Rural Demographics Racial/Ethnic Diversification in Metropolitan and Nonmetropolitan Population Change in the United States: Implications for Health Care Provision in Rural America

The diversification of the rural population of the United States provides substantial challenges to the current and to future health care systems in rural areas. Because of a variety of historical, discriminatory, and other factors, minority populations have had lower levels of access to health care in rural as well as urban areas and higher rates of both mortality and morbidity than nonminority populations. Although minority health issues have often been seen as primarily urban issues, this article demonstrates that minority population growth has become a major component of total population growth in rural areas in the past several decades (accounting for nearly 62% of the net growth in the nonmetropolitan population of the United States in the 1980s and for nearly 42% in the 1990s), that future US population growth is likely to be largely a product of minority population growth (nearly 89% of US net population growth from 2000 to 2100 is projected to be due to minority population growth), and that the incidence of diseases and disorders in the US population will come to increasingly involve minority populations (by 2050 roughly 43% of all disease/disorder incidences would involve minority population members). The growth of younger minority populations with disproportionately impoverished socioeconomic characteristics will pose challenges for rural areas and health care systems, which also are likely to face health issues created by disproportionately older populations.     

The Human MitoChip: a high-throughput sequencing microarray for mitochondrial mutation detection

Somatic mitochondrial mutations are common in human cancers, and can be used as a tool for early detection of cancer. We have developed a mitochondrial Custom Reseq microarray as an array-based sequencing platform for rapid and high-throughput analysis of mitochondrial DNA. The MitoChip contains oligonucleotide probes synthesized using standard photolithography and solid-phase synthesis, and is able to sequence >29 kb of double-stranded DNA in a single assay. Both strands of the entire human mitochondrial coding sequence (15,451 bp) are arrayed on the MitoChip; both strands of an additional 12,935 bp (84% of coding DNA) are arrayed in duplicate. We used 300 ng of genomic DNA to amplify the mitochondrial coding sequence in three overlapping long PCR fragments. We then sequenced >2 million base pairs of mitochondrial DNA, and successfully assigned base calls at 96.0% of nucleotide positions. Replicate experiments demonstrated >99.99% reproducibility. In matched fluid samples (urine and pancreatic juice, respectively) obtained from five patients with bladder cancer and four with pancreatic cancer, the MitoChip detected at least one cancer-associated mitochondrial mutation in six (66%) of nine samples. The MitoChip is a high-throughput sequencing tool for the reliable identification of mitochondrial DNA mutations from primary tumors in clinical samples.     

Iodine deficiency disorders in Bangladesh

An extensive iodine deficiency disorders survery was conducted in Bangladesh in 1993 to assess the latest iodine nutriture status of the country. The clinical variables of the survey were goitre and cretinism, and the biochemical variable was urinary iodine. The “EPI-30 cluster” sampling methodology was followed for selecting the survey sites. In each survey site, the study population consisted of boys and girls, aged 5–11 years, and men and women, aged 15–44 years, in about equal populations. the total number of survey sites was 78 and the total number of respondents was 30 072. The total number of urine samples was 4512 (15% sub-sample). The current total goitre rate (grade 1+grade 2) in Bangladesh is 47.1% (hilly, 44.4%; flood-prone, 50.7%; and plains, 45.6%). The prevalence of cretinism in the country is 0.5% (hilly, 0.8%; flood-prone, 0.5%; and plains, 0.3%). Nearly 69% of Bangladeshi population have biochemical iodine deficiency (urinary iodine excretion [UIE]<10 mg/dl) (hilly, 84.4; flood-prone, 67.1%; and plains 60.4%). Women and children are more affected than men, in terms of both goitre prevalence and UIE. The widespread severe iodine deficiency in all ecological zones indicates that the country as a whole is an iodine-deficient region. Important recommendations of global interest are made from the experience of the survey. An erratum to this article is available at .     

Quantitative methylation-specific polymerase chain reaction gene patterns in urine sediment distinguish prostate cancer patients from control subjects.

PURPOSE: Aberrant promoter hypermethylation of several known or putative tumor suppressor genes occurs frequently during the pathogenesis of prostate cancers and is a promising marker for cancer detection. We sought to develop a test for prostate cancer based on a quantitative methylation-specific polymerase chain reaction (QMSP) of multiple genes in urine sediment DNA. PATIENTS AND METHODS: We tested urine sediment DNA for aberrant methylation of nine gene promoters (p16INK4a, p14(ARF), MGMT, GSTP1, RARbeta2, CDH1 [E-cadherin], TIMP3, Rassf1A, and APC) from 52 patients with prostate cancer and 21 matched primary tumors by quantitative fluorogenic real-time polymerase chain reaction. We also analyzed urine sediments from 91 age-matched individuals without any history of genitourinary malignancy as controls. RESULTS: Promoter hypermethylation of at least one of the genes studied was detected in urine samples from all 52 prostate cancer patients. Urine samples from the 91 controls without evidence of genitourinary cancer revealed no methylation of the p16, ARF, MGMT, and GSTP1 gene promoters, whereas methylation of RARbeta2, TIMP3, CDH1, Rassf1A, and APC was detected at low levels. CONCLUSION: Overall, methylation found in urine samples matched the methylation status in the primary tumor. A combination of only four genes (p16, ARF, MGMT, and GSTP1) would theoretically allow us to detect 87% of prostate cancers with 100% specificity. Our data support further development of the noninvasive QMSP assay in urine DNA for early detection and surveillance of prostate cancer.     

Cellular and molecular pathophysiology in the progression of Parkinson’s disease

Metabolic Brain Disease - Parkinson’s disease (PD) is a neurodegenerative disorder etiologically linked to the loss of substantia nigra (SN) dopaminergic neurons in the mid-brain. The...     

β-Hydroxybutyrate protects from alcohol-induced liver injury via a Hcar2-cAMP dependent pathway

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PEGylation of Carbonate Apatite Nanoparticles Prevents Opsonin Binding and Enhances Tumor Accumulation of Gemcitabine

pH sensitives carbonate apatite (CA) has emerged as a targeted delivery vehicle for chemotherapeutics agent with tremendous potential to increase the effectivity of breast cancer treatment. The major challenge for intravenous delivery of drug-incorporated nanoparticles is their rapid opsonization, resulting in accumulation within the organs of reticuloendothelial system, such as liver and spleen. Therefore, surface modification by polyethylene glycol was implemented to improve the half-life of drug-particle complexes and enhance their uptake by target tissues. A simple, rapid, and sensitive triple quadrupole liquid chromatography–mass spectrometry method was developed and validated for quantification of gemcitabine in plasma, various organs and tumor tissues of mice with breast carcinoma, whereas sodium dodecyl sulfate-polyacrylamide gel electrophoresis, quadrupole-time of flight liquid chromatography–mass spectrometry and analysis by SwissProt.Mus_musculus database were performed for protein separation, identification, and homology search by comparing the de novo sequence tag. PEGylated CA exhibited almost 6-fold increase in gemcitabine accumulation in tumor with significant reduction in other organs within 1 h of intravenous administration, compared to free drug. In addition, plasma drug amount was found to be higher in PEGylated particles, implying their role in prolonging blood circulation time of particle-bound gemcitabine. Investigation of protein corona composition demonstrated notable reduction in opsonin interactions after PEGylation of CA particles. Overall, the results indicate that the composition and dynamics of protein corona subjected to alteration by PEGylation play crucial roles in affecting successful nanoparticle-based targeted delivery of a cytotoxic drug.