Background::The prevalence of type 2 diabetes has been growing among younger and middle-aged adults in the United States. A portion of this increase for this age group may be attributable to shared type 2 diabetes risks with family members. How family history of type 2 diabetes history is associated with type 2 diabetes risk among younger and middle-aged adults is not well understood.Methods::This population-based retrospective cohort study uses administrative, genealogical, and electronic medical records from the Utah Population Database. The study population comprises offspring born between 1970 and 1990 and living in the four urban Utah counties in the United States between 1990 and 2015. The sample comprises 360,907 individuals without a type 2 diabetes diagnosis and 14,817 with a diagnosis. Using multivariate logistic regressions, we estimate the relative risk (RR) of type 2 diabetes associated with the number of affected first- (FDRs), second- (SDRs), and third-degree (first cousin) relatives for the full sample and for Hispanic-specific and sex-specific subsets.Results::Individuals with 2+ FDRs with type 2 diabetes have a significant risk of type 2 diabetes in relation to those with no affected FDRs (RR = 3.31 [3.16, 3.48]). Individuals with 2+ versus no SDRs with type 2 diabetes have significant but lower risks (RR = 1.32 [1.25, 1.39]). Those with 2+ versus no affected first cousins have a similarly low risk (RR= 1.28 [1.21, 1.35]). Larger RRs are experienced by males (2+ vs. 0 FDRs, RR = 3.55) than females (2+ vs. 0 FDRs, RR = 3.18) ( p < 0.05 for the interaction). These familial associations are partly mediated by the individual's own obesity. Conclusions::The risks of type 2 diabetes are significantly associated with having affected first-, second-, and third-degree relatives, especially for men. One of the forces contributing to the rising patterns of type 2 diabetes among young and middle-aged adults is their connection to affected, often older, kin.

Background::The prevalence of type 2 diabetes has been growing among younger and middle-aged adults in the United States. A portion of this increase for this age group may be attributable to shared type 2 diabetes risks with family members. How family history of type 2 diabetes history is associated with type 2 diabetes risk among younger and middle-aged adults is not well understood.Methods::This population-based retrospective cohort study uses administrative, genealogical, and electronic medical records from the Utah Population Database. The study population comprises offspring born between 1970 and 1990 and living in the four urban Utah counties in the United States between 1990 and 2015. The sample comprises 360,907 individuals without a type 2 diabetes diagnosis and 14,817 with a diagnosis. Using multivariate logistic regressions, we estimate the relative risk (RR) of type 2 diabetes associated with the number of affected first- (FDRs), second- (SDRs), and third-degree (first cousin) relatives for the full sample and for Hispanic-specific and sex-specific subsets.Results::Individuals with 2+ FDRs with type 2 diabetes have a significant risk of type 2 diabetes in relation to those with no affected FDRs (RR = 3.31 [3.16, 3.48]). Individuals with 2+ versus no SDRs with type 2 diabetes have significant but lower risks (RR = 1.32 [1.25, 1.39]). Those with 2+ versus no affected first cousins have a similarly low risk (RR= 1.28 [1.21, 1.35]). Larger RRs are experienced by males (2+ vs. 0 FDRs, RR = 3.55) than females (2+ vs. 0 FDRs, RR = 3.18) ( p < 0.05 for the interaction). These familial associations are partly mediated by the individual's own obesity. Conclusions::The risks of type 2 diabetes are significantly associated with having affected first-, second-, and third-degree relatives, especially for men. One of the forces contributing to the rising patterns of type 2 diabetes among young and middle-aged adults is their connection to affected, often older, kin.

INTRODUCTION: Misuse of prescription medicines and the harms associated with such use are growing threats across the world. There is currently, however, limited data on the extent of prescription medicine misuse in Singapore and whether this is a current threat in the country. METHODS: An online survey, limited to 1,000 individuals (aged 21 years and over) who were residents in Singapore, was administered through a survey panel company in September 2015. The survey collected information on participant demographics, and their awareness, self-reported lifetime and past-year misuse of commonly available prescription medicines in Singapore as well as the use of a range of recreational drugs and novel psychoactive substances (NPS). RESULTS: Lifetime (6.7%) and past-year (4.8%) misuse of any prescription medicine was comparable to lifetime (6.0%) and past-year (3.0%) use of any recreational drugs/NPS. The top five prescription medicines for lifetime misuse were: diazepam (2.7%); codeine (2.3%); dhasedyl (promethazine, codeine and ephedrine; 1.6%); panadeine (paracetamol and codeine; 1.5%); and methylphenidate (1.2%). The top five drugs for past-year misuse were: diazepam (1.6%); codeine (0.9%); panadeine (0.7%); alprazolam (0.6%); baclofen (0.6%); and gabapentin (0.6%). CONCLUSION Misuse of prescription medicine in Singapore was common, with prevalence comparable to the use of recreational drugs/NPS. A common source for misused drugs was physicians. Further studies are required to determine whether this is more widespread in Singapore and establish the different forms of drug diversion, so that appropriate prevention strategies can be implemented.
Humans ; Illicit Drugs/adverse effects* ; Public Health ; Singapore/epidemiology* ; Substance-Related Disorders/drug therapy* ; Prescription Drugs/adverse effects* ; Codeine ; Diazepam ; Prescriptions

Well characterized, stable, p16-defective canine mammary cancer (CMT) cell lines and normal canine mammary epithelial cells were used to investigate expression of the major breast cancer-specific hormone receptors estrogen receptor alpha (ER1) and progesterone receptor (PR) as well as luminal epithelial-specific proto-oncogenes encoding c-erbB-1 (epidermal growth factor receptor/EGFr), c-erbB-2/HER2, c-erbB-3, and c-erbB-4 receptors. The investigation developed and validated quantitative reverse transcriptase polymerase chain reaction assays for each transcript to provide rapid assessment of breast cancer phenotypes for canine cancers, based on ER1, PR, and c-erbB-2/HER2 expressions, similar to those in human disease. Roles for relatively underexplored c-erbB-3 and c-erbB-4 receptor expressions in each of these breast cancer phenotypes were also evaluated. Each quantitative assay was validated by assessment of amplicon size and DNA sequencing following amplification. Differential expression of ER1, PR, and c-erbB-2 in CMT cell lines clearly defined distinct human-like breast cancer phenotypes for a selection of CMT-derived cell lines. Expression profiles for EGFr family genes c-erbB-3 and c-erbB-4 in CMT models also provided an enriched classification of canine breast cancer identifying new extended phenotypes beyond the conventional luminal-basal characterization used in human breast cancer.
Breast Neoplasms* ; Breast* ; Cell Line ; Classification ; Epithelial Cells ; Estrogen Receptor alpha ; Estrogens* ; Humans ; Phenobarbital ; Phenotype* ; Progesterone* ; Proto-Oncogenes ; Receptors, Progesterone* ; Reverse Transcriptase Polymerase Chain Reaction ; RNA, Messenger* ; Sequence Analysis, DNA

Variations in drug metabolism may alter drug efficacy and cause toxicity; better understanding of the mechanisms and risks shall help to practice precision medicine. At the 21International Symposium on Microsomes and Drug Oxidations held in Davis, California, USA, in October 2-6, 2016, a number of speakers reported some new findings and ongoing studies on the regulation mechanisms behind variable drug metabolism and toxicity, and discussed potential implications to personalized medications. A considerably insightful overview was provided on genetic and epigenetic regulation of gene expression involved in drug absorption, distribution, metabolism, and excretion (ADME) and drug response. Altered drug metabolism and disposition as well as molecular mechanisms among diseased and special populations were presented. In addition, the roles of gut microbiota in drug metabolism and toxicology as well as long non-coding RNAs in liver functions and diseases were discussed. These findings may offer new insights into improved understanding of ADME regulatory mechanisms and advance drug metabolism research.

We have examined the role of readmission of oxygen in the initiation of reperfusion-induced arrhythmias by separating readmission flow from readmission of oxygen on a temporal basis. Isolated rat hearts (n=12/group) were subjected to 10 minutes of global ischemia and reperfusion. In controls reperfused with aerobic perfusion medium, 100% of hearts developed ventricular tachycardia 1.48±0.78 seconds after reperfusion, and ventricular fibrillation occurred 13.47±2.91 seconds after reperfusion. Also in hearts reperfused with anoxic perfusion medium, 100% of hearts developed ventricular tachycardia 1.98±0.96 seconds after reperfusion, and ventricular fibrillation occurred 27.01±18.52 seconds after reperfusion. But the duration of the time from reperfusion to the onset of ventricular fibrillation were statistically differrent in these two groups (p<0.05). In conclusion anoxic reperfusion delayed ventricular fibrillation but prevent neither ventricular fibrillation nor ventricular tachycardia. This implies that oxygen-derived free radicals may play an important role in the initiation of reperfusion-induced arrhythmias, but are unneccessary for arrhythmogenesis.