Publications by authors named "Werk A"

Native Americans (Indigenous Americans) have high rates of serious illness in the United States. Informal caregivers are heavily relied on in caring for patients in low-resource settings. The needs of caregivers residing on reservations are sorely underreported.

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Aim: To explore (1) perspectives and attitudes of Native Americans regarding transitions from serious illness to death, and (2) awareness about hospice and palliative care service models in a Great Plains reservation-based community.

Design: Qualitative descriptive study.

Methods: Community members and clinicians were invited to participate in a semi-structured focus group or interview by Tribal Advisory Board members.

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Nurse educators are called to increase diversity in the clinical and faculty workforce; promote safe, inclusive learning environments; develop curricula that provide an anti-biased view of patients and health conditions; and provide students with educational opportunities to learn from individuals with diverse backgrounds. An innovative curriculum design inclusive of Indigenous worldviews was implemented at a tribal college. It provides an exemplar that supports diverse student learning, retention, and graduation.

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An associate degree in nursing program was established six years ago at the tribal college of the Fort Belknap Indian Reservation, home of the Aaniiih and Nakoda people. As this program continues to evolve and grow, it offers a successful example of how to increase diversity in nursing and potentially improve the health outcomes of Native Americans living on and nearby reservation communities.

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: A history of unethical research and deficit-based paradigms have contributed to profound mistrust of research among Native Americans, serving as an important call to action. Lack of cultural safety in research with Native Americans limits integration of cultural and contextual knowledge that is valuable for understanding challenges and making progress toward sustainable change. : To identify strategies for promoting cultural safety, accountability, and sustainability in research with Native American communities.

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Genetic polymorphism of drug metabolizing enzymes and transporters may influence drug response. The frequency varies substantially between ethnicities thus having implications on appropriate selection and dosage of various drugs in different populations. The distribution of genetic polymorphisms in healthy Pakistanis has so far not been described.

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Article Synopsis
  • This text indicates that there is a correction to a previously published article identified by the DOI number 10.1371/journal.pone.0162866.
  • The correction may involve updates or clarifications regarding the study's findings, methodology, or conclusions.
  • Readers should refer to the corrected version for accurate information related to the research presented in the original article.
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Pharmacogenomics aims to correlate inter-individual differences of drug efficacy and/or toxicity with the underlying genetic composition, particularly in genes encoding for protein factors and enzymes involved in drug metabolism and transport. In several European populations, particularly in countries with lower income, information related to the prevalence of pharmacogenomic biomarkers is incomplete or lacking. Here, we have implemented the microattribution approach to assess the pharmacogenomic biomarkers allelic spectrum in 18 European populations, mostly from developing European countries, by analyzing 1,931 pharmacogenomics biomarkers in 231 genes.

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Cancer pharmacogenetics usually considers tumor-specific targets. However, hereditary genetic variants may interfere with the pharmacokinetics of antimetabolites and other anti-cancer drugs, which may lead to severe adverse events. Areas covered: Here, the impact of hereditary genes considered in drug labels such as thiopurine S-methyltransferase (TPMT), UDP-glucuronosyltransferase 1A1 (UTG1A1) and dihydropyrimidine dehydrogenase (DPYD) are discussed with respect to guidelines of the Clinical Pharmacogenetics Implementation Consortium (CPIC).

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Objective: Flupirtine is a nonopioid analgesic with regulatory approval in a number of European countries. Because of the risk of serious liver injury, its use is now limited to short-term pain management. We aimed to identify genetic risk factors for flupirtine-related drug-induced liver injury (DILI) as these are unknown.

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Purpose: Although bone tissue engineering techniques have become more and more sophisticated than in the past, natural bone healing mechanisms have not been sufficiently considered for further improvement of these techniques so far. We used an established animal model with transcriptome analysis to generate an unbiased picture of early bone healing to support tissue engineering concepts.

Material And Methods: In 30 Wistar rats, a 3-mm bone defect was created in the mandibular angle.

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Background: Tacrolimus is established as immunosuppressant after kidney transplantation. Polymorphism of the cytochrome P450 3A5 (CYP3A5) gene contributes significantly to tacrolimus dose requirements. Recently, CYP3A4*22 was reported to additionally affect tacrolimus pharmacokinetics (PK).

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Functional gene variants of CYP3A4.

Clin Pharmacol Ther

September 2014

Cytochrome P450 3A4 (CYP3A4) is involved in the metabolism of more drugs in clinical use than any other foreign compound-metabolizing enzyme in humans. Recently, increasing evidence has been found showing that variants in the CYP3A4 gene have functional significance and--in rare cases--lead to loss of activity, implying tremendous consequences for patients. This review article highlights the functional consequences of all CYP3A4 variants recognized by the Human Cytochrome P450 (CYP) Allele Nomenclature Database.

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Background: The functional influence of single-nucleotide polymorphisms (SNPs) of the ATP-binding cassette (ABC) transporter ABCC2 (MRP2) has been characterized in numerous studies. The aim of this study was to address the question of whether distinct ABCC2 haplotypes, which differ in their mRNA secondary structures, show an influence on the degree of mRNA and protein downregulation through miRNA interaction.

Methods: A model using human peripheral blood monocytic cells (PBMCs) isolated from healthy Caucasian volunteers, with three defined ABCC2 haplotypes comprising the 5'-UTR SNP -24C>T, the 1249G>A SNP (V417I), and the silent 3972C>T SNP, was outlined.

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MicroRNAs (miRNAs) are small noncoding RNAs, which regulate the expression of their target genes post-transcriptionally by RNA interference. They are involved in almost all cellular processes, including proliferation, differentiation, apoptosis, cell survival and the maintenance of tissue specificity. Recent findings also suggest that efflux pumps of the ABC (ATP-binding cassette) transporter family are subject to miRNA-mediated gene regulation.

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Background: Resistance of the highly aggressive glioblastoma multiforme (GBM) to drug therapy is a major clinical problem resulting in a poor patient's prognosis. Beside promoter methylation of the O6-methylguanine-DNA-methyltransferase (MGMT) gene the efflux transporters ABCB1 and ABCG2 have been suggested as pivotal factors contributing to drug resistance, but the methylation of ABCB1 and ABCG2 has not been assessed before in GBM.

Methods: Therefore, we evaluated the proportion and prognostic significance of promoter methylation of MGMT, ABCB1 and ABCG2 in 64 GBM patient samples using pyrosequencing technology.

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Cytochrome P450 3A4 (CYP3A4) is a major drug-metabolizing enzyme that is widely investigated. So far, no homozygous inactive variant has been described. We report on a 19-year-old kidney transplant patient suffering from Alport syndrome, who experienced unexpected high tacrolimus plasma trough levels during immunosuppressant therapy.

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The attempt to optimize drug treatment of patients by using evidenced-based medicine considering individual physiological and disease-related conditions is standard of modern medicine. Pharmacogenetics (PGx) has contributed to individualization considering hereditary genetic information; however, increasingly, pharmacogenomics is becoming essential, particularly in relation to modern oncology. New technologies such as next-generation sequencing and rapid development of computational and information sciences will help to better elucidate the consequences of genetic variation, considering also epigenetics and gene-environmental interactions and their translation into clinically relevant individual phenotypes.

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Purpose: To evaluate the effectiveness of blood pressure [BP] screenings through community-based health fairs. Effectiveness was measured by those with high BP readings who either made an appointment with or actually followed up with their primary care provider [PCP] in person following post-screening referral.

Data Sources: Anonymized data were provided for 958 individuals who obtained BP screening through a three-day health fair provided by the Ceres Police Department Nurse Program.

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microRNAs (miRNAs), which contribute to the post-transcriptional processing through 3'-untranslated region-interference, have been shown to be involved in the regulation of ATP-binding cassette (ABC) membrane transporters. The aim of this study was to investigate whether ABCC2, an important efflux transporter for various endogenous and exogenous compounds at several compartment barriers, is subject to miRNA-mediated post-transcriptional gene regulation. We screened the expression of 377 human miRNAs in HepG2 cells after 48 h of treatment with 5 μM rifampicin [a pregnane X receptor (PXR) ligand] or vehicle using reverse transcription-polymerase chain reaction-based low-density arrays.

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Although substance abuse is frequently encountered in men receiving services in violence treatment settings, systematic study of these 'dual-problem' men has lagged. This study had two main objectives: (1) the characterization of psychoactive substance abuse disorders in a naturalistic sample of men in domestic violence treatment; and (2) clarification of the role of substance abuse on the sociodemographic, personality, psychosocial, and abuse characteristics of dual-problem men. Fifty-three adult men who were attending domestic violence treatment were recruited.

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Linkage between marital violence and substance abuse has been noted in men seeking treatment for substance-use disorders. The present study examined (1) the incidence of family violence in men admitted into substance abuse treatment; (2) the psychosocial characteristics associated with marital violence; and (3) the comparability of violent substance abusers to their treatment cohorts. Fifty-nine men in substance abuse treatment involved in a significant relationship in the past year were assessed for substance abuse, family violence, psychosocial functioning, and personality attributes.

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