Explore the vast range of titles available.

The current study aims to investigate the neurodevelopment of premature infants after intravitreal injections of bevacizumab (IVB) for the treatment of retinopathy of prematurity (ROP) up to the age of 2 years. The study design was retrospective observational case series conducted at an institutional referral center. Infants with type 1 ROP were classified into 3 groups: laser only, IVB only, and a combination of IVB and laser treatment. Main Outcome Measures were neurodevelopmental outcomes of the patients after treatment were assessed by Bayley Scales for Infant Development. Sixty-one patients who finished the neurodevelopmental survey were included. No detrimental effects on neurodevelopment were found in IVB group compared with the patients who received laser treatment only. The patients in the IVB + laser group had a higher incidence of significant mental (p = 0.028) and psychomotor (p = 0.002) impairment at 24 months than the patients in the laser group. The odds ratio of having severe psychomotor defects in the IVB + laser group was 5.3 compared with the laser group (p = 0.041). The causal source for the differences that were detected remained unknown due to lack of randomization in the study and accompanying bias in patient selection. Two years after laser and/or intravitreal injections of bevacizumab for infants with retinopathy of prematurity, no difference on neurodevelopment for those who received only bevacizumab versus only laser treatment were found. Those infants who required rescue therapy with laser or bevacizumab injection after initial, unsuccessful treatment showed some detrimental, neurodevelopmental effects.

Achieving robust cancer-specific lethality is the ultimate clinical goal. Here, we identify a compound with dual-inhibitory properties, named a131, that selectively kills cancer cells, while protecting normal cells. Through an unbiased CETSA screen, we identify the PIP4K lipid kinases as the target of a131. Ablation of the PIP4Ks generates a phenocopy of the pharmacological effects of PIP4K inhibition by a131. Notably, PIP4Ks inhibition by a131 causes reversible growth arrest in normal cells by transcriptionally upregulating PIK3IP1 , a suppressor of the PI3K/Akt/mTOR pathway. Strikingly, Ras activation overrides a131-induced PIK3IP1 upregulation and activates the PI3K/Akt/mTOR pathway. Consequently, Ras-transformed cells override a131-induced growth arrest and enter mitosis where a131’s ability to de-cluster supernumerary centrosomes in cancer cells eliminates Ras-activated cells through mitotic catastrophe. Our discovery of drugs with a dual-inhibitory mechanism provides a unique pharmacological strategy against cancer and evidence of cross-activation between the Ras/Raf/MEK/ERK and PI3K/AKT/mTOR pathways via a Ras˧PIK3IP1˧PI3K signaling network. The Ras/Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways are essential for cancer cell survival. Here, the authors describes a molecule a131 with dual-inhibitory properties, which targets PI5P4K and mitosis, and it is involved in Ras/Raf/MEK/ERK and PI3K/Akt/mTOR crosstalk, thereby causing reversible growth arrest in normal cells and cell death of tumor cells.

Few studies have demonstrated an association of sarcopenia-associated body measurements with chronic diseases through a comprehensive methodology. This study aims to examine the relationship between sarcopenia-associated body measurements and chronic diseases. This is a cohort study. We recruited 316 community dwellers, including 76 patients with sarcopenia and 240 controls, and obtained their body measurements associated with sarcopenia. We collected three-dimensional anthropometric body-surface measurements from 11,158 participants during 2000–2008 and followed up this cohort for 15 years to examine the association of these measurements with the risk of chronic diseases such as hypertension, type 2 diabetes mellitus (T2DM), heart disease, and nephrotic syndrome. Univariate analysis, canonical correlation, and Cox regression analysis were performed to explore the associations. Decreased waist width, upper left arm circumference, and left thigh circumference were significantly associated with sarcopenia. The adverse body measure score (ABMS) was derived by combining significant measurements, namely left upper arm circumference, waist width, and left thigh circumference, and used to predict the risk of hypertension, T2DM, heart diseases, and nephrotic syndrome. A positive association was observed between the ABMS and chronic diseases. Considering the first quartile of the ABMS as a reference, we determined hazard ratios of 2.259, 2.495, 1.332, and 1.595 for hypertension, T2DM, heart disease, and nephrotic syndrome, respectively, in the fourth quartile. Chronic diseases were more strongly associated with the ABMS than with sarcopenia-related body measurements alone. A high ABMS, which includes higher upper arm circumference, higher waist width, and lower thigh circumference, can significantly predict chronic diseases.

ObjectiveOlder patients are likely to have higher disease complexity and more drug prescriptions of which are associated with a higher incidence of adverse drug reactions (ADR). This study aimed to investigate factors associated with ADR occurrence, prognosis and medical expenses in older inpatients.DesignA nested case–control study.SettingA medical centre located in north Taiwan.Participants539 reported ADR cases from a patient cohort containing 108 548 older inpatients were collected from 2006 to 2012. There were 1854 non-ADR matched controls; a maximum of 1:5 matched by age, sex and principal diagnosis were collected.ExposurePolypharmacy, the number of drugs prescribed, comorbidities and the admission department were factors associated with ADRs, as well as subsequent poor prognosis, length of stay and medical expenses.Primary and secondary outcome measuresADR occurrence and poor prognosis (mortality, discharge against medical advice in critical conditions, or admitted to intensive care unit) were the primary outcomes. Additional medical expenses and the length of hospital stay were the secondary outcomes.ResultsThe admission department, number of comorbidities and number of drug prescriptions before ADRs were associated with ADR occurrence among older inpatients. ADR severity was a significant prognostic factor among ADR cases. The multivariate-adjusted OR of 1.63 (95% CI 1.36 to 1.95) for poor prognosis was found as the number of comorbidities increased. Patients prescribed ≥11 drugs including psychoactive drugs showed 2.45-fold (95% CI 1.40 to 4.28) poorer prognosis than other patients. ADRs caused the addition of US$1803.8, US$360.8 and 5.6 days in total medical expenses, drug expenses and length of stay among affected older inpatients, respectively.ConclusionsThe number of comorbidities and polypharmacy including the use of psychoactive drugs has significant impacts on ADR occurrence and prognosis among older inpatients. The findings provide clues for future prescription modification and patient’s safety improvement in geriatric care.

Taiwan is experiencing a decline in the number of doctoral students in higher education. How to provide incentives for students to pursue a doctoral degree is a widely discussed issue. This paper constructs an occupational choice model with heterogeneous individuals in an overlapping generations model rationally choosing to study abroad, enter domestic doctoral programs, or work in industry. The framework captures the features of the two-stage Ph.D. labor market and the spillover effect of knowledge production on the industry sector. We also highlight the productivity differential between overseas-trained professors and their domestic counterparts. The model is used to quantify the effects of various subsidies on higher education. Our quantitative analysis suggests that providing a subsidy to domestic doctoral students is more effective in boosting the number of doctoral students than subsidizing professors' research. Nevertheless, in fields with a relatively large productivity differential, this policy does not necessarily improve average welfare because of fewer overseas-trained professors and lower knowledge accumulation.

Family disease history plays a vital role in type 2 diabetes mellitus (T2DM) risk. However, the familial aggregation of T2DM among different kinship relatives warrants further investigation. This nationwide kinship relationship study collected 2000-2016 data of two to five generations of the Taiwanese population from the National Health Insurance Research Database. Approximately 4 million family trees were constructed from the records of 20, 890, 264 Taiwanese residents during the study period. T2DM was diagnosed on the basis of ICD-9-CM codes 250.x0 or 250.x2, with three consecutive related prescriptions. The Cox proportional hazard model was used for statistical analysis. Compared with their counterparts, individuals who had first-degree relatives with T2DM were more likely to develop T2DM during the follow-up period (hazard ratio [HR], 2.37-27.75), followed by individuals who had second-degree relatives with T2DM (HR, 1.29-1.88). T2DM relative risk was higher in those with an affected mother than in those with affected father. The HR for T2DM was 20.32 (95%CI = 15.64-26.42) among male individuals with an affected twin brother, whereas among female individuals with an affected twin sister, it was 60.07 (95%CI = 40.83-88.36). The HRs presented a dose-response relationship with the number of affected family members. The study suggests a significant familial aggregation of T2DM occurrence; these findings could aid in identifying the high-risk group for T2DM and designing early intervention strategies and treatment plans.

Chronic exposure to inorganic arsenic results in many cancers in susceptible persons. The metabolism of inorganic arsenic and genomic susceptibility are thought to be associated with cancer occurrence. This study aims to examine the interaction of genomic susceptibility markers and urinary methylation capacity indicators involved in inorganic arsenic metabolism with all-cancer occurrence. This study conducted a follow-up on 96 residents to determine their urinary inorganic arsenic metabolites and genomic assay from an arseniasis area. Among them, 24 cancer developed. Multivariable Cox proportional hazards model was used to determine and estimate the candidate independent variables for cancer development. The residents with high inorganic arsenic exposure, high primary methylation index (PMI; MMA/InAs) (but lower secondary methylation index (SMI)), and non-heterogeneity type of genomic markers, including GSTO1, AS3MT, and MPO, tend to develop cancers. Subjects with higher PMI are at higher risk of developing cancers (HR = 1.66; 95% CI = 1.30-2.12). Cancer occurrence was greater among the CC type of GSTO1 (HR = 3.33; 95% CI = 1.11-10.00), CC type of AS3MT (HR = 19.21; 95% CI = 1.16-318.80), and AA type of MPO (HR = 13.40; 95% CI = 1.26-142.40). After adjusting confounders, a mutually moderating effect was revealed between genomic markers and methylation capacity on cancer occurrence. This study found the hypermethylation responses to inorganic arsenic exposure and an array of genomic markers may increase the susceptibility of a wide range of organ cancers. The findings indicated a high-risk arsenic-exposed population to develop cancers. The phenotype of arsenic metabolism and genomic polymorphism suggested a potential preventive strategy for arsenic carcinogenesis.

Workers in high technology industry are experiencing stressful environment and have been ranked as a high risk group for adverse health effects. The effectiveness of worksite health promotion is important for occupational health. This study is to investigate the effect of health interventions on body measurement changes while examining the role of their lifestyle factors. A total of 904 participants aged over 30 years were recruited from 14 semiconductor worksites in Taiwan from 2011 to 2015. A multi-settings, quasi-experimental study was conducted that assigned participants into two intervention programs, including exercise program and diet-plus-exercise program. The outcomes include the changes of body weight, waist circumference, body mass index (BMI), and biophysiological indicators. Lifestyle variables include alcohol consumption, cigarette smoking, and regular exercise. Multiple linear regression analyses were performed to test the association. The findings have demonstrated that one kilogram body weight reduction is associated with a decrease of 0.58 mmHg SBP (p < 0.001), 0.29 mmHg DBP (p < 0.001), 3.33 mg/dL triglyceride (p < 0.001), 0.96 mg/dL total cholesterol (p < 0.001), and 0.68 mg/dL LDL (p < 0.001). The diet-plus-exercise group had more significant effect on both weight changes and biophysiological changes than exercise-only group (p < 0.001). Lifestyle factors, including cigarette smoking, alcohol consumption, and regular exercise, were significant moderators of the effectiveness of health interventions. Both exercise and diet interventions are important to the effectiveness of health promotion in occupational sectors. Lifestyle modifications are vital for weight control programs in improving body shape changes and biophysiological indicators.

Background. An accurate and comprehensive anthropometric measure for predicting type 2 diabetes mellitus (T2DM) has not yet been depicted. Methods. A total of 8450 nondiabetic participants were recruited during 2000–2010 in Taiwan. The cohort was followed up to the end of 2013, over an average of 8.87 years. At recruitment, participants completed a questionnaire related to basic demographics, lifestyle variables, personal disease history, and family disease history. 3D body surface scanning was used to obtain 35 anatomical measurements. A Cox proportional hazard model was used to conduct multivariable analyses. Results. A total of 2068 T2DM cases at an incidence rate of 27.59 × 10−3 (year−1) were identified during the follow-up period. Multivariable-adjusted hazard ratios (HRs) demonstrated that neck circumference (NC) (HR = 1.048; 95% CI = 1.033–1.064), waist width (WW) (HR = 1.061; 95% CI = 1.040–1.081), and left thigh circumference (TC) (HR = 0.984; 95% CI = 0.972–0.995) were significant predictors of the occurrence of T2DM. While dividing body measurement into median high/low groups, an increased risk of T2DM was observed among participants with a larger NC and smaller TC (HR = 1.375; 95% CI = 1.180–1.601) and a larger WW and smaller TC (HR = 1.278; 95% CI = 1.085–1.505) relative to other participants. Conclusions. This study suggests that as well as using traditional waist and TC measurements, NC can be used as an indicator to provide an early prediction of developing T2DM, while providing clues for future mechanistic investigations of T2DM.