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BACKGROUND: Hyperthyroidism is frequently under-recognized and leads to heart failure and mortality. Timely identification of high-risk patients is a prerequisite to effective antithyroid therapy. Since the heart is very sensitive to hyperthyroidism and its electrical signature can be demonstrated by electrocardiography, we developed an artificial intelligence model to detect hyperthyroidism by electrocardiography and examined its potential for outcome prediction. METHODS: The deep learning model was trained using a large dataset of 47,245 electrocardiograms from 33,246 patients at an academic medical center. Patients were included if electrocardiograms and measurements of serum thyroid-stimulating hormone were available that had been obtained within a three day period. Serum thyroid-stimulating hormone and free thyroxine were used to define overt and subclinical hyperthyroidism. We tested the model internally using 14,420 patients and externally using two additional test sets comprising 11,498 and 596 patients, respectively. RESULTS: The performance of the deep learning model achieves areas under the receiver operating characteristic curves (AUCs) of 0.725-0.761 for hyperthyroidism detection, AUCs of 0.867-0.876 for overt hyperthyroidism, and AUC of 0.631-0.701 for subclinical hyperthyroidism, superior to a traditional features-based machine learning model. Patients identified as hyperthyroidism-positive by the deep learning model have a significantly higher risk (1.97-2.94 fold) of all-cause mortality and new-onset heart failure compared to hyperthyroidism-negative patients. This cardiovascular disease stratification is particularly pronounced in subclinical hyperthyroidism, surpassing that observed in overt hyperthyroidism. CONCLUSIONS: An innovative algorithm effectively identifies overt and subclinical hyperthyroidism and contributes to cardiovascular risk assessment.
Hyperthyroidism occurs when the thyroid gland produces too much hormone and can cause various symptoms including faster heartbeat, weight loss, and nervousness. Diagnosis is often missed, which can lead to heart problems and even death. Measurements of the heart's electrical activity can be obtained using Electrocardiograms (ECGs). We made a computational model that can detect hyperthyroidism from ECGs. Our model was better able to identify people with hyperthyroidism than currently available methods, especially the more severe forms of the condition. If future work demonstrates our model is safe and accurate, it could potentially be used to detect hyperthyroidism sooner, enabling faster treatment and improved health of people with hyperthyroidism.
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3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, however over 200 studies demonstrate that acute (e.g. hyperthermia, rhabdomyolysis) and chronic (e.g. neurotoxicity) toxicity effects of MDMA were observed in different animals. Methimazole (MMI), an inhibitor of thyroid hormone synthesis, was found to significantly reduce the HSP72 expression of heat stress induced in fibroblasts. Hence, we attempted to understand the effects of MMI on MDMA induced changes in vivo. Male SD rats were randomly divided into four groups as follows:(a) water-saline (b) water-MDMA (c) MMI-saline and (d) MMI-MDMA group. In the temperature analysis test, MMI was found to alleviate MDMA-induced hyperthermia and increase the heat loss index (HLI), revealing its peripheral vasodilation effect. PET experiment suggested that MDMA induced elevated glucose uptake by skeletal muscles, which was resolved by MMI pretreatment. IHC staining (serotonin transporter, SERT) showed the evidence of neurotoxicity caused by MDMA (serotonin fiber loss), which was alleviated by MMI. Furthermore, the animal behaviour test (forced swimming test, FST) showed higher swimming time but lower immobility time in MMI-MDMA and MMI-saline groups. Taken together, treatment of MMI shows benefits such as lowered body temperature, alleviation of neurotoxicity and excited behaviour. However, further investigations should be conducted in the future to provide in-depth evidence for its clinical use.
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Hipertermia Inducida , N-Metil-3,4-metilenodioxianfetamina , Síndromes de Neurotoxicidad , Ratas , Masculino , Animales , N-Metil-3,4-metilenodioxianfetamina/toxicidad , Metimazol/toxicidad , Ratas Sprague-Dawley , Temperatura Corporal , Síndromes de Neurotoxicidad/tratamiento farmacológico , Síndromes de Neurotoxicidad/etiología , Hipertermia Inducida/efectos adversosRESUMEN
The modified dose (MD) regimen of pembrolizumab (2 mg/kg or 100 mg every 3 weeks) is an alternative option to reduce the financial burden resulting from the extremely high cost of the standard dose (SD) regimen (200 mg every 3 weeks). However, the clinical effectiveness and prognostic outcomes have not been fully elucidated in real-word clinical practice. Sixty-four consecutive patients in Taiwan receiving pembrolizumab for advanced NSCLC between 2018 and 2020 were recruited in this study. Comparisons of overall survival (OS) and progression-free survival (PFS) were performed using Kaplan−Meier survival curves. Additionally, 12 predictors, including pembrolizumab regimen, dose, neutrophil-to-lymphocyte ratio (NLR), age, sex, histopathology, smoking history, ECOG PS, EGFR mutation, PD-L1 expression, distant metastases and treatment line, were analyzed in multivariable Cox models for predicting OS and PFS. The results showed that the MD group and the SD group had similar OS and PFS, especially in patients beyond first-line treatment or with a pretreatment NLR < 5. The NLR was the only independent factor associated with both OS (adjusted HR = 0.052; p = 0.010) and PFS (adjusted HR = 0.259; p = 0.021). The results of this study assure the clinical effectiveness of MD pembrolizumab and suggest that the pretreatment NLR could highlight patients who may benefit from MD pembrolizumab.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Anticuerpos Monoclonales Humanizados/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Humanos , Neoplasias Pulmonares/genética , PronósticoRESUMEN
Granulocyte colony-stimulating factor (G-CSF) has been reported to modulate pain function following nerve injury. However, the expression of endogenous G-CSF in the dorsal root ganglion (DRG) and the response to nerve injury remain unclear. In the present study, we demonstrated that G-CSF and G-CSFR are mainly expressed in both small- and medium-diameter DRG neurons in rats and are responsible for transmitting pain responses. G-CSF and G-CSFR were co-expressed in certain nociceptive DRG neurons. In addition, G-CSF was expressed in satellite glial cells around large-diameter DRG neurons. After sciatic nerve injury, the number of G-CSF-positive DRG neurons was increased in both the ipsilateral and contralateral lesion sites in rats. However, G-CSF expression in satellite glial cells was not affected by nerve injury. To clarify the role of G-CSF in pain, exogenous G-CSF was administered to a rat model of neuropathic pain induced by partial sciatic nerve transaction (PST). Our results indicate that treatment with G-CSF did not attenuate but exacerbated neuropathic pain. In summary, G-CSF may directly activate sensory neurons and contribute to nociceptive signaling.
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BACKGROUND: Increasing numbers of animal studies have found that sudden sensorineural hearing loss (SSNHL) is related to the mechanism of serotonergic modulation. However, the relationship between antidepressants and SSNHL is unclear in humans. Therefore, this study aimed to evaluate the association between antidepressant use and risk of SSNHL. METHODS: Data from 218 466 antidepressant users and 1 116 518 nonusers were obtained from the Taiwan Longitudinal Health Insurance Database. We used propensity-score matching (PSM) and inverse-probability treatment weighting (IPTW) to eliminate any bias. Each patient was tracked for 5 years to ascertain whether or not they were diagnosed with SSNHL. Cox proportional-hazard regression analyses were performed to calculate the SSNHL risk. RESULTS: The adjusted hazard ratio (aHR) of SSNHL for antidepressant users was 1.36 compared with nonusers in the full cohort study. The aHR for antidepressant users was 1.44 and 1.49 compared with the nonusers in the IPTW and PSM cohorts, respectively. All classes of antidepressants consistently increased the SSNHL risk. Additionally, patients receiving four classes of antidepressants were associated with a much higher SSNHL risk (aHR, 2.05) and those receiving one or two classes of antidepressants had a relatively lower SSNHL risk. CONCLUSION: Antidepressants increased SSNHL risk, regardless of their class. Furthermore, patients who took a higher number of antidepressant classes showed an increased risk of developing SSNHL than those who took a lower number of antidepressant classes. Therefore, physicians should estimate the risks and benefits of antidepressant use and avoid prescribing antidepressants concurrently.
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Pérdida Auditiva Sensorineural , Antidepresivos/efectos adversos , Estudios de Casos y Controles , Estudios de Cohortes , Pérdida Auditiva Sensorineural/inducido químicamente , Pérdida Auditiva Sensorineural/epidemiología , Humanos , Incidencia , Factores de RiesgoRESUMEN
BACKGROUND: Inflammation may mediate the relationship between major depressive disorder (MDD) and psoriasis. However, it is unclear whether anti-depressants can decrease the subsequent risk of psoriasis among MDD patients. This study investigated the effects of anti-depressants on the subsequent risk of psoriasis in MDD patients. METHODS: This was a population-based cohort study in Taiwan. 58,454 MDD patients who had received anti-depressants and 6,034 MDD patients who did not receive anti-depressants were included. Each patient was tracked for 5 years to confirm a diagnosis of psoriasis following the index date. Cox proportional hazards models were performed to estimate the hazard ratio (HR) for psoriasis. RESULTS: In this study, after using time-dependent Cox regression with both inverse probability of treatment weighting (IPTW) and adjustment for confounders, anti-depressant users had a significantly lower risk of psoriasis than the nonusers (IPTW-adjusted HR [aHR] = 0.69). Additionally, most types and dosages of anti-depressants tended to protect against psoriasis. Selective serotonin reuptake inhibitor use (IPTW-aHR = 0.67) and low-dose anti-depressant use (IPTW-aHR = 0.66) had significant protective effects even after IPTW and adjustment for confounders. LIMITATIONS: This study had no information about over-the-counter medications. CONCLUSIONS: This study revealed the protective effects of anti-depressants on psoriasis risk in patients with MDD. Antidepressant users had significantly lower risk of psoriasis than the nonusers. Further analyses indicated that the usage of SSRIs and low antidepressant dosage could statistically decrease risk of psoriasis.
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Trastorno Depresivo Mayor , Psoriasis , Estudios de Cohortes , Trastorno Depresivo Mayor/tratamiento farmacológico , Trastorno Depresivo Mayor/epidemiología , Trastorno Depresivo Mayor/prevención & control , Humanos , Psoriasis/complicaciones , Psoriasis/tratamiento farmacológico , Psoriasis/epidemiología , Estudios Retrospectivos , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Taiwán/epidemiologíaRESUMEN
Hp-s1 ganglioside is isolated from the sperm of sea urchin (Hemicentrotus pulcherrimus). In addition to neuritogenic activity, the biological function of Hp-s1 in neuroinflammation is unknown. In this study, we investigated the anti-neuroinflammatory effect of Hp-s1 on lipopolysaccharide (LPS)-stimulated microglial cells. MG6 microglial cells were stimulated with LPS in the presence or absence of different Hp-s1 concentrations. The anti-inflammatory effect and underlying mechanism of Hp-s1 in LPS-activated microglia cells were assessed through a Cell Counting kit-8 assay, Western blot analysis, and immunofluorescence. We found that Hp-s1 suppressed not only the expression of inducible nitric oxide synthase and cyclooxygenase-2 but also the expression of proinflammatory cytokines, such as TNF-α, IL-1ß, and IL-6. Hp-s1 inhibited the LPS-induced NF-κB signaling pathway by attenuating the phosphorylation and translocation of NF-κB p65 and by disrupting the degradation and phosphorylation of inhibitor κB-α (IκBα). Moreover, Hp-s1 inhibited the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Hp-s1 also reduced the expression of myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factors 6 (TRAF6), which are prerequisites for NF-κB and MAPKs activation. These findings indicated that Hp-s1 alleviated LPS-induced proinflammatory responses in microglial cells by downregulating MyD88-mediated NF-κB and JNK/p38 MAPK signaling pathways, suggesting further evaluation as a new anti-neuroinflammatory drug.
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Antiinflamatorios/farmacología , Gangliósidos/farmacología , Inflamación/tratamiento farmacológico , Microglía/efectos de los fármacos , Animales , Antiinflamatorios/aislamiento & purificación , Línea Celular , Citocinas/metabolismo , Gangliósidos/aislamiento & purificación , Hemicentrotus/metabolismo , Inflamación/patología , Lipopolisacáridos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Microglía/patología , Factor 88 de Diferenciación Mieloide/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
While Parkinson's disease (PD) and attention-deficit hyperactivity disorder (ADHD) are two distinct conditions, it has been hypothesized that they share several overlapping anatomical and neurochemical changes. In order to investigate that hypothesis, this study used claims data from Taiwan's Longitudinal Health Insurance Database 2000 to provide the significant nationwide population-based evidence of an increased risk of PD among ADHD patients, and the connection between the two conditions was not the result of other comorbidities. Moreover, this study showed that the patients with PD were 2.8 times more likely to have a prior ADHD diagnosis compared with those without a prior history of ADHD. Furthermore, an animal model of ADHD was generated by neonatally injecting rats with 6-hydroxydopamine (6-OHDA). These rats were subjected to behavior tests and the 99mTc-TRODAT-1 brain imaging at the juvenile stage. Compared to control group rats, the 6-OHDA rats showed a significantly reduced specific uptake ratio in the striatum, indicating an underlying PD-linked pathology in the brains of these ADHD phenotype-expressing rats. Overall, these results support that ADHD shares a number of anatomical and neurochemical changes with PD. As such, improved knowledge of the neurochemical mechanisms underlying ADHD could result in improved treatments for various debilitating neurological disorders, including PD.
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Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Enfermedad de Parkinson/complicaciones , Anciano , Anciano de 80 o más Años , Animales , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Modelos Animales de Enfermedad , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/diagnóstico por imagen , Ratas Sprague-Dawley , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Existing evidence indicates that both iron deficiency anemia and sickle cell anemia have been previously associated with hearing loss. However, human data investigating the association between anemia and auditory threshold shifts at different frequencies in the adolescent, adult and elderly population are extremely limited to date. Therefore, this cross-sectional study used the dataset from the US National Health and Nutrition Examination Survey from 2005 to 2012 to explore differences in low- or high-frequency hearing thresholds and hearing loss prevalence between participants with and without anemia. A total of 918 patients with anemia and 8213 without anemia were included. Results indicated that low- and high-frequency pure tone average were significantly higher in patients with anemia than that in those without anemia in the elderly, but not in adult or adolescent population. In addition, the prevalence of low-frequency hearing loss but not high-frequency hearing loss was also higher in patients with anemia than in those without anemia in the elderly population. After adjusting various confounders, multiple regression models still indicated that patients with anemia tended to have larger threshold shift. In conclusion, anemia was associated with auditory threshold shifts in the elderly population, especially those vulnerable to low-frequency hearing loss.
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Anemia/epidemiología , Umbral Auditivo , Adolescente , Adulto , Anciano , Estudios Transversales , Femenino , Pérdida Auditiva , Humanos , Masculino , Encuestas NutricionalesRESUMEN
Among central nervous system tumors, glioblastoma (GBM) is the most common and the most malignant type. Even under current standard treatments, the overall survival rate is still low and the recurrence rate is high. Therefore, developing novel and effective therapy is urgently needed. CC12, a synthesized small molecule, was evaluated for the potential anti-GBM effects in two GBM cell lines, U87MG and U118MG. The observations of cell morphology, MTT assay, flow cytometry-based apoptosis after CC12 treatment, were conducted. Western blot was performed for the investigation of the apoptotic mechanism. Positron emission tomography scan analysis and bioluminescent imaging assay using a mouse xenograft model were performed for the effect of CC12 in vivo. After treated by 10 µM CC12 for 24 h, both U118MG and U87MG cells showed tumor cell death. MTT assay results showed that the survival rates decreased when the CC12 concentrations or the treatment periods increased. Ki-67 expression and flow cytometry results indicated that the proliferation was inhibited in GBM cells, and G1 phase arrest was shown. The results of 7-AAD, Br-dUTP, and JC-1 staining all showed the apoptosis of GBM cells after CC12 treatment. Increased γH2AX, caspase-3, and poly (ADP-ribose) polymerase (PARP) levels meant the DNA damage, and increased Bcl2 family proteins after CC12 treatment indicated the intrinsic apoptotic pathway was involved in CC12 induced apoptosis. Furthermore, CC12 can induce the decrease of tumor prognostic marker DcR3. In vivo experiment results showed the effect of CC12 on tumor size reduction of CC12. In addition, the ability to cross the brain-blood barrier of CC12 was also confirmed. CC12 may have anti-tumor ability through the regulation of cell cycle and apoptosis in vitro and in vivo.
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Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Imidazoles/farmacología , Sulfuros/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/farmacocinética , Barrera Hematoencefálica/efectos de los fármacos , Barrera Hematoencefálica/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas , Citometría de Flujo/métodos , Humanos , Imidazoles/química , Imidazoles/farmacocinética , Espectrometría de Masas , Ratones , Tomografía de Emisión de Positrones , Sulfuros/química , Sulfuros/farmacocinética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This study examined the association between digoxin use and subsequent psoriasis risk using a population-based database in Taiwan. This cohort study enrolled 15 545 digoxin users and 15 545 propensity score-matched non-users from the Taiwan National Health Insurance Research Database. Each patient was independently followed up for 5 years to confirm whether they had been diagnosed with psoriasis. Cox proportional hazard regression was used to estimate psoriasis risk among digoxin users. Subgroup and sensitivity analyses were also performed. The psoriasis incidence rates were 3.02 and 2.27 per 1000 person-years among digoxin users and non-users, respectively. After adjustment for confounders, psoriasis risk was significantly higher among digoxin users than among non-users. Notably, in most subgroup analyses, digoxin use tended to increase psoriasis risk, particularly among patients with heart failure, diabetes, hypertension and hyperlipidaemia. Moreover, significantly increased psoriasis risk was noted over 2, 3, 4 and 5 years of digoxin use. In conclusion, our findings confirm that digoxin use increases subsequent psoriasis risk. Thus, physicians should be aware of this association and accordingly estimate the risks and benefits of digoxin use. Nevertheless, some patient variables, such as body mass index and obesity, were unavailable in this study. The findings in this study should be elucidated carefully because the potential effects of these factors could not be considered.
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Fibrilación Atrial/tratamiento farmacológico , Digoxina/efectos adversos , Insuficiencia Cardíaca/tratamiento farmacológico , Psoriasis/epidemiología , Reclamos Administrativos en el Cuidado de la Salud/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/epidemiología , Prescripciones de Medicamentos/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/epidemiología , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Psoriasis/inducido químicamente , Factores de Riesgo , Taiwán/epidemiologíaRESUMEN
OBJECTIVES: The administration of androgen deprivation therapy (ADT) to patients with metastatic prostate cancer might be associated with some adverse effects such as anaemia; however, few studies have been performed in East Asian populations. This study aimed to investigate the association between ADT and iron-deficiency anaemia (IDA) among patients with prostate cancer in a population-based nationwide cohort. DESIGN: Cohort study. SETTING: Taiwan. PARTICIPANTS: Data for the cohort study were retrieved from the Taiwan National Health Insurance Research Database. Propensity score matching was used to select 7262 patients with prostate cancer who received ADT as the study group and 3631 patients who did not receive ADT as the control group. PRIMARY AND SECONDARY OUTCOME MEASURES: This study individually tracked patients over a 3-year study period and identified those who were subsequently diagnosed with IDA following the index date. RESULTS: The incidence rates of IDA in the study and control groups were 1.66 (95% CI CI 1.45 to 1.86) and 1.01 per 100 person-years (95% CI 0.78 to 1.25), respectively. Furthermore, proportional Cox regression revealed an HR of 1.62 (95% CI 1.24 to 2.12) for IDA in the study group after adjusting for patients' age, monthly income, geographic location, residential urbanisation level and incidence of hyperlipidaemia, diabetes, hypertension, coronary heart disease, inflammatory bowel disease, other cancers and gastrointestinal bleeding. CONCLUSION: Compared with its non-use among patients with prostate cancer, ADT use was associated with a higher risk of IDA.
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Antagonistas de Andrógenos/uso terapéutico , Anemia Ferropénica/epidemiología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/epidemiología , Factores de Edad , Anciano , Antagonistas de Andrógenos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Puntaje de Propensión , Neoplasias de la Próstata/patología , Estudios Retrospectivos , Factores de Riesgo , Factores Socioeconómicos , Taiwán/epidemiologíaRESUMEN
Methylenedioxymethamphetamine (MDMA) is a psychostimulant with high abuse potential and severe neurotoxicity. According to our previous study, MDMA promotes autophagosome accumulation and contributes to cell death in cultured cortical and serotonergic neurons. However, the detailed mechanism underlying autophagy dysfunction remains unclear. Lysosomes play an important role in autophagic degradation. The present study aimed to examine the role of lysosomal function in autophagic flux in neuronal cultures exposed to MDMA. We showed that MDMA induced enlarged vesicles that accumulate in SH-SY5Y neuroblastoma cells. In addition, we demonstrated that MDMA stimulated dynamin-dependent but clathrin-independent endocytosis, which might contribute to vacuole expansion. Morphological and Western blot analyses revealed that MDMA induced lysosomal swelling, whereas the activity of the lysosomal hydrolytic enzymes cathepsin B and cathepsin D was decreased in SH-SY5Y and cultured cortical neurons, which might lead to autophagosome accumulation and autophagic degradation blockage. Intriguingly, inactivation of cathepsins B and D led to cell death and autophagy-lysosomal dysregulation, which mimicked MDMA-induced neurotoxicity. Consequently, impairment of lysosomal proteolysis and blockage of autophagy degradation contributed to MDMA-induced neurotoxicity in neuronal cultures.
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Autofagia/efectos de los fármacos , Lisosomas/efectos de los fármacos , Lisosomas/patología , N-Metil-3,4-metilenodioxianfetamina/toxicidad , Neuroblastoma/patología , Neuronas/efectos de los fármacos , Neuronas/patología , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Humanos , Lisosomas/metabolismo , Neuronas/metabolismo , Células Tumorales CultivadasRESUMEN
Neoadjuvant chemotherapy induces metastasis of residual breast cancers through activation of tumor-associated macrophages. Previous studies have indicated that calcium channel blockers (CCBs) exert anti-inflammatory and antimigratory effects on macrophages via attenuating Ca2+ entry into macrophages. However, no existing empirical research has addressed the relationship between previous CCB use and breast cancer recurrence. In this study, 4840 Taiwanese women aged ≥20 years with breast cancer who underwent breast surgery from January 1, 2007, to December 31, 2015, were enrolled. The date of cancer recurrence was defined as the index date. Logistic regression was performed to evaluate the relationship between previous CCB exposure and cancer recurrence among female patients who underwent surgery for breast cancer. After adjusting for demographic characteristics, comorbidities, and tumor-node-metastasis stage, the adjusted odds ratio (OR) for CCB exposure within 5 years before the index date in women with recurrence compared with nonrecurrent controls was 0.73 (95% confidence interval [CI], 0.53-0.97). Further analysis revealed that the adjusted OR for CCB exposure between the surgery and index dates in women with recurrence relative to nonrecurrent controls was 0.72 (95%CI, 0.66-0.95). In particular, prior CCB use was significantly associated with a lower risk (34%) of breast cancer recurrence among women 20 to 54 years old (OR, 0.66; 95%CI, 0.47-0.83). This study uncovered a protective association between previous CCB use and breast cancer recurrence.
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Neoplasias de la Mama/cirugía , Bloqueadores de los Canales de Calcio/administración & dosificación , Recurrencia Local de Neoplasia/prevención & control , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Persona de Mediana Edad , Oportunidad Relativa , Recurrencia , Sistema de Registros , Riesgo , Taiwán , Macrófagos Asociados a Tumores/efectos de los fármacosRESUMEN
BACKGROUND: Previous studies have presented an unclear association between major depressive disorder (MDD) and tinnitus. Therefore, in this study, we aimed to demonstrate the actual association between MDD and new-onset tinnitus using a large, population-based dataset in Taiwan. METHOD: This case-control study used the data from the National Health Insurance Database. In total, 18,365 patients with tinnitus were recruited as cases, and 18,365 propensity score-matched patients without tinnitus were identified as controls. Logistic regression models were constructed to calculate the odds ratios (ORs) and to estimate the association between prior MDD and tinnitus. RESULTS: MDD was found in 396 (2.16%) patients with tinnitus and 228 (1.24%) controls without tinnitus. The logistic regression model indicated that prior MDD was associated with tinnitus (adjusted OR, 1.74; 95% CI, 1.47-2.05). Moreover, MDD was positively associated with tinnitus among most subgroups. Notably, a significant association between MDD and tinnitus was observed among patients with diabetes (adjusted OR, 2.05) and hyperlipidemia (adjusted OR, 1.94). Furthermore, sensitivity analyses consistently found a relationship between prior MDD and tinnitus. LIMITATIONS: The database used in this study does not provide information regarding the lifestyle and gene factors. CONCLUSIONS: Our results showed a positive association between prior MDD and tinnitus. In addition, MDD may be one of the risk factors for tinnitus onset. Therefore, we recommended that the clinicians should be alert about the tinnitus condition among patients with MDD and provide appropriate interventions for them.
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Trastorno Depresivo Mayor , Acúfeno , Estudios de Casos y Controles , Trastorno Depresivo Mayor/epidemiología , Humanos , Factores de Riesgo , Taiwán/epidemiología , Acúfeno/epidemiologíaRESUMEN
To date, population-based studies on the healthcare service utilization among stable heart, kidney, and liver transplant recipients with different calcineurin inhibitors are still scarce. Therefore, we used the Taiwan National Health Insurance Research Database to conduct a nationwide cross-sectional study to estimate the healthcare utilization of stable transplant recipients with tacrolimus or cyclosporine (n = 3,482). The sampled patients in this study comprised 377 heart, 1,693 kidney, and 1,412 liver transplant recipients between 1 January 2011 and 31 December 2011. Each subject was followed for a 1-year period to evaluate his/her healthcare service utilization. Outcome variables of the healthcare service utilization were stated as below: numbers of outpatient visits, outpatient costs, numbers of inpatient days, inpatients costs, and total costs of all healthcare services. As for all healthcare service utilization, stable transplant recipients on tacrolimus had significantly more outpatient visits (40.7 vs. 38.6), outpatient costs (US$10,383 vs. US$8,155), and total costs (US$12,516 vs. US$10,372) of all healthcare services than those on cyclosporine during the 1-year follow-up period. Additionally, further analysis showed that heart transplant recipients receiving tacrolimus incurred 1.7-fold higher inpatient costs compared to patients receiving cyclosporine. We concluded that transplant recipients using tacrolimus had significantly higher utilization of all healthcare services than those receiving cyclosporine as immunosuppressive therapy.
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Erupciones por Medicamentos/etiología , Agonistas de Receptores de GABA-A/efectos adversos , Psoriasis/inducido químicamente , Estudios de Cohortes , Erupciones por Medicamentos/epidemiología , Estudios de Seguimiento , Humanos , Incidencia , Puntaje de Propensión , Psoriasis/epidemiología , Medición de Riesgo , Factores de TiempoRESUMEN
This study investigated the effect of dextromethorphan (DXM) against Parkinson's disease (PD) in rats and explored the association between DXM dose and PD risk in elderly patients 65 years and older using a population-based database. The PD rat model (Sprague Dawley rats) was induced by injecting 6-hydroxydopamine (6-OHDA) into the unilateral medial forebrain bundle of the rat brain. DXM (20â¯mg/kg) was administered intraperitoneally twice daily from 7 days before the appearance of a 6-OHDA lesion to 28 days after the lesion appeared. The availability of dopamine transporter (DAT) and serotonin transporter (SERT) in the striatum of the rat brain was measured using positron emission tomography. The apomorphine-induced rotation test was performed to study the hypersensitivity of the brain regions with lesions. This animal study demonstrated that DXM significantly attenuated 6-OHDA-induced DAT and SERT loss, correlating to rotational behaviors. The population-based human study analyzed the data from the Taiwan Longitudinal Health Insurance Database 2005 between January 2005 and December 2013 and then used the DXM dose-response curve to investigate the trend of its protective effect against PD. In the human study, low cumulative doses of DXM may potentially achieve a protective effect for PD; however, high cumulative doses seem to be a risk for PD.
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Dextrometorfano/administración & dosificación , Enfermedad de Parkinson Secundaria/prevención & control , Enfermedad de Parkinson/prevención & control , Sustancias Protectoras/administración & dosificación , Anciano , Anciano de 80 o más Años , Animales , Técnicas de Observación Conductual , Conducta Animal/efectos de los fármacos , Estudios de Casos y Controles , Cuerpo Estriado/diagnóstico por imagen , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/análisis , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/metabolismo , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Oxidopamina/toxicidad , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson Secundaria/inducido químicamente , Enfermedad de Parkinson Secundaria/patología , Tomografía de Emisión de Positrones , Ratas , Ratas Sprague-Dawley , Proteínas de Transporte de Serotonina en la Membrana Plasmática/análisis , Proteínas de Transporte de Serotonina en la Membrana Plasmática/metabolismo , Taiwán/epidemiología , Microtomografía por Rayos XRESUMEN
BACKGROUND: To provide clinicians with sufficient information for selecting optimal access strategies for patients with end-stage renal disease, the utilization of health-care services of patients receiving arteriovenous fistulas (AVFs), arteriovenous grafts (AVGs), and central venous catheters (CVCs) are crucial topics that require investigation. MATERIALS AND METHODS: This study involved 1248, 431, and 323 patients with end-stage renal disease who had received an AVF, AVG, or CVC, respectively. All sampled patients were monitored over the course of a 1-y study period to evaluate their medical utilization. The utilization were further categorized into nephrology and nonnephrology services. This study also performed univariate and multivariate regressions to estimate the effects of vascular accesses. RESULTS: Regarding the utilization of health care services, significant differences were observed for mean outpatient visits (45.30 versus 49.71 versus 48.80), outpatient costs (US$19117 versus US$21015 versus US$19280), inpatient days (9.77 versus 14.41 versus 21.60), inpatient costs (US$2627 versus US$3810 versus US$5238), and total costs (US$21743 versus US$24825 versus US$24518) among patients who had received an AVF, AVG, or CVC, respectively. Furthermore, patients receiving an AVF had lower total costs for all health care services and nonnephrology services than patients undergoing AVG or CVC across the categories of men, women, adults, and elderly individuals. Multiple regressions found that patients undergoing AVF had significantly lower total costs for all health services than patients undergoing other vascular accesses after adjustments. CONCLUSIONS: This study displayed that patients who received an AVF fully used health care and nonnephrology services than patients who received an AVG or CVC.
Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Catéteres Venosos Centrales/efectos adversos , Aceptación de la Atención de Salud/estadística & datos numéricos , Complicaciones Posoperatorias/terapia , Diálisis Renal/efectos adversos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Diálisis Renal/métodos , TaiwánRESUMEN
This study investigated the protective effects of dextromethorphan (DXM) on noise-induced hearing loss (NIHL) in rats. This study aimed to improve the auditory threshold and to understand the protective effects of DXM against N-methyl-d-aspartate (NMDA)-induced neurite degeneration of serotonergic neurons. The animals were exposed to 8-kHz narrowband noise at a 118-dB sound pressure level for 3.5â¯h. The hearing thresholds were determined by measuring the auditory brainstem response to click stimuli. Serotonin transporter (SERT) expression was determined through micro-positron emission tomography (PET) using N,N-dimethyl-2-(2-amino-4-18F-fluorophenylthio)benzylamine (4-[18F]-ADAM). We also investigated the effects of DXM on NMDA-induced morphological changes in the primary cultures of rat serotonergic neurons. NIHL significantly improved after prophylactic treatment with DXM (pâ¯<â¯.05). SERT density in DXM-treated rats was significantly higher than that in non-DXM-treated rats. Because prophylactic medication restored the NMDA-inhibited neurite length of serotonergic neurons and presented SERT density, DXM could be a potential agent in alleviating NIHL.