Significantly shortened telomere length and altered androgen receptor level in cumulus cells from women with polycystic ovary syndrome.

OBJECTIVE: The aim of this study was to investigate the correlation between hormone receptor levels and telomere length (TL) in infertile women with and without polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: This prospective cohort study recruited a total of 431 cumulus oocyte complex (COC) from 88 infertile women between July 2012 and June 2014. The participants were divided into three groups: young age (<38 years, n = 42 and 227 COC), advanced age (≥38 years, n = 33 and 107 COC) and PCOS patients (n = 13 and 97 COC). Cumulus cells were collected from individual follicle during oocyte pick-up, and the mRNA levels of hormone receptors and TL were measured using real-time PCR. RESULTS: The cumulus cells of PCOS patients demonstrated lower mRNA levels of LH receptor (75.57 ± 138.10 vs. 171.07 ± 317.68; p < 0.01) and androgen receptor (1.13 ± 1.52 vs. 4.08 ± 9.57; p < 0.01), as well as a shorter TL (2.39 ± 2.58 vs. 3.96 ± 4.72; p < 0.01) compared to those of the young age group. In the young age group, only androgen receptor mRNA level showed a significant association with TL (rho = 0.148, p = 0.026), while FSH receptor mRNA level was the only factor associated with TL (rho = 0.247, p = 0.015) in PCOS patients. For advanced-aged patients, no significant relationship was observed between hormone receptor mRNA levels and TL. Alternative splicing of androgen receptors was identified in some PCOS patients but not in young age controls. CONCLUSION: The findings suggest that the androgen receptor level and function may be altered in the cumulus cells of PCOS patients, leading to a shorter TL in cumulus cells in PCOS patients.

Precipitating factors of bradycardia after remdesivir administration: ICU admission and cutoff value for declining heart rate.

BACKGROUND: Despite increasing concerns about the association between remdesivir and bradycardia in severe coronavirus disease 2019 (COVID-19) patients receiving remdesivir, information on its clinical course and precipitating factors is limited. Our aim was to investigate possible triggers of bradycardia after remdesivir administration. METHODS: We retrieved the medical records of hospitalized severe and critical COVID-19 patients who received remdesivir from May 1, 2021 to June 30, 2021. Bradycardia was defined as two episodes of a heart rate (HR) < 60 bpm in 24 h. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the discriminability of heart rate pattern on the occurrence of bradycardia. The precipitating factors of bradycardia were examined by a logistic regression model. RESULTS: Regardless of bradycardia status, the median heart rate dropped during remdesivir treatment (from 85 to 72 bpm, p < 0.001), with the heart rate dropping considerably within the first two days of remdesivir treatment. Among various heart rate descriptors, HR ratiomin (d2-d1) had the best discrimination (AUC = 0.7336), and a reduction in HR ratiomin (d2-d1) by 14.65% was associated with bradycardia. Intensive care unit (ICU) admission was associated with an increased risk of bradycardia (odds ratio: 3.41; 95% CI: 1.12-10.41). CONCLUSIONS: In severe COVID-19 patients receiving remdesivir, the risks of bradycardia were influenced by a substantial reduction in heart rate during the first two days of remdesivir treatment and ICU admission. These findings suggest that clinical practitioners should intensively monitor heart rates during remdesivir treatment.

The presence of vacuoles in blastocysts is negatively associated with euploidy and live birth rates.

OBJECTIVE: To investigate whether the presence of vacuoles in biopsied blastocysts is associated with the likelihood of aneuploidy and clinical outcomes. DESIGN: Retrospective observational study. SETTING: A single reproductive center. INTERVENTION(S): None. PATIENT(S): This study retrospectively analyzed data obtained through preimplantation genetic testing for aneuploidy performed on 3351 blastocysts from 826 patients at a single reproductive center between August 2018 and July 2020. Ultimately, 167 single euploid blastocyst transfers were performed in these patients. Vacuoles existing in the trophectoderm or inner cell mass were observed using blastocyst biopsy. After the biopsy, all blastocysts were vitrified, and embryo transfer was performed in a subsequent treatment cycle. MAIN OUTCOME MEASURE(S): The associations between vacuoles and euploidy or live birth rates were assessed using logistic regression models and estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULT(S): Of the 3351 blastocysts from 826 patients, 903 (26.9%) were discovered to have vacuoles. The vacuole-positive group had a significantly lower percentage of euploid blastocysts after TE biopsy than the vacuole-negative group (28.8% vs. 35.5%). Embryos with vacuoles were significantly more likely to be poor quality (30.6% vs. 18.2%). Logistic regression analyses revealed that euploid blastocysts were positively associated with the absence of vacuoles, maternal age, and good embryo quality (vacuole-negative group: adjusted OR 1.291; 95% CI: 1.089-1.530; age <38 years: adjusted OR 1.989; 95% CI: 1.692-2.337; good embryo quality: adjusted OR 1.703; 95% CI: 1.405-2.064). The implantation and live birth rates were significantly lower for the transferred single euploid blastocysts with vacuoles than those without (35.5% vs. 56.6%; 29.0% vs. 52.2%, respectively). The live birth rate was positively associated with the absence of vacuoles (adjusted OR 2.792; 95% CI: 1.180-6.608). CONCLUSION(S): The formation of vacuoles in blastocysts is associated with lower rates of euploidy and live birth. Blastocysts without vacuoles should thus be prioritized for embryo transfer in vitro fertilization cycles.

Emotional disturbance and risk factors among COVID-19 confirmed cases in isolation hotels.

Patients with coronavirus disease 2019 (COVID-19) has been isolated in hospital-managed isolation hotels under a policy of the Taiwan government. Centrally isolation patients are more likely to experience psychological symptoms. The purpose of the study was to investigate emotional disturbance during their isolation period and then pinpoint the factors during their isolation period associated with the emotional disturbance. We retrospectively analysed the medical charts of the patients confined to a Banqiao isolation hotel between May 28 and July 3, 2021. The 5-item brief symptom rating scale (BSRS-5) was used to evaluate emotional disturbance levels. Descriptive and logistic regression was used for the data analysis. In total, 197 complete medical records were reviewed, and of these 84 (42.6%) showed emotional disturbance. The majority of them reported only minor disturbance (n = 49, 58.3%). After controlling for confounding factors, being satisfied about medical information was the only protective factor associated with emotional disturbance (OR = 0.2, P = 0.018). Being a male patient (OR = 3.0, P = 0.005), worrying about stigmatization (OR = 2.2, P = 0.041) and being unable to contact family members (OR = 2.9, P = 0.018) increased the risk of experiencing emotional disturbance. Patients with clinical symptoms, namely sore throat (OR = 3.4, P = 0.013) and muscle aches (OR = 6.3, P = 0.005), were also found to be more likely to report emotional disturbance. Mental disturbance commonly occurs among patient with COVID-19 who are isolated in a hospital-managed hotel. Being a male patient, having symptoms, namely a sore throat and muscle pain, being unable to contact family and/or a failure to receive sufficient medical information were found to be associated with emotional disturbance. In order to help isolated patients, government officials should provide a clear rationale for isolation and recognize the patients' efforts to follow the government's policy, which will help to minimize social stigma.

Stabilization of AURKA by the E3 ubiquitin ligase CBLC in lung adenocarcinoma.

CBL family proteins (CBL, CBLB and CBLC in mammals) are E3 ubiquitin ligases of protein tyrosine kinases. CBL mediates the lysosomal degradation of activated EGFR through K63-linked ubiquitination, while CBLC has an oncogenic function by positively regulating EGFR activation through K6 and K11-linked ubiquitination in EGFR mutant lung adenocarcinoma (LAD). Here, we used immunoprecipitation and mass spectrometry to study the CBLC interactome, and found that CBLC is also involved in cell cycle regulation by stabilizing Aurora kinase A (AURKA). CBLC interacted with the kinase domain of AURKA and positively regulated the stability of AURKA by conjugating monoubiquitination and K11/K63-linked polyubiquitination, which are protective from degrading K11/K48 polyubiquitination. CBLC depletion markedly decreased the half-life of AURKA in cycloheximide-treated LAD cells. When LAD cells were synchronized with double thymidine block at the G1/S boundary and then released into mitotic arrest, CBLC depletion delayed the accumulation and activation of AURKA and prevented cancer cells from entering mitosis. CBLC deficiency significantly delayed cell cycle progression, reduced the mitotic population, and increased apoptosis of LAD cells. Targeting CBLC inhibited tumor growth of LAD cells and enhanced their sensitivity to paclitaxel in xenograft models. Immunohistochemical staining of the tissue microarray also revealed a positive correlation between the expression of CBLC and AURKA in normal and LAD tissues, further supporting the positive regulation of AURKA expression by CBLC. In summary, these findings indicate that the oncogenic E3 ligase CBLC plays a role in mitotic entry by stabilizing AURKA via ubiquitination in LAD. This work demonstrates that targeting CBLC combined with paclitaxel might be a potential option for the treatment of LAD patients who have no available targeted therapies.

Calycosin Influences the Metabolism of Five Probe Drugs in Rats.

BACKGROUND: Calycosin (CAL), a type of O-methylated isoflavone extracted from the herb Astralagusmembranaceus (AM), is a bioactive chemical with antioxidative, antiphlogistic and antineoplastic activities commonly used in traditional alternative Chinese medicine. AM has been shown to confer health benefits as an adjuvant in the treatment of a variety of diseases. AIM: The main objective of this study was to determine whether CAL influences the cytochrome P450 (CYP450) system involved in drug metabolism. METHODS: Midazolam, tolbutamide, omeprazole, metoprolol and phenacetin were selected as probe drugs. Rats were randomly divided into three groups, specifically, 5% Carboxymethyl cellulose (CMC) for 8 days (Control), 5% CMC for 7 days + CAL for 1 day (single CAL) and CAL for 8 days (conc CAL), and metabolism of the five probe drugs evaluated using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: No significant differences were observed for omeprazole and midazolam, compared to the control group. T max and t1/2 values of only one probe drug, phenacetin, in the conc CAL group were significantly different from those of the control group (T max h: 0.50±0.00 vs 0.23±0.15; control vs conc CAL). C max of tolbutamide was decreased about two-fold in the conc CAL treatment group (conc vs control: 219.48 vs 429.56, P<0.001). CONCLUSION: Calycosin inhibits the catalytic activities of CYP1A2, CYP2D6 and CYP2C9. Accordingly, we recommend caution, particularly when combining CAL as a modality therapy with drugs metabolized by CYP1A2, CYP2D6 and CYP2C9, to reduce the potential risks of drug accumulation or ineffective treatment.

Effects of chronic unpredictable mild stress on ovarian reserve in female rats: Feasibility analysis of a rat model of premature ovarian failure.

Premature ovarian failure (POF) results from a number of disorders. The POF model is primarily based on chemotherapeutic injury, and hence is not suitable for assessing the effects of chronic stress on ovarian function. Therefore, improved animal models are required to analyze the effects of chronic stress on ovarian reserve. The feasibility of the chronic unpredictable mild stress (CUMS) method for establishing a model of POF was examined. The depressive behavior exhibited by rats was evaluated with the open field and sucrose preference tests. Vaginal smears were obtained for assessment of the estrous cycle. The ovarian reserve of the animals was evaluated using the estrous cycle, ovarian histology and serum levels of gonadotropin releasing hormone (GnRH), follicle­stimulating hormone (FSH), estradiol (E2), and anti­Müllerian hormone (AMH). Compared with the control group, body weight, time spent in the center, horizontal movement, vertical frequency, consumption of sucrose, sucrose preference, number of small follicles from the rats, and serum E2, AMH and GnRH levels were significantly decreased in the CUMS group (all P<0.05). However, the estrous cycle was prolonged significantly (P<0.05) and serum FSH levels were increased significantly (P<0.01). These results suggested that the CUMS model rats exhibited depression­like behaviors. CUMS may induce psychological stress and decrease ovarian reserve in female rats. Thus, the CUMS model may be used to assess the effects of chronic stress on female reproductive function.

Effects of salidroside on rat CYP enzymes by a cocktail of probe drugs.

OBJECTIVES: In this study, we aimed to evaluate the effect of salidroside on the activities of the different drug-metabolizing enzymes CYP1A2, CYP2B6, CYP2C9, CYP2D6 and CYP3A4 in rats, in which a specific probe drug was used for each enzyme. MATERIALS AND METHODS: After pretreatment with salidroside, five probe drugs were simultaneously administered to rats by gavage. The given dose was 2.0 mg/kg for phenacetin (CYP1A2 activity), 4.0 mg/kg for bupropion (CYP2B6 activity), 2.0 mg/kg for losartan (CYP2C9 activity), 8.0 mg/kg for metoprolol (CYP2D6 activity) and 1.0 mg/kg for midazolam (CYP3A4 activity). Then, an ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the concentrations of rats' blood, which were collected at different corresponding times. RESULTS: Our data showed that salidroside exhibited an inductive effect on CYP1A2, CYP2B6, CYP2C9 and CYP3A4 activities by changing the main pharmacokinetic parameters (t1/2, CL/F, Cmax and AUC(0-∞)) of the four probe drugs in rats. However, no significant changes in CYP2D6 activity were observed. CONCLUSION: In a word, the results displayed that salidroside could induce the activities of CYP1A2, CYP2B6, CYP2C9 and CYP3A4, which may influence the disposition of the drugs that are mainly metabolized by these pathways. Our research can provide the basis for the study of related herb-drug interactions in clinic.

Correlation of serum anti-Mullerian hormone to follicular follicle stimulating hormone and implantation potential of the ensuing embryos.

Serum anti-Mullerian hormone (AMH) is a predictor of the pregnancy outcome in assisted reproductive technology (ART) cycles, particularly for older women. This study attempts to elucidate the effect of serum AMH on follicular hormone profiles and implantation outcome of the ensuing embryos in ART cycles. A total of 412 patients undergoing ART cycles at a private infertility center were included and 780 follicular fluid samples were collected. Levels of follicular hormones, including FSH, LH, inhibin B, AMH, estradiol, progesterone, and androstenedione were measured. The implantation outcome of the ensuing embryos was traced as a main outcome measure. We demonstrated that the follicular levels of estradiol, progesterone, and androstenedione were considerably similar, but the overall implantation rates increased as the serum AMH increased. Logistic regression analysis revealed that the best predictor for embryo implantation was follicular FSH (>9.64mIU/mL, odds ratio [OR] 0.9). Furthermore, serum AMH (Spearman's rho=-0.352) and female age (rho=0.369) are correlated with follicular FSH levels in those follicles. In conclusion, the serum AMH might affect follicular hormone profiles by interaction with gonadotrophin rather than with steroidogenesis. The follicular FSH levels are correlated with the implantation potential of the ensuing embryos.

Survival benefit of surgical approach for advanced oropharyngeal and hypopharyngeal cancer: A retrospective analysis.

BACKGROUND: Head and neck cancer is increasingly being managed through nonsurgical approaches. Evidence comes from studies that have mainly examined patients with laryngeal cancer. Few studies, with limited sample size, have focused on the comparative outcomes of surgical and nonsurgical approaches in patients with advanced oropharyngeal or hypopharyngeal cancer. METHODS: Using a national cancer database, we identified 1603 and 1512 patients with clinical stage III/IVA oropharyngeal and hypopharyngeal cancer, respectively, treated between 2004 and 2009. The study cohort was followed until 2012, and analyzed through Kaplan-Meier survival analysis and Cox regression. RESULTS: Overall, 31.4% of patients with advanced oropharyngeal cancer and 42.2% of patients with hypopharyngeal cancer received surgery as their primary treatment. Receiving primary surgery for advanced oropharyngeal and hypopharyngeal cancer was associated with higher survival rates after controlling for potential confounders. CONCLUSION: We recommend that surgery be considered a first-line treatment for advanced oropharyngeal and hypopharyngeal cancers.

The outcomes and controversies of transplant tourism-Lessons of an 11-year retrospective cohort study from Taiwan.

BACKGROUND: Transplant tourism has increased rapidly in the past two decades, accounting for about 10% of world organ transplants. However it is ethically controversial and discouraged by professional guidelines. We conducted this study to investigate the outcomes and trends of overseas kidney and liver transplantation in Taiwan to provide a sound basis for ethical reflection. METHODS AND FINDINGS: The Taiwanese National Health Insurance Research Database was used to identify 2381 domestic and 2518 overseas kidney transplant (KT) recipients from 1998 to 2009 and 1758 domestic and 540 overseas liver transplantation (LT) recipients from 1999 to 2009. Cox proportional hazards models were used to assess the risks of mortality and graft failure. The numbers of overseas transplantation increased after 2000, reached a peak in 2005 and decreased after 2007. Compared to their domestic counterparts, the overseas KT recipients were older, male predominant, with shorter pre-op dialysis period and more comorbidities. Similarly, the overseas LT recipients were older, male predominant and had more hepatocellular carcinoma cases. The 1-, 5-, and 10-year patient survival rates were 96.9%, 91.7% and 83.0% respectively for domestic KT and 95.8%, 87.8% and 73.1% for overseas KT (p<0.001). The 1-, 5-, and 10-year patient survival rates were 89.2%, 79.5%, 75.2% for domestic LT and 79.8%, 54.7%, 49.9% for overseas LT (p<0.001). CONCLUSION: The poorer outcomes of the overseas groups may be due to more older patients, more comorbidities (KT), or more hepatocellular carcinoma recurrences (LT). After domestic reform and international ethical challenges, the numbers of organ tourism decreased but the practice still persisted surreptitiously. Compulsory registration policies for overseas transplantation with international conventions to sanction organ trafficking and transplant tourism should be considered to stop these controversial practices.

Diffusion radiomics analysis of intratumoral heterogeneity in a murine prostate cancer model following radiotherapy: Pixelwise correlation with histology.

PURPOSE: To investigate the biological meaning of apparent diffusion coefficient (ADC) values in tumors following radiotherapy. MATERIALS AND METHODS: Five mice bearing TRAMP-C1 tumor were half-irradiated with a dose of 15 Gy. Diffusion-weighted images, using multiple b-values from 0 to 3000 s/mm2 , were acquired at 7T on day 6. ADC values calculated by a two-point estimate and monoexponential fitting of signal decay were compared between the irradiated and nonirradiated regions of the tumor. Pixelwise ADC maps were correlated with histological metrics including nuclear counts, nuclear sizes, nuclear spaces, cytoplasmic spaces, and extracellular spaces. RESULTS: As compared with the nonirradiated region, the irradiated region exhibited significant increases in ADC, extracellular space, and nuclear size, and a significant decrease in nuclear counts (P < 0.001 for all). Optimal ADC to differentiate the irradiated from nonirradiated regions was achieved at a b-value of 800 s/mm2 by the two-point method and monoexponential curve fitting. ADC positively correlated with extracellular spaces (r = 0.74) and nuclear sizes (r = 0.72), and negatively correlated with nuclear counts (r = -0.82, P < 0.001 for all). CONCLUSION: As a radiomic biomarker, ADC maps correlating with histological metrics pixelwise could be a means of evaluating tumor heterogeneity and responses to radiotherapy. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:483-489.

Association of a Bundled-Payment Program With Cost and Outcomes in Full-Cycle Breast Cancer Care.

IMPORTANCE: Value-driven payment system reform is a potential tool for aligning economic incentives with the improvement of quality and efficiency of health care and containment of cost. Such a payment system has not been researched satisfactorily in full-cycle cancer care. OBJECTIVE: To examine the association of outcomes and medical expenditures with a bundled-payment pay-for-performance program for breast cancer in Taiwan compared with a fee-for-service (FFS) program. DESIGN, SETTING, AND PARTICIPANTS: Data were obtained from the Taiwan Cancer Database, National Health Insurance Claims Data, the National Death Registry, and the bundled-payment enrollment file. Women with newly diagnosed breast cancer and a documented first cancer treatment from January 1, 2004, to December 31, 2008, were selected from the Taiwan Cancer Database and followed up for 5 years, with the last follow-up data available on December 31, 2013. Patients in the bundled-payment program were matched at a ratio of 1:3 with control individuals in an FFS program using a propensity score method. The final sample of 17 940 patients included 4485 (25%) in the bundled-payment group and 13 455 (75%) in the FFS group. MAIN OUTCOMES AND MEASURES: Rates of adherence to quality indicators, survival rates, and medical payments (excluding bonuses paid in the bundled-payment group). The Kaplan-Meier method was used to calculate 5-year overall and event-free survival rates by cancer stage, and the Cox proportional hazards regression model was used to examine the effect of the bundled-payment program on overall and event-free survival. Sensitivity analysis for bonus payments in the bundled-payment group was also performed. RESULTS: The study population included 17 940 women (mean [SD] age, 52.2 [10.3] years). In the bundled-payment group, 1473 of 4215 patients (34.9%) with applicable quality indicators had full (100%) adherence to quality indicators compared with 3438 of 12 506 patients (27.5%) with applicable quality indicators in the FFS group (P < .001). The 5-year event-free survival rates for patients with stages 0 to III breast cancer were 84.48% for the bundled-payment group and 80.88% for the FFS group (P < .01). Although the 5-year medical payments of the bundled-payment group remained stable, the cumulative medical payments for the FFS group steadily increased from $16 000 to $19 230 and exceeded pay-for-performance bundled payments starting in 2008. CONCLUSIONS AND RELEVANCE: In Taiwan, compared with the regular FFS program, bundled payment may lead to better adherence to quality indicators, better outcomes, and more effective cost-control over time.

Magneto-optical properties of ABC-stacked trilayer graphene.

The generalized tight-binding model is developed to investigate the magneto-optical absorption spectra of ABC-stacked trilayer graphene. The absorption peaks can be classified into nine categories of inter-Landau-level optical excitations, including three intra-group and six inter-group ones. Most of them belong to the twin-peak structures because of the asymmetric Landau level spectrum. The threshold absorption peak alone comes from a certain excitation channel, and its frequency is associated with a specific interlayer atomic interaction. The Landau-level anticrossings cause extra absorption peaks. Moreover, a simple relationship between the absorption frequency and the field strength is absent. The magneto-optical properties of ABC-stacked trilayer graphene are totally different from those of AAA- and ABA-stacked ones, such as the number, intensity and frequency of absorption peaks.

Acoustic radiation force impulse elastography of the liver in healthy patients: test location, reference range and influence of gender and body mass index.

The objective of this study was to evaluate the best test location and study factors associated with acoustic radiation force impulse (ARFI) elastography measurements in healthy individuals. When ARFI elastography was performed on 68 healthy patients after controlling for all known test condition factors except segmental location, the median shear wave velocities (SWVs) derived from five valid measurements in the area between S5 and S8 in patients in the supine position had a significantly lower mean and the narrowest 95% confidence interval, followed by those for the S8 supine and S8 semidecubitus locations (p = 0.045). Analysis of mean SWVs revealed similar, although statistically insignificant, findings (p = 0.078). Male patients had significantly higher median SWVs (p = 0.0073) and mean SWVs (p = 0.0043) than female patients. Patients with body mass indexes >22 had significantly lower median SWVs (p = 0.0033) and mean SWVs (p = 0.0008) than those with body mass indexes ≤22. S5/8 supine was the better test location for ARFI. The reference ranges for median and mean SWV were 0.81-1.27 and 0.82-1.27 m/s, respectively. Gender and body mass index, but not age, were the significant factors associated with ARFI SWV values.

A simple method to improve the quality of diffusion-weighted magnetic resonance imaging with rapid histologic correlation in a murine model.

Diffusion-weighted magnetic resonance imaging (DW-MRI) has been used extensively in biomedical research. However, this technique has often suffered from distortion artifacts because of the magnetic field inhomogeneity surrounding the tissues. Histology is important for validating MRI interpretations, but correlating MRIs with tissue samples is challenging. Here we propose a method to improve DW-MRI and facilitate the matching between MRIs and tissue samples. A cryostat embedding medium, optimal cutting temperature (OCT) compound, was used to cover the examined target during the MRI studies. Frozen OCT compound could aid the examined target to be sectioned in parallel with the imaging plane. Phantom experiments demonstrated that embedding in OCT compound improved the magnetic field inhomogeneity while maintaining the apparent diffusion coefficient. Animal experiments revealed significantly reduced distortions in DW images in both the axial and coronal planes. The in vivo MRIs were easily matched with histologic specimens in a slice-to-slice fashion to examine the corresponding tissue microenvironment. This simple method might improve the quality of DW-MRI and provide histologic information for MRI to serve as an image biomarker.

Directly observed therapy reduces tuberculosis-specific mortality: a population-based follow-up study in Taipei, Taiwan.

OBJECTIVES: To determine the effect of directly observed therapy (DOT) on tuberculosis-specific mortality and non-TB-specific mortality and identify prognostic factors associated with mortality among adults with culture-positive pulmonary TB (PTB). METHODS: All adult Taiwanese with PTB in Taipei, Taiwan were included in a retrospective cohort study in 2006-2010. Backward stepwise multinomial logistic regression was used to identify risk factors associated with each mortality outcome. RESULTS: Mean age of the 3,487 patients was 64.2 years and 70.4% were male. Among 2471 patients on DOT, 4.2% (105) died of TB-specific causes and 15.4% (381) died of non-TB-specific causes. Among 1016 patients on SAT, 4.4% (45) died of TB-specific causes and 11.8% (120) died of non-TB-specific causes. , After adjustment for potential confounders, the odds ratio for TB-specific mortality was 0.45 (95% CI: 0.30-0.69) among patients treated with DOT as compared with those on self-administered treatment. Independent predictors of TB-specific and non-TB-specific mortality included older age (ie, 65-79 and ≥80 years vs. 18-49 years), being unemployed, a positive sputum smear for acid-fast bacilli, and TB notification from a general ward or intensive care unit (reference: outpatient services). Male sex, end-stage renal disease requiring dialysis, malignancy, and pleural effusion on chest radiography were associated with increased risk of non-TB-specific mortality, while presence of lung cavities on chest radiography was associated with lower risk. CONCLUSIONS: DOT reduced TB-specific mortality by 55% among patients with PTB, after controlling for confounders. DOT should be given to all TB patients to further reduce TB-specific mortality.

Risks perception of electromagnetic fields in Taiwan: the influence of psychopathology and the degree of sensitivity to electromagnetic fields.

Little is known about the perceived health risks of electromagnetic fields (EMFs) and factors associated with risk perception in non-Western countries. Psychological conditions and risk perception have been postulated as factors that facilitate the attribution of health complaints to environmental factors. This study investigated people's perceived risks of EMFs and other environmental sources, as well as the relationships between risk perception, psychopathology, and the degree of self-reported sensitivity to EMFs. A total of 1,251 adults selected from a nationwide telephone interviewing system database responded to a telephone survey about the relationships between environmental sources and human health. The interview included questions assessing participants' psychiatric conditions and the presence and degree of sensitivity to EMFs. One hundred and seventy participants were self-identified as having sensitivity to EMFs, and 141 met the criteria for psychiatric conditions without EMF sensitivity. More than half of the survey respondents considered power lines and mobile phone base stations to affect people's health to a big extent. Higher sensitivity to EMFs, psychopathology, being female, being married, more years of education, and having a catastrophic illness had positive associations with perceived risks of EMF-related environmental sources as well as for all environmental sources combined. We observed no moderating effect of psychopathology on the association between degree of sensitivity to EMF and risk perception. Thus, psychopathology had influence on general people's risk perception without having influence on the relationship between people's degree of sensitivity to EMF and risk perception. The plausible explanations are discussed in the text.

Noninvasive monitoring of microvascular changes with partial irradiation using dynamic contrast-enhanced and blood oxygen level-dependent magnetic resonance imaging.

PURPOSE: The microvasculature of a tumor plays an important role in its response to radiation therapy. Dynamic contrast-enhanced magnetic resonance imaging (DCE MRI) and blood oxygen level-dependent (BOLD) MRI are both sensitive to vascular characteristics. The present study proposed a partial irradiation approach to a xenograft tumor to investigate the intratumoral response to radiation therapy using DCE and BOLD MRI. METHODS AND MATERIALS: TRAMP-C1 tumors were grown in C57BL/6J mice. Partial irradiation was performed on the distal half of the tumor with a single dose of 15 Gy. DCE MRI was performed to derive the endothelium transfer constant, K(trans), using pharmacokinetic analysis. BOLD MRI was performed using quantitative R2 measurements with carbogen breathing. The histology of the tumor was analyzed using hematoxylin and eosin staining and CD31 staining to detect endothelial cells. The differences between the irradiated and nonirradiated regions of the tumor were assessed using K(trans) values, ΔR2 values in response to carbogen and microvascular density (MVD) measurements. RESULTS: A significantly increased K(trans) and reduced BOLD response to carbogen were found in the irradiated region of the tumor compared with the nonirradiated region (P<.05). Histologic analysis showed a significant aggregation of giant cells and a reduced MVD in the irradiated region of the tumor. The radiation-induced difference in the BOLD response was associated with differences in MVD and K(trans). CONCLUSIONS: We demonstrated that DCE MRI and carbogen-challenge BOLD MRI can detect differential responses within a tumor that may potentially serve as noninvasive imaging biomarkers to detect microvascular changes in response to radiation therapy.

Prevalence and psychiatric comorbidity of self-reported electromagnetic field sensitivity in Taiwan: a population-based study.

BACKGROUND/PURPOSE: Psychological factors have been implicated in the etiology of idiopathic environmental illness in many studies. Few studies have ever reported psychiatric morbidity among individuals with electromagnetic hypersensitivity. We aimed to estimate the prevalence and identify the associated factors of self-reported electromagnetic field sensitivity (SREMFS) in adults of Taiwan. METHODS: A total of 1251 adults selected from a nationwide Computer-Assisted Telephone Interviewing system received a telephone survey about the perception of risk from various environmental agents and their effects on health and well-being. RESULTS: The estimated prevalence of people with SREMFS was 13.3 % (95% confidence interval: 11.2-15.3). People aged >65 years were associated with a lower risk of reporting sensitivity to electromagnetic fields, whereas people with a very poor self-reported health status, those who were unable to work, and those who had psychiatric morbidity were associated with a higher risk of having SREMFS. CONCLUSION: The prevalence of SREMFS in the general population of Taiwan is higher than that reported in western countries. People with psychiatric morbidity are more likely to report sensitivity to electromagnetic fields. The cross-sectional design precludes the causal inference of all identified correlates and electromagnetic field sensitivity.