative aberrometry (IA). Methods: This prospective, single-arm, observational study of refractive and visual outcomes included 40 eyes of 34 subjects. Preoperative biometry was performed with the Argos, FLACS and digital marking with LenSx, and IA and DT with ORA. Eyes were implanted with the Clareon PanOptix toric IOL. Study outcome measures included absolute prediction error, residual refractive astigmatism, and monocular uncorrected and distance corrected visual acuity at distance (UDVA, CDVA), intermediate (UIVA, DCIVA; 60cm), and near (UNVA, DCNVA; 40cm). Results: Mean absolute prediction error (spherical equivalent) was 0.43 ± 0.36 D, and the percentage of eyes with absolute prediction error ≤ 0.5 D was 72.5% (29/40 eyes). Mean residual astigmatism was 0.36 ± 0.65 D, and the percentage of eyes with residual astigmatism ≤ 0.5 D was 80% (32/40 eyes). Monocular UDVA, UIVA, and UNVA was 20/25 or better in 75%, 64%, and 87% of eyes respectively. Monocular CDVA, DCIVA, and DCNVA was 20/25 or better in 95%, 64%, and 87% of eyes respectively. Conclusion: The results of this study suggest that trifocal toric implantation with SS-OCT, FLACS, DT, and IA can provide excellent refractive and visual outcomes.

When the natural lens inside the eye becomes opaque (develops a cataract), it can be surgically replaced with a clear artificial intraocular lens (IOL). There are many different technologies available to the cataract surgeon in order to maximize postoperative visual outcomes with implanted IOLs. These include, modern biometers, femtosecond laser-assisted cataract surgery (FLACS), trifocal IOLs, toric IOLs, image-guided digital tracking (DT), and intraoperative aberrometry (IA). Individually, good refractive outcomes have been reported with these technologies. However, there is minimal data on outcomes using a combination of all of them. The purpose of this study was to determine the refractive and visual acuity outcomes when using modern biometers, toric IOLs, FLACS, DT, IA, and trifocal IOLs. The results of this study suggest that trifocal toric implantation with modern biometry, FLACS, DT, and IA can provide excellent refractive and visual outcomes.

Global protein turnover quantification in Escherichia coli reveals cytoplasmic recycling under nitrogen limitation.

Protein turnover is critical for proteostasis, but turnover quantification is challenging, and even in well-studied E. coli, proteome-wide measurements remain scarce. Here, we quantify the turnover rates of ~3200 E. coli proteins under 13 conditions by combining heavy isotope labeling with complement reporter ion quantification and find that cytoplasmic proteins are recycled when nitrogen is limited. We use knockout experiments to assign substrates to the known cytoplasmic ATP-dependent proteases. Surprisingly, none of these proteases are responsible for the observed cytoplasmic protein degradation in nitrogen limitation, suggesting that a major proteolysis pathway in E. coli remains to be discovered. Lastly, we show that protein degradation rates are generally independent of cell division rates. Thus, we present broadly applicable technology for protein turnover measurements and provide a rich resource for protein half-lives and protease substrates in E. coli, complementary to genomics data, that will allow researchers to study the control of proteostasis.

Clinical Efficacy and Safety of Long-Term Treatment of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate for Chronic Hepatitis B in Vietnam.

INTRODUCTION: Hepatitis B virus (HBV) infection is a contagious condition posing a major public health risk in various nations, including Vietnam. In 2019, the Ministry of Health introduced tenofovir alafenamide (TAF) to treat patients with chronic HBV infection and reduce the long-term toxicity of tenofovir disoproxil fumarate (TDF). This study aimed to assess the effectiveness and safety of these 2 medications in individuals with hepatitis B e antigen (HBeAg)-positive chronic HBV. METHODS: This retrospective cohort study included data collected from the medical records of patients with chronic HBV who visited the Liver Clinic at University Medical Center Ho Chi Minh City between 2018 and 2020. RESULTS: After 2 years of treatment, the proportion of HBeAg loss in the TAF group was twice that of the TDF group (22.4% vs 11.2%), indicating a statistically significant difference in the probability of HBeAg loss (adjusted hazard ratio = 2.22; 95% confidence interval [CI] 1.43-3.42; P < 0.01). In addition, there was a statistically significant difference in the rate and ability of antiviral response between patients treated with TAF and TDF (65% vs 54.5%, respectively; adjusted hazard ratio = 1.34; 95% CI 1.08-1.69; P < 0.01). A total of 93.9% of patients achieved the goal of restoring alanine aminotransferase to normal, a higher percentage compared with the 81.2% in the TDF group, and the likelihood of achieving normal alanine aminotransferase levels with TAF was greater compared with those on TDF (adjusted hazard ratio = 1.67; 95% CI 1.38-2.01; P < 0.01). Moreover, there was a statistically significant difference in the variation in renal function between the TAF and TDF groups. Serum creatinine levels in the TAF group increased less than those in the TDF group by 0.03 mg/dL every 6 months (95% CI -0.04 to -0.01, P < 0.01), and the estimated glomerular filtration rate in the TAF group was higher than that in the TDF group every 6 months by 2.78 mL/min/1.73 m 2 (95% CI 0.98-4.57, P < 0.01). However, there was no statistically significant difference in the likelihood of HBeAg seroconversion between patients with chronic hepatitis B treated with TAF or TDF (adjusted hazard ratio = 1.79; 95% CI 0.91-3.53; P = 0.09), nor in the risk of adverse events between the 2 groups (adjusted odds ratio = 1.34; 95% CI 0.88-2.05; P = 0.17). In addition, although the HBsAg concentration in the TAF group was lower than in the TDF group by an average of 0.05 log 10 IU/mL every 6 months (95% CI -0.15 to 0.05), this difference also did not reach statistical significance ( P = 0.35). DISCUSSION: TAF has been demonstrated to achieve some therapeutic efficacy goals and reduce nephrotoxicity better than TDF. However, no differences were found in seroconversion or adverse events between the patient groups.

Live birth after vitrification of oocytes from capacitation in vitro maturation.

Female fertility preservation is a rapidly growing field in medicine. Oocyte cryopreservation and assisted reproductive technique with vitrified-warmed oocytes have been successful with in vivo matured oocytes after conventional ovarian stimulation protocols. The use of in vitro matured oocytes after vitrification and warming has been limited. Capacitation in vitro maturation (CAPA-IVM) represents the latest refinement of IVM protocols and provides in vitro matured oocytes with improved competence. This case report describes the first successful live birth following oocyte vitrification from a CAPA-IVM cycle. This milestone achievement holds a significant promise to expand fertility preservation options and improve accessibility for women wishing to cryopreserve their eggs for future use.

Law enforcement-led, pre-arrest diversion-to-treatment may reduce crime recidivism, incarceration, and overdose deaths: Program evaluation outcomes.

INTRODUCTION: Substance use disorder (SUD), overdose, and drug use-related crime continue to increase in the U.S. Pre-arrest diversion-to-treatment programs may decrease crime recidivism and overdose deaths. We assessed the impact of a community-wide diversion-to-treatment initiative on crime, incarceration, and overdose. METHODS: This article reports on the prospective evaluation of a law enforcement-led, pre-arrest diversion-to-treatment program on crime, incarceration, and overdose deaths compared between participants who did not engage (non-engaged; n = 103), engaged but did not complete (non-completers; n = 60) and completed (completers; n = 100) the program. Participants included 263 adults apprehended by police officers for low-level, drug use-related crimes between September 1, 2017 and August 31, 2020. The program offered eligible persons participation in a six-month program consisting of a clinical assessment, referral to addiction treatment services based on each individual's needs, connection to recovery peer support, and treatment engagement monitoring. Completers had their initial criminal charges 'voided,' while non-engaged and non-Completer participants had their original charges filed with local prosecutors. The project collected participant-level data on arrests and incarceration within 12 months before and 12 months after program enrollment and data on fatal overdose within 12 months after program enrollment. Logistic regression predicted outcomes using baseline demographics (sex, age, race, housing status) and pre-index crime arrest and incarceration indices as covariates. RESULTS: After accounting for baseline demographics and pre-enrollment arrest/incarceration history, logistic regression models found that the non-engaged and the non-Completer groups were more likely than completers to be arrested (odds ratios [ORs]: 3.9 [95 % CI, 2.0-7.7] and 3.6 [95 % CI, 1.7-7.5], respectively) and incarcerated (ORs: 10.3 [95 % CI, 5.0-20.8] and 21.0 [95 % CI, 7.9-55.7], respectively) during the 12-month follow-up. Rates of overdose deaths during the 12-month follow-up were greatest in non-engaged (6/103, 5.8 %) and non-Completer (2/60, 3.3 %) groups; completers had the lowest rate (2/100, 2.0 %), with all deaths occurring after completion of the six-month treatment/monitoring program. CONCLUSIONS: Collaboration between law enforcement, clinicians, researchers, and the broader community to divert adults who commit a low-level, drug use-related crime from criminal prosecution to addiction treatment may effectively reduce crime recidivism, incarceration, and overdose deaths.

Evaluation of a prototype metal artifact reduction algorithm for cone beam CT in patients undergoing radioembolization.

Metal artifacts notoriously pose significant challenge in computed tomography (CT), leading to inaccuracies in image formation and interpretation. Artifact reduction tools have been designed to improve cone beam computed tomography (CBCT) image quality by reducing artifacts caused by certain high-density materials. Metal artifact reduction (MAR) tools are specific algorithms that are applied during image reconstruction to minimize or eliminate artifacts degrading CBCT images. The purpose of the study is to evaluate the effect of a MAR algorithm on image quality in CBCT performed for evaluating patients before transarterial radioembolization (TARE). We retrospectively included 40 consecutive patients (aged 65 ± 13 years; 23 males) who underwent 45 CBCT examinations (Allura FD 20, XperCT Roll protocol, Philips Healthcare, Best, The Netherlands) in the setting of evaluation for TARE between January 2017 and December 2018. Artifacts caused by coils, catheters, and surgical clips were scored subjectively by four readers on a 5-point scale (1 = artifacts affecting diagnostic information to 5 = no artifacts) using a side-by-side display of uncorrected and MAR-corrected images. In addition, readers scored tumor visibility and vessel discrimination. MAR-corrected images were assigned higher scores, indicating better image quality. The differences between the measurements with and without MAR were most impressive for coils with a mean improvement of 1.6 points (95%CI [1.5 1.8]) on the 5-point likert scale, followed by catheters 1.4 points (95%CI [1.3 1.5]) and clips 0.7 points (95%CI [0.3 1.1]). Improvements for other artifact sources were consistent but relatively small (below 0.25 points on average). Interrater agreement was good to perfect (Kendall's W coefficient = 0.68-0.95) and was higher for MAR-corrected images, indicating that MAR improves diagnostic accuracy. A metal artifact reduction algorithm can improve diagnostic and interventional accuracy of cone beam CT in patients undergoing radioembolization by reducing artifacts caused by diagnostic catheters and coils, lowering interference of metal artifacts with adjacent major structures, and improving tumor visibility.

Ultrasensitive electrochemical microRNA-21 detection based on MXene and ATRP photocatalytic strategy.

A Ti3C2TxMXene-based biosensor has been developed and the photocatalytic atom transfer radical polymerization (photo ATRP) amplification strategy applied to detect target miRNA-21 (tRNA). Initially, Ti3C2TxMXene nanosheets were synthesized from the Ti3AlC2 MAX precursor via selective aluminum etching. Then, functionalization of Ti3C2TxMXene nanosheets with 3-aminopropyl triethoxysilane (APTES) via silylation reactions to facilitate covalent bonding with hairpin DNA biomolecules specifically designed for tRNA detection. Upon binding with the tRNA, the hairpin DNA liberated the azide (N3) group, initiating a click reaction to affix to the photo ATRP initiator. Through the ATRP photoreaction, facilitated by an organic photoredox catalyst and light, a significant amount of ferrocenyl methyl methacrylate (FMMA) monomer was immobilized on the electrode. Therefore, the electrochemical signal is amplified. The electrochemical efficacy of the biosensor was assessed using square wave voltammetry (SWV). Under optimized conditions, the biosensor demonstrated remarkable sensitivity in detecting tRNA, with a linear detection range from 0.01 fM to 10 pM and a detection limit of 2.81 aM. The findings elucidate that the developed biosensor, in conjunction with the photo ATRP strategy, offers reproducibility, stability, and increased sensitivity, underscoring its potential applications within the experimental medical sector of the biomolecular industry.

Antioxidant potentials of extracts from different parts of Clinacanthus nutans (Burm. f.) Lindau.

The research aimed to explore the antioxidant potential of extracts from different parts of Clinacanthus nutans growing in Vietnam, a member of the Acanthaceae family. The plant's roots, stem and leaves were extracted using 96% ethanol. The antioxidant actions of these extracts were evaluated by DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate) assay on thin-layer plates and 96 well plates. The extract with the most potent activity was applied for distribution extraction with solvents with different polarities, including dichloromethane, ethyl acetate and water. Dry column vacuum chromatography was utilized to obtain the most antioxidant-potent extract fractions. The stem extract had the lowest IC50 value of 6.85µg/mL, showing the most potent antioxidant activity. The ethyl acetate fraction from the stem extract expressed the lowest IC50 value of 9.67µg/mL. Meanwhile, fraction 5, separated from the ethyl acetate fraction of the stem extract, had the lowest IC50 value of 9.89µg/mL. In conclusion, the extracts from different parts of Clinacanthus nutans all expressed antioxidant action at different levels, in which the stem extract, the ethyl acetate fraction and fraction 5 from the ethyl acetate fraction displayed the most effective actions. These findings highlight the promising potential of Clinacanthus nutans in treating oxidative stress-associated diseases, inspiring further research and exploration in this area.

Fear of Falling: Exploring Associated Factors among Elderly Residents in the Rural Communities of Vietnam.

This research aimed to explore factors associated with the fear of falling (FOF) among community-dwelling older adults in Vietnam. A cross-sectional study was conducted in five communes in Soc Son, Hanoi, Vietnam, from March to June 2017. We recruited a total of 487 participants, which provided sufficient data for analysis. The outcome variable was fear of falling. Several covariates, including demographics, medical history, general health status, geriatric syndromes, eye diseases, assessment of fall risk environment, timed up-and-go test, and number of standing up in 30 s, were collected. A multivariable logistic regression model was performed to determine predictors associated with FOF. The results showed that 54.6% of the participants had FOF. Furthermore, the logistic multivariable regression model revealed several factors associated with FOF among participants in the research sites, including polypharmacy status (OR: 1.79; 95%CI 1.07-2.99), higher scores in quality of life according to the EQ-5D-5L index (OR:6.27; 95%CI: 2.77-14.17), and having fallen during the past 12 months (OR:4.4; 95%CI: 2.39-8.11). These findings contribute to a comprehensive understanding of the intricate relationship between FOF and several associated factors, notably polypharmacy status, quality of life, and having a fall during the past 12 months.

Case report: A novel somatic SDHB variant in a patient with bladder paraganglioma.

Background: Paragangliomas (PGL) are rare neuroendocrine tumors derived from the autonomic nervous system paraganglia. Urinary bladder paragangliomas (UBPGL) originate from the sympathetic neurons of the urinary bladder wall and represent 0.7% of all paragangliomas and <0.05% of all bladder tumors. PGL and UBPGL can be associated with SDHB, SDHD, NF1, and VHL gene variants, with the most common germline alterations found in SDHB and VHL. Case report: We report a case of a 42-year-old woman who presented with menorrhagia/hematuria, uterine leiomyomas, as well as cardiac and bladder masses. The cardiac mass was favored to be a myxoma based on clinical findings, while the bladder mass was diagnosed as UBPGL. A novel SDHB mutation (c.642G>A, p Q214Q), detected in the UBPGL, was proven to be somatic. Although this variant was seemingly synonymous, it was predicted to have a loss of function due to the splice site effect, which was further supported by the immunohistochemical loss of SDHB. Conclusion: This case highlights the challenges of diagnosing an extremely rare entity, bladder paraganglioma, with an emphasis on the multidisciplinary approach to navigate various clinical and imaging findings that may initially be misleading. In addition, a novel loss of function SDHB variant that could have been overlooked as a synonymous variant is herein reported, while also illustrating the importance of both germline and somatic mutation testing.

Medication errors in emergency departments: a systematic review and meta-analysis of prevalence and severity.

BACKGROUND: Medication errors significantly compromise patient safety in emergency departments. Although previous studies have investigated the prevalence of these errors in this setting, results have varied widely. AIM: The aim was to report pooled data on the prevalence and severity of medication errors in emergency departments, as well as the proportion of patients affected by these errors. METHOD: Systematic searches were conducted in Embase, PubMed, and the Cochrane Library from database inception until June 2023. Studies provided numerical data on medication errors within emergency departments were eligible for inclusion. Random-effects meta-analysis was employed to pool the prevalence of medication errors, the proportion of patients experiencing these errors, and the error severity levels. Heterogeneity among studies was assessed using the I2 statistic and Cochran's Q test. RESULTS: Twenty-four studies met the inclusion criteria. The meta-analysis gave a pooled prevalence of medication errors in emergency departments of 22.6% (95% Confidence Interval [CI] 19.2-25.9%, I2 = 99.9%, p < 0.001). The estimated proportion of patients experiencing medication errors was 36.3% (95% CI 28.3-44.3%, I2 = 99.8%, p < 0.001). Of these errors, 42.6% (95% CI 5.0-80.1%) were potentially harmful but not life-threatening, while no-harm errors accounted for 57.3% (95% CI 14.1-100.0%). CONCLUSION: The prevalence of medication errors, particularly those potentially harmful, underscores potential safety issues in emergency departments. It is imperative to develop and implement effective interventions aimed at reducing medication errors and enhancing patient safety in this setting.