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Abstract Background This cohort study determines the predictors for cause-specific and timing of deaths in patients with COVID-19 in Taiwan. Methods Patients with laboratory-confirmed COVID-19 admitted to Taipei City Hospital from January 1 to July 31, 2022, were recruited in this cohort. All patients were followed up until death, discharge from the hospital, or August 31, 2022. Early deaths within the first 2 weeks were recorded, and the cause of death was confirmed by the death certificate database of Taiwan. Predictors of cause-specific and timing of deaths of patients with COVID-19 were determined using multinomial Cox proportional hazards regression analysis. Results Of the 195 (8.0%) patients who died during hospitalization, 147 (84.0%) had COVID-19-specific deaths. Moreover, 54.9% of the deceased patients had early death. After controlling for other covariates, patients aged ≥ 65 years had a higher risk of COVID-19-specific, non-COVID-19-specific, early, and late deaths [adjusted hazards ratio (AHR): 3.85, 6.45, 3.33, and 6.57; 95% confidence interval (CI): 1.91–7.78, 1.17–35.68, 1.51–7.36, and 2.18–19.76, respectively]. Fully vaccinated patients had a lower risk of COVID-19-specific (AHR: 0.68; 95% CI: 0.47–0.98) and early deaths (AHR: 0.54; 95% CI: 0.35–0.84), whereas comorbid patients with chronic obstructive pulmonary disease had a higher risk of non-COVID-19-specific deaths (AHR: 5.43; 95% CI: 1.73–17.03). Conclusions This study suggests that prioritizing COVID-19 vaccination and carefully monitoring comorbid patients during hospitalization can reduce the risk of COVID-19-specific and early deaths and non-COVID-19-specific mortalities, respectively.

The concept of the oral-systemic link is important in both basic and clinical dentistry. The microbiome (microbiota) and exosomes are two prevalent issues in the modern medical researches. The common advent of oral and general microbiological investigation originated from the initial observations of oral bacteria within the dental plaque known as oral microbiome. In addition to oral diseases related to oral microbiome, the disruption of the oral and intestinal microbiome could result in the onset of systemic diseases. In the past decade, the exosomes have emerged in the field of the medical researches as they play a role in regulating the transport of intracellular vesicles. However, with the rapid advancement of exosomes researches in recent years, oral tissues (such as dental pulp stem cells and salivary gland cells) are used as the research materials to further promote the development of regenerative medicine. This article emphasized the importance of the concept of the oral-systemic link through the examples of microbiome (microbiota) and exosomes. Through the researches related to microbiome (microbiota) and exosomes, many evidences showed that as the basic dentistry developed directly from the assistance of the basic medicine, indirectly the progress of the basic dentistry turns back to promote the development of the basic medicine, indicating the importance of the concept of the oral-systemic link. The understanding of the oral-systemic link is essential for both clinicians and medical researchers, regardless of their dental backgrounds.

Background: Evidence on the health benefits of occupational physical activity (OPA) is inconclusive. We examined the associations of baseline OPA and OPA changes with all-cause, cardiovascular disease (CVD), and cancer mortality and survival times. Methods: This study included prospective and longitudinal data from the MJ Cohort, comprising adults over 18 years recruited in 1998–2016, 349,248 adults (177,314 women) with baseline OPA, of whom 105,715 (52,503 women) had 2 OPA measures at 6.3 ± 4.2 years (mean ± SD) apart. Exposures were baseline OPA, OPA changes, and baseline leisure-time physical activity. Results: Over a mean mortality follow-up of 16.2 ± 5.5 years for men and 16.4 ± 5.4 years for women, 11,696 deaths (2033 of CVD and 4631 of cancer causes) in men and 8980 deaths (1475 of CVD and 3689 of cancer causes) in women occurred. Combined moderately heavy/heavy baseline OPA was beneficially associated with all-cause mortality in men (multivariable-adjusted hazard ratio (HR) = 0.93, 95% confidence interval (95%CI): 0.89–0.98 compared to light OPA) and women (HR = 0.86, 95%CI: 0.79–0.93). Over a mean mortality follow-up of 12.5 ± 4.6 years for men and 12.6 ± 4.6 years for women, OPA decreases in men were detrimentally associated (HR = 1.16, 95%CI: 1.01–1.33) with all-cause mortality, while OPA increases in women were beneficially (HR = 0.83, 95%CI: 0.70–0.97) associated with the same outcome. Baseline or changes in OPA showed no associations with CVD or cancer mortality. Conclusion: Higher baseline OPA was beneficially associated with all-cause mortality risk in both men and women. Our longitudinal OPA analyses partly confirmed the prospective findings, with some discordance between sex groups.

ObjectiveCollege students showed a high prevalence of stress, anxiety, and depression, with medical and nursing students experiencing particularly elevated levels of mental health challenges.Optimism significantly influences overall well-being by promoting a healthy lifestyle and cognitive responses. However, the association of optimism with sleep quality, stress, and mental health in college students remains unexplored. This study aimed to (1) explore the associations of optimism with sleep quality, stress, and mental health and (2) ascertain whether sleep quality and stress mediate the association between optimism and mental health among college students.MethodsA cross-sectional study was conducted using online surveys with students from health science majors at a public university in the northeast United States from September to December 2022. A total of 222 students participated in the study, providing data on sociodemographics, optimism, sleep quality, stress, anxiety, and depression. Parallel and serial mediation models were utilized to examine the potential mediating roles of sleep quality and stress in the association between optimism and mental health.ResultsThe study found that optimism influences anxiety and depression through both direct and indirect pathways. In line with predictions, the parallel mediation analysis revealed that the impact of optimism on anxiety (βtotal = −0.598, 95% confident interval [CI]: −0.778 to −0.392) and depression (βtotal = −0.724, 95% CI: −0.919 to −0.519) was mediated by stress and sleep quality. Furthermore, the serial mediation models revealed that stress and sleep quality co-mediated the relationship betweenoptimism and anxiety (indirect effect [IE] = −0.074, 95% CI: −0.135 to −0.029) or depression (IE = −0.084, 95% CI: −0.142 to −0.036) in a sequential manner.ConclusionOptimism was negatively correlated with poor sleep quality, stress, anxiety, and depression. Enhanced optimism was linked to high sleep quality and less stress, anxiety, and depression. These insights emphasize the potential for school-based optimism interventions to improve sleep quality, ameliorate stress-related concerns, and alleviate mental health challenges in college students.

Abstract Background Ritodrine hydrochloride is a widely used beta-adrenergic agonist used to stop preterm labor in Taiwan. Many side effects causing maternal morbidity and mortality have been reported. We report a case complicated with ritodrine-induced side effects and mirror syndrome that was associated with placental chorioangioma. Case presentation A 36-year-old singleton pregnant woman at 25 6/7 weeks of gestation, with an undiagnosed placental chorioangioma, underwent tocolysis due to preterm uterine contractions. Her clinical condition deteriorated, attributed to mirror syndrome and adverse events induced by ritodrine. An emergency cesarean section was performed at 27 1/7 weeks of gestation, delivering an infant with generalized subcutaneous edema. A placental tumor measuring 8.5 cm was discovered during the operation, and pathology confirmed chorioangioma. Gradual improvement in her symptoms and laboratory data was observed during the postpartum period. Identifying mirror syndrome and ritodrine-induced side effects poses challenges. Therefore, this case is educational and warrants discussion. Conclusion Our case demonstrates mirror syndrome induced by chorioangioma, which is rare, and ritodrine-induced side effects. The cessation of intravenous ritodrine and delivery are the best methods to treat maternal critical status due to fluid overload.

We hypothesized and investigated whether prenatal exposure to preeclampsia (PE) would simultaneously affect perinatal cardiovascular features and angiotensin system expressions. This prospective study was composed of mother-neonate dyads with (n = 49) and without maternal preeclampsia (n = 48) in a single tertiary medical center. The neonates exposed to PE had significantly larger relative sizes for the left and right coronary arteries and a higher cord plasma level of aminopeptidase-N, which positively correlated with the maternal diastolic blood pressures and determined the relative sizes of the left and right coronary arteries, whereas the encoding aminopeptidase-N (ANPEP) mRNA level in the PE cord blood leukocytes was significantly decreased, positively correlated with the neonatal systolic blood pressures (SBPs), and negatively correlated with the cord plasma-induced endothelial vascular cell adhesion molecule-1 mRNA levels. The PE cord plasma significantly induced higher endothelial mRNA levels of angiotensin II type 1 receptor (AT1R) and AT4R, whereas in the umbilical arteries, the protein expressions of AT2R and AT4R were significantly decreased in the PE group. The endothelial AT1R mRNA level positively determined the maternal SBPs, and the AT4R mRNA level positively determined the neonatal chamber size and cardiac output. In conclusion, PE may influence perinatal angiotensin system and cardiovascular manifestations of neonates across placentae. Intriguing correlations between these two warrant further mechanistic investigation.

Abstract Background Older patients tend to have decreased physical functions and more comorbidities than younger patients. At present, the best management for very elderly patients with lung cancer is not known. In this study, we aimed to investigate treatment and mortality risk of older adults with non‐small cell cancer (NSCLC) in Taiwan. Methods This study analyzed data from the Taiwan Cancer Registry database. Patients aged ≥80 years with newly diagnosed NSCLC between 2010 and 2017 were included. Treatment options were categorized as curative, palliative, and no treatment. Patients were followed up until death or December 31, 2020. Univariable and multivariable Cox proportional hazards models were used to estimate mortality risk, and Kaplan–Meier survival curves were drawn. Results A total of 11 941 patients, aged ≥80 years, with newly diagnosed NSCLC between 2010 and 2017 were identified from the Taiwan Cancer Registry and followed up until 2020. The mean age was 84.4 ± 3.7 years old, and 7468 (62.54%) were men. The Kaplan–Meier survival curves showed significant differences across the three treatment options (log‐rank p

The development of sensitive and specific exosome detection tools is essential because they are believed to provide specific information that is important for early detection, screening, diagnosis, and monitoring of cancer. Among the many detection tools, surface-plasmon resonance (SPR) biosensors are analytical devices that offer advantages in sensitivity and detection speed, thereby making the sample-analysis process faster and more accurate. In addition, the penetration depth of the SPR biosensor, which is

This study presents a novel label-free approach for characterizing cell death states, eliminating the need for complex molecular labeling that may yield artificial or ambiguous results due to technical limitations in microscope resolution. The proposed holographic tomography technique offers a label-free avenue for capturing precise three-dimensional (3D) refractive index morphologies of cells and directly analyzing cellular parameters like area, height, volume, and nucleus/cytoplasm ratio within the 3D cellular model. We showcase holographic tomography results illustrating various cell death types and elucidate distinctive refractive index correlations with specific cell morphologies complemented by biochemical assays to verify cell death states. These findings hold promise for advancing in situ single cell state identification and diagnosis applications.

Abstract Neonates who are born preterm (PT) are usually characterized by immature physiological development, and preterm birth (PTB) is the leading cause of neonatal morbidity and mortality if intensive medical care is not available to PTB neonates. Early prediction of a PTB enables medical personnel to make preparations in advance, protecting the neonate from the subsequent health risks. Therefore, many studies have worked on identifying invasive or noninvasive PT biomarkers. In this study, we collected amniocentesis-derived (at the second trimester of gestation) amniotic fluid (AF) samples. At delivery, AF samples were classified into PTB or full-term birth (FTB). We first applied protein mass spectrometry technology to globally screen AF proteins, followed by specific protein validation with ELISA. We identified four protein biomarkers of PTB, including lactotransferrin (LTF), glutathione-disulfide reductase (GSR), myeloperoxidase (MPO) and superoxide dismutase 2 (SOD2). Further analyses demonstrated that their abundances were negatively correlated with neonatal weight and gestational age. In addition, by mimicking survival rate analysis widely used in tumor biology, we found that LTF and SOD2 were prognostic factors of gestational age, with higher levels denoting shorter gestational age. Finally, using the abundances of the four protein biomarkers, we developed a prediction model of PTB with an auROC value of 0.935 (sensitivity = 0.94, specificity = 0.89, p value = 0.0001). This study demonstrated that the abundances of specific proteins in amniotic fluid were not only the prognostic factors of gestational age but also the predictive biomarkers of PTB. These four AF proteins enable identification of PTB early in the second trimester of gestation, facilitating medical intervention to be applied in advance.

Abstract Background The risk of ischemic heart disease (IHD) due to the impact of gonadotropin‐releasing hormone (GnRH) agonists among female patients with breast cancer remains a controversy. Methods Information from the Registry for Catastrophic Illness, the National Health Insurance Research Database (NHIRD), and the Death Registry Database in Taiwan were analyzed. Female patients with breast cancer were selected from the Registry for Catastrophic Illness from January 1, 2000, to December 31, 2018. All the breast cancer patients were followed until new‐onset IHD diagnosis, death, or December 31, 2018. A Kaplan–Meier survival curve was drawn to show the difference between patients treated with and without GnRH agonists. The Cox regression analysis was used to investigate the effects of GnRH agonists and the incidence of IHD. Results A total of 172,850 female patients with breast cancer were recognized with a mean age of 52.6 years. Among them, 6071(3.5%) had received GnRH agonist therapy. Kaplan–Meier survival curves showed a significant difference between patients with and without GnRH therapy (log‐rank p

A 36-year-old woman, gravida 3, para 1 (previous cesarean section), with one medical abortion, and no history of systemic diseases presented an unremarkable medical history during prenatal visits. The final prenatal ultrasound at 38 weeks of gestation showed a vertex presentation, a weight of 2600 g, a normal amniotic fluid level, and the placenta located on the posterior wall of the uterus. Fetal cardiotocography conducted before delivery reported a reactive heart rate without decelerations. The Doppler wave analysis of the fetal umbilical artery was normal (the ratio of peak-systolic flow velocity to the end-diastolic flow velocity was 2.5) without the absence or reversal of end-diastolic velocity. The total score of the fetal biophysical profile by ultrasound was 8. The night before the scheduled cesarean section, she experienced heightened anxiety and was unable to sleep, noting “crazy” fetal movements throughout the night. During the cesarean section, it was discovered that the umbilical cord was wrapped around the newborn’s legs, resembling ankle shackles. The fetal weight was 2740 g, and Apgar scores were 9 at the first minute and 10 at the fifth minute. The motility of the neonatal legs was normal without cyanosis or neurological adverse outcomes.

Background: This study examined the joint associations of sleep patterns and physical activity (PA) with all-cause, cardiovascular disease (CVD), and cancer mortality. Methods: A total of 341,248 adults (mean age = 39.7 years; men: 48.3%) were included in the study, with a 15-year follow-up. Participants reported sleep duration and disturbances (difficulty falling asleep, easily awakened, or use of sleeping medication). PA was classified into 4 levels: 8 h/day had higher risk for all-cause mortality (hazard ratio (HR) = 1.307, 95% confidence interval (95%CI): 1.248–1.369), CVD mortality (HR = 1.298, 95%CI: 1.165–1.445), and cancer mortality (HR = 1.128, 95%CI: 1.042–1.220). Short sleep duration was not associated with mortality risk. Increased risk of all-cause and CVD mortality was found in participants who had difficulty falling asleep (HR = 1.120, 95%CI: 1.068–1.175; HR = 1.163, 95%CI: 1.038–1.304, respectively), and used sleeping medication (HR = 1.261, 95%CI: 1.159–1.372; HR = 1.335, 95%CI: 1.102–1.618, respectively) compared with those who slept well. Long sleep duration and sleep disturbances were not associated with risk of all-cause and CVD mortality among individuals achieving a PA level of ≥15 MET-h/week, and in particular among those achieving ≥30 MET-h/week. Conclusion: Long sleep duration, difficulty falling asleep, and use of sleeping medication were related to a higher risk of death. Being physically active at a moderate intensity for 25–65 min/day eliminated these detrimental associations.

Background and purpose: Although leisure-time physical activity (PA) has established health benefits in older adults, it is equivocal if exercising in environments with high levels of PM2.5 concentrations is equally beneficial for them. To explore the independent and joint associations of ambient PM2.5 and PA with all-cause mortality among adults aged 60 or older and to assess the modifying effect of age (60–74 years vs. 75+ years) on the joint associations. Methods: A prospective cohort study based on the MJ Cohort repeat examinations (2005–2016) and the Taiwan Air Quality Monitoring Network and death registry linkages (2005–2022). We included MJ Cohort participants aged 60 or more at baseline who attended the health check-ups at least twice (n = 21,760). Metabolic equivalent hours per week (MET-h/week) of leisure-time PA were computed. Multivariable adjusted associations were examined using time-varying Cox proportional hazard models. Results: There were 3539 all-cause deaths over a mean follow-up of 12.81 (SD = 3.67) years. Ambient PM2.5 and physical inactivity are both independently associated with all-cause mortality. The joint associations of PA and PM2.5 concentrations with all-cause mortality differed in the young-old (60–74 years) and the older-old (75+ years) (P for interaction = 0.01); Higher levels of long-term PM2.5 exposures (≥25 μg/m3) had little influence on the associations between PA and mortality in the young-old (HR = 0.68 (0.56–0.83) and HR = 0.72 (0.59–0.88) for participants with 7.5–

Abstract Studies to examine the impact of end-of-life (EOL) discussions on the utilization of life-sustaining treatments near death are limited and have inconsistent findings. This nationwide population-based cohort study determined the impact of EOL discussions on the utilization of life-sustaining treatments in the last three months of life in Taiwanese cancer patients. From 2012 to 2018, this cohort study included adult cancer patients, which were confirmed by pathohistological reports. Life-sustaining treatments during the last three months of life included cardiopulmonary resuscitation, intubation, and defibrillation. EOL discussions in cancer patients were confirmed by their medical records. Association of EOL discussions with utilization of life-sustaining treatments were assessed using multiple logistic regression. Of 381,207 patients, the mean age was 70.5 years and 19.4% of the subjects received life-sustaining treatments during the last three months of life. After adjusting for other covariates, those who underwent EOL discussions were less likely to receive life-sustaining treatments during the last three months of life compared to those who did not (Adjusted odds ratio [AOR] 0.87; 95% confidence interval [CI] 0.85–0.89). Considering the type of treatments, EOL discussions correlated with a lower likelihood of receiving cardiopulmonary resuscitation (AOR = 0.45, 95% CI 0.43–0.47), endotracheal intubation (AOR = 0.92, 95%CI 0.90–0.95), and defibrillation (AOR = 0.54, 95%CI 0.49–0.59). Since EOL discussions are associated with less aggressive care, our study supports the importance of providing these discussions to cancer patients during the EOL treatment.

PurposeLong COVID, also known as post-acute sequelae of COVID-19, refers to the constellation of long-term symptoms experienced by people suffering persistent symptoms for one or more months after SARS-CoV-2 infection. Blood biomarkers can be altered in long COVID patients; however, biomarkers associated with long COVID symptoms and their roles in disease progression remain undetermined. This study aims to systematically evaluate blood biomarkers that may act as indicators or therapeutic targets for long COVID.MethodsA systematic literature review in PubMed, Embase, and CINAHL was performed on 18 August 2022. The search keywords long COVID-19 symptoms and biomarkers were used to filter out the eligible studies, which were then carefully evaluated.ResultsIdentified from 28 studies and representing six biological classifications, 113 biomarkers were significantly associated with long COVID: (1) Cytokine/Chemokine (38, 33.6%); (2) Biochemical markers (24, 21.2%); (3) Vascular markers (20, 17.7%); (4) Neurological markers (6, 5.3%); (5) Acute phase protein (5, 4.4%); and (6) Others (20, 17.7%). Compared with healthy control or recovered patients without long COVID symptoms, 79 biomarkers were increased, 29 were decreased, and 5 required further determination in the long COVID patients. Of these, up-regulated Interleukin 6, C-reactive protein, and tumor necrosis factor alpha might serve as the potential diagnostic biomarkers for long COVID. Moreover, long COVID patients with neurological symptoms exhibited higher levels of neurofilament light chain and glial fibrillary acidic protein whereas those with pulmonary symptoms exhibited a higher level of transforming growth factor beta.ConclusionLong COVID patients present elevated inflammatory biomarkers after initial infection. Our study found significant associations between specific biomarkers and long COVID symptoms. Further investigations are warranted to identify a core set of blood biomarkers that can be used to diagnose and manage long COVID patients in clinical practice.

Abstract The intuitive assessment of palliative care (PC) needs and Palliative Care Screening Tool (PCST) are the assessment tools used in the early detection of patients requiring PC. However, the comparison of their prognostic accuracies has not been extensively studied. This cohort study aimed to compare the validity of intuitive assessment and PCST in terms of recognizing patients nearing end-of-life (EOL) and those appropriate for PC. All adult patients admitted to Taipei City Hospital from 2016 through 2019 were included in this prospective study. We used both the intuitive assessment of PC and PCST to predict patients’ 6-month mortality and identified those appropriate for PC. The c-statistic value was calculated to indicate the predictive accuracies of the intuition and PCST. Of 111,483 patients, 4.5% needed PC by the healthcare workers’ intuitive assessment, and 6.7% had a PCST score ≥ 4. After controlling for other covariates, a positive response ‘yes’ to intuitive assessment of PC needs [adjusted odds ratio (AOR) = 9.89; 95% confidence interval (CI) 914–10.71] and a PCST score ≥ 4 (AOR = 6.59; 95%CI 6.17–7.00) were the independent predictors of 6-month mortality. Kappa statistics showed moderate concordance between intuitive assessment and PCST in predicting patients' 6-month mortality (k = 0.49). The c-statistic values of the PCST at recognizing patients’ 6-month mortality was significantly higher than intuition (0.723 vs. 0.679; p

Abstract Background To examine the association between teeth loss and nasogastric tube feeding dependency in older people. Methods The National Health Interview Survey (NHIS) 2005, 2009, and 2013 in Taiwan. Participants were selected by a multistage stratified sampling method and baseline characteristics, including socioeconomic status and health habits, were obtained by well-trained interviewers. The NHIS was linked with the National Health Insurance research database 2000–2016 and the National Deaths Dataset, which contains all the medical information of ambulatory and inpatient care. Cox regression was used to examine the association between the number of teeth lost and nasogastric tube feeding dependency. Results There were 6165 adults older than 65 years old enrolled in the analysis, with 2959 male (48%) and the mean (SD) age was 73.95(6.46) years old. The mean follow-up duration was 6.5(3.3) years. Regarding the teeth loss categories, 1660 (26.93%), 2123 (34.44%), and 2382 (38.64%) of participants were categorized as having no teeth loss, loss of 1–9 teeth, and loss of 10–28 teeth, respectively. During 39,962 person-years of follow-up, new-onset nasogastric feeding dependency was recognized in 220(13.25%), 256(12.06%), and 461(19.35%) participants who were categorized as having no teeth loss, loss of 1–9 teeth, and loss of 10–28 teeth, respectively. Kaplan-Meier curves demonstrated significant findings (Log-rank P

Purpose: Cancer patients with COVID-19 likely express biomarker changes in circulation. However, the biomarkers used in SARS-CoV-2 infected cancer patients for COVID-19 severity and prognosis are largely unclear. Therefore, this systematic review aims to determine what biomarkers were measured in cancer patients with COVID-19 and their prognostic utility. Methods: A systematic literature review in PubMed, Embase, and Scopus was performed on June 16th, 2021. The search keywords coronavirus, neoplasm, biomarkers, and disease progression were used to filter out 17 eligible studies, which were then carefully evaluated. Results: A total of 4,168 patients, 16 types of cancer, and 60 biomarkers were included. Seven up-regulated markers, including CRP, d-dimer, ferritin, IL-2R, IL-6, LDH, and PCT, were identified in eligible studies. Albumin and hemoglobin were significantly down-regulated in cancer patients with COVID-19. Moreover, we observed that the SARS-CoV-2 infected cancer patients with lower CRP, ferritin, and LDH levels successfully survived from COVID-19 treatments. Conclusion: Several important clinical biomarkers, such as CRP, ferritin, and LDH, may serve as the prognostic markers to predict the outcomes following COVID-19 treatment and monitor the deterioration of COVID-19 in cancer patients.

Abstract Gamma‐delta (γδ) T cells have a promising future in various therapies due to their anti‐cancer and anti‐infectious function. As the unique T cell subset plays a vital role in the connection between innate and adaptive immunity, we discussed the potential application of γδ T cell‐based therapy combined with other anti‐tumour treatments. For comprehensive investigation, a three‐dimensional (3D) cell culture system can be applied to evaluate the therapeutic efficacy of γδ T cells. Hence, we also summarized and discussed the potential use of the 3D cell culture system for therapeutic developments in γδ T cells.

Background: Patent ductus arteriosus (PDA) remains a critical issue in prematurity care. To predict the PDA closure early, we aimed to clarify the association of PDA closure with the initial postnatal 24-hour clinical characteristics and maternal and gestational histories of preterm neonates. Methods: A retrospective cohort study was conducted in a pediatric-neonatal-intensive-care-unit from 2008 to 2013. Data relating to birth histories, maternal histories, and clinical data from the first 24 h of life were analyzed according to three types of PDA closure—non-treated, medically-responsive, and surgically-ligated PDA and birth body weights (BBWs). Univariate analysis was performed using non-parametric analysis and Chi-square test or Fisher's exact test. Multivariate analysis was performed using multinomial logistic regression to determine the independent risk factors for the PDA closure. Results: This study involved 682 preterm infants with median gestational age of 31 (interquartile, IQR: 28–34) weeks and BBW of 1360 (IQR: 1085–1861) g. Inclusively, 16.7% of (P)DAs underwent medical and/or surgical treatment. For very low birth body weight (VLBW) neonates, surfactant use not only predicted the requirement of PDA treatment, but together with dopamine use and the larger amount of first 24-hour intravenous fluid (IVF) per kilogram of BBW, it also predicted the possibility of surgical ligation. Meanwhile, the cut-off values of the IVF amount (87 and 89.5 ml/kg/day, respectively) might predict the PDA treatment necessity and surgical ligation. For neonates with BBW ≥1500 g, placenta previa and lower BBW and systolic blood pressure (SBP) predicted the risk of treatment for PDA and its treatment response. Conclusions: Neonatal care for PDA in prematurity should be meticulously personalized. Surfactant use, dopamine administration and the first 24-hour IVF management may be critical for PDA closure in VLBW neonates. Antepartum history of placenta previa, BBW and SBP control may be important for BBW≥1500 g.

Senescence in the cerebral endothelium has been proposed as a mechanism that can drive dysfunction of the cerebral vasculature, which precedes vascular dementia. Cysteine-rich angiogenic inducer 61 (Cyr61/CCN1) is a matricellular protein secreted by cerebral endothelial cells (CEC). CCN1 induces senescence in fibroblasts. However, whether CCN1 contributes to senescence in CEC and how this is regulated requires further study. Aging has been associated with the formation of four-stranded Guanine-quadruplexes (G4s) in G-rich motifs of DNA and RNA. Stabilization of the G4 structures regulates transcription and translation either by upregulation or downregulation depending on the gene target. Previously, we showed that aged mice treated with a G4-stabilizing compound had enhanced senescence-associated (SA) phenotypes in their brains, and these mice exhibited enhanced cognitive deficits. A sequence in the 3′-UTR of the human CCN1 mRNA has the ability to fold into G4s in vitro. We hypothesize that G4 stabilization regulates CCN1 in cultured primary CEC and induces endothelial senescence. We used cerebral microvessel fractions and cultured primary CEC from young (4-months old, m/o) and aged (18-m/o) mice to determine CCN1 levels. SA phenotypes were determined by high-resolution fluorescence microscopy in cultured primary CEC, and we used Thioflavin T to recognize RNA-G4s for fluorescence spectra. We found that cultured CEC from aged mice exhibited enhanced levels of SA phenotypes, and higher levels of CCN1 and G4 stabilization. In cultured CEC, CCN1 induced SA phenotypes, such as SA β-galactosidase activity, and double-strand DNA damage. Furthermore, CCN1 levels were upregulated by a G4 ligand, and a G-rich motif in the 3′-UTR of the Ccn1 mRNA was folded into a G4. In conclusion, we demonstrate that CCN1 can induce senescence in cultured primary CEC, and we provide evidence that G4 stabilization is a novel mechanism regulating the SASP component CCN1.

Objective: Aortic dissection is a rare but lethal disease. We demonstrate a rare case of acute complicated Stanford type A aortic dissection in the third trimester. Case report: A 41-year-old primiparous patient with chronic hypertension was brought to our emergency department at 34 weeks of gestation. She presented with acute tearing chest pain radiating to her back. Computed tomography revealed a Stanford type A aortic dissection. Primary cesarean section followed by open cardiovascular surgery was performed. However, ischemic bowels and bowel perforation occurred on the 9th and 11th postoperative days, respectively, and the patient died of septic shock on the 12th postoperative day. Conclusion: Aortic dissection must be taken into consideration for pregnant women with chronic hypertension who present with acute tearing chest pain and pulseless unilateral extremities. Bowel ischemia may occur in patients with complicated Stanford type A aortic dissection.

Abstract Background Maternal obesity is an emerging problem in the modern world. Growing evidence suggests that intrauterine high-fat (HF) exposure may predispose progeny to subsequent metabolic challenges. Progeny born to mothers who ate an HF diet also tends to eat an HF diet when growing and aggravate metabolic issues. Thus, the generational transmission of obesity is cyclical. Developing a strategy to prevent the occurrence of metabolic syndrome related to prenatal and/or postnatal HF diet is important. In this study, the reprogramming effects of maternal resveratrol treatment for the progeny with maternal HF/postnatal HF diets were investigated. Methods Sprague-Dawley dams were fed either a control or a high-fat/high sucrose diet (HFHS) from mating to lactation. After weaning, the progeny was fed chow or an HF diet. Four experimental groups were yielded: CC (maternal/postnatal control diet), HC (maternal HF/postnatal control diet), CH (maternal control/postnatal HFHS diet), and HH (maternal/postnatal HFHS diet). A fifth group (HRH) received a maternal HFHS diet plus maternal resveratrol treatment and a postnatal chow diet to study the effects of maternal resveratrol therapy. Results Maternal resveratrol treatment lessened the weight and adiposity of progeny that were programmed by combined prenatal and postnatal HFHS diets. Maternal resveratrol therapy ameliorated the decreased abundance of the sirtuin 1 (SIRT1) enzyme in retroperitoneal tissue and the altered leptin/soluble leptin receptor ratio of progeny. Maternal resveratrol therapy also decreased lipogenesis and increased lipolysis for progeny. Conclusions Maternal resveratrol intervention can prevent adiposity programmed by maternal and postnatal HFHS diets by inducing lipid metabolic modulation. This study offers a novel reprogramming role for the effect of maternal resveratrol supplements against obesity.

Abstract Background Pregnant women have high serum concentrations of sex steroid hormones, which are major regulators of paracrine and autocrine responses for many maternal and placental functions. The main purpose of this study was to compare patients with preeclampsia and patients with uncomplicated pregnancies in terms of serum steroid hormones (estradiol [E2], progesterone [P4], dehydroepiandrosterone sulfate [DHEAS], and testosterone [T]) throughout pregnancy and the levels of cord blood and placental steroid receptors during the third trimester. Methods Quantitative real-time reverse transcription PCR, western blotting, and immunohistochemistry were used to determine the levels of steroid hormones in the serum and cord blood and the placental levels of estrogen receptor-α (ERα), ERβ, androgen receptor (AR), and progesterone receptor (PR). Results There were 45 women in the uncomplicated pregnancy group and 30 women in the preeclampsia group. Serum levels of T were greater and serum levels of E2 were reduced in the preeclampsia group, but the two groups had similar levels of P4 and DHEAS during the third trimester. Cord blood had a decreased level of DHEAS in the preeclampsia group, but the two groups had similar levels of P4, E2, and T. The two groups had similar placental mRNA levels of ERα, ERβ, AR, and PR, but the preeclampsia group had a higher level of ERβ protein and a lower level of ERα protein. Immunohistochemistry indicated that the preeclampsia group had a greater level of ERβ in the nucleus and cytoplasm of syncytiotrophoblasts and stromal cells. Conclusions Women with preeclampsia had lower levels of steroid hormones, estrogen, and ERα but higher levels of T and ERβ. These molecules may have roles in the pathogenesis of preeclampsia.

Background: Despite clinical success with anti-spike vaccines, the effectiveness of neutralizing antibodies and vaccines has been compromised by rapidly spreading SARS-CoV-2 variants. Viruses can hijack the glycosylation machinery of host cells to shield themselves from the host's immune response and attenuate antibody efficiency. However, it remains unclear if targeting glycosylation on viral spike protein can impair infectivity of SARS-CoV-2 and its variants. Methods: We adopted flow cytometry, ELISA, and BioLayer interferometry approaches to assess binding of glycosylated or deglycosylated spike with ACE2. Viral entry was determined by luciferase, immunoblotting, and immunofluorescence assays. Genome-wide association study (GWAS) revealed a significant relationship between STT3A and COVID-19 severity. NF-κB/STT3A-regulated N-glycosylation was investigated by gene knockdown, chromatin immunoprecipitation, and promoter assay. We developed an antibody-drug conjugate (ADC) that couples non-neutralization anti-spike antibody with NGI-1 (4G10-ADC) to specifically target SARS-CoV-2-infected cells. Findings: The receptor binding domain and three distinct SARS-CoV-2 surface N-glycosylation sites among 57,311 spike proteins retrieved from the NCBI-Virus-database are highly evolutionarily conserved (99.67%) and are involved in ACE2 interaction. STT3A is a key glycosyltransferase catalyzing spike glycosylation and is positively correlated with COVID-19 severity. We found that inhibiting STT3A using N-linked glycosylation inhibitor-1 (NGI-1) impaired SARS-CoV-2 infectivity and that of its variants [Alpha (B.1.1.7) and Beta (B.1.351)]. Most importantly, 4G10-ADC enters SARS-CoV-2-infected cells and NGI-1 is subsequently released to deglycosylate spike protein, thereby reinforcing the neutralizing abilities of antibodies, vaccines, or convalescent sera and reducing SARS-CoV-2 variant infectivity. Interpretation: Our results indicate that targeting evolutionarily-conserved STT3A-mediated glycosylation via an ADC can exert profound impacts on SARS-CoV-2 variant infectivity. Thus, we have identified a novel deglycosylation method suitable for eradicating SARS-CoV-2 variant infection in vitro. Funding: A full list of funding bodies that contributed to this study can be found in the Acknowledgements section

Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.

Metabolic disorders can start in utero. Maternal transmission of metabolic phenotypes may increase the risks of adverse metabolic outcomes, such as nonalcoholic fatty liver disease (NAFLD); effective intervention is essential to prevent this. The gut microbiome plays a crucial role in fat storage, energy metabolism, and NAFLD. We investigated the therapeutic use of probiotic Lactobacillus reuteri and postbiotic butyrate gestation in the prevention of perinatal high-fat diet-induced programmed hepatic steatosis in the offspring of pregnant Sprague–Dawley rats who received regular chow or a high-fat (HF) diet 8 weeks before mating. L. reuteri or sodium butyrate was administered via oral gavage to the gestated rats until their sacrifice on day 21 of gestation. Both treatments improved liver steatosis in pregnant dams; L. reuteri had a superior effect. L. reuteri ameliorated obesity and altered the metabolic profiles of obese gravid dams. Maternal L. reuteri therapy prevented maternal HF diet-induced fetal liver steatosis, and reformed placental remodeling and oxidative injury. Probiotic therapy can restore lipid dysmetabolism in the fetal liver, modulate nutrient-sensing molecules in the placenta, and mediate the short-chain fatty acid signaling cascade. The therapeutic effects of maternal L. reuteri on maternal NAFLD and NAFLD reprogramming in offspring should be validated for further clinical translation.

Abstract Background Prenatal dexamethasone treatment has been shown to enhance the susceptibility of offspring to postnatal high-fat (HF) diet-induced programmed obesity. We investigated the metabolic phenotypes, nutrient-sensing signal and circadian-clock genes in adipose tissue that are programmed by prenatal dexamethasone exposure and postnatal HF diet. Methods Male offspring of Sprague-Dawley rats were divided into four experimental groups: normal diet, prenatal dexamethasone exposure, postnatal HF diet, and prenatal dexamethasone plus postnatal HF diet. Postnatal HF diet was prescribed from weaning to 6 months of age. Results Prenatal dexamethasone and postnatal HF diet exerted synergistic effects on body weight and visceral adiposity, whereas prenatal dexamethasone and postnatal HF diet altered the metabolic profile and caused leptin dysregulation. Prenatal dexamethasone and postnatal HF diet distinctly influenced nutrient-sensing molecules and circadian-clock genes in adipose tissue. The mRNA expression of mTOR, AMPK-α2, PPAR-α, and PPAR-γ was suppressed by prenatal dexamethasone but enhanced by postnatal HF diet. Conclusion Prenatal dexamethasone and postnatal HF treatment cause dysregulation of nutrient-sensing molecules and circadian-clock genes in visceral adipose tissue. Characterizing altered nutrient-sensing molecules and circadian-clock genes has potential therapeutic relevance with respect to the pathogenesis and treatment of prenatal stress and postnatal HF diet-related metabolic disorders.

Placenta accreta spectrum (PAS) accounts for 7% of maternal mortality and is associated with intraoperative and postoperative morbidity caused by massive blood loss, infection, and adjacent organ damage. The aims of this study were to identify the protein biomarkers of PAS and to further explore their pathogenetic roles in PAS. For this purpose, we collected five placentas from pregnant subjects with PAS complications and another five placentas from normal pregnancy (NP) cases. Then, we enriched protein samples by specifically isolating the trophoblast villous, deeply invading into the uterine muscle layer in the PAS patients. Next, fluorescence-based two-dimensional difference gel electrophoresis (2D-DIGE) and MALDI-TOF/MS were used to identify the proteins differentially abundant between PAS and NP placenta tissues. As a result, nineteen spots were determined as differentially abundant proteins, ten and nine of which were more abundant in PAS and NP placenta tissues, respectively. Then, specific validation with western blot assay and immunohisto/cytochemistry (IHC) assay confirmed that heat shock 70 kDa protein 4 (HSPA4) and chorionic somatomammotropin hormone (CSH) were PAS protein biomarkers. Further tube formation assays demonstrated that HSPA4 promoted the in vitro angiogenesis ability of vessel endothelial cells, which is consistent with the in vivo scenario of PAS complications. In this study, we not only identified PAS protein biomarkers but also connected the promoted angiogenesis with placenta invasion, investigating the pathogenetic mechanism of PAS.

Objectives To investigate whether uveitis is a predictor of acute myocardial infarction (AMI) among patients with Behcet’s disease (BD).Design Retrospective cohort study.Setting Patients with BD were retrieved from the whole population of the Taiwan National Health Insurance Research Database from 1 January 2001 to 31 December 2013.Participants Among the 6508 patients with BD, 2517 (38.7%) were in the uveitis group and 3991 were in the non-uveitis group.Primary and secondary outcome measures Kaplan-Meier curves were generated to compare the cumulative hazard of AMI in the uveitis and non-uveitis groups. Multivariate Cox regression analysis was used to estimate the adjusted HRs and 95% CI of AMI, and was adjusted for age, gender, systemic comorbidities (eg, hypertension, diabetes, hyperlipidaemia, smoking) and clinical manifestation of BD (eg, oral ulcers, genital ulcers, skin lesions, arthritis and gastrointestinal involvement).Results The mean age of the BD cohort was 38.1±15.1 years. Compared with non-uveitis patients, uveitis patients were significantly younger and male predominant. There was no significant difference between the two groups for most proportions of systemic comorbidities and clinical manifestations. The Kaplan-Meier method with the log-rank test showed that the uveitis group had a significantly higher cumulative hazard for patients with AMI compared with the non-uveitis group (p

Purpose. The iStent provides a direct pathway for aqueous outflow from the anterior chamber to Schlemm’s canal in patients with open-angle glaucoma (OAG). We performed a meta-analysis to evaluate the effectiveness of iStent as a standalone operation in patients with OAG in reducing the intraocular pressure (IOP) and the number of topical glaucoma medications. Methods. We searched various databases between January 1, 2000, and September 30, 2019, and included only peer-reviewed, prospective, or retrospective clinical studies in our analyses. Details regarding the IOP and the number of medications at baseline and end point were recorded from each study. Standardized mean differences (SMDs) of IOP and medication numbers were calculated. Furthermore, the success rate (the proportion of IOP ≤18 mmHg and IOP reduction ≥20% at end point) and the complication rate were also summarized. Finally, a subgroup analysis was done based on the iStent generation (first and second), follow-up duration (≤6, 6–18, 18–36, and >36 months), and iStent number (one, two, and three). The outcome measures were aggregated SMDs computed from each study. Results. A total of 17 studies with 978 eyes were included in this analysis. All studies demonstrated a reduction in IOP after iStent implantation. Aggregated SMDs of IOP revealed a significant reduction (SMD = −2.64, 95% confidence interval (CI): −3.21 to −2.07). The success rate was significantly good, and most of the complication rates were low. The number of medications was also significantly reduced (SMD = −1.71, 95% CI: −2.18 to −1.24). The subgroup analysis revealed a reduction in IOP and medication burden in each category of iStent generation, follow-up duration of up to 42 months, and iStent numbers. Conclusion. Use of iStent as a standalone procedure does reduce the IOP and the number of glaucoma medications. The benefit of iStent lasts for at least 42 months.

Saponins from Momordica charantia L. are a class of triterpenoid glucoside molecules that contribute to the bitter flavour of the plant and possess pharmacological properties. However, little is known about how the bioactivity and bitter flavour of saponins are affected by thermal processing. We established saponin profiles in bitter gourd extracts using a UPLC-ESI-MS/MS method. Seven saponins including momordicoside F1, momordicoside F2, momordicoside I, momordicoside K, momordicoside L, 3β,7β,25-trihydroxycucurbita-5, 23(E)-dien-19-al, and momordicine I were monitored for the effects of thermal processing on their stabilities. The results showed that both 3β,7β,25-trihydroxycucurbita-5,23(E)-dien-19-al and momordicoside L were extremely sensitive to heat treatment, particularly when they were heated at 100°C for more than 10 mins and under 121°C for 20 mins. Other saponins were reduced significantly by autoclaving, but they remained unchanged at lower temperatures. In conclusion, specific bitter gourd saponins are affected by thermal treatment, which may modify the bioactive components or bitter flavour of the bitter gourd extracts.

Glioblastoma multiforme (GBM), a highly recurrent malignant disease, is a grade IV glioma with poor prognosis. Glioblastoma stem cells (GSCs) are the new potential target for GBM intervention. To develop an improved treatment by targeting GSCs, we identified neriifolin, an active principle in extracts of Cerbera manghas L., as an effective inhibitor for the growth and migration of GBM cell lines and their tumorspheres. In this study, neriifolin effectively inhibited the growth and colony formation of CD133+ GBM tumorspheres. Both C. manghas extracts and neriifolin inhibited Akt activation and caused cell cycle G1 arrest. They also reduced the expression of the stem cell marker Sox2. Treatment with their higher doses induced the apoptosis of GBM tumorspheres. Furthermore, neriifolin inhibited the growth of CD133+ GBM tumorsphere-derived tumors in vivo. In summary, neriifolin obtained from extracts of C. manghas may serve as a drug lead compound for GBM therapies.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) can develop in prenatal stages and can be exacerbated by exposure to a postnatal high-fat (HF) diet. We investigated the protective effects of resveratrol on prenatal and postnatal HF diet-induced NAFLD. Methods Male Sprague–Dawley rat offspring were placed in five experimental groups (n = 10–12 per group): normal diet (VNF), maternal HF diet (ONF), postnatal HF diet (VHF), and maternal HF diet/postnatal HF diet (OHF). A therapeutic group with resveratrol for maternal HF diet/postnatal HF diet (OHFR) was used for comparison. Resveratrol (50 mg/kg/day) was dissolved in drinking water for offspring from post-weaning to postnatal day (PND) 120. Results We found that HF/HF-induced NAFLD was prevented in adult offspring by the administration of resveratrol. Resveratrol administration mediated a protective effect on rats on HF/HF by regulating lipid metabolism, reducing oxidative stress and apoptosis, restoring nutrient-sensing pathways by increasing Sirt1 and leptin expression, and mediating the renin-angiotensin system (RAS) to decrease angiotensinogen, renin, ACE1, and AT1R levels and increased ACE2, AT2R and MAS1 levels compared to those in the OHF group. Conclusion Our results suggest that a maternal and post-weaning HF diet increases liver steatosis and apoptosis via the RAS. Resveratrol might serve as a therapeutic target by mediating protective actions against NAFLD in offspring exposed to a combination of maternal and postnatal HF diet.

Abstract Background Previous cross-sectional studies revealed a higher prevalence of depression among glaucoma patients. However, cohort studies were in lack to build the risk of incident depression after the diagnosis of glaucoma. The aim of our study was to investigate the association between glaucoma and the subsequent risk of developing depression and to assess risk factors associated with depression in glaucoma patients. Methods A population-based retrospective cohort study using the Taiwan National Health Insurance Research Database was conducted from January 1, 2001 through December 31, 2011. Glaucoma patients (n = 8777) and age- and gender-matched control subjects without glaucoma (n = 35,108) were enrolled in the study. Kaplan-Meier curves were generated to compare the cumulative hazard of subsequent depression between the glaucoma and control groups. A Cox regression analysis estimated the crude and adjusted hazard ratios (HRs) for depression. Risk factors leading to depression were investigated among the glaucoma patients. Results Glaucoma patients had a significantly higher cumulative hazard of depression compared to the control group (p-value

l-Arginine is an important nutrient in the infant diet that significantly regulates the maturation of the immune system in neonates, including the maturation of CD4+ T cells. The biological activities of CD4+ T cells differ substantially between neonates and adults, and these differences may be governed by epigenetic processes. Investigating these differences and the causative processes may help understand neonatal and developmental immunity. In this study, we compared the functional DNA methylation profiles in CD4+ T cells of neonates and adults, focusing on the role of l-arginine supplementation. Umbilical cord blood and adult CD4+ T cells were cultured with/without l-arginine treatment. By comparing DNA methylation in samples without l-arginine treatment, we found that CD4+ T cells of neonatal cord blood generally showed higher DNA methylation than those of adults (average CpG methylation percentage 0.6305 for neonate and 0.6254 for adult, t-test p-value < 0.0001), suggesting gene silencing in neonates. By examining DNA methylation patterns of CpG dinucleotides induced by l-arginine treatment, we found that more CpG dinucleotides were hypomethylated and more genes appeared to be activated in neonatal T-cells as compared with adult. Genes activated by l-arginine stimulation of cord blood samples were more enriched regarding immune-related pathways. CpG dinucleotides at IL-13 promoter regions were hypomethylated after l-arginine stimulation. Hypomethylated CpG dinucleotides corresponded to higher IL-13 gene expression and cytokine production. Thus, DNA methylation partially accounts for the mechanism underlying differential immune function in neonates. Modulatory effects of l-arginine on DNA methylation are gene-specific. Nutritional intervention is a potential strategy to modulate immune function of neonates.

Abstract Background Intervention of diabetes care education with regular laboratory check-up in outpatient visits showed long-term benefits to reduce the risk of macrovascular complications among people with type 2 diabetes. However, research on the level of a priori health knowledge to the prevention of diabetic complications in community settings has been scarce. We therefore aimed to investigate the association of health knowledge and stroke incidence in patients with type 2 diabetes in Taiwan. Methods A nationally representative sample of general Taiwanese population was selected using a multistage systematic sampling process from Taiwan National Health Interview Survey (NHIS) in 2005. Subjects were interviewed by a standardized face-to-face questionnaire in the survey, obtaining information of demographics, socioeconomic status, family medical history, obesity, health behaviors, and 15-item health knowledge assessment. The NHIS dataset was linked to Taiwan National Health Insurance claims data to retrieve the diagnosis of type 2 diabetes in NHIS participants at baseline and identify follow-up incidence of stroke from 2005 to 2013. Univariate and multivariate Cox regressions were used to estimate the effect of baseline health knowledge level to the risk of stroke incidence among this group of people with type 2 diabetes. Results A total of 597 diabetic patients with a mean age of 51.28 years old and nearly half of males were analyzed. During the 9-year follow-up period, 65 new stroke cases were identified among them. Kaplan–Meier curves comparing the three groups of low/moderate/high knowledge levels revealed a statistical significance (p-value of log-rank test

Objective: Urinalysis is included in the prenatal examination in the first trimester in Taiwan, in contrast to Western countries. We aimed to investigate whether asymptomatic pyuria as detected by urinalysis was associated with adverse perinatal outcomes. Materials and Methods: A total of 1187 singleton pregnant women who received prenatal care at Kaohsiung Chang Gung Memorial Hospital between January 2012 and December 2013 were included for retrospective analysis. We defined asymptomatic pyuria as the presence of 15 or more white blood cells/μL in midstream urine without symptoms. Adverse perinatal outcomes including preterm delivery, preterm premature rupture of membrane, low birth weight, and Apgar scores were analyzed. Univariate and multivariate logistic regression analyses were used to identify independent predictors. Results: The prevalence of asymptomatic pyuria was 21.3% in our cohort. Univariate analysis showed that pyuria was the only factor associated with preterm delivery before 36 weeks of pregnancy, preterm premature rupture of membrane, and low birth weight. In multivariate analysis, both pyuria (odds ratio: 4.89, 95% confidence interval: 1.80–13.25, p=0.002) and a maternal age of 35 years or older (odds ratio: 3.46, 95% confidence interval: 1.11–10.78, p=0.033) were significant independent predictors for a low 5 minute Apgar score (

Purpose. This population-based, retrospective cohort study was to investigate whether metformin is associated with a lower risk of subsequent age-related macular degeneration (AMD) in patients with type 2 diabetes. Methods. Using the Taiwan National Health Insurance Research Database from 2001 to 2013, 68205 subjects with type 2 diabetes were enrolled in the study cohort. Among them, 45524 were metformin users and 22681 were nonusers. The metformin and nonmetformin groups were followed until the end of 2013. Cox regression analyses were used to estimate hazard ratios (HRs) for AMD development associated with metformin use. Confounders included for adjustment were age, sex, and comorbidities (hypertension, hyperlipidemia, coronary artery disease, obesity, diabetic retinopathy, chronic kidney disease, and insulin treatment). Furthermore, propensity score (PS) matching method was used to choose the matched sample, and PS-adjusted Cox regression was performed. Finally, how HRs changed according to metformin treatment duration and dose was also evaluated in the metformin group. Results. After adjusting for confounders, the metformin group had a significantly lower risk of AMD (adjusted HR = 0.54; 95% confidence interval [CI], 0.50–0.58). In the PS-matched sample, the significance remained (adjusted HR = 0.57; 95% CI, 0.52–0.63). In the metformin group, the adjusted HRs for the second (1.5–4 years) and third (≥4 years) tertiles of metformin treatment duration were 0.52 and 0.14, respectively, compared with the first tertile (