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Hedgehog (Hh) signaling relies on the primary cilium, a cell surface organelle that serves as a signaling hub for the cell. Using proximity labeling and quantitative proteomics, we identify Numb as a ciliary protein that positively regulates Hh signaling. Numb localizes to the ciliary pocket and acts as an endocytic adaptor to incorporate Ptch1 into clathrin-coated vesicles, thereby promoting Ptch1 exit from the cilium, a key step in Hh signaling activation. Numb loss impedes Sonic hedgehog (Shh)-induced Ptch1 exit from the cilium, resulting in reduced Hh signaling. Numb loss in spinal neural progenitors reduces Shh-induced differentiation into cell fates reliant on high Hh activity. Genetic ablation of Numb in the developing cerebellum impairs the proliferation of granule cell precursors, a Hh-dependent process, resulting in reduced cerebellar size. This study highlights Numb as a regulator of ciliary Ptch1 levels during Hh signal activation and demonstrates the key role of ciliary pocket-mediated endocytosis in cell signaling.
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Cerebelo , Cilios , Proteínas Hedgehog , Proteínas del Tejido Nervioso , Receptor Patched-1 , Transducción de Señal , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Cilios/metabolismo , Animales , Receptor Patched-1/metabolismo , Receptor Patched-1/genética , Ratones , Proteínas del Tejido Nervioso/metabolismo , Proteínas del Tejido Nervioso/genética , Cerebelo/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Humanos , Endocitosis , Diferenciación Celular , Proliferación Celular , Células-Madre Neurales/metabolismo , Células-Madre Neurales/citología , Ratones NoqueadosAsunto(s)
Técnicas Biosensibles , Imagen Óptica , Técnicas Biosensibles/métodos , Humanos , AnimalesRESUMEN
Functionalized with the Au-S bond, gold nanoflares have emerged as promising candidates for theranostics. However, the presence of intracellular abundantly biothiols compromises the conventional Au-S bond, leading to the unintended release of cargoes and associated side-effects on non-target cells. Additionally, the hypoxic microenvironment in diseased regions limits treatment efficacy, especially in photodynamic therapy. To address these challenges, high-fidelity photodynamic nanoflares constructed on Pt-coated gold nanoparticles (Au@Pt PDNF) were communicated to avoid false-positive therapeutic signals and side-effects caused by biothiol perturbation. Compared with conventional photodynamic gold nanoflares (AuNP PDNF), the Au@Pt PDNF were selectively activated by cancer biomarkers and exhibited high-fidelity phototheranostics while reducing side-effects. Furthermore, the ultrathin Pt-shell catalysis was confirmed to generate oxygen which alleviated hypoxia-related photodynamic resistance and enhanced the antitumor effect. This design might open a new venue to advance theranostics performance and is adaptable to other theranostic nanomaterials by simply adding a Pt shell.
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Antineoplásicos , Oro , Nanopartículas del Metal , Platino (Metal) , Nanomedicina Teranóstica , Oro/química , Humanos , Platino (Metal)/química , Nanopartículas del Metal/química , Antineoplásicos/química , Antineoplásicos/farmacología , Fotoquimioterapia , Supervivencia Celular/efectos de los fármacos , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Proliferación Celular/efectos de los fármacosRESUMEN
Triplex DNA switches are attractive allosteric tools for engineering smart nanodevices, but their poor triplex-forming capacity at physiological conditions limited the practical applications. To address this challenge, we proposed a low-entropy barrier design to facilitate triplex formation by introducing a hairpin duplex linker into the triplex motif, and the resulting triplex switch was termed as CTNSds. Compared to the conventional clamp-like triplex switch, CTNSds increased the triplex-forming ratio from 30 % to 91 % at pHâ 7.4 and stabilized the triple-helix structure in FBS and cell lysate. CTNSds was also less sensitive to free-energy disturbances, such as lengthening linkers or mismatches in the triple-helix stem. The CTNSds design was utilized to reversibly isolate CTCs from whole blood, achieving high capture efficiencies (>86 %) at pHâ 7.4 and release efficiencies (>80 %) at pHâ 8.0. Our approach broadens the potential applications of DNA switches-based switchable nanodevices, showing great promise in biosensing and biomedicine.
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ADN , Concentración de Iones de Hidrógeno , ADN/química , Humanos , Entropía , Conformación de Ácido Nucleico , Técnicas BiosensiblesRESUMEN
BACKGROUND: The Internet Plus Nursing Service (IPNS) is being instigated in all provincial-level regions throughout China, in which registered nurses (with more than five years of experience from qualified medical institutions) will provide services to those in their communities or homes after receiving online applications. The growing shortage of human resources in nursing is a critical issue for this project, so effective policies for recruiting and retaining nurses are critical. OBJECTIVE: This study aims to pinpoint the significant job characteristics that play a crucial role in shaping the job decisions of sharing nurses in the IPNS program, and to estimate the strength of job attributes. METHODS: A discrete choice experiment (DCE) was used to assess job attributes influencing sharing nurses' preferences. A qualitative design, including in-depth interview and focus interview methods, was conducted to determine the inclusion of attributes. The final included six attributes were: work modes, duration per visit, income per visit, personal safety, medical risk prevention, and refresher training. This study was conducted at 13 hospitals in Guangdong Province, China, from April to June 2022, and a total of 220 registered sharing nurses participated in the survey. The multinomial logit model explored attributes and relative valued utility. Preference heterogeneity is explored via latent class analysis (LCA) models. RESULTS: A total of 220 participants answered the questionnaire. Income was the most influential characteristic of a sharing nursing position, followed by personal safety management, duration per visit, medical risk prevention, and refresher training, and nurses' preferences differed among different types of classes. CONCLUSIONS: Sharing nurses place most value on income and personal safety with career-related decisions, which indicates an urgent need to develop complete security for personal safety. This study can be helpful to decision-makers in the Chinese government.
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The American College of Medical Genetics and Genomics (ACMG) recommends carrier screening for all pregnant women regardless of race or ethnicity. In recent years, the ACMG broadened the guidelines to include expanded carrier screening (ECS) which can screen for 112 conditions. This study seeks to explore the perceptions of pregnant Latina women about the benefits and concerns related to ECS use. Partnering with prenatal clinics in Texas, we conducted semi-structured qualitative interviews with 32 pregnant Latina women in their second or third trimester of pregnancy. NVivo 8 was used to conduct content analysis and emergent coding of the data. Participants reported the benefits of ECS as helping them prepare for the baby's arrival, informing them of the baby's risk for genetic conditions, ensuring the health of their baby, and preventing diseases before birth. The ECS-related concerns expressed by the participants included worries surrounding potential positive ECS results, insufficient knowledge about the genetic diseases screened for by ECS, the accuracy of the ECS, the potential harm ECS may cause the baby, and the affordability of ECS. After weighing both their perceived benefits and concerns, nearly all the participants believed that ECS should be offered to all pregnant women. This study contributes to an understudied research area in the genetic/genomic field. Our findings can help increase the awareness of obstetricians, genetic professionals, and other healthcare providers regarding pregnant Latina women's views on ECS and inform the design of culturally appropriate care as ECS is adopted into routine clinical practice.
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CONTEXT: Despite prevalent anti-osteoporosis medication (AOM) switching in real-world osteoporosis management, few studies have evaluated the impact of persistent AOM treatment, allowing for AOM switching, on the risk of subsequent fracture. OBJECTIVE: We examined the association between persistence in AOM and subsequent fractures, allowing for medication switching among patients with osteoporotic fractures. METHODS: This retrospective cohort study used Taiwan National Health Insurance claims data to select patients who initiated AOM between 2013 and 2016. Treatment persistence was defined as use of any AOM on a given day of interest with a 45-day grace period. Medication switch was allowed for persistence if remaining on treatment. AOMs with long-lasting inhibition of bone resorption (zoledronate and denosumab) were categorized as high-potency; others as low-potency. Multivariate Cox models were used to evaluate risk of subsequent fractures ≥3 months after initiating AOM. RESULTS: A total of 119 473 patients were included (mean [SD] follow-up 46.4 [15.6] months), and 26.8% switched from the index AOM. Within 1 year, 52% remained persistent with AOM. Compared to patients with persistent AOM, those not persistent had higher risk of subsequent hip (adjusted hazard ratio [aHR] = 1.31; 95% CI, 1.21-1.42), vertebral (aHR = 1.17; 95% CI, 1.13-1.22), and radius fractures (aHR = 1.16; 95% CI, 1.08-1.25). Patients with persistent AOM who switched from high- to low-potency AOM had higher risk of subsequent vertebral fractures than those with persistent AOM and no potency switch (aHR = 1.28; 95% CI, 1.02-1.60). CONCLUSION: Patients with non-persistent AOM had higher risk of subsequent fractures than persistent users when allowing AOM switch. Switching AOM potency may influence the risk of subsequent vertebral fractures and warrants further investigation.
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Conservadores de la Densidad Ósea , Osteoporosis , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Fracturas Osteoporóticas/inducido químicamente , Fracturas Osteoporóticas/epidemiología , Conservadores de la Densidad Ósea/efectos adversos , Estudios Retrospectivos , Osteoporosis/complicaciones , Osteoporosis/tratamiento farmacológico , Osteoporosis/epidemiología , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/complicacionesRESUMEN
OBJECTIVES: To describe the occurrence of recurrent atherosclerotic cardiovascular disease (ASCVD) events within 3 years after a new-onset event, the associated disease burden and statin prescribing in patients with ASCVD in Taiwan. DESIGN: Retrospective cohort study. SETTING: This was a retrospective cohort study using Taiwan's National Health Insurance Research Database. PARTICIPANTS: In total, 111 399, 133 538 and 21 572 patients who were hospitalised with diagnosis of coronary heart disease (CHD), cerebrovascular disease (CBVD) and peripheral artery disease (PAD), respectively, between 1 January 2012 and 31 December 2014. PRIMARY AND SECONDARY OUTCOME MEASURES: For each index and recurrent event, patients were observed for 12 months after admission to quantify risks of mortality, recurrent events, statin treatment and healthcare use. RESULTS: We identified 97 321, 120 914 and 14 794 patients with new-onset CHD, CBVD and PAD, respectively. The proportions of developing first, second and third recurrent events were 22.5%, 25.6% and 30.9% for CHD; 20.9%, 26.2% and 32.4% for CBVD and 40.2%, 41.4% and 43.6% for PAD, respectively. Most patients had the same type of ASCVD for their recurrent events as their new-onset event. The mortality rates increased with each recurrent event (p<0.05 for all three ASCVD groups). The rates of hospital readmission and emergency room (ER) visit increased with increasing recurrent events. For example, in the CHD group, the 1-year readmission rates following the index, first and second recurrent events were 43.1%, 47.6% and 55.3%, respectively, and the proportions of visiting ER were 46.4%, 51.9% and 57.8%, respectively. Statin prescribing was suboptimal at time of index event and recurrent events. CONCLUSION: Recurrent ASCVD events were associated with a higher risk of recurrent event and mortality and greater healthcare use. However, statin prescriptions at index event and after each recurrent event were suboptimal.
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Aterosclerosis , Enfermedades Cardiovasculares , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Enfermedades Cardiovasculares/epidemiología , Estudios Retrospectivos , Taiwán/epidemiología , Aterosclerosis/epidemiología , Atención a la Salud , Factores de RiesgoRESUMEN
Background: Consistent and effective self-management is a major challenge for people with diabetes and long-term effects can be difficult to sustain despite the many interventions. Interventions often fail to take patients' perceptions of self-management into account from their perspective. Exploring the needs preferences and the influencing factors of self-management in patients can improve the effectiveness of self-management. Methods: This study used a mixed research approach, exploring patient needs and preferences through web crawl methods and using qualitative interviews to explore the logic of preferences. 1605 data were obtained from 4 online health communities through web crawlers. Data were coded using grounded theory to analyze self-management needs. The codes were also coded for frequency statistics and ranked to explain the self-management preferences. The second phase explained the logic of the ranked distribution of preferences through one-on-one interviews with 22 patients. Results: This study summarized six self-management needs of people with diabetes through web crawler data, among which medication management and conflict between disease and daily life were the most important concerns of patients. The reasons why patients are particularly concerned about these two needs were explored through qualitative interviews, and it was found that patients' concerns about medication were mainly due to the following three aspects: the effect of drugs is direct and obvious, medication use makes life less complicated, and progressive side effects. The patients' concerns about the conflict between disease and daily life are often caused by the following three aspects: diabetes impacts social roles, disease complicates life, and reducing the impact of the disease on life. Conclusion: The self-management needs of Chinese diabetics have six themes. Medication management, conflict between disease and daily life, diet, diabetes knowledge, blood glucose monitoring and exerciseIn order of frequency of mention and possible preference: medication management, conflict between disease and daily life were the most frequent needs, while diet, knowledge about diabetes, blood glucose monitoring and exercise were their least frequent needs.Understanding the individual's perception and understanding of diabetes self-management and the expression of the patient's daily life situations can guide the medical team to optimize collaboration on personalized care plans.
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BACKGROUND: Due to the poor specificity of D-dimer, more accurate thrombus biomarkers are clinically needed to improve the diagnostic power of VTE. METHODS: The plasma samples were classified into low-risk group (n = 6) and high-risk group (n = 6) according to the Caprini Thrombosis Risk Assessment Scale score. Data-independent acquisition mass spectrometry (DIA-MS) was performed to identify the proteins in the 12 plasma samples. Bioinformatics analysis including volcano plot, heatmap, KEGG pathways and chord diagram analysis were drawn to analyze the significantly differentially expressed proteins (DEPs) between the two groups. Then, another 26 plasma samples were collected to verify the key proteins as potential biomarkers of VTE in orthopedic surgery patients. RESULTS: A total of 371 proteins were identified by DIA-MS in 12 plasma samples. Volcano plotting showed that there were 30 DEPs. KEGG pathway enrichment analysis revealed that the DEPs were majorly involved in the blood coagulation pathway. The chord diagram analysis demonstrated that proteins SAA1, VWF, FLNA, ACTB, VINC, F13B, F13A and IPSP in the DEPs were significantly related to blood coagulation. VWF and F13B were selected for validation experiments. ELISA test showed that, as compared with those in the low-risk group, the level of VWF in the high-risk sera was significantly increased. CONCLUSIONS: The level of VWF in the high-risk group of thrombosis after orthopedic surgery was significantly higher than that in the low-risk group of preoperative thrombosis, suggesting that VWF may be used as a potential thrombus biomarker in orthopedic surgery patients.
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Procedimientos Ortopédicos , Trombosis , Tromboembolia Venosa , Humanos , Factor de von Willebrand/análisis , Factor de von Willebrand/metabolismo , Proteómica , Medición de Riesgo , Biomarcadores , Trombosis/diagnóstico , Trombosis/etiología , Procedimientos Ortopédicos/efectos adversosRESUMEN
With the advance of genetic technologies, the use of expanded carrier screening (ECS) in the prenatal setting is growing. ECS tests for a wide range of inherited genetic disorders regardless of racial/ethnic background and family history. Latinxs are an important ECS stakeholder group as they are the largest minority group with the highest fertility rate in the United States. Yet, the Latinx population has, to date, been underrepresented and understudied in genetics/genomics research. We conducted a study to explore the knowledge and perspectives of pregnant Latinas regarding ECS in which descriptive statistics and content analysis were used to analyze the data. Thirty-two pregnant Latinas - mostly of low educational levels (no education beyond high school) and with less than $20,000 annual household income living in rural areas were surveyed, provided with education about ECS, and interviewed. Participants were found to possess limited knowledge about ECS prior to being interviewed. Most (68.8%), however, expressed interest in pursuing ECS following the educational component that explained ECS. Their interest was mainly driven by the desire to know their baby's chance of developing a genetic disorder, the low risk of ECS procedures for both pregnant Latinas and their fetus, and the opportunity to better prepare for raising a child with a genetic condition. Our findings contribute to the limited research in the genetics/genomics field by providing in-depth insights into the perspectives of pregnant Latinas regarding ECS. Obstetric providers and genetic counselors should provide culturally appropriate education and counseling to empower pregnant Latinas to make informed decisions about the use of ECS.
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Consejeros , Asesoramiento Genético , Embarazo , Femenino , Niño , Humanos , Asesoramiento Genético/métodos , Tamización de Portadores Genéticos/métodos , Consejo , Hispánicos o Latinos/genéticaRESUMEN
BACKGROUND: The diabetes disease burden in China is heavy, and medical standards such as diabetes guidelines are the core reference guidelines for diabetes management for health care providers and patients. However, patients' guideline compliance is too low, which correlates with the gap between guidelines and patients' self-management needs. Incorporating patient needs into the guideline development would reduce this gap. OBJECTIVE: We sought to capture the needs of patients with diabetes for self-management in everyday situations and to clarify the contradictions and misalignments between medical standards, such as guidelines, and patient needs. METHODS: This study collected crawler-based data from 4 online health communities. We selected 1605 text records collected from Chinese patients with diabetes between March 2020 and July 2020 for analysis. The text analysis applied grounded theory to separate issues that concerned patients into 3 themes, 7 subthemes, and 25 entries. RESULTS: Altogether, 69.03% (1108/1605) of texts were related to issues concerning disease treatment (theme B) and mainly inquired about medication use (B2 and B3; 686/1108, 61.91%), including medication choice, change in medication administration, side effects, and postmedication effects. In addition, 222 (N=1605, 13.8%) texts (theme A) concerned the explanation of disease etiology and knowledge of diabetes, and 275 (N=1605, 17.1%) texts (theme C) discussed lifestyle changes and various restrictions on life brought about by the disease. CONCLUSIONS: Our findings suggest an urgent need to improve diabetes health education and guideline development strategies and to develop health management strategies from a patient perspective to bridge the misalignment between patient needs and current medical standards.
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Diabetes Mellitus Tipo 2 , Envío de Mensajes de Texto , Humanos , Diabetes Mellitus Tipo 2/terapia , Investigación Cualitativa , Cooperación del Paciente , Estilo de VidaRESUMEN
BACKGROUND: Dementia has become a global public health problem, and general practitioners (GPs) play a key role in diagnosing and managing dementia. However, in Chinese primary care settings, dementia is underdiagnosed and inefficiently managed, and dementia screening and management services provided by GPs are suboptimal. The reasons underlying this gap are poorly understood. This study aimed to determine the barriers that hinder GPs from actively promoting dementia screening and management, and thereby provide insights for the successful promotion of dementia screening and management services in primary care. METHODS: Purposive sampling was used. And focus groups and in-depth interviews were conducted face-to-face among GPs from community health service centers (CHSCs) in South China. Thematic analysis was used to identify barriers to screening and managing dementia and map them to the Capability/Opportunity/Motivation-Behavior model (COM-B model). RESULTS: Fifty-two GPs were included. The COM-B model found nine barriers to implementing dementia screening and management services in primary healthcare: (1) poor capability: lack of systematic knowledge of dementia and inadequate dementia screening skills; (2) little opportunity: unclear pathways for referral, insufficient time for dementia screening and management, lack of dementia-specific leaders, and no guarantee of services continuity; (3) low motivation: outside of GP scope, worries associated with dementia stigma rooted in culture beliefs, and insufficient financial incentives. CONCLUSIONS: Our study concluded that GPs were not yet ready to provide dementia screening and management services due to poor capability related to knowledge and skills of dementia, little opportunity associated with an unsupportive working environment, and low motivation due to unclear duty and social pressure. Accordingly, systematic implementation strategies should be taken, including standardized dementia training programs, standardized community-based dementia guidelines, expansion of primary care workforces, development of dedicated leaders, and the eradication of stigma attached to dementia to promote dementia screening and management services in primary care.
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Demencia , Médicos Generales , Humanos , Motivación , Investigación Cualitativa , Grupos Focales , Demencia/diagnóstico , Demencia/epidemiología , Demencia/terapiaRESUMEN
ObjectiveThe present study aims to examine the impacts of a mandatory physical activity (PA) course on exercise motivation among predominately Hispanic college students. The course was designed based on the Self-Determination Theory to increase students' PA motivation. Methods: A total of 383 college students (nmales=126; nfemales=257; Mage=19.6; 67.6% Hispanic/Latino[a]) participated in the course and completed the Behavioral Regulation to Exercise Questionnaire-2 at the beginning (pretest) and the end of the course (post-test). This questionnaire measured five motivation constructs: amotivation, intrinsic motivation, extrinsic motivation, introjected regulation, and identified regulation. Results: Findings showed significant increases from pretest to post-test in all five motivation constructs (ps < 0.01). Conclusions: Although the mandatory PA curriculum successfully increased the intrinsic motivation, extrinsic motivation, introjected regulation, and identified regulation among college students, amotivation was also increased. These outcomes suggested some positive impacts on Hispanic college students' motivation to participate in PA. Findings can assist researchers and educators in developing, implementing, and evaluating required PA courses in colleges and universities.
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Curriculum , Ejercicio Físico , Motivación , Femenino , Humanos , Masculino , Hispánicos o Latinos , Estudiantes , UniversidadesRESUMEN
Deciphering signaling mechanisms critical for the extended pluripotent stem cell (EPSC) state and primed pluripotency is necessary for understanding embryonic development. Here, a membrane protein, podocalyxin-like protein 1 (PODXL) as being essential for extended and primed pluripotency, is identified. Alteration of PODXL expression levels affects self-renewal, protein expression of c-MYC and telomerase, and induced pluripotent stem cell (iPSC) and EPSC colony formation. PODXL is the first membrane protein reported to regulate de novo cholesterol biosynthesis, and human pluripotent stem cells (hPSCs) are more sensitive to cholesterol depletion than fibroblasts. The addition of exogenous cholesterol fully restores PODXL knockdown-mediated loss of pluripotency. PODXL affects lipid raft dynamics via the regulation of cholesterol. PODXL recruits the RAC1/CDC42/actin network to regulate SREBP1 and SREBP2 maturation and lipid raft dynamics. Single-cell RNA sequencing reveals PODXL overexpression enhanced chimerism between human cells in mouse host embryos (hEPSCs 57%). Interestingly, in the human-mouse chimeras, laminin and collagen signaling-related pathways are dominant in PODXL overexpressing cells. It is concluded that cholesterol regulation via PODXL signaling is critical for ESC/EPSC.
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Treatment persistence was higher among the patients who initially received an anti-osteoporosis medication (AOM) with a long-dose-interval. PURPOSE: With long-dose-interval anti-osteoporosis medications (AOMs) available for osteoporosis management, it is important to evaluate persistence of any AOM as long as it is continuously used. The purpose of this study was to investigate the treatment pattern and persistence of AOMs, allowing for medication switch. METHODS: This study was an observational retrospective cohort study using Taiwan's National Health Insurance claims data. We selected patients who first initiated an AOM between January 1, 2013, and June 30, 2016. AOM therapy included alendronate, raloxifene, teriparatide, denosumab, zoledronate, and ibandronate; the latter three were categorized as long-dose-interval medications. Persistence was defined as continual prescription of any AOM at a given time point with a grace period of 45 days within which to obtain prescription refill. The competing risk model was used to examine the factors affecting patients switching their initial AOM. RESULTS: During the study period, 126,539 patients with mean age of 75 years met the inclusion criteria; 85% were female. For initial AOM, 43.3%, 25.6%, 14.6%, 9.3%, 5.3%, and 1.9% of the patients received alendronate, denosumab, raloxifene, zoledronate, ibandronate, and teriparatide, respectively. During a mean 36-month follow-up, 29.6% of the patients who received at least two AOM pharmacy claims throughout the study period have ever switched their initial medication. Long-dose-interval medications, mainly denosumab and zoledronate, were the preferred choice for medication switch. Treatment persistence was higher in patients who initiated with long-dose-interval AOMs. CONCLUSION: The real-world data reveal long-dose-interval therapy as an initial treatment or at the first switch stage may improve management of persistent AOM treatment.
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Conservadores de la Densidad Ósea , Osteoporosis , Anciano , Alendronato/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Denosumab/uso terapéutico , Femenino , Humanos , Ácido Ibandrónico/uso terapéutico , Masculino , Cumplimiento de la Medicación , Osteoporosis/inducido químicamente , Osteoporosis/tratamiento farmacológico , Clorhidrato de Raloxifeno/uso terapéutico , Estudios Retrospectivos , Taiwán/epidemiología , Teriparatido/uso terapéutico , Ácido Zoledrónico/uso terapéuticoRESUMEN
BACKGROUND: Effect of laparoscopic sleeve gastrectomy (LSG) on thyroid function of patients with obesity remains unclear. The aim of this study was to evaluate the changes in thyroid function before and after LSG in patients with obesity. METHODS: Data was retrieved from a retrospectively collected database of patients with morbid obesity and normal thyroid function who received LSG. At 12 months after surgery, changes of thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), and intact parathyroid hormone (iPTH) were evaluated. In addition, the correlation between thyroid hormone levels and body mass index (BMI) and other metabolic indicators and anthropometric parameters were analyzed. RESULTS: Eighty-five patients were included in the study. The concentrations of FT3 (5.7 ± 0.7 vs 5.1 ± 0.6, p < 0.001) and TSH (2.2 ± 1.0 vs 1.9 ± 0.9, p = 0.002) significantly decreased 12 months postsurgery, while mean FT4 levels increased from12.0 ± 1.9 vs 12.4 ± 2.0 pmol/L (p = 0.013). Furthermore, mean iPTH decreased from 53.3 ± 48.3 to 38.7 ± 13.2 pg/mL (p = 0.011). Multiple stepwise regression analysis showed that changes in LDL levels were an independent factor contributing to changes in TSH levels (ß = 0.362, p = 0.001). Moreover, TSH did not correlate with BMI. CONCLUSIONS: In this study, FT3, TSH, and iPTH were decreased in euthyroid patients with obesity after LSG, while FT4 was significantly increased. Changes in TSH were positively correlated with LDL, but no statistically significant correlation was found with BMI. Additionally, FT3, FT4, and iPTH were correlated with VB12, age, and BMI, respectively.
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Laparoscopía , Obesidad Mórbida , Gastrectomía , Humanos , Obesidad Mórbida/cirugía , Estudios Retrospectivos , Glándula Tiroides , Hormonas Tiroideas , Tirotropina , TiroxinaRESUMEN
Oligodendrocytes are glial cells located in the central nervous system (CNS) that play essential roles in the transmission of nerve signals and in the neuroprotection of myelinated neurons. The dysfunction or loss of oligodendrocytes leads to demyelinating diseases such as multiple sclerosis (MS). To treat demyelinating diseases, the development of a therapy that promotes remyelination is required. In the present study, we established an in vitro method to convert human fibroblasts into induced oligodendrocyte-like cells (iOLCs) in 3 days. The induced cells displayed morphologies and molecular signatures similar to oligodendrocytes after treatment with valproic acid and exposure to the small molecules Y27632, SU9516, and forskolin (FSK). To pursue the development of a cell-free remyelination therapy in vivo, we used a cuprizone-induced demyelinated mouse model. The small molecules (Y27632, SU9516, and FSK) were directly injected into the demyelinated corpus callosum of the mouse brain. This combination of small molecules rescued the demyelination phenotype within two weeks as observed by light and electron microscopy. These results provide a foundation for exploring the development of a treatment for demyelinating diseases via regenerative medicine.
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Cuprizona , Enfermedades Desmielinizantes , Animales , Cuerpo Calloso , Cuprizona/efectos adversos , Enfermedades Desmielinizantes/inducido químicamente , Enfermedades Desmielinizantes/tratamiento farmacológico , Enfermedades Desmielinizantes/genética , Ratones , Ratones Endogámicos C57BL , Oligodendroglía/fisiologíaRESUMEN
Studies of arousal and emotion show that generalized physiological arousal can enhance emotional experience for a range of different emotions. Other research shows that different emotions may be associated with specific patterns of physiological reactivity. Together these findings suggest that while nonspecific autonomic activation can be sufficient in the generation of emotion, specific patterns of reactivity may appear once the emotion is established. This study aimed to test this hypothesis by examining the effects of generalized arousal on emotional experience, as well as the physiological responses associated with positive and negative emotions. One hundred and nine participants either sat or stood during the viewing of positive and negative film clips while emotion ratings and cardiorespiratory measures were taken. Those who stood during the videos reported greater levels of emotion than those who sat, indicating that generalized arousal due to standing heightened emotional experience. In addition, participants exhibited greater high-frequency heart rate variability and lower respiration rate during the negative video than the positive video, indicating that physiological reactivity differed between the positive and negative emotions. These results suggest that while patterns of physiological reactivity may be specific to individual emotions, nonspecific arousal is sufficient to enhance diverse emotions.
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The prevalence of autism spectrum disorders (ASD) in Taiwan has been increasing, and genetic testing for ASD has been available and provided to parents of children diagnosed with ASD in Taiwan. However, there is still limited understanding of Taiwanese parents' knowledge of and attitudes toward such testing. Therefore, the present study addressed this gap by assessing the attitudes toward as well as actual and perceived knowledge of ASD genetic testing among Taiwanese parents of children diagnosed with ASD. A sample of 443 parents of children with ASD recruited from 236 public schools in Taiwan completed a paper-and-pencil survey. Although parents generally held favorable attitudes toward ASD genetic testing, they had deficient knowledge of such test (with only a 31.4% average correct rate on the actual knowledge scale). Tailored health education materials should be developed to improve the knowledge of ASD genetic testing among parents with affected children in Taiwan.