A key enzyme involved in the production of potentially carcinogenic estrogen metabolites and the activation of environmental carcinogens is cytochrome P450 1B1 (CYP1B1), the predominant member of the ...CYP1 family expressed in normal breast tissue and breast cancer. Because of the preeminent role of CYP1B1 in mammary estrogen/carcinogen metabolism, we examined the CYP1B1 gene to determine whether genetic differences could account for interindividual differences in breast cancer risk. We focused on exon 3, because it encodes the catalytically important heme binding domain of the enzyme, and discovered three polymorphisms of which two are associated with amino acid substitutions in codons 432 (Val-->Leu) and 453 (Asn-->Ser), designated as m1 and m2, respectively. Approximately 40% of Caucasian women have the m1 Val allele compared with nearly 70% of African-American women (P < 0.0001). The allele frequency also differs significantly in m2, with the rare Ser allele being present in 17.4% of Caucasians but only in 3.4% of African Americans (P < 0.0003). To determine whether the polymorphic CYP1B1 alleles hold implications as potential breast cancer risk factors, we compared the CYP1B1 genotypes in 164 Caucasian and 59 African-American breast cancer cases with those in age-, race-, and frequency-matched controls. Odds ratio calculations failed to show a significant association between any of the genotypes and breast cancer. Because CYP1B1 is known to be involved in mammary estrogen metabolism, we investigated whether the estrogen receptor status is influenced by the CYP1B1 genotypes. Caucasian patients with the m1 Val/Val genotype have a significantly higher percentage of estrogen receptor-positive (P = 0.02) and progesterone receptor-positive breast cancers (P = 0.003). There was no correlation with the m2 genotypes. These data suggest that the CYP1B1 polymorphisms in exon 3 are not associated with increased breast cancer risk but that the m1 polymorphism may be functionally important for steroid receptor expression in breast cancer of Caucasian patients.
Fetal alcohol spectrum disorder (FASD) is caused by intrauterine exposure to alcohol and can cause a full range of abnormalities to brain development, as well as long-term sequelae of cognitive, ...sensory and motor impairments. The incidence is estimated to be as high as 2% to 5% in children born within the US, however the prevalence is even higher in low socioeconomic populations. Despite the various mechanisms thought to explain the etiology of FASD, molecular targets of ethanol toxicity during development are not completely understood. More recent findings explore the role of GABA-A and GABA-B mechanisms, as well as cell death, cell signaling and gene expression malfunctions. Stem cell based therapies have grown exponentially over the last decade, which have lead to novel clinical interventions across many disciplines. Thus, early detailed understanding of the therapeutic potential of stem cell research has provided promising applications across a wide range of illnesses. Consequently, these potential benefits may ultimately lead to a reduced incidence and severity of this highly preventable and prevalent birth defect. It is recognized that stem cell derivations provide unique difficulties and limitations of therapeutic applications. This review will outline the current knowledge, along with the benefits and challenges of stem cell therapy for FASD.
•Fetal alcohol spectrum disorder (FASD) is caused by intrauterine exposure to alcohol.•FASD-associated cell death is mediated by GABA, cell signaling, and gene expression malfunctions.•Stem cell therapy has made remarkable progress in the field of neural transplantation.•Preclinical studies are warranted in advancing stem cell therapy for FASD.
Incarceration affects the lives of many African American men and often leads to poverty, ill health, violence, and a decreased quality of life. There has been an unprecedented increase in ...incarceration among African American males since 1970. In 2009, the incarceration rate among black males was 6.7 times that of white males and 2.6 times of Hispanic males. Substance abuse in African American males leads to higher mortality rates, high rates of alcohol-related problems, more likely to be victims of crimes, and HIV/AIDS. African Americans comprised only 14% of the U.S. population but comprised 38% of the jail population. The cost of incarcerating persons involved in substance related crimes has increased considerably over the past two decades in the U.S. A reduction in the incarceration rate for non-violent offences would save an estimated $17 billion per year. Substance use disorder makes the individual more prone to polysubstance use and leads to impulse control problems, selling drugs, and other crimes. The high rate of incarceration in U.S. may adversely affect health care, the economy of the country, and will become a burden on society. Implementation of good mental health care, treatment of addiction during and after incarceration will help to decrease the chances of reoffending. Therapeutic community programs with prison-based and specialized treatment facilities, cognitive behavioral therapy treatment for 91-180 days, and 12-step orientation with staff specialized in substance abuse can be helpful. It is essential for health care professionals to increase public awareness of substance abuse and find ways to decrease the high rates of incarceration.
Despite years of research, vaccines against HIV and HCV are not yet available, due largely to effective viral immunoevasive mechanisms. A novel escape mechanism observed in viruses that cause chronic ...infection is suppression of viral-specific effector CD4(+) and CD8(+) T cells by stimulating regulatory T cells (Tregs) educated on host sequences during tolerance induction. Viral class II MHC epitopes that share a T cell receptor (TCR)-face with host epitopes may activate Tregs capable of suppressing protective responses. We designed an immunoinformatic algorithm, JanusMatrix, to identify such epitopes and discovered that among human-host viruses, chronic viruses appear more human-like than viruses that cause acute infection. Furthermore, an HCV epitope that activates Tregs in chronically infected patients, but not clearers, shares a TCR-face with numerous human sequences. To boost weak CD4(+) T cell responses associated with persistent infection, vaccines for HIV and HCV must circumvent potential Treg activation that can handicap efficacy. Epitope-driven approaches to vaccine design that involve careful consideration of the T cell subsets primed during immunization will advance HIV and HCV vaccine development.
Eucalypts are the cornerstone of ecological restoration efforts across the highly modified agricultural landscapes of southern Australia. ‘Local provenancing’ is the established strategy for sourcing ...germplasm for ecological restoration plantings, yet this approach gives little consideration to the persistence of these plantings under future climates. This paper provides a synopsis of recent and ongoing research that the authors are undertaking on climate adaptation in eucalypts, combining new genomic approaches with ecophysiological evidence from provenance trials. These studies explore how adaptive diversity is distributed within and among populations, whether populations are buffered against change through capacity for phenotypic plasticity, and how this informs provenancing strategies. Results to date suggest that eucalypts have some capacity to respond to future environmental instability through adaptive phenotypic plasticity or selection of putatively adaptive alleles. Despite this, growing evidence suggests that eucalypts will still be vulnerable to change. Provenancing strategies that exploit adaptations found in non-local provenances could thus confer greater climate-resilience in ecological restoration plantings, although they will also need to account for potential interactions between climate adaptations and other factors (e.g. cryptic evolutionary variation, non-climate-related adaptations, herbivory and elevated CO2).
Transesophageal echocardiography (TEE) is the diagnostic modality of choice for visualizing the left atrial appendage (LAA). This study defined the morphology of the LAA in normal autopsy specimen ...hearts and considered the implications of these findings for TEE studies.
Five hundred normal autopsy hearts were reviewed (25 male and 25 female subjects from each decade for 10 decades). LAA length, width, orifice size, and number of lobes were recorded. Number of lobes was compared between sexes with the rank sum test and regressed against age. Mean length, width, and orifice size increased with age, up to age 20 years, in both sexes. Rates were significantly different between sexes for LAA size (P=.011) and width (P=.006). After age 20, statistically significant but clinically insignificant age-related changes were observed. Fifty-four percent of LAAs had two lobes (range, 1 to 4), with no age or sex differences. Lobes exist in different planes of the heart. Most pectinate muscles were > or = 1 mm in width. Pectinate muscles < 1 mm (2.6% of cases) were seen in only the first and last decades.
Age- and sex-related differences in LAA dimensions exist. These differences and the existence of multilobed appendages are important in the accurate TEE evaluation of LAA. Because lobes exist in different planes, imaging must be done in multiple planes to visualize the entire LAA.
Health care reform under the Patient Protection and Affordable Care Act (PPACA, ACA) of 2010 may be the most significant health care-related legislation enacted since the establishment of Medicare ...and Medicaid several decades ago. Over two years ago the U.S. Supreme Court upheld the constitutionality of the individual mandate of the Patient Protection and Affordable Care Act. This legislation has emerged as a significant and ambitious undertaking for all levels of the U.S. government. With the need to accommodate the estimated 30 million people projected over time to become newly insured it is increasingly important to understand the necessity of reform, how the legislation has been interpreted and implemented to fit the goals of the federal, state, and local governments, and what the potential benefits and consequences of changing the system are, in particular, as it relates to mental health care.
Background: Government regulation is intended to enhance quality, safety, fairness, or competition in the regulated industry. Such regulation entails both direct and indirect costs. Objectives: To ...estimate the costs associated with the regulation of quality of the nursing home industry. Sample: This study includes 11,168 free-standing nursing homes nationally, between 2004 and 2006. Research Design: Data included information from the Medicare cost reports, Minimum Data Set, Medicare Denominator file, OSCAR, and a survey of States' Certification and Licensing Offices conducted by the authors. These data were used to create variables measuring nursing homes costs, outputs, wages, competition, adjusted deficiency citations, ownership, state-fixed effects, and an index of each state's regulatory stringency. We estimated hybrid cost functions which included the regulatory stringency index. Results: The estimated cost functions demonstrated the typical behavior expected of nursing home cost functions. The stringency index was positively and significantly associated with costs, indicating that nursing homes located in states with more stringent regulatory requirements face higher costs, ceteris paribus. The average incremental costs of a 1 standard deviation increase in the stringency index resulted in a 1.1% increase in costs. Conclusions: This study for the first time places a price tag on the regulation of quality in nursing homes. It offers an order of magnitude on the costs to the industry of complying with the current set of standards and given the current level of enforcement. Complementary studies of the benefits that these regulations entail are needed to gain a comprehensive assessment of the effect of the regulation.
Using EHRs to advance epilepsy care Mbwana, Juma S; Grinspan, Zachary M; Bailey, Russell ...
Neurology. Clinical practice
9, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The improved use of Electronic Health Record (EHR) Systems provides an opportunity to improve the overall efficiency and quality of care of patients with epilepsy. Tools and strategies that may be ...incorporated into the use of EHRs include utilizing patient generated data, clinical decision support systems and natural language processing systems. Standardization of data from EHR systems may lead to improvement in clinical research through the creation of data collections and multi-center collaborations. Challenges to collaborative use of EHR Systems across centers include costs and the diversity of EHR systems.
Genetically based differences in carcinogen metabolism have been related to polymorphisms of the cytochrome P450IA1 gene (CYPIA1) and the null genotypes of glutathione S-transferase classes mu and ...theta (GSTM1 and GSTT1). By PCR we examined the genotypes of CYPIA1, GSTM1, and GSTT1 in relation to breast cancer risk in Caucasian and African-American women. The study included 164 Caucasian and 59 African-American women with primary invasive breast cancer and age-matched female controls. Enzyme polymorphisms included in this study were the null deletions of GSTM1 and GSTT1 and the m1 (MspI), m2 (codon 462: isoleucine-->valine), m3 (MspI-AA), and m4 (codon 461: threonine-->asparagine) polymorphisms of CYPIA1. Contrary to previous reports by other investigators, none of the enzyme genotypes, individually or combined, appear to associate with an increased risk for breast cancer in Caucasian or African-American women. We also report that the recently described m4 allele occurs at a lower frequency in African-Americans than Caucasians and is not linked with breast cancer in either race. Thus, it is unlikely that polymorphisms of GSTM1, GSTT1, or CYPIA1 represent susceptibility factors for breast cancer in Caucasians or African-Americans.
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