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1.
Gerodontology ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720436

RESUMEN

BACKGROUND AND OBJECTIVES: Poor oral health disproportionately affects low-income older adults, for whom food insecurity and poor mental health may affect dental health. We explored the associations between food insecurity, mental health, and dental health. Furthermore, we examined whether mental health impacted the associations between food insecurity and dental health. MATERIALS AND METHODS: We conducted a cross-sectional study with a convenience sample of 226 older adults (aged 50+), employing survey and dental screening data. Participants were recruited from seven community-based organisations in Washington State, USA. We calculated descriptive statistics and conducted Chi-square tests, t tests, and logistic regression analyses to assess the associations between aspects of dental health (untreated decay, gum disease, and unmet dental needs), mental health (depression and cognitive function), and food insecurity. RESULTS: In our sample, food insecurity was observed in 28.4%, 40.6% had untreated decay, 31.6% gum disease, and 42.5% unmet dental needs. Food insecurity was associated with a higher occurrence of untreated decay and unmet dental needs. Participants experiencing food insecurity had higher odds of gum disease (aOR = 2.3; 95% CI: 1.1, 5.2) and unmet dental needs (aOR = 3.2; 95% CI:1.4, 7.6). Greater gum disease due to food insecurity was observed among individuals with lower levels of cognitive impairment. CONCLUSION: Food insecurity is associated with poorer oral health among older adults and cognitive function may modify this relationship. These findings underscore the importance of addressing both food insecurity and cognitive impairment as integral components of efforts to improve the oral health of older adults.

2.
Talanta ; 275: 126073, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38688085

RESUMEN

Methicillin-resistant Staphylococcus aureus (MRSA) has a high incidence in infectious hospitals and communities, highlighting the need for early on-site detection due to its resistance to methicillin antibiotics. The present study introduces a highly sensitive detection system for mecA, a crucial methicillin marker, utilizing an RCA-based isothermal exponential amplification reaction. The G-quadruplex-based isothermal exponential amplification reaction (GQ-EXPAR) method designs probes to establish G-quadruplex secondary structures incorporating thioflavin T for fluorescence. The system, unlike conventional genetic detection methods, works with portable isothermal PCR devices (isoQuark), facilitating on-site detection. A detection limit of 0.1 fmol was demonstrated using synthetic DNA, and effective detection was proven using thermal lysis. The study also validated the detection of targets swabbed from surfaces within bacterial 3D nanostructures using the GQ-EXPAR method. After applying complementary sequences to the padlock probe for the target, the GQ-EXPAR method can be used on various targets. The developed method could facilitate rapid and accurate diagnostics within MRSA strains.

3.
J Arthroplasty ; 2024 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-38492823

RESUMEN

BACKGROUND: Long-term (minimum 19-year) outcome data on clinical results and patient satisfaction after posterior-stabilized total knee arthroplasties (TKAs) are missing in the literature. The purpose of the study was to evaluate the clinical and radiographic results as well as patient satisfaction at a mean of 21.2 years after posterior-stabilized TKAs. METHODS: This study included 756 patients (1,350 knees) who had undergone TKAs. There were 96 men and 660 women (mean age, 58 years; range, 40 to 84). The mean follow-up was 21.2 years (range, 19 to 23). At each follow-up visit, the patients were assessed radiographically and clinically. Furthermore, patient satisfaction was determined. RESULTS: The Knee Society total, pain, function, and deformity scores were 42, 18, 33, and 5 points, respectively, at the final follow-up. The mean Western Ontario and McMaster Universities Arthritis Index score was 25 points at the final follow-up. With revision or aseptic loosening as the end point, the 23-year intimated survival for the implant was 96% (95% confidence interval, 91 to 100%). The overall patient satisfaction score at the final follow-up was 83.3 points (range, 81 to 86). Patient satisfaction scores with regard to pain, housework, recreation, and surgery were 84, 81, 82, and 86 points, respectively. CONCLUSIONS: The findings of the present, mean 21-year follow-up clinical study suggest excellent results with regard to the revision rates and survivorship of the posterior-stabilized total knee implants. However, consistent with the literature, we found that about 80% of patients expressed overall satisfaction with their primary TKAs. About 8% of patients were either somewhat or very dissatisfied with the procedure.

4.
J Nutr ; 154(4): 1404-1413, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38432561

RESUMEN

BACKGROUND: Blueberries and anthocyanins, their key bioactive component, may improve eye health. However, few long-term studies have examined blueberries and anthocyanins with cataract and age-related macular degeneration (AMD). OBJECTIVES: To investigate the prospective association between blueberry and anthocyanin intake with incident cataract, total AMD, and visually significant AMD among middle-aged and older women. METHODS: A total of 36,653 and 35,402 women initially free of AMD and cataract, respectively, aged ≥45 y from the Women's Health Study provided semiquantitative food frequency questionnaire data on blueberry intake categorized as none, 1-3 servings/mo, 1 serving/wk, or ≥2 servings/wk, plus a combined category of ≥1 serving/wk. Total anthocyanin intake and major subclasses were energy-adjusted and categorized into quintiles. Self-reported risk factors of eye disease were adjusted in multivariable hazard ratios (HRs) (95% confidence intervals [CIs]) of confirmed cataract, AMD, and visually significant AMD with mean follow-up of 11 y. RESULTS: Among the participants, 10.5% consumed ≥1 serving/wk of blueberries, with mean total anthocyanin intake of 11.2 mg/d. Compared to no blueberry intake, women consuming 1-3 servings/mo, 1 serving/wk, and ≥2 servings/wk had corresponding multivariable HRs of total AMD of 0.90 (95% CI: 0.73, 1.11), 0.71 (95% CI: 0.50, 1.00), and 0.36 (95% CI: 0.14, 0.93) (Ptrend = 0.011); those consuming ≥1 servings/wk had an HR of 0.68 (95% CI: 0.47, 0.98). A similar magnitude of HRs were found for visually significant AMD (Ptrend = 0.012) but not for cataract. There were no significant associations between increasing total anthocyanin quintiles and total and visually significant AMD, but there was a modest inverse association with cataract (Ptrend = 0.022), driven by a 10% reduction in cataract in the upper 2 quintiles. CONCLUSIONS: Greater blueberry intake significantly reduced total AMD, but not visually significant AMD or cataract. However, the magnitude of effect for visually significant AMD was similar to total AMD. There was a modest but significant inverse association between dietary anthocyanin intake with cataract but not AMD.


Asunto(s)
Arándanos Azules (Planta) , Catarata , Persona de Mediana Edad , Humanos , Femenino , Anciano , Antocianinas , Estudios de Seguimiento , Factores de Riesgo , Catarata/epidemiología , Catarata/prevención & control
5.
J Med Virol ; 96(4): e29558, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38533898

RESUMEN

Human papillomavirus (HPV) infection poses a significant risk to women's health by causing cervical cancer. In addition to HPV, cervical cancer incidence rates can be influenced by various factors, including human immunodeficiency virus and herpes, as well as screening policy. In this study, a mathematical model with stochastic processes was developed to analyze HPV transmission between genders and its subsequent impact on cervical cancer incidence. The model simulations suggest that both-gender vaccination is far more effective than female-only vaccination in preventing an increase in cervical cancer incidence. With increasing stochasticity, the difference between the number of patients in the vaccinated group and the number in the nonvaccinated group diminishes. To distinguish the patient population distribution of the vaccinated from the nonvaccinated, we calculated effect size (Cohen's distance) in addition to Student's t-test. The model analysis suggests a threshold vaccination rate for both genders for a clear reduction of cancer incidence when significant stochastic factors are present.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Masculino , Vacunación , Modelos Biológicos , Virus del Papiloma Humano , Procesos Estocásticos
6.
Artículo en Inglés | MEDLINE | ID: mdl-38488491

RESUMEN

CONTEXT: Declining muscle strength and performance in older adults are associated with falls, fractures, and premature death. OBJECTIVE: To determine whether supplementation with vitamin D3 or omega-3 fatty acids vs. placebo for 2 years improves physical performance measures. DESIGN: VITamin D and OmegA-3 TriaL (VITAL) was a double-blinded, placebo-controlled randomized trial of supplemental vitamin D3 and/or omega-3 fatty acids vs. placebo in the prevention of cancer and cardiovascular disease in 25,871 U.S. adults. This ancillary study was completed in a New England sub-cohort that had in-person evaluations at baseline and 2-year follow-up. SETTING: Center for Clinical Investigations in Boston. PARTICIPANTS: 1,054 participants (men ≥50 and women ≥55 years). INTERVENTIONS: 2x2 factorial design of supplemental vitamin D3 (cholecalciferol, 2000 IU/day) and/or marine omega-3 fatty acids (1 g/day). MAIN OUTCOME MEASURES: 2-year changes in physical performance measures of grip strength, walking speed, standing balance, repeated chair stands, and Timed-up and Go (TUG). RESULTS: At 2 years, all randomized groups showed worsening walking speeds and TUG. There were no differences in changes in grip strength, walking speeds, Short Physical Performance Battery (composite of walking speed, balance, and chair stands), and TUG between the vitamin D3-treated and the placebo-treated groups and between the omega-3-treated and the placebo-treated groups. Effects overall did not vary by sex, age, body mass index, or baseline measures of total or free 25-hydroxyvitamin D (25[OH]D) or plasma n-3 index; TUG slightly worsened with vitamin D supplementation, compared to placebo, in participants with baseline total 25(OH)D levels above the median (p=0.01, p for interaction=0.04). CONCLUSIONS: Neither supplemental vitamin D3 nor marine omega-3 fatty acids for 2 years improved physical performance in this generally healthy adult population.

7.
Support Care Cancer ; 32(3): 156, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38349581

RESUMEN

PURPOSE: Despite proven benefits, few cancer patients exercise during chemotherapy. The American College of Sports Medicine's Exercise is Medicine® (EIM) initiative describes a model to integrate exercise into oncology care, based upon assessing patients' ability to exercise safely, advising on exercise benefits, and referring patients to exercise. We developed and tested a strategy to implement EIM in a community-based oncology clinic, to assess-advise-refer 20 patients undergoing chemotherapy to a 3-month online exercise class, and measured implementation outcomes. METHODS: Using a community-based provider participation in research (CBPPR) model, researchers and staff co-designed and tested a 4-level implementation strategy, with a goal of assessing-advising-referring 20 cancer patients to exercise. Surveys and interviews were conducted with 12 (100%) staff at baseline and post-implementation on acceptability/appropriateness/feasibility, perceptions of individual implementation roles, and organizational strengths/conditions. Data were analyzed using correlations, t-tests, and content analysis. RESULTS: The proposed strategy was revised in collaboration with staff who requested assistance for recruitment and data collection. EIM was successfully implemented with 41 (92%) patients assessed, 37 (90%) advised, and 22 (60%) referred to exercise classes. Barriers to implementation were staff shortages and time constraints; facilitators included research team supports. Staff's perceived organizational strengths were positively correlated with exercise promotion acceptability, appropriateness, and feasibility. There were no statistically significant changes in implementation outcomes (acceptability/appropriateness/feasibility) post-implementation. CONCLUSIONS: Using a collaborative model, EIM was successfully implemented in a community oncology clinic; however, the clinic required significant support from the research team. Adaptations to the EIM process may be required to improve implementation outcomes.


Asunto(s)
Neoplasias , Medicina Deportiva , Deportes , Humanos , Ejercicio Físico , Oncología Médica , Neoplasias/terapia
8.
JAMA Netw Open ; 7(2): e2355808, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38349654

RESUMEN

Importance: Higher prepandemic physical activity (PA) levels have been associated with lower risk and severity of COVID-19. Objective: To investigate the association between self-reported prepandemic PA levels and the risk and severity of COVID-19 in older US adults. Design, Setting, and Participants: This cohort study combined cohorts from 3 ongoing prospective randomized clinical trials of US adults aged 45 years or older who provided prepandemic self-reports of baseline leisure-time PA and risk factors for COVID-19 outcomes using the most recent questionnaire completed as of December 31, 2019, as the baseline PA assessment. In multiple surveys from May 2020 through May 2022, participants indicated whether they had at least 1 positive COVID-19 test result or were diagnosed with or hospitalized for COVID-19. Exposure: Prepandemic PA, categorized into 3 groups by metabolic equivalent hours per week: inactive (0-3.5), insufficiently active (>3.5 to <7.5), and sufficiently active (≥7.5). Main Outcome and Measures: Primary outcomes were risk of COVID-19 and hospitalization for COVID-19. Multivariable logistic regression was used to estimate odd ratios (ORs) and 95% CIs for the association of COVID-19 diagnosis and/or hospitalization with each of the 2 upper PA categories vs the lowest PA category. Results: The pooled cohort included 61 557 participants (mean [SD] age, 75.7 [6.4] years; 70.7% female), 20.2% of whom were inactive; 11.4%, insufficiently active; and 68.5%, sufficiently active. A total of 5890 confirmed incident cases of COVID-19 were reported through May 2022, including 626 hospitalizations. After controlling for demographics, body mass index, lifestyle factors, comorbidities, and medications used, compared with inactive individuals, those insufficiently active had no significant reduction in infection (OR, 0.96; 95% CI, 0.86-1.06) or hospitalization (OR, 0.98; 95% CI, 0.76-1.28), whereas those sufficiently active had a significant reduction in infection (OR, 0.90; 95% CI, 0.84-0.97) and hospitalization (OR, 0.73; 95% CI, 0.60-0.90). In subgroup analyses, the association between PA and SARS-CoV-2 infection differed by sex, with only sufficiently active women having decreased odds (OR, 0.87; 95% CI, 0.79-0.95; P = .04 for interaction). Conclusions and Relevance: In this cohort study of adults aged 45 years or older, those who adhered to PA guidelines before the pandemic had lower odds of developing or being hospitalized for COVID-19. Thus, higher prepandemic PA levels may be associated with reduced odds of SARS-CoV-2 infection and hospitalization for COVID-19.


Asunto(s)
Prueba de COVID-19 , COVID-19 , Femenino , Humanos , Anciano , Adulto , Persona de Mediana Edad , Masculino , Estudios de Cohortes , Estudios Prospectivos , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Ejercicio Físico , Hospitalización
9.
J Dent Anesth Pain Med ; 24(1): 47-56, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38362256

RESUMEN

Background: Among the various pain-related diseases that can be encountered at the clinic, there is a neuropathic pain that is difficult to treat. Numerous methods have been proposed to treat neuropathic pain, such as taking medication, nerve block with lidocaine, or neurolysis with alcohol or phenol. Recently, a method of perineural injection using dextrose instead of lidocaine was proposed. This study was designed to compare the effects of perineural injection therapy (PIT) with buffered 5% dextrose or 0.5% lidocaine on neuropathic pain. Methods: The data were collected from the database of pain clinic from August 1st, 2019 to December 31st, 2022 without any personal information. The inclusion criteria were patients diagnosed with postherpetic neuralgia (PHN), trigeminal neuralgia (TN), complex regional pain syndrome (CRPS), or peripheral neuropathy (PN), and patients who had undergone PIT with buffered 5% dextrose (Dextrose group) or 0.5% lidocaine (Lidocaine group) for pain control. The data of patients, namely sex, age, and pain score (numerical rating scale, NRS) were collected before PIT. The data of NRS, side effects, and satisfaction grade (excellent, good, fair, or poor) were collected one week after each of the four PIT, and two weeks after the last PIT. Results: Overall, 112 subjects were enrolled. The Dextrose group included 89 and Lidocaine group included 23 patients. Because the number of patients in the Lidocaine group was too small to allow statistical analysis, the trend in Lidocaine group was just observed in each disease. There were no significant side effects except for a few bruise cases on the site of injection in all groups. The NRS in most Dextrose groups except CRPS were reduced significantly; however, the Lidocaine group showed a trend of pain reduction only in PHN. The Dextrose group except CRPS showed increased satisfaction two weeks after the final PIT. Conclusion: From the results, it is suggested that PIT with buffered 5% dextrose may have a good effect for neuropathic pain without any side effect except for patients with CRPS. This may offer a window into a new tool that practitioners can employ in their quest to help patients with neuropathic pain.

10.
Cell Commun Signal ; 22(1): 8, 2024 01 02.
Artículo en Inglés | MEDLINE | ID: mdl-38167009

RESUMEN

BACKGROUND: Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME) that play an important role in cancer progression. Although the mechanism by which CAFs promote tumorigenesis has been well investigated, the underlying mechanism of CAFs activation by neighboring cancer cells remains elusive. In this study, we aim to investigate the signaling pathways involved in CAFs activation by gastric cancer cells (GC) and to provide insights into the therapeutic targeting of CAFs for overcoming GC. METHODS: Alteration of receptor tyrosine kinase (RTK) activity in CAFs was analyzed using phospho-RTK array. The expression of CAFs effector genes was determined by RT-qPCR or ELISA. The migration and invasion of GC cells co-cultured with CAFs were examined by transwell migration/invasion assay. RESULTS: We found that conditioned media (CM) from GC cells could activate multiple receptor tyrosine kinase signaling pathways, including ERK, AKT, and STAT3. Phospho-RTK array analysis showed that CM from GC cells activated PDGFR tyrosine phosphorylation, but only AKT activation was PDGFR-dependent. Furthermore, we found that connective tissue growth factor (CTGF), a member of the CCN family, was the most pronouncedly induced CAFs effector gene by GC cells. Knockdown of CTGF impaired the ability of CAFs to promote GC cell migration and invasion. Although the PDGFR-AKT pathway was pronouncedly activated in CAFs stimulated by GC cells, its pharmacological inhibition affected neither CTGF induction nor CAFs-induced GC cell migration. Unexpectedly, the knockdown of SRC and SRC-family kinase inhibitors, dasatinib and saracatinib, significantly impaired CTGF induction in activated CAFs and the migration of GC cells co-cultured with CAFs. SRC inhibitors restored the reduced expression of epithelial markers, E-cadherin and Zonula Occludens-1 (ZO-1), in GC cells co-cultured with CAFs, as well as CAFs-induced aggregate formation in a 3D tumor spheroid model. CONCLUSIONS: This study provides a characterization of the signaling pathways and effector genes involved in CAFs activation, and strategies that could effectively inhibit it in the context of GC. Video Abstract.


Asunto(s)
Fibroblastos Asociados al Cáncer , Factor de Crecimiento del Tejido Conjuntivo , Neoplasias Gástricas , Humanos , Fibroblastos Asociados al Cáncer/metabolismo , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Factor de Crecimiento del Tejido Conjuntivo/metabolismo , Fibroblastos/metabolismo , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Neoplasias Gástricas/metabolismo , Microambiente Tumoral
11.
Am J Clin Nutr ; 119(1): 39-48, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38070683

RESUMEN

BACKGROUND: Some prior randomized clinical trials (RCTs) that tested the effects of cocoa extract (CE), a source of flavanols, on late-life cognition have yielded promising findings. A long-term RCT using in-person neuropsychological tests covering multiple cognitive domains may clarify the cognitive effects of CE. OBJECTIVES: To test whether daily supplementation with CE, compared with placebo, produces better cognitive change over 2 y. METHODS: The COcoa Supplement and Multivitamin Outcomes Study (COSMOS) is a 2 × 2 factorial RCT of CE [500 mg flavanols/d, including 80 mg (-)-epicatechin] and/or a daily multivitamin-mineral supplement for cardiovascular disease and cancer prevention among 21,442 United States adults aged ≥60 y. There were 573 participants in the clinic subcohort of COSMOS (that is, COSMOS-Clinic) who completed all cognitive tests at baseline; of these, 492 completed 2-y follow-up assessments. The primary outcome was global cognition (averaging z-scores across 11 tests). Secondary outcomes were episodic memory and executive function/attention. Repeated measures models were used to compare randomized groups. RESULTS: Participants' mean age (standard deviation) was 69.6 (5.3); 49.2% were females. Daily supplementation with CE, compared with placebo, had no significant effect on 2-y change in global cognition {mean difference [95% confidence interval (CI)]: -0.01 (-0.08, 0.05) standard deviation units (SU)}. CE, compared with placebo, had no significant effects on 2-y change in episodic memory [mean difference (95% CI): -0.01 (-0.13, 0.10) SU] or executive function/attention [mean difference (95% CI): 0.003 (-0.07, 0.08) SU]. Subgroup analyses uncorrected for multiple-testing suggested cognitive benefits of CE supplementation, compared with placebo among those with poorer baseline diet quality. CONCLUSIONS: Among 573 older adults who underwent repeat in-person, detailed neuropsychological assessments over 2 y, daily CE supplementation, compared with placebo, showed no overall benefits for global or domain-specific cognitive function. Possible cognitive benefits of CE among those with poorer diet quality warrant further study. TRIAL REGISTRATION: This trial was registered at clinicaltrials.gov with identifier - NCT02422745.


Asunto(s)
Cacao , Vitaminas , Anciano , Femenino , Humanos , Masculino , Cognición , Suplementos Dietéticos , Método Doble Ciego , Función Ejecutiva
12.
Pain ; 165(3): 635-643, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37878483

RESUMEN

ABSTRACT: A diet supplemented with vitamin D and marine omega-3 fatty acids may prevent and treat painful disorders by promoting the resolution of inflammation. However, large, randomized placebo-controlled trials evaluating the effects of supplementation with omega-3 fatty acids and vitamin D on the presence and severity of pain are lacking. VITamin D and OmegA-3 triaL-Pain (VITAL-Pain) is an ancillary study to the VITAL trial, a large randomized, double-blind, placebo-controlled trial of vitamin D (2000 IU/day) and omega-3 supplementation (1 g/day) over 5.3 years of median follow-up, among 25,871 older men and women. We assessed pain among those reaching the end of the VITAL intervention phase using questions from the 2012 National Health Interview Survey. We used ordinal logistic regression to test the effect of vitamin D and omega-3 fatty acids on the odds ratio (OR) and 95% confidence interval [CI] of reporting higher pain prevalence or severity. Overall, 19,611 participants provided complete pain information at the end of the VITAL trial. The ORs for higher pain prevalence or severity for vitamin D and omega-3 supplementation vs placebo were 0.99 ([CI] 0.94-1.05) and 0.99 ([CI] 0.94-1.04), respectively. There was no interaction between the 2 active treatments. Dietary supplementation with commonly used moderate doses of vitamin D or omega-3 fatty acids over a median of 5.3 years did not result in a lower prevalence or severity of pain in middle-aged and older U.S. adults.


Asunto(s)
Ácidos Grasos Omega-3 , Vitamina D , Masculino , Persona de Mediana Edad , Humanos , Femenino , Anciano , Vitamina D/uso terapéutico , Ácidos Grasos Omega-3/uso terapéutico , Prevalencia , Vitaminas/uso terapéutico , Colecalciferol/uso terapéutico , Suplementos Dietéticos , Método Doble Ciego , Dolor/tratamiento farmacológico , Dolor/epidemiología
13.
Int J Oral Sci ; 15(1): 55, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062012

RESUMEN

Ameloblasts are specialized cells derived from the dental epithelium that produce enamel, a hierarchically structured tissue comprised of highly elongated hydroxylapatite (OHAp) crystallites. The unique function of the epithelial cells synthesizing crystallites and assembling them in a mechanically robust structure is not fully elucidated yet, partly due to limitations with in vitro experimental models. Herein, we demonstrate the ability to generate mineralizing dental epithelial organoids (DEOs) from adult dental epithelial stem cells (aDESCs) isolated from mouse incisor tissues. DEOs expressed ameloblast markers, could be maintained for more than five months (11 passages) in vitro in media containing modulators of Wnt, Egf, Bmp, Fgf and Notch signaling pathways, and were amenable to cryostorage. When transplanted underneath murine kidney capsules, organoids produced OHAp crystallites similar in composition, size, and shape to mineralized dental tissues, including some enamel-like elongated crystals. DEOs are thus a powerful in vitro model to study mineralization process by dental epithelium, which can pave the way to understanding amelogenesis and developing regenerative therapy of enamel.


Asunto(s)
Esmalte Dental , Durapatita , Ratones , Animales , Durapatita/farmacología , Durapatita/análisis , Durapatita/metabolismo , Esmalte Dental/metabolismo , Ameloblastos/metabolismo , Amelogénesis , Células Madre , Organoides
14.
Cell Death Dis ; 14(12): 822, 2023 12 13.
Artículo en Inglés | MEDLINE | ID: mdl-38092725

RESUMEN

Jagged1 (JAG1) is a Notch ligand that correlates with tumor progression. Not limited to its function as a ligand, JAG1 can be cleaved, and its intracellular domain translocates to the nucleus, where it functions as a transcriptional cofactor. Previously, we showed that JAG1 intracellular domain (JICD1) forms a protein complex with DDX17/SMAD3/TGIF2. However, the molecular mechanisms underlying JICD1-mediated tumor aggressiveness remains unclear. Here, we demonstrate that JICD1 enhances the invasive phenotypes of glioblastoma cells by transcriptionally activating epithelial-to-mesenchymal transition (EMT)-related genes, especially TWIST1. The inhibition of TWIST1 reduced JICD1-driven tumor aggressiveness. Although SMAD3 is an important component of transforming growth factor (TGF)-ß signaling, the JICD1/SMAD3 transcriptional complex was shown to govern brain tumor invasion independent of TGF-ß signaling. Moreover, JICD1-TWIST1-MMP2 and MMP9 axes were significantly correlated with clinical outcome of glioblastoma patients. Collectively, we identified the JICD1/SMAD3-TWIST1 axis as a novel inducer of invasive phenotypes in cancer cells.


Asunto(s)
Glioblastoma , Humanos , Línea Celular Tumoral , Transición Epitelial-Mesenquimal/genética , Glioblastoma/genética , Proteínas de Homeodominio/metabolismo , Ligandos , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal , Proteína smad3/genética , Proteína smad3/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Proteína 1 Relacionada con Twist/genética , Proteína 1 Relacionada con Twist/metabolismo
15.
Nat Commun ; 14(1): 8153, 2023 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-38071202

RESUMEN

Accurate diagnosis of Alzheimer's disease (AD) in its earliest stage can prevent the disease and delay the symptoms. Therefore, more sensitive, non-invasive, and simple screening tools are required for the early diagnosis and monitoring of AD. Here, we design a self-assembled nanoparticle-mediated amplified fluorogenic immunoassay (SNAFIA) consisting of magnetic and fluorophore-loaded polymeric nanoparticles. Using a discovery cohort of 21 subjects, proteomic analysis identifies adenylyl cyclase-associated protein 1 (CAP1) as a potential tear biomarker. The SNAFIA demonstrates a low detection limit (236 aM), good reliability (R2 = 0.991), and a wide analytical range (0.320-1000 fM) for CAP1 in tear fluid. Crucially, in the verification phase with 39 subjects, SNAFIA discriminates AD patients from healthy controls with 90% sensitivity and 100% specificity in under an hour. Utilizing tear fluid as a liquid biopsy, SNAFIA could potentially aid in long-term care planning, improve clinical trial efficiency, and accelerate therapeutic development for AD.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Enfermedad de Alzheimer/metabolismo , Proteómica , Reproducibilidad de los Resultados , Inmunoensayo , Diagnóstico Precoz , Biomarcadores/metabolismo , Péptidos beta-Amiloides
16.
BMJ Open ; 13(12): e071735, 2023 12 06.
Artículo en Inglés | MEDLINE | ID: mdl-38056939

RESUMEN

OBJECTIVES: Fibromyalgia treatment trends vary globally; however, the trend in South Korea has not been investigated yet. This study aimed to analyse the fibromyalgia treatment trends in South Korea. DESIGN: Retrospective, observational study using serial cross-sectional data. SETTING: The National Patient Samples of the Korean Health Insurance Review & Assessment Service from 2011 to 2018 were used. PARTICIPANTS: A total of 31 059 patients with fibromyalgia were included in this study. The basic characteristics of the patients were stratified by sex, age and comorbidity. A patient was considered to have a condition if it was recorded as a principal diagnosis at least once in a year. PRIMARY AND SECONDARY OUTCOME MEASURES: Trends in the types of medical visits and prescribed treatments were investigated and the values are presented as rates per 100 patients. The types of pharmacological treatment were presented according to the existing clinical guidelines. Additionally, combination prescription trends and associated characteristics were investigated. RESULTS: Of the patients, 66.2% were female. Visits to internal medicine departments showed the most significant increase (2011: 11.34; 2018: 21.99; p<0.001). Non-pharmacological treatment rates declined (physical therapy 2011: 18.11; 2018: 13.69; p<0.001, acupuncture 2011: 52.03; 2018: 30.83; p<0.001). Prescription rates increased for analgesics, relaxants, antiepileptics and antidepressants. Non-steroidal anti-inflammatory drug prescriptions had the highest increase (2011: 27.65; 2018: 40.02; p<0.001). Serotonin-norepinephrine reuptake inhibitor prescriptions showed significant growth (2011: 2.4; 2018: 8.05; p<0.001). Prescription durations were generally longer for women (p<0.001), with higher rate increases in this group. Combinations of ≥3 medication classes increased (2011: 8.2; 2018: 9.64; p=0.041). Women were more likely to receive combination prescriptions (crude OR 1.47 (95% CI 1.29 to 1.68), adjusted 1.18 (95% CI 1.03 to 1.36)). CONCLUSIONS: Our findings provide basic reference data for the development and application of national guidelines for fibromyalgia.


Asunto(s)
Fibromialgia , Humanos , Femenino , Masculino , Fibromialgia/epidemiología , Fibromialgia/terapia , Fibromialgia/complicaciones , Estudios Retrospectivos , Estudios Transversales , Analgésicos/uso terapéutico , Inhibidores Selectivos de la Recaptación de Serotonina , Seguro de Salud
17.
J Pain Res ; 16: 3971-3977, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38026451

RESUMEN

Purpose: Urticaria is a common mast-cell-driven disease that poses a great burden on patients and society. Suggested therapeutic methods include avoidance of triggers and the use of medications, such as H1-antihistamines; however, limitations remain regarding efficacy, dealing with comorbidities, and adverse events. Cupping therapy (CT) at CV8 Shenque has been used in traditional Chinese medicine for the treatment of various dermatological diseases, including urticaria. The efficacy of the treatment has been revealed by previous clinical trials and case reports. This study was performed to provide a protocol for a systematic review and meta-analysis to analyze the effectiveness and safety of CT at CV8 Shenque for urticaria patients. Patients and Methods: Searches of electronic databases using manual searches and contact with the corresponding authors will be performed using predefined criteria for all randomized controlled trials on CT at CV8 Shenque for urticaria patients. Every part of the process will be conducted by two independent researchers, with conflicts being solved by a third author. The primary outcomes will be symptom scores, quality of life, and effective rate. Secondary outcomes will be adverse events and diagnostic test results. RevMan 5.4 software will be used to perform the meta-analysis. The Cochrane Collaboration "Risk of bias" tool will be used for risk of bias judgments. Results: Our study will evaluate the effectiveness and safety of CT at CV8 Shenque as a treatment option for urticaria. Conclusion: This systematic review is the first to investigate the effect of CT at CV8 Shenque for urticaria patients. Our study will provide objective evidence of an alternative approach to urticaria for clinicians and patients. Study Registration: PROSPERO (Registration number: CRD42023434913).

18.
Sci Adv ; 9(47): eadi8454, 2023 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-38000027

RESUMEN

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.


Asunto(s)
Reprogramación Celular , Células Madre Pluripotentes Inducidas , Reprogramación Celular/genética , Células Madre Pluripotentes Inducidas/metabolismo
19.
Hum Resour Health ; 21(1): 89, 2023 Nov 21.
Artículo en Inglés | MEDLINE | ID: mdl-37990265

RESUMEN

BACKGROUND: Achieving the targeted organizational goals through effective training can increase employee satisfaction. Since 2015, the Supranational Reference Laboratory Uganda (SRL Uganda) has trained National Tuberculosis Reference Laboratories (NTRLs) from 21 countries in a variety of areas that cover both technical and programmatic aspects pertinent to TB laboratories. The Laboratory Quality Management System (LQMS) under SRL coordinates actions intended to ensure sustained quality of the laboratory services offered by the National TB Reference Laboratories. In order for laboratory results to be helpful in a clinical or public health setting, they must be accurate, reliable, and timely. The LQMS course aims to provide learners with knowledge on how to attain and maintain this quality. Prior to this study, there was hardly any data available on the effectiveness of LQMS trainings provided by SRL Uganda; using Kirkpatrick model, which is popular among researchers for evaluating the efficacy of the training program, this paper seeks to establish the effectiveness of the LQMS training offered by the SRL Uganda. METHOD: We evaluated the effectiveness of LQMS training within the Uganda's SRL network for courses offered during the period 2017 and 2021 for participants from the Southern and East African sub-Saharan region. RESULTS: In 2017 and 2021, respectively, test results from 10/17 and 9/17 showed overall post-test scores above 80%. Of the 18 labs evaluated, 14 showed improvement; of these, 7 labs were from the Eastern region and the other 7 were from Southern Africa; one facility in this region also maintained its accreditation. In the post-evaluation assessment, attendees of the LQMS course gave feedback of strongly agree and agree variety. CONCLUSION: More SRL Uganda network laboratories in the regions achieved a 5-star SLIPTA level rating and among these, 5 NTRLs got ISO 15189:2012 accredited by the end of 2021, while one maintained its accreditation status. This proves that the Laboratory Quality Management System training program was an effective tool in improving the quality of laboratory services, work practices, and processes.


Asunto(s)
Laboratorios , Tuberculosis , Humanos , Uganda , Tuberculosis/diagnóstico , Tuberculosis/tratamiento farmacológico , Encuestas y Cuestionarios , África del Norte
20.
Diabetes Care ; 46(12): 2278-2284, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37816167

RESUMEN

OBJECTIVE: Observational studies have indicated that cocoa flavanol supplementation may be a promising strategy for type 2 diabetes (T2D) prevention. We aimed to directly evaluate its clinical efficacy in a large randomized clinical trial (RCT). RESEARCH DESIGN AND METHOD: The Cocoa Supplement and Multivitamin Outcomes Study (COMSOS) was a 2 × 2 factorial RCT performed from June 2015 to December 2020 that tested cocoa extract and a multivitamin for the prevention of cardiovascular disease (CVD) and cancer. A total of 21,442 U.S. adults free of CVD and recent cancer, including 12,666 women aged ≥65 years and 8,776 men aged ≥60 years, were randomly assigned to receive cocoa extract [500 mg/day cocoa flavanols, including 80 mg (-)-epicatechin] or placebo. In this study, we included 18,381 participants without diabetes at enrollment and examined the effect of cocoa extract supplementation on incident self-reported T2D in intention-to-treat analyses. RESULTS: During a median follow-up of 3.5 years, 801 incident T2D cases were reported. Compared with placebo, taking a cocoa extract supplement did not reduce T2D (adjusted hazard ratio 1.04, 95% CI 0.91-1.20, P = 0.58). Stratification analyses showed that the effect of cocoa extract supplementation was not significantly modified by sex, race, BMI, smoking, physical activity, dietary quality, flavanol status at baseline, or randomized multivitamin assignment. CONCLUSIONS: Middle-aged and older adults taking a cocoa extract supplement for a median of 3.5 years did not reduce their risk of incident T2D. Further studies of cocoa extract supplementation beginning earlier in adulthood and in populations with different background diets are warranted.


Asunto(s)
Cacao , Enfermedades Cardiovasculares , Diabetes Mellitus Tipo 2 , Neoplasias , Masculino , Persona de Mediana Edad , Femenino , Humanos , Anciano , Suplementos Dietéticos , Vitaminas/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus Tipo 2/prevención & control , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Extractos Vegetales/uso terapéutico , Neoplasias/tratamiento farmacológico , Método Doble Ciego
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