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1.
Prev Med Rep ; 43: 102772, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38952432

RESUMEN

Objectives: This study aims to investigate the influence of socioeconomic status (SES) on variations in physical activity (PA) levels and diabetes-related cognitive dysfunction and impairment amidst disruptions caused by the COVID-19 pandemic. Methods: With the sample of old population, comprising about 20 thousand from the Fact-Finding Survey on the Status of Senior Citizens (FSSSC) released by Ministry of Health and Welfare of South Korea in 2017 and 2020, we empirically tested the direct and indirect effects of SES on cognitive dysfunction using structural equation modeling (SEM). Two SEMs provided the comparison on the effects of COVID-19. Results: Household income had a negative impact on the likelihood of dementia diagnosis via PA related diabetes during the pandemic (p < 0.001), whereas no effects of household income on dementia diagnosis were found in 2017, due to no direct effect of PA on diabetes confirmation in 2017. The disparity in PA based on SES becomes more prominent among the older individuals during the pandemic (z = 11.7) than 2017 (z = 6.0), emphasizing the significance of PA in mitigating diabetes-induced cognitive dysfunction during the pandemic. SES affects access to PA, contributing to diabetes-induced cognitive dysfunctions in the older population with lower SES during the pandemic. Conclusion: PA may serve as a preventive measure against diabetes-induced cognitive dysfunction and dementia in the older population. Thorough investigation of these mechanisms is imperative to establish the role of PA in preventing diabetes-induced cognitive impairment, particularly among the older population with lower SES.

2.
Mycobiology ; 52(3): 172-182, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38948453

RESUMEN

Truffles, belonging to the genus Tuber, are ectomycorrhizal (ECM) fungi that form underground ascocarps and primarily establish symbiosis with oaks and hazels. The cultivation of Tuber spp. involves transplanting inoculated seedlings that have formed ectomycorrhiza with Tuber species, with mulching being effective for truffle cultivation. In this study, we investigated the effects of mulching on the mycelial growth of four Tuber species (T. himalayense, T. koreanum, T. melanosporum, and T. borchii) in the Korean natural environment, highlighting the potential for Korea as a truffle cultivation site. We developed and tested species-specific primers for quantifying the soil mycelial biomass of Tuber spp. by qRT-PCR, determined the superior mulch color for mycelial growth, and identified the Tuber species exhibiting the highest growth rate in the Korean field environment. Our results demonstrated that white mulch significantly enhanced mycelial growth in Tuber species than black mulch, likely owing to its ability to maintain low soil temperatures, control weeds, and improve host plant growth. Among the Tuber species, T. himalayense showed the greatest growth potential in the Korean natural environment. Additionally, a significant and positive correlation was observed between the mycelial biomass of Tuber species and the growth of inoculated seedlings, as measured by the total stem length and the number of leaves, thereby indicating the importance of symbiosis between ECM fungi and host plants. This study provides valuable insights into truffle cultivation in Korea and highlights the potential of using white mulch to promote mycelial growth, thereby contributing essential data for understanding the appropriate environmental conditions for Tuber spp. cultivation in Korea. Further study is needed to assess the long-term impact of mulching and to explore the effectiveness of other mulching materials.

3.
Biomed Eng Lett ; 14(4): 747-754, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38946821

RESUMEN

This study was performed to investigate the effects of fibular osteotomy and release of medial soft tissues including posterior tibial tendon (PTT), and deep deltoid ligaments, which act as medial stabilizing structures in medial open wedge SMO. Twelve fresh frozen human legs were obtained and disarticulated below the knee. Experiments were conducted in four steps. First, medial open wedge tibial osteotomy was performed. Second, fibular osteotomy was performed in an inferomedial direction at the same level as the tibial osteotomy. Third, the deep deltoid ligament was released from tibial attachments. Forth, total tenotomy of the PTT was performed behind the medial malleolus. After finishing each step, contact area and peak and mean pressures were measured in the tibiotalar and talofibular joints. Fibular osteotomy after medial open wedge SMO significantly decreased mean pressure in the tibiotalar joint, mean and peak pressures in the talofibular joint. Medial soft tissue release resulted in a remarkable lateral shift and decreased tibiotalar joint loading. However, no remarkable change was observed in the tibiotalar joint during releasing medial soft tissues. The overall peak pressure distribution tended to shift more laterally compared to the value of normal alignment. In conclusion, concomitant fibular osteotomy and release of the deltoid ligament and PTT provide a useful means of minimizing tibiotalar joint stress. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-024-00370-7.

4.
Cells ; 13(12)2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38920692

RESUMEN

The PI3K signaling pathway plays an essential role in cancer cell proliferation and survival. PI3K pathway inhibitors are now FDA-approved as a single agent treatment or in combination for solid tumors such as renal cell carcinoma or breast cancer. However, despite the high prevalence of PI3K pathway alterations in gynecological cancers and promising preclinical activity in endometrial and ovarian cancer models, PI3K pathway inhibitors showed limited clinical activity in gynecological cancers. In this review, we provide an overview on resistance mechanisms against PI3K pathway inhibitors that limit their use in gynecological malignancies, including genetic alterations that reactivate the PI3K pathway such as PIK3CA mutations and PTEN loss, compensatory signaling pathway activation, and feedback loops causing the reactivation of the PI3K signaling pathway. We also discuss the successes and limitations of recent clinical trials aiming to address such resistance mechanisms through combination therapies.


Asunto(s)
Resistencia a Antineoplásicos , Neoplasias de los Genitales Femeninos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Transducción de Señal , Humanos , Femenino , Neoplasias de los Genitales Femeninos/tratamiento farmacológico , Neoplasias de los Genitales Femeninos/genética , Neoplasias de los Genitales Femeninos/patología , Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3/uso terapéutico , Transducción de Señal/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Animales
5.
Radiol Artif Intell ; : e230601, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900043

RESUMEN

"Just Accepted" papers have undergone full peer review and have been accepted for publication in Radiology: Artificial Intelligence. This article will undergo copyediting, layout, and proof review before it is published in its final version. Please note that during production of the final copyedited article, errors may be discovered which could affect the content. Purpose To evaluate the performance of an automated deep learning method in detecting ascites and subsequently quantifying its volume in patients with liver cirrhosis and ovarian cancer. Materials and Methods This retrospective study included contrast-enhanced and noncontrast abdominal-pelvic CT scans of patients with cirrhotic ascites and patients with ovarian cancer from two institutions, National Institutes of Health (NIH) and University of Wisconsin (UofW). The model, trained on The Cancer Genome Atlas Ovarian Cancer dataset (mean age, 60 years ± 11 [SD]; 143 female), was tested on two internal (NIH-LC and NIH-OV) and one external dataset (UofW-LC). Its performance was measured by the Dice coefficient, standard deviations, and 95% confidence intervals, focusing on ascites volume in the peritoneal cavity. Results On NIH-LC (25 patients; mean age, 59 years ± 14; 14 male) and NIH-OV (166 patients; mean age, 65 years ± 9; all female), the model achieved Dice scores of 85.5% ± 6.1% (CI: 83.1%-87.8%) and 82.6% ± 15.3% (CI: 76.4%-88.7%), with median volume estimation errors of 19.6% (IQR: 13.2%-29.0%) and 5.3% (IQR: 2.4%- 9.7%), respectively. On UofW-LC (124 patients; mean age, 46 years ± 12; 73 female), the model had a Dice score of 83.0% ± 10.7% (CI: 79.8%-86.3%) and median volume estimation error of 9.7% (IQR: 4.5%-15.1%). The model showed strong agreement with expert assessments, with r2 values of 0.79, 0.98, and 0.97 across the test sets. Conclusion The proposed deep learning method performed well in segmenting and quantifying the volume of ascites in concordance with expert radiologist assessments. ©RSNA, 2024.

6.
Sci Rep ; 14(1): 13303, 2024 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-38858399

RESUMEN

Dengue virus (DENV) infection is a public health concern in several countries and is associated with severe diseases, such as dengue hemorrhagic fever and dengue shock syndrome. DENVs are transmitted to humans via the bites of infected Aedes mosquitoes, and no antiviral therapeutics are currently available. In this work, we aimed to identify antiviral drugs against DENV type 2 (DENV2) infections and selected pimecrolimus as a potential antiviral drug candidate. Pimecrolimus significantly inhibited DENV2-mediated cell death and replication in vitro. We also confirmed a decrease in the number of plaques formed as well as in the envelope protein levels of DENV2. The time-of-addition and course experiments revealed that pimecrolimus inhibited DENV2 infection during the early stages of the virus replication cycle. In an experimental mouse model, orally administered pimecrolimus alleviated body weight loss and lethality caused by DENV2 infection, which we used as readouts of the drug's antiviral potency. Furthermore, pimecrolimus significantly inhibited the DENV2 load and ameliorated focal necrosis in the liver and spleen. Taken together, our in vitro and in vivo findings suggest that pimecrolimus is a promising antiviral drug candidate for the treatment of DENV2 infection.


Asunto(s)
Antivirales , Virus del Dengue , Dengue , Tacrolimus , Replicación Viral , Animales , Virus del Dengue/efectos de los fármacos , Antivirales/farmacología , Antivirales/uso terapéutico , Tacrolimus/análogos & derivados , Tacrolimus/farmacología , Tacrolimus/uso terapéutico , Replicación Viral/efectos de los fármacos , Ratones , Dengue/tratamiento farmacológico , Dengue/virología , Humanos , Modelos Animales de Enfermedad , Chlorocebus aethiops , Línea Celular , Células Vero
7.
J Community Health Nurs ; : 1-15, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900001

RESUMEN

PURPOSE: This article describes the trends and contributing factors in the human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) epidemiology in the Philippines from 2010 to 2022. This is the first trend analysis of the Philippine HIV/AIDS situation. DESIGN: Using time trend research design, 13-year longitudinal epidemiological data were collected and analyzed to present a dynamic perspective of the Philippine HIV/AIDS epidemic. METHODS: Secondary data analysis of HIV surveillance public documents from 2010 to 2022 was conducted. The Centers for Disease Control's socioecological model was used to guide the literature and interpretation of findings. Frequency, percentage distribution, and Sieve-bootstrap t-test for linear trends were used to analyze the results. FINDINGS: There is an increased trend in HIV incidence, late diagnosis, and AIDS-related mortality in all geographical regions in the country from 2010-2022. The majority of HIV cases are males, ages 25-34, and reside in the nation's capital. Increased HIV incidence among overseas workers, sex workers, and HIV-positive blood products were noted. CONCLUSION: Trends in Philippine HIV epidemiology are contrary to global trends. Community-based HIV prevention programs targeting specific high-risk populations are needed. CLINICAL EVIDENCE: Community health nurses in the Philippines play a critical role in reversing the rising trend of HIV/AIDS. They are positioned to lead targeted education and prevention programs for high-risk groups using the socioecological model to implement community-based strategies that address factors contributing to the epidemic. Their efforts in early detection and linkage to care are essential in reducing late diagnosis and AIDS-related mortality.

8.
Ophthalmol Ther ; 13(8): 2209-2225, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38878130

RESUMEN

INTRODUCTION: SB15 is a proposed biosimilar product of reference aflibercept (Eylea®), an approved biological drug product for retinal diseases including neovascular age-related macular degeneration (nAMD). This study aimed to assess the analytical similarity between SB15 and its commercially available reference product (RP) sourced from the United States (US-aflibercept) and European Union (EU-aflibercept) in terms of structural, physicochemical, and biological properties. METHODS: A panel of state-of-the-art analytical methods was used for the comprehensive characterization of SB15 and US/EU-aflibercept. In terms of the structural and physicochemical properties, primary structure; post-translational modifications (PTM); higher-order structure; purity and impurities; charge variants; and glycosylation were compared. In addition, biological characterization including mechanism of action (MoA)-related and Fc-related biological activities was conducted. RESULTS: Analytical similarity between SB15 and US/EU-aflibercept was demonstrated. The primary and higher-order structure of SB15 was confirmed to be comparable to that of US/EU-aflibercept. In addition, there were no meaningful differences in the physicochemical properties in terms of size and charge heterogeneity between SB15 and its RP. SB15 and RP were similar in biological activities including MoA-related binding activities, potencies, and Fc-related biological functions. Consequently, SB15 was confirmed to be highly similar to US/EU-aflibercept. CONCLUSIONS: Based on a comprehensive analytical similarity assessment of structural, physicochemical, and biological properties, SB15 was demonstrated to be highly similar to US/EU-aflibercept RP, supporting safe and effective use of SB15.

9.
In Vivo ; 38(4): 1740-1749, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38936885

RESUMEN

BACKGROUND/AIM: To date, therapeutic options for T-cell acute lymphoblastic leukemia (T-ALL) remain very limited. This study evaluated the efficacy of monotherapies and combination therapies including a selective BCL-2 inhibitor for T-ALL cell lines, namely Jurkat, CCRF-CEM, and Loucy. MATERIALS AND METHODS: Loucy is an early T-precursor ALL (ETP-ALL) cell line characterized by an immature phenotype, whereas Jurkat and CCRF-CEM are late T-cell progenitor ALL (LTP-ALL) cell lines. Monotherapy was conducted with venetoclax, cytarabine, bendamustine, or azacytidine, whereas combination therapy was performed with venetoclax plus cytarabine, venetoclax plus bendamustine, or venetoclax plus azacytidine. Cell viability assay was conducted after 48 h using Trypan blue and the 3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS). Statistical analysis for evaluating synergistic interactions between anticancer drugs was performed by using the SynergyFinder Plus and drc R package. RESULTS: Adding venetoclax to cytarabine, bendamustine, or azacitidine achieved an additive effect, with Loewe synergic scores ranging from -10 to 10 in Jurkat and CCRF-CEM. Conversely, the combination of venetoclax and cytarabine displayed an additive effect (Loewe synergic score: 8.45 and 5.82 with MTS and Trypan blue assays, respectively), whereas venetoclax plus bendamustine or azacitidine exhibited a synergistic effect (Loewe synergic score >10 with MTS assay) in Loucy. Remarkably, the Bliss/Loewe score revealed that the combination of venetoclax and bendamustine was the most synergistic, yielding a score of 13.832±0.55. CONCLUSION: The combination of venetoclax and bendamustine demonstrated the greatest synergistic effect in suppressing ETP-ALL cell proliferation. Further studies are warranted to determine the mechanisms for the synergism between venetoclax and bendamustine in high-risk T-ALL.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Clorhidrato de Bendamustina , Compuestos Bicíclicos Heterocíclicos con Puentes , Sinergismo Farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras , Sulfonamidas , Humanos , Clorhidrato de Bendamustina/administración & dosificación , Clorhidrato de Bendamustina/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacología , Leucemia-Linfoma Linfoblástico de Células T Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Células Jurkat , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos
10.
Transl Vis Sci Technol ; 13(5): 18, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38776108

RESUMEN

Purpose: We aimed to design, develop, and evaluate an internet of things-enabled patch (IoT patch) for real-time remote monitoring of adherence (or patch wear time) during patch treatment in child participants in clinical trials. This study provides healthcare providers with a tool for objective, real-time, and remote assessment of adherence and for making required adjustments to treatment plans. Methods: The IoT patch had two temperature microsensors and a wireless chip. One sensor was placed closer to the skin than the other, resulting in a temperature difference depending on whether the patch was worn. When the patch was worn, it measured temperatures every 30 seconds and transmitted temperature data to a cloud server via a mobile application every 15 seconds. The patch was evaluated via 2 experiments with 30 healthy adults and 40 children with amblyopia. Results: Excellent monitoring accuracy was observed in both adults (mean delay of recorded time data, 0.4 minutes) and children (mean, 0.5 minutes). The difference between manually recorded and objectively recorded patch wear times showed good agreement in both groups. Experiment 1 showed accurate monitoring over a wide range of temperatures (from 0 to 30°C). Experiment 2 showed no significant differences in wearability (ease-of-use and comfort scores) between the IoT and conventional patches. Conclusions: The IoT patch offers an accurate, real-time, and remote system to monitor adherence to patch treatment. The patch is comfortable and easy to use. The utilization of an IoT patch may increase adherence to patch treatment based on accurate monitoring. Translational Relevance: Results show that the IoT patch can enable real-time adherence monitoring in clinical trials, improving treatment precision, and patient compliance to enhance outcomes.


Asunto(s)
Internet de las Cosas , Tecnología Inalámbrica , Humanos , Femenino , Masculino , Adulto , Niño , Tecnología Inalámbrica/instrumentación , Cooperación del Paciente , Diseño de Equipo/métodos , Preescolar , Adulto Joven , Dispositivos Electrónicos Vestibles , Tecnología de Sensores Remotos/instrumentación , Tecnología de Sensores Remotos/métodos
11.
Gynecol Oncol ; 187: 105-112, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38759516

RESUMEN

OBJECTIVE: Combination cediranib/olaparib has reported activity in relapsed ovarian cancer. This phase 2 trial investigated the activity of cediranib/olaparib in relapsed ovarian cancer and its association with homologous recombination deficiency (HRD). METHODS: Seventy patients were enrolled to cohorts of either platinum-sensitive or platinum-resistant ovarian cancer and received olaparib tablets 200 mg twice daily and cediranib tablets 30 mg once daily under a continuous dosing schedule. HRD testing was performed on pre-treatment, on-treatment and archival biopsies by sequencing key homologous recombination repair (HRR) genes and by genomic LOH analysis. The primary objective for the platinum-sensitive cohort was the association of HRD, defined as presence of HRR gene mutation, with progression-free survival (PFS). The primary objective for the platinum-resistant cohort was objective response rate (ORR), with a key secondary endpoint evaluating the association of HRD status with activity. RESULTS: In platinum-sensitive ovarian cancer (N = 35), ORR was 77.1% (95% CI 59.9-89.6%) and median PFS was 16.4 months (95% CI 13.2-18.6). Median PFS in platinum-sensitive HRR-HRD cancers (N = 22) was 16.8 months (95% CI 11.3-18.6), and 16.4 months (95% CI 9.4-NA) in HRR-HR proficient cancers (N = 13; p = 0.57). In platinum-resistant ovarian cancer (N = 35), ORR was 22.9% (95% CI 10.4-40.1%) with median PFS 6.8 months (95% CI 4.2-9.1). Median PFS in platinum-resistant HRR-HRD cancers (N = 7) was 10.5 months (95% CI 3.6-NA) and 5.6 months (95% CI 3.6-7.6) in HRR-HR proficient cancers (N = 18; p = 0.23). CONCLUSIONS: Cediranib/olaparib had clinical activity in both platinum-sensitive and -resistant ovarian cancer. Presence of HRR gene mutations was not associated with cediranib/olaparib activity in either setting.

12.
Health Econ ; 33(8): 1811-1830, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38728372

RESUMEN

We utilize the phased rollout of COVID-19 vaccines by exact birth date in South Korea as a natural experiment for testing risk compensation. People may resume face-to-face social activities following vaccination because they perceive lower risk of infection. Applying a regression discontinuity design based on birth date cutoffs for vaccine eligibility, we find no evidence of risk-compensating behaviors, as measured by large, high-frequency data from credit card and airline companies as well as survey data. We find some evidence of self-selection into vaccine take-up based on perception toward vaccine effectiveness and side effects, but the treatment effects do not differ between compliers and never-takers.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Humanos , República de Corea , Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , Vacunación , Femenino , SARS-CoV-2 , Masculino , Adulto
13.
Food Sci Nutr ; 12(4): 2736-2746, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38628170

RESUMEN

Previous research has suggested that the impact of smoke affected wines require human evaluation due to in-mouth changes in perception, perhaps associated with saliva. Smoke affected wines (n = 36) from three major wine growing regions in the US were sourced from commercial wineries. A subset of these wines (n = 7) were evaluated by a consumer panel (n = 57) and electronic tongue (e-tongue) to determine the influence of saliva in the sensory profile. Consumers assessed the wines for aroma and other sensory attributes, before and after individual saliva addition. Pooled saliva from consumers was used to treat all wines obtained (n = 36) and then analyzed using the e-tongue. Results showed that saliva did not significantly alter the overall aroma, other than fruity or woody aroma liking by consumers (p > .05). However, the presence of saliva significantly lowered overall liking in both red and white wines that were affected by smoke (p ≤ .05). Consumers rated the subset of smoke affected wines below the "might purchase" category, indicating these wines were not considered acceptable by consumers. When individual pairs of smoke affected wines (before and after saliva additions) were assessed using the e-tongue, the device was able to differentiate the pairs, validating potential usefulness to discern wine changes, though the discrimination indices were moderate to low (68.8% to 11.9%). Based on these data, in human ratings of the aroma and appearance of smoked affected wines, saliva decreased overall liking, and this was somewhat distinguishable by e-tongue analysis.

14.
Nat Commun ; 15(1): 2805, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38555285

RESUMEN

The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR). Secondary outcomes were safety and progression-free survival (PFS). 49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6). Among the 39 RECISTv1.1-evaluable patients, ORR was 33.3% in cohort 5 and 28.6% in cohort 6. Primary endpoint was not evaluable due to early stop of the trial. The median PFS was 4 months in cohort 5 and 6 months in cohort 6. Toxicity was manageable. Translational research was an exploratory endpoint. Potential biomarkers were investigated using pre-treatment fresh biopsies and serial blood samples. Transcriptomic analysis revealed high levels of DNA replication-related genes (POLA1, POLE, GINS3) associated with lack of clinical benefit [defined post-hoc as PFS < 6 months]. Subsequent preclinical experiments demonstrated significant cytotoxicity of POLA1 silencing in combination with CHK1i in platinum-resistant HGSOC cell line models. Therefore, POLA1 expression may be predictive for CHK1i resistance, and the concurrent POLA1 inhibition may improve the efficacy of CHK1i monotherapy in this hard-to-treat population, deserving further investigation.


Asunto(s)
Proteína BRCA1 , Neoplasias Ováricas , Pirazinas , Femenino , Humanos , Proteína BRCA1/genética , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Carcinoma Epitelial de Ovario/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Pirazoles/farmacología , Pirazoles/uso terapéutico , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proteínas Cromosómicas no Histona
15.
J Pineal Res ; 76(2): e12949, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38528668

RESUMEN

Melatonin, a pineal hormone that modulates circadian rhythms, sleep, and neurotransmitters, is widely used to treat sleep disorders. However, there are limited studies on the safety of melatonin. Therefore, we aimed to present the overall patterns of adverse events (AEs) following melatonin administration and identify potential safety signals associated with melatonin. Using VigiBase, a global individual case safety report (ICSRs) database managed by the World Health Organization (WHO), we conducted a retrospective, observational, pharmacovigilance study of melatonin between January 1996 and September 2022. Disproportionality analysis was conducted using two comparator settings: all other drugs and other sleep medications. We used multivariable logistic regression to estimate reporting odds ratios (RORs) with 95% confidence intervals (CIs) to compare the frequencies of AEs reporting between melatonin and each comparator setting. Furthermore, we assessed adverse events of special interests (AESIs) that could potentially be associated with melatonin. Signals were identified when the following criteria were met: cases ≥3, x2 ≥ 4, IC025 ≥ 0, and the lower end of the 95% CI of ROR > 2. These signals were then compared with the AE information on the drug labels provided by regulatory bodies. A total of 35 479 AE reports associated with melatonin were identified, with a higher proportion of reports from females (57.1%) and individuals aged 45-64 years (20.8%). We identified 21 AEs that were commonly detected as safety signals in the disproportionality analyses, including tic, educational problems, disturbance in social behavior, body temperature fluctuation, and growth retardation. In AESI analyses, accidents and injuries (adjusted ROR 2.97; 95% CI, 2.80-3.16), fall (2.24; 2.12-2.37), nightmare (4.90; 4.37-5.49), and abnormal dreams (3.68; 3.19-4.25) were detected as a signal of melatonin when compared to all other drugs, whereas those signals were not detected when compared to other sleep medications. In this pharmacovigilance study, exogenous melatonin showed safety profiles comparable to other sleep medications. However, several unexpected potential safety signals were identified, underscoring the need for further investigation at the population level.


Asunto(s)
Melatonina , Farmacovigilancia , Femenino , Humanos , Sistemas de Registro de Reacción Adversa a Medicamentos , Melatonina/efectos adversos , Estudios Retrospectivos , Organización Mundial de la Salud
16.
J Food Sci ; 89(5): 3006-3018, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38532705

RESUMEN

Wine faults threaten brand recognition and consumer brand loyalty. The objective of this study was to compare the acuteness of e-tongue and human sensory evaluation of wine fault development in Riesling wine over 42 days of storage. Riesling wines uninoculated (control) or inoculated with 104 CFU/mL cultures of Wickerhamomyces anomalus, Acetobacter aceti, Lactobacillus brevis, or Pediococcus parvulus were assessed every 7 days with the e-tongue and a rate-all-that-apply (RATA) sensory panel. After 7 days of storage, the e-tongue detected differences in all four wine spoilage microorganism treatments, compared to control wine, with discrimination indices over 86%. The RATA sensory panel detected significant differences beginning on day 35 of storage, 28 days after the e-tongue detected differences. This study showed that the e-tongue was more sensitive than the human panel as a detection tool, without sensory fatigue. PRACTICAL APPLICATION: This research is useful for winemakers seeking additional instrumental methods in the early detection of wine faults. Given the results of this study, the e-tongue can be a useful tool for detecting early chemical changes in white wines that have undergone microbial spoilage, providing winemakers with time to mitigate faults before they surpass sensory thresholds.


Asunto(s)
Gusto , Vino , Vino/análisis , Vino/microbiología , Humanos , Nariz Electrónica , Odorantes/análisis , Adulto , Microbiología de Alimentos/métodos , Femenino , Masculino , Almacenamiento de Alimentos/métodos
17.
J Orthop Res ; 42(8): 1771-1779, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38440854

RESUMEN

The need for additional fibular osteotomy (FO) when performing supramalleolar osteotomy (SMO) in the varus ankle arthritis (VAA) is controversial. Some cadaveric studies have been performed to prove this; however, it is difficult to implement deformities including talar tilting and translation in cadavers. In this study, we created a model of VAA with the tilting and translation using three-dimensional (3-D) finite element (FE) analysis and analyzed the results of SMO with or without FO depending on the types of VAA. The validated normal foot and ankle 3-D FE model was constructed including the ankle cartilages of the talar dome and tibia plafond. The VAA models were determined and reconstructed by following the classification of VAA, VAA with medial translation for stage 3a, VAA with varus tilting (7.5°) for stage 3b. The postoperative SMO models (SMO with and without FO) were reconstructed by corresponding to each VAA models. The FE analysis conditions were commonly applied. The boundary condition of ankle joint was defined as "sliding condition" and applied 0.002 friction coefficient to realize lubricative property. Loading condition was assumed as a two-leg standing position and half of the subject body weight (325 N) was loaded on center of ground to vertical direction. Contact pressure changes were predicted at the medial ankle cartilage. As a result, in VAA with medial translation, isolated SMO may provide sufficient pressure reduction at the medial ankle joint. However, in VAA with varus tilting, SMO combined with FO could appropriately relieve concentrated pressure at the medial ankle joint.


Asunto(s)
Articulación del Tobillo , Análisis de Elementos Finitos , Osteotomía , Humanos , Osteotomía/métodos , Articulación del Tobillo/cirugía , Articulación del Tobillo/fisiopatología , Peroné , Presión , Masculino , Femenino , Persona de Mediana Edad , Adulto
18.
Healthcare (Basel) ; 12(3)2024 Jan 26.
Artículo en Inglés | MEDLINE | ID: mdl-38338208

RESUMEN

Healthcare professionals should support autonomy in their patients in order for them to maintain the motivation to cope actively with their conditions. The Health Care Climate Questionnaire (HCCQ) is useful for assessing patients' perceptions of the autonomy support provided to them. We aimed to validate the psychometric properties of the Korean version of the HCCQ (HCCQ-K) among Korean cancer survivors. This study evaluated the factor structure, concurrent validity, and internal consistency. Data from 367 cancer survivors were analyzed using confirmatory factor analysis (CFA), Pearson's correlations, and Cronbach's α values. The CFA validated that the single-factor structure of the HCCQ-K had an excellent fit that was consistent with that of the original English version. Concurrent validity was confirmed by moderate correlations between the HCCQ-K and both psychological well-being and self-management. Reliability was verified by satisfactory internal consistency, with a Cronbach's α value of 0.91 and strong item-total and inter-item correlations. The HCCQ-K is therefore a valid and reliable tool for assessing autonomy support provided by healthcare professionals to Korean cancer survivors. The HCCQ-K may help healthcare professionals understand their patients' needs for autonomy support and develop strategies to motivate active coping behaviors.

19.
Plant Dis ; 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38345541

RESUMEN

Grapevine yellow speckle viroid 2 (GYSVd-2; Pospiviroidae, Apscaviroid) causes yellow speckle disease in grapevine (Koltunow et al. 1989) and was found in Australia, Iran, Italy, China, and Nigeria (Koltunow et al. 1989; Habili 2017; Zongoma et al. 2018). In the U.S., GYSVd-2 was found in the State of Washington (Vitis vinifera L. cv. Merlot; Alabi et al., 2012). Australian grapevine viroid (AGVd; Pospiviroidae, Apscaviroid) was reported in Australia, Italy, China, Tunisia, Iran, and in the U.S. wine grapes (V. vinifera) (Habili 2017). In the U.S., AGVd was reported from California (Al Rwahnih et al. 2009), from Washington State (V. vinifera cv. Syrah; GU327604), and from the State of New York (an unknown cv. of V. vinifera; KY081960). In Idaho, two other viroids, hop stunt viroid (HSVd; Pospiviroidae, Hostuviroid) and grapevine yellow speckle viroid 1 (GYSVd-1; Pospiviroidae, Apscaviroid), common in grapevines were previously found in wine grapes (Thompson et al. 2019) but neither GYSVd-2 nor AGVd were identified in the same high-throughput sequencing (HTS) outputs. In September 2020, 16 leaf and petiole samples were collected from six vineyards in Canyon and Nez Perce counties of Idaho, representing six different wine grape cultivars and an unknown table grape cultivar, and subjected to HTS analysis. One of the samples was from a table grape plant at the edge of a declining 'Chardonnay' wine grape block that was grown next to a wine tasting room deck for aesthetic, ornamental purposes; the table grape and 'Chardonnay' plants were own-rooted and planted in 1981. Ribodepleted total RNAs prepared from these samples, as described previously, were subjected to a HTS analysis on a NovaSeq platform (Dahan et al. 2023), producing 15,095,042 to 31,500,611 250-bp paired-end reads per sample. Raw reads were adapter and quality cleaned and mapped against the V. vinifera, reference genome. Unmapped paired-end reads were assembled, and contigs were analyzed using BLASTn and DIAMOND (Buchfink et al. 2021) programs. Fifteen samples were found infected with HSVd and with GYSVd-1, while one was infected with GYSVd-2 and AGVd; in particular, the table grape plant (arbitrarily designated RBTG) was found infected with all four viroid species. The HTS-derived, 490-nt GYSVd-2-specific contig from the table grape sample represented ∼1.35 genome of the Idaho isolate of GYSVd-2 (GYSVd-2-RBTG) and was 100% identical to the GYSVd-2 sequence JQ686716 from Iran. The HTS-derived, 488-nt AGVd-specific contig represented ∼1.32 genome of the Idaho isolate of AGVd (AGVd-RBTG) and was 100% identical to the AGVd sequence KF876037 from Iran. To validate the HTS data and confirm the presence of the four viroids in the original 16 samples, all of them were subjected to RT-PCR using the viroid-specific primers described by Gambino et al. (2014); all 16 samples were found positive for HSVd and GYSVd-1, and one found positive for AGVd. The RBTG sample was confirmed to be infected with HSVd, GYSVd-1, and AGVd by RT-PCR. GYSVd-2 sequence was not amplified, although primers designed by Gambino et al. (2014) matched the HTS-derived GYSVd-2-RBTG sequence; this may be related to a lower concentration of this viroid in the sample and to properties of the primers. The sampled table grape plant was asymptomatic; all four viroids were apparently not associated with any visible abnormalities in this table grape plant, consistent with the findings that viroids found in grapevines typically do not seem to be associated with visible diseases (Habili 2017).

20.
Clin Orthop Surg ; 16(1): 141-148, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38304214

RESUMEN

Background: To evaluate the degree of deformation in patients with ankle osteoarthritis (OA), it is essential to measure the three-dimensional (3D), in other words, stereoscopic alignment of the ankle, subtalar, and foot arches. Generally, measurement of radiological parameters use two-dimensional (2D) anteroposterior and lateral radiographs in a weight-bearing state; however, computer-aided 3D analysis (Disior) using weight-bearing cone-beam computed tomography (CBCT) has recently been introduced. Methods: In this study, we compared the 2D human radiographic method with a stereoscopic image in patients with ankle arthritis. We enrolled 57 patients diagnosed with OA (28 left and 29 right) and obtained both standing radiographs and weight-bearing CBCT. Patients were divided by the Takakura stage. The interclass correlation coefficient (ICC) for each result was confirmed. Results: On the ICC between 2D radiographs and 3D analysis, the tibiotalar surface angle and lateral talo-1st metatarsal angle showed a good ICC grade (> 0.6), while other parameters did not have significant ICC results. Three-dimension was superior to radiographs in terms of statistical significance. Conclusions: We demonstrated that 2D and stereoscopic images are useful for the diagnosis of OA. Our study also confirmed that the radiographic features affected by ankle OA varied. However, according to the results, the typical radiography is not sufficient to diagnose and determine a treatment plan for ankle OA. Therefore, the method of using 3D images should be considered.


Asunto(s)
Tobillo , Osteoartritis , Humanos , Radiografía , Articulación del Tobillo/diagnóstico por imagen , Osteoartritis/diagnóstico por imagen , Soporte de Peso , Computadores , Reproducibilidad de los Resultados
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