Search

Discusses the abstract of the study 'Outcomes of an Intensive Course in Cancer Risk Assessment for Genetic Counselors and Nurses,' presented at the 21st Annual Education Conference of the National Society of Genetic Counselors held in Phoenix, Arizona in November 2002.

Abstract The terrain is well explored regarding genes whose gene expression is up-regulated upon binding of thyroid hormone (TH) to its nuclear receptor. This regulation mechanism has been intensively studied and is well understood. In contrast, a lot of white spots remain on the map when it comes to target genes whose expression is down-regulated upon binding of TH to the thyroid hormone receptor (TR). Since no consistent mechanism has been proposed to explain ligand-dependent down-regulation of target gene transcription several working hypotheses favour different molecular mechanisms. Some working theories suggest a direct binding of TR to regulatory elements of target genes. Others favour models that are independent of a direct DNA binding event. However recent data suggested that a direct binding of TR to DNA is dispensable for TH-dependent negative gene transcription.

An abstract of the study "Corpus Luteum Development After Follicle Aspiration Is Related to Characteristics of the Aspirated Follicle in Dairy Cows," by A. Vernunft et al. is presented.

Discusses the abstract of the study 'Communicating Cancer Risk Information and Assessing Risk Perception,' presented at the 21st Annual Education Conference of the National Society of Genetic Counselors held in Phoenix, Arizona in November 2002.

The enhanced growth performance of calves fed a higher plane of nutrition pre-weaning is well documented, and the effect of butyrate on the development of the gastrointestinal tract in calves has been evaluated. The aim of this study was to examine the synergistic effects of ad libitum milk replacer (MR) feeding and butyrate supplementation on growth performance and energy metabolism in calves. Sixty-four (32 male, 32 female) Holstein calves were examined from birth until wk 11 of life. Calves received MR either ad libitum (Adl) or restrictively (Res) with (AdlB+, ResB+) or without (AdlB-, ResB-) 0.24% butyrate supplementation. Colostrum and transition milk were fed in predefined amounts (Res or Adl) for the first 3 d postpartum. Ad libitum and restrictive MR feeding with or without butyrate was performed from d 4 until wk 8 of age. From wk 9 to 10, all calves were gradually weaned and were fed 2 L/d until the end of the trial. Concentrate (CON), hay, and water were freely available. Intakes of MR and CON were measured daily. Calves were weighed at birth and weekly thereafter. Blood was drawn on d 1 before the first colostrum intake; on d 2, 4, and 7; and weekly thereafter until the end of the study to measure plasma concentrations of metabolites and hormones. Liver samples were taken at d 50 and at the end of the study to determine gene expression related to glucose metabolism. Milk, MR, and total nutrient intake were greater, but CON intake was lower in Adl than in Res calves, resulting in a greater body weight, but partially lower gain to feed ratio in Adl than in Res. Plasma concentrations of glucose and insulin were higher during the ad libitum milk-feeding period, whereas plasma β-hydroxybutyrate was lower in Adl than in Res. Plasma concentrations of nonesterified fatty acids, lactate, total bilirubin, and cortisol were lower, but triglyceride and cholesterol concentrations were higher in Adl than in Res at specific time points. Feed intake, growth performance, and metabolic and endocrine changes were insignificantly affected by butyrate, and hepatic gene expression of enzymes related to endogenous glucose production was barely influenced by ad libitum MR feeding and butyrate supplementation. Intensive MR feeding indicated greater stimulation of growth and anabolic metabolism, but butyrate supplementation did not further improve postnatal growth or anabolic processes either in intensive or restrictive MR-fed calves. [ABSTRACT FROM AUTHOR]

Quercetin has been shown to be a potent antioxidant, acts hepatoprotectively, and affects glucose and lipid metabolism in monogastrics. If this is also true in ruminants, quercetin could be beneficial in periparturient high-yielding dairy cows by ameliorating the negative effects of free radical formation and reducing the severity of liver lipidosis and ketosis. In a first attempt to evaluate effects of a long-term quercetin treatment, we intraduodenally administered twice daily 18 mg of quercetin (Q)/kg of body weight to 5 late-lactation (215 d in milk) dairy cows over a period of 28 d. Frequent blood samples were taken before and during administration to determine plasma concentrations of flavonols and metabolites. Before and after 1 and 4 wk of Q administration, glycogen and fat content as well as mRNA expression of selected genes were measured in liver biopsies. Furthermore, euglycemic, hyperinsulinemic, and hyperglycemic clamp studies were conducted before and after 2 wk of Q administration. During the experiment, dry matter intake and most other zootechnical data remained unchanged. Milk protein content was increased in wk 2 and 4 of Q administration compared with basal values, whereas fat and lactose contents of milk remained unchanged. Plasma nonesterified fatty acids, γ-glutamyl transferase, cholesterol, glutamate dehydrogenase, triglyceride, and albumin concentrations, as well as liver fat and glycogen concentrations, were not affected by Q supplementation. Plasma glucose and β-hydroxybutyrate concentrations in plasma decreased and increased, respectively, under the influence of quercetin. During hyperglycemic clamp conditions, the relative increase of plasma insulin was higher after 2 wk of Q administration, and a tendency for an increased rQUICKI (revised quantitative insulin sensitivity check index) was observed. The relative mRNA expression levels of selected genes related to glucose metabolism, fat metabolism, and antioxidative status were not altered after 1 or 4 wk of Q supplementation. In conclusion, the effects on insulin release and sensitivity support the assumption that administration of Q could have positive effects on the metabolic adaption of high-yielding cows to early lactation. The increase of milk protein content in response to Q supplementation needs to be verified. [ABSTRACT FROM AUTHOR]

Liver-related side effects are a known complication of treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for cystic fibrosis (CF). Gilbert's syndrome is caused by a genetic mutation that reduces activity of the enzyme UDP glucuronosyltransferase 1 polypeptide A1 (UGT1A1), causing elevated levels of unconjugated bilirubin in the blood and duodenal bile. The presence of Gilbert's syndrome and CF might represent additive risk factors for liver-related adverse events during ETI treatment. This case series describes six people with CF (pwCF) in whom previously unknown Gilbert's syndrome was unmasked after initiation of treatment with ETI. Although all patients had some level of hepatic dysfunction and/or elevated levels of bilirubin after initiation of ETI, the clinical course varied. Only one patient had to stop ETI therapy altogether, while the others were able to continue treatment (some at a reduced dosage and others at the full recommended daily dosage). All patients, even those using a lower dosage, experienced clinical benefit during ETI therapy. Gilbert's syndrome is not a contraindication for ETI therapy but may be mistaken for a risk factor for liver-related adverse events in pwCF. This is something that physicians need to be aware of in pwCF who show liver adverse events during ETI therapy., (© 2024. The Author(s).)

Background: Immune checkpoint blockade (ICB) has presented a breakthrough in the treatment of malignant tumors and increased the overall survival of patients with various tumor entities. ICB may also cause immune-related adverse events, such as pneumonitis or interstitial lung disease. The lung clearance index (LCI) is a multiple-breath washout technique offering information on lung pathology in addition to conventional spirometry. It measures the degree of pulmonary ventilation inhomogeneity and allows early detection of pulmonary damage, especially that to peripheral airways. Methods: This cross-sectional study compared the lung function of patients with melanoma or metastatic cutaneous squamous cell carcinoma who received programmed cell death 1 (PD-1) and cytotoxic T-Lymphocyte-associated Protein 4 (CTLA-4) antibodies, alone or in combination, to age- and sex-matched controls. Lung function was assessed using spirometry, according to American Thoracic Society and European Respiratory Society standards, the LCI, and a diffusion capacity of carbon monoxide (DLCO) measurement. Results: Sixty-one screened patients and thirty-eight screened controls led to nineteen successfully included pairs. The LCI in the ICB-treated patients was 8.41 ± 1.15 (mean ± SD), which was 0.32 higher compared to 8.07 ± 1.17 in the control group, but the difference was not significant ( p = 0.452). The patients receiving their ICB therapy for under five months showed a significantly lower LCI (7.98 ± 0.77) compared to the ICB patients undergoing therapy for over five months (9.63 ± 1.22) at the point of testing ( p = 0.014). Spirometric analysis revealed that the forced expiratory volume between 25 and 75% of the forced vital capacity (FEF25-75%) in the ICB-treated patients was significantly reduced ( p = 0.047) compared to the control group. DLCO (%predicted and adjusted for hemoglobin) was 94.4 ± 19.7 in the ICB patients and 93.4 ± 21.7 in the control group ( p = 0.734). Conclusions: The patients undergoing ICB therapy showed slightly impaired lung function compared to the controls. Longer periods of ICB treatment led to deterioration of the LCI, which may be a sign of a subclinical inflammatory process. The LCI is feasible and may be easily integrated into the clinical daily routine and could contribute to early detection of pulmonary (auto-)inflammation.

The analytical procedure life cycle (APLC) provides a holistic framework to ensure analytical procedure fitness for purpose. USP's general chapter <1220> considers the validation activities that take place across the entire analytical procedure lifecycle and provides a three-stage framework for its implementation. Performing ongoing analytical procedure performance verification (OPPV) (stage 3) ensures that the procedure remains in a state of control across its lifecycle of use post validation (qualification) and involves an ongoing program to collect and analyze data that relate to the performance of the procedure. Knowledge generated during stages 1 (procedure design) and 2 (procedure performance qualification) is used as the basis for the design of the routine monitoring plan to support performance verification (stage 3). The extent of the routine monitoring required should be defined based on risk assessment, considering the complexity of the procedure, its intended purpose, and knowledge about process/procedure variability. The analytical target profile (ATP) can be used to provide or guide the establishment of acceptance criteria used to verify the procedure performance during routine use (e.g., through a system/sample suitability test (SST) or verification criteria applicable to procedure changes or transfers). An ATP however is not essentially required to perform OPPV, and a procedure performance monitoring program can be implemented even if the full APLC framework has not been applied. In these situations, verification criteria can be derived from existing validation or system suitability criteria. Elements of the life cycle approach can also be applied retrospectively if deemed useful.

Background: Early identification of germline mutation carriers may be relevant for the optimal management of prostate cancer and to inform cancer risk in relatives. However, population minorities have limited access to genetic testing. The aim of this study was to describe the frequency of DNA repair gene pathogenic variants (PVs) among Mexican men with prostate cancer referred for Genomic Cancer Risk Assessment and testing., Methods: Patients diagnosed with prostate cancer who meet criteria for genetic testing and enrolled in the Clinical Cancer Genomics Community Research Network at the Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán in Mexico City were included. Descriptive statistics were performed using frequency and proportions for categorical variables and median and range for quantitative variables. X 2 and t test were used for group comparisons., Results: A total of 199 men were enrolled, median age at diagnosis was 66 (range 44-88) years; 45% were de novo metastatic and 44% were high- very high and 10% were intermediate risk group. Four (2%) had a pathogenic germline variant; one each of the following genes: ATM, CHEK2, BRIP1, and MUTYH (all monoallelic). Younger men at diagnosis were more likely to carry a PV than older age at diagnosis (56.7 vs. 66.4 years, P = .01)., Conclusion: Our results showed a low prevalence of known prostate cancer associated PVs and no BRCA PVs in Mexican men with prostate cancer. This suggests that the genetic and/or epidemiologic risk factors for prostate cancer are not well characterized in this specific population., Competing Interests: Disclosure Y Chavarri-Guerra: Research support from Roche; Invitae Speaker´s bureau; Pfizer travel expenses; Novartis travel expenses. MT Bourlon: Astra Zeneca Speaker´s bureau; Janssen Speaker´s bureau and travel expenses; Pfizer Speaker´s bureau and travel expenses; Foundation One Speaker´s bureau. J Weitzel: Natera employee,;Astra Zeneca Speaker´s bureau., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Parkinson's disease is frequently treated with combinations of levodopa/carbidopa and, at the occurrence of motor fluctuations, levodopa/carbidopa/entacapone. For these (and other) medications, using generic versions can reduce costs. To show that generic drugs are equivalent to the originator drug, regulations usually refer to the bioavailability of active ingredients, which is influenced by the selected dosage form and the chosen excipients. However, while registration trials administer drugs under standardized conditions, these conditions often do not reflect the conditions of patients' daily intake. Thus, this study aimed to characterize levodopa combinations from different manufacturers in biorelevant media. Dissolution profiles of bioequivalent levodopa/carbidopa combinations and levodopa/carbidopa/entacapone combinations were tested in different media, such as tap water, gastric fluid without pepsin and whole milk. Results showed distinct discrepancies in the drugs' dissolution profiles between manufactures. Using whole milk as a dissolution medium led to the most differing dissolution profiles. Furthermore, carbidopa was unstable in tap water and milk, and it rapidly degraded. This effect was less pronounced if entacapone was present. In contrast to reports in the literature, stability testing did not show that vitamin C helps to protect against carbidopa degradation. Entacapone hardly dissolved in an acidic environment. This study found that dissolution of bioequivalent levodopa formulations varied with changing media. Further, the stability of carbidopa was found to be critical. As an implication, an acidic environment must be ensured when these drugs are applied, and generic exchange of levodopa combinations should be considered only with great caution., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objectives: Generic exchange is common practice in most healthcare systems. This study investigated how patients with Parkinson disease (PD) perceived a switch of their levodopa medication and the resulting effects on their PD symptoms., Methods: A questionnaire was developed, piloted, and finally distributed to 13,857 members of the national PD patient support group. It was designed to be completed by patients and their pharmacies. χ 2 tests for independence statistics with or without Monte Carlo simulation were performed. Cramér φ and Cramér V were calculated. McNemar test was used to investigate whether a generic switch of a levodopa-containing medication had an impact on PD symptoms., Results: Analyses were done with 410 finalized respondents of 13,857 distributed questionnaires. More than half of the responders were 75 years or older and rated themselves Hoehn and Yahr stages 3 to 5. Most patients were confused by a change of their medication. A total of 54.7% of the switchers (n = 148) reported swallowing difficulties with medication, which was significantly more frequent than with nonswitchers (37.3% of 204, P = 0.001). Adverse effects related to the switch were reported by 26.6% of all switchers (switchback rate, 20.5%). The patients at higher Hoehn and Yahr stages were affected to a greater extend., Conclusions: Patients, who experienced any brand switch of their levodopa medication, frequently expressed distrust and confusion. Swallowing difficulties and negative effects on their symptoms were problems, which were more pronounced in advanced disease stages. It remains unclear whether the detrimental impact on therapy was caused by the brand switch or by a nocebo effect., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The purpose of this theoretical article is to analyze the utility of postcolonial and Indigenous feminist frameworks in informing nursing research and practice specific to addressing intimate partner violence (IPV) in the lives of Indigenous women. Prevailing feminist narratives of the 20th century focused overwhelmingly on patriarchy as the sole source of oppression against women and root cause of IPV. These narratives failed to consider the complex historical ways in which patriarchy intersected with colonialism and racism to produce violence, affecting the contemporary realities of Indigenous women. In contrast, postcolonial and Indigenous feminist frameworks consider the colonial history that has disempowered Indigenous women and their nations over centuries of settler occupation. Situating IPV within historical, legal, social, and political contexts can unmask how current research and health care discourses may continue to constrain, rather than improve, access, care, and services for Indigenous victims of IPV.

Recent changes in the pharmaceutical industry have led to significant paradigm shifts in the pharmaceutical quality environment. Globalization of the pharmaceutical industry, increasingly rapid development of novel therapies, and adoption of new manufacturing techniques have presented numerous challenges for the established regulatory framework and quality environment and are impacting the approaches utilized to ensure the quality of pharmaceutical products. Regulators, industry, and standards-setting organizations have begun to recognize the need to rely more on integrated risk-based approaches and to create more nimble and flexible standards to complement these efforts. They also increasingly have recognized that quality needs to be built into systems and processes throughout the lifecycle of the product. Moreover, the recent COVID-19 crisis has emphasized the need to adopt practices that better promote global supply chain resilience. In this paper, the USP Quality Advisory Group explores the various paradigm shifts currently impacting pharmaceutical quality and the approaches that are being taken to adapt to this new environment. Broad adoption of the Analytical Procedure Lifecycle approach, improved data management, and utilization of digital technologies are identified as potential solutions that can help meet the challenges of these quality paradigm shifts. Further discussion and collaboration among stakeholders are needed to pursue these and other solutions that can ensure a continued focus on quality while facilitating pharmaceutical innovation and development., (© 2021. The Author(s).)

Purpose: Breast cancer risks for CHEK2 and ATM pathogenic variant (PV) carriers are modified by an 86-single nucleotide polymorphism polygenic risk score (PRS) and individual clinical factors. Here, we describe comprehensive risk prediction models for women of European ancestry combining PV status, PRS, and individual clinical variables., Materials and Methods: This study included deidentified clinical records from 358,095 women of European ancestry who received testing with a multigene panel (September 2013 to November 2019). Model development included CHEK2 PV carriers (n = 4,286), ATM PV carriers (n = 2,666), and women negative for other breast cancer risk gene PVs (n = 351,143). Odds ratios (ORs) were calculated using multivariable logistic regression with adjustment for familial cancer history. Risk estimates incorporating PV status, PRS, and Tyrer-Cuzick v7.02 were calculated using a Fixed-Stratified method that accounts for correlations between risk factors. Stratification of PV carriers into risk categories on the basis of remaining lifetime risk (RLR) was assessed in independent cohorts of PV carriers., Results: ORs for association of PV status with breast cancer were 2.01 (95% CI, 1.88 to 2.16) and 1.83 (95% CI, 1.68 to 2.00) for CHEK2 and ATM PV carriers, respectively. ORs for PRS per one standard deviation were 1.51 (95% CI, 1.37 to 1.66) and 1.45 (95% CI, 1.30 to 1.64) in CHEK2 and ATM PV carriers, respectively. Using the combined model (PRS plus Tyrer-Cuzick plus PV status), RLR was low (≤ 20%) for 24.2% of CHEK2 PV carriers, medium (20%-50%) for 63.8%, and high (> 50%) for 12.0%. Among ATM PV carriers, RLR was low for 31.5% of patients, medium for 58.5%, and high for 9.7%., Conclusion: In CHEK2 and ATM PV carriers, risk assessment including PRS, Tyrer-Cuzick, and PV status has the potential for more precise direction of screening and prevention strategies., Competing Interests: Shannon Gallagher Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Elisha Hughes Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Allison W. Kurian Research Funding: Myriad Genetics Other Relationship: Ambry Genetics, Color Genomics, GeneDx/BioReference, InVitae, Genentech Susan M. Domchek Honoraria: AstraZeneca, Clovis Oncology, Bristol Myers Squibb Research Funding: AstraZeneca, Clovis Oncology Open Payments Link: https://openpaymentsdata.cms.gov/physician/917904 Judy Garber Consulting or Advisory Role: Novartis, GTx, Helix BioPharma, Konica Minolta, Aleta BioTherapeutics, H3 Biomedicine, Kronos Bio Research Funding: Novartis, Ambry Genetics, InVitae, Myriad Genetics Other Relationship: Susan G. Komen for the Cure, AACR, Diana Helis Henry Medical Foundation, James P. Wilmot Foundation, Adrienne Helis Malvin Medical Research Foundation, Breast Cancer Research Foundation, Facing Our Risk of Cancer Empowered Braden Probst Employment: Myriad Genetics Brian Morris Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Placede Tshiaba Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Stephanie Meek Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Eric Rosenthal Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Benjamin Roa Employment: Myriad Genetics Leadership: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Research Funding: Myriad Genetics Patents, Royalties, Other Intellectual Property: Intellectual Property held by employer Myriad Genetics Travel, Accommodations, Expenses: Myriad Genetics Thomas P. Slavin Employment: Myriad Genetics Leadership: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Susanne Wagner Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Patents, Royalties, Other Intellectual Property: Co-author of patents held by Myriad Genetics, no royalties Jeffrey Weitzel Speakers' Bureau: AstraZeneca Alexander Gutin Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics, Gilead Sciences Jerry S. Lanchbury Employment: Myriad Genetics Leadership: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Patents, Royalties, Other Intellectual Property: I am an inventor on Multiple patents filed by Myriad Genetics Travel, Accommodations, Expenses: Myriad Genetics Mark Robson Consulting or Advisory Role: Change HealthCare Research Funding: AstraZeneca, Pfizer, Merck Other Relationship: Research to Practice, Clinical Care Options, Physicans' Education Resource, Invitae, Pfizer Uncompensated Relationships: Merck, Pfizer, Daiichi Sankyo, Epic Sciences Open Payments Link: https://openpaymentsdata.cms.gov/physician/612669/summary No other potential conflicts of interest were reported.Shannon Gallagher Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Elisha Hughes Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Allison W. Kurian Research Funding: Myriad Genetics Other Relationship: Ambry Genetics, Color Genomics, GeneDx/BioReference, InVitae, Genentech Susan M. Domchek Honoraria: AstraZeneca, Clovis Oncology, Bristol Myers Squibb Research Funding: AstraZeneca, Clovis Oncology Open Payments Link: https://openpaymentsdata.cms.gov/physician/917904 Judy Garber Consulting or Advisory Role: Novartis, GTx, Helix BioPharma, Konica Minolta, Aleta BioTherapeutics, H3 Biomedicine, Kronos Bio Research Funding: Novartis, Ambry Genetics, InVitae, Myriad Genetics Other Relationship: Susan G. Komen for the Cure, AACR, Diana Helis Henry Medical Foundation, James P. Wilmot Foundation, Adrienne Helis Malvin Medical Research Foundation, Breast Cancer Research Foundation, Facing Our Risk of Cancer Empowered Braden Probst Employment: Myriad Genetics Brian Morris Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Placede Tshiaba Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Stephanie Meek Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Eric Rosenthal Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Benjamin Roa Employment: Myriad Genetics Leadership: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Research Funding: Myriad Genetics Patents, Royalties, Other Intellectual Property: Intellectual Property held by employer Myriad Genetics Travel, Accommodations, Expenses: Myriad Genetics Thomas P. Slavin Employment: Myriad Genetics Leadership: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Susanne Wagner Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Patents, Royalties, Other Intellectual Property: Co-author of patents held by Myriad Genetics, no royalties Jeffrey Weitzel Speakers' Bureau: AstraZeneca Alexander Gutin Employment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics, Gilead Sciences Jerry S. Lanchbury Employment: Myriad Genetics Leadership: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Patents, Royalties, Other Intellectual Property: I am an inventor on Multiple patents filed by Myriad Genetics Travel, Accommodations, Expenses: Myriad Genetics Mark Robson Consulting or Advisory Role: Change HealthCare Research Funding: AstraZeneca, Pfizer, Merck Other Relationship: Research to Practice, Clinical Care Options, Physicans' Education Resource, Invitae, Pfizer Uncompensated Relationships: Merck, Pfizer, Daiichi Sankyo, Epic Sciences Open Payments Link: https://openpaymentsdata.cms.gov/physician/612669/summary No other potential conflicts of interest were reported., (© 2021 by American Society of Clinical Oncology.)

We tested the hypothesis that the maternal supply of essential fatty acids (EFA), especially α-linolenic acid, and conjugated linoleic acid (CLA), affects glucose metabolism, the endocrine regulation of energy metabolism and growth, and the intestinal development of neonatal calves. We studied calves from dams that received an abomasal infusion of 76 g/d coconut oil (CTRL; n = 9), 78 g/d linseed oil and 4 g/d safflower oil (EFA; n = 9), 38 g/d Lutalin (BASF SE) containing 27% cis-9,trans-11 and trans-10,cis-12 CLA (CLA; n = 9), or a combination of EFA and CLA (EFA+CLA; n = 11) during the last 63 d of gestation and early lactation. Calves received colostrum and transition milk from their own dam for the first 5 d of life. Insulin-like growth factor (IGF)-I, leptin, and adiponectin concentrations were measured in milk. Blood samples were taken before first colostrum intake, 24 h after birth, and from d 3 to 5 of life before morning feeding to measure metabolic and endocrine traits in plasma. On d 3 of life, energy expenditure was evaluated by a bolus injection of NaH 13 CO 3 and determination of CO 2 appearance rate. On d 4, additional blood samples were taken to evaluate glucose first-pass uptake and 13 CO 2 enrichment after [ 13 C 6 ]-glucose feeding and intravenous [6,6- 2 H 2 ]-glucose bolus injection, as well as postprandial changes in glucose, nonesterified fatty acids (NEFA), insulin, and glucagon. On d 5, calves were killed 2 h after feeding and samples of small intestinal mucosa were taken for histomorphometric measurements. The concentrations of IGF-I, adiponectin, and leptin in milk decreased during early lactation in all groups, and the concentrations of leptin in first colostrum was higher in EFA than in CTRL cows. Plasma glucose concentration before first colostrum intake was higher in EFA calves than in non-EFA calves and was lower in CLA calves than in non-CLA calves. Plasma IGF-I concentration was higher on d 1 before colostrum intake in EFA calves than in EFA+CLA calves and indicated an overall CLA effect, with lower plasma IGF-I in CLA than in non-CLA calves. Postprandial NEFA concentration was lowest in EFA and CLA calves. The postprandial rise in plasma insulin was higher in EFA than in non-EFA calves. Plasma adiponectin concentration increased from d 1 to d 2 in all groups and was higher on d 3 in CLA than in non-CLA calves. Plasma leptin concentration was higher on d 4 and 5 in EFA than in non-EFA calves. Maternal fatty acid treatment did not affect energy expenditure and first-pass glucose uptake, but glucose uptake on d 4 was faster in EFA than in non-EFA calves. Crypt depth was lower, and the ratio of villus height to crypt depth was higher in the ilea of CLA than non-CLA calves. Elevated plasma glucose and IGF-I in EFA calves immediately after birth may indicate an improved energetic status in calves when dams are supplemented with EFA. Maternal EFA and CLA supplementation influenced postprandial metabolic changes and affected factors related to the neonatal insulin response., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: The impact of various breast-cancer treatments on patients with a BRCA2 mutation has not been studied. We sought to estimate the impact of bilateral oophorectomy and other treatments on breast cancer-specific survival among patients with a germline BRCA2 mutation., Methods: We identified 664 women with stage I-III breast cancer and a BRCA2 mutation by combining five different datasets (retrospective and prospective). Subjects were followed for 7.2 years from diagnosis to death from breast cancer. Tumour characteristics and cancer treatments were patient-reported and derived from medical records. Predictors of survival were determined using Cox proportional hazard models, adjusted for other treatments and for prognostic features., Results: The 10-year breast-cancer survival for ER-positive patients was 78.9% and for ER-negative patients was 82.3% (adjusted HR = 1.23 (95% CI, 0.62-2.45, p = 0.55)). The 10-year breast-cancer survival for women who had a bilateral oophorectomy was 89.1% and for women who did not have an oophorectomy was 59.0% (adjusted HR = 0.45; 95% CI, 0.28-0.72, p = 0.001). The adjusted hazard ratio for chemotherapy was 0.83 (95% CI, 0.65-1.53: p = 0.56)., Conclusions: For women with breast cancer and a germline BRCA2 mutation, positive ER status does not predict superior survival. Oophorectomy is associated with a reduced risk of death from breast cancer and should be considered in the treatment plan.

Sufficient glucose availability is crucial for exploiting the genetic potential of milk production during early lactation, and endocrine changes are mainly related to repartitioning of nutrient supplies toward the mammary gland. Long-chain fatty acids, such as essential fatty acids (EFA) and conjugated linoleic acid (CLA), have the potential to improve negative energy balance and modify endocrine changes. In the present study, the hypothesis that combined CLA and EFA treatment supports glucose metabolism around the time of calving and stimulates insulin action and the somatotropic axis in cows in an additive manner was tested. Rumen-cannulated German Holstein cows (n = 40) were investigated from wk 9 antepartum (AP) until wk 9 postpartum (PP). The cows were abomasally supplemented with coconut oil (CTRL, 76 g/d); 78 g/d of linseed and 4 g/d of safflower oil (EFA); Lutalin (CLA, isomers cis-9,trans-11 and trans-10,cis-12 CLA, each 10 g/d); or the combination of EFA+CLA. Blood samples were collected several times AP and PP to determine the concentrations of plasma metabolites and hormones related to glucose metabolism and the somatotropic axis. Liver tissue samples were collected several days AP and PP to measure glycogen concentration and the mRNA abundance of genes related to gluconeogenesis and the somatotropic axis. On d 28 AP and 21 PP, endogenous glucose production (eGP) and glucose oxidation (GOx) were measured via tracer technique. The concentration of plasma glucose was higher in CLA than in non-CLA-treated cows, and the plasma β-hydroxybutyrate concentration was higher in EFA than in non-EFA cows on d 21 PP. The eGP increased from AP to PP with elevated eGP in EFA and decreased eGP in CLA-treated cows; GOx was lower in CLA than in CTRL on d 21 PP. The plasma insulin concentration decreased after calving in all groups and was higher in CLA than in non-CLA cows at several time points. Plasma glucagon and cortisol concentrations on d 21 PP were lower in CLA than non-CLA groups. The glucagon/insulin and glucose/insulin ratios were higher in CTRL than in CLA group during the transition period. Plasma IGF-I concentration was lower in EFA than non-EFA cows on d 42 AP and was higher during the dry period and early lactation in CLA than in non-CLA cows. The IGF binding protein (IGFBP)-3/-2 ratio in blood plasma was higher in CLA than in non-CLA cows. Hepatic glycogen concentration on d 28 PP was higher, but the mRNA abundance of PC and IGFBP2 was lower in CLA than non-CLA cows on d 1 PP. The EFA treatment decreased the mRNA abundance of IGFBP3 AP and PCK1, PCK2, G6PC, PCCA, HMGCS2, IGFBP2, and INSR at several time points PP. Results indicated elevated concentrations of plasma glucose and insulin along with the stimulation of the somatotropic axis in cows treated with CLA, whereas EFA treatment stimulated eGP but not mRNA abundance related to eGP PP. The systemic effects of the combined EFA+CLA treatment were very similar to those of CLA treatment, but the effects on hepatic gene expression partially corresponded to those of EFA treatment., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

The health of refugee women after settlement in a new country, can be adversely or positively affected by individual, interpersonal, community, and organizational factors. While much of the previous literature highlights these factors individually, there is a lack of comprehensive synthesis regarding how the factors interact to influence the health of refugee women. We conducted a thematic analysis in our literature review to elucidate how providers can work with refugee women to prevent adverse health outcomes and intervene at multiple levels to improve their health outcomes after resettlement. We reviewed peer-reviewed literature from 2009 to 2019 from Google Scholar, JSTOR, Global Health, PubMed, CINAHL, Sociological Abstracts, and Social Service Abstracts, and also used citation chaining, to identify relevant information pertaining to refugee women's health. The key terms used for our literature review were, health care, violence, social support, and mental health. In total, we included 52 articles, 3 books, and 8 other sources. We found that refugee women are vulnerable to violence during migration and typically have high rates of post-traumatic stress disorder. There were also concerns of secondary victimization by providers after resettlement. We also found that social support is an important factor for reducing isolation, and improving access to health care, as well as improving mental health outcomes. However, social support was often difficult to maintain, and was moderated by factors such as English language fluency. Health care was influenced by health literacy, cultural difference, communication concerns, and access issues. The findings suggest that at the individual and interpersonal levels there is a need to address language barriers, improve provider-patient communication, and provide appropriate medical and mental health screenings. At the organizational level, inter-organizational communication and awareness are vital. At the community level, providers can work with community leaders, to educate, create dialogue and collaboration, to help facilitate understanding and bolster community social support. Improved communication and knowledge about the unique needs and concerns of refugee women through an integrated, multi-system approach is necessary to improve their health outcomes.

There are well-established disparities in cancer incidence and outcomes by race/ethnicity that result from the interplay between structural, socioeconomic, socio-environmental, behavioural and biological factors. However, large research studies designed to investigate factors contributing to cancer aetiology and progression have mainly focused on populations of European origin. The limitations in clinicopathological and genetic data, as well as the reduced availability of biospecimens from diverse populations, contribute to the knowledge gap and have the potential to widen cancer health disparities. In this review, we summarise reported disparities and associated factors in the United States of America (USA) for the most common cancers (breast, prostate, lung and colon), and for a subset of other cancers that highlight the complexity of disparities (gastric, liver, pancreas and leukaemia). We focus on populations commonly identified and referred to as racial/ethnic minorities in the USA-African Americans/Blacks, American Indians and Alaska Natives, Asians, Native Hawaiians/other Pacific Islanders and Hispanics/Latinos. We conclude that even though substantial progress has been made in understanding the factors underlying cancer health disparities, marked inequities persist. Additional efforts are needed to include participants from diverse populations in the research of cancer aetiology, biology and treatment. Furthermore, to eliminate cancer health disparities, it will be necessary to facilitate access to, and utilisation of, health services to all individuals, and to address structural inequities, including racism, that disproportionally affect racial/ethnic minorities in the USA.

The objective of this study was to test the effects of essential fatty acids (EFA), particularly α-linolenic acid (ALA), and conjugated linoleic acid (CLA) supplementation on metabolic and endocrine traits related to energy metabolism, including the somatotropic axis, in mid-lactation dairy cows. Four cows (126 ± 4 d in milk) were used in a dose-escalation study design and were abomasally infused with coconut oil (CTRL; 38.3 g/d; providing saturated fatty acids), linseed and safflower oils (EFA; 39.1 and 1.6 g/d; n-6:n-3 FA ratio = 1:3), Lutalin (CLA; cis-9,trans-11 and trans-10,cis-12 CLA, 4.6 g/d of each), or EFA and CLA (EFA+CLA) for 6 wk. The initial dosage was doubled twice after 2 wk, resulting in 3 dosages (dosages 1, 2, and 3). Each cow received each fat treatment at different times. Cows were fed with a corn silage-based total mixed ration providing a low-fat content and a high n-6:n-3 fatty acid ratio. Plasma concentrations of metabolites and hormones (insulin-like growth factor-binding proteins only on wk 0 and 6) were analyzed at wk 0, 2, 4, and 6 of each treatment period. Liver biopsies were taken before starting the trial and at wk 6 of each treatment period to measure hepatic mRNA abundance of genes linked to glucose, cholesterol and lipid metabolism, and the somatotropic axis. The changes in the milk and blood fatty acid patterns and lactation performance of these cows have already been published in a companion paper. The plasma concentration of total cholesterol increased with dosage in all groups, except CLA, reaching the highest levels in EFA+CLA and CTRL compared with CLA. The high-density lipoprotein cholesterol plasma concentration increased in CTRL and was higher than that in EFA and CLA, whereas the concentration of low-density lipoprotein cholesterol increased in a dose-dependent manner in EFA and EFA+CLA, and was higher than that in CLA. Hepatic mRNA expression of 3-hydroxy-3-methyl-glutaryl-CoA synthase 1 was upregulated in all groups but was highest in EFA+CLA. Expression of sterol regulatory element-binding factor 1 tended to be lowest due to EFA treatment, whereas expression of long chain acyl-CoA-synthetase was lower in EFA than in CTRL. Hepatic mRNA expression of GHR1A tended to be higher in EFA+CLA than in CTRL. The plasma concentration of insulin-like growth factor I increased in CLA, and the plasma IGFBP-2 concentration was lower in EFA+CLA than in CTRL at wk 6. The plasma concentration of adiponectin decreased in EFA+CLA up to dosage 2. Plasma concentrations of albumin and urea were lower in CLA than in CTRL throughout the experimental period. Supplementation with EFA and CLA affected cholesterol and lipid metabolism and their regulation differently, indicating distinct stimulation after the combined EFA and CLA treatment. The decreased IGFBP-2 plasma concentration and upregulated hepatic mRNA abundance of GHR1A in EFA+CLA-supplemented cows indicated the beneficial effect of the combined EFA and CLA treatment on the somatotropic axis in mid-lactation dairy cows. Moreover, supplementation with CLA might affect protein metabolism in dairy cows., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Purpose: Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising demand for genetic services., Methods: A multidisciplinary consensus conference that included experts, stakeholders, and national organization leaders was convened in response to current practice challenges and to develop a genetic implementation framework. Evidence review informed questions using the modified Delphi model. The final framework included criteria with strong (> 75%) agreement (Recommend) or moderate (50% to 74%) agreement (Consider)., Results: Large germline panels and somatic testing were recommended for metastatic PCA. Reflex testing-initial testing of priority genes followed by expanded testing-was suggested for multiple scenarios. Metastatic disease or family history suggestive of hereditary PCA was recommended for GT. Additional family history and pathologic criteria garnered moderate consensus. Priority genes to test for metastatic disease treatment included BRCA2, BRCA1, and mismatch repair genes, with broader testing, such as ATM , for clinical trial eligibility. BRCA2 was recommended for active surveillance discussions. Screening starting at age 40 years or 10 years before the youngest PCA diagnosis in a family was recommended for BRCA2 carriers, with consideration in HOXB13, BRCA1, ATM , and mismatch repair carriers. Collaborative (point-of-care) evaluation models between health care and genetic providers was endorsed to address the genetic counseling shortage. The genetic evaluation framework included optimal pretest informed consent, post-test discussion, cascade testing, and technology-based approaches., Conclusion: This multidisciplinary, consensus-driven PCA genetic implementation framework provides novel guidance to clinicians and patients tailored to the precision era. Multiple research, education, and policy needs remain of importance.

Purpose: Women with a family history of breast cancer are frequently referred for hereditary cancer genetic testing, yet < 10% are found to have pathogenic variants in known breast cancer susceptibility genes. Large-scale genotyping studies have identified common variants (primarily single-nucleotide polymorphisms [SNPs]) with individually modest breast cancer risk that, in aggregate, account for considerable breast cancer susceptibility. Here, we describe the development and empirical validation of an SNP-based polygenic breast cancer risk score., Methods: A panel of 94 SNPs was examined for association with breast cancer in women of European ancestry undergoing hereditary cancer genetic testing and negative for pathogenic variants in breast cancer susceptibility genes. Candidate polygenic risk scores (PRSs) as predictors of personal breast cancer history were developed through multivariable logistic regression models adjusted for age, cancer history, and ancestry. An optimized PRS was validated in 2 independent cohorts (n = 13,174; n = 141,160)., Results: Within the training cohort (n = 24,259), 4,291 women (18%) had a personal history of breast cancer and 8,725 women (36%) reported breast cancer in a first-degree relative. The optimized PRS included 86 variants and was highly predictive of breast cancer status in both validation cohorts ( P = 6.4 × 10 -66 ; P < 10 -325 ). The odds ratio (OR) per unit standard deviation was consistent between validations (OR, 1.45 [95% CI, 1.39 to 1.52]; OR 1.47 [95% CI, 1.45 to 1.49]). In a direct comparison, the 86-SNP PRS outperformed a previously described PRS of 77 SNPs., Conclusion: The validation and implementation of a PRS for women without pathogenic variants in known breast cancer susceptibility genes offers potential for risk stratification to guide surveillance recommendations., Competing Interests: The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated unless otherwise noted. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/po/author-center. Open Payments is a public database containing information reported by companies about payments made to US-licensed physicians (Open Payments. Elisha HughesEmployment: Myriad Genetics Stock and Other Ownership Interests: Myriad GeneticsPlacede TshiabaEmployment: Myriad Genetics Stock and Other Ownership Interests: Myriad GeneticsShannon GallagherEmployment: Myriad Genetics Stock and Other Ownership Interests: Myriad GeneticsSusanne WagnerEmployment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Patents, Royalties, Other Intellectual Property: Co-author of patents held by Myriad Genetics, no royaltiesThaddeus JudkinsEmployment: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Travel, Accommodations, Expenses: Myriad GeneticsBenjamin RoaEmployment: Myriad Genetics Leadership: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Research Funding: Myriad Genetics Patents, Royalties, Other Intellectual Property: Intellectual property held by employer Myriad Genetics (Inst) Travel, Accommodations, Expenses: Myriad GeneticsEric RosenthalEmployment: Myriad Genetic Laboratories Stock and Other Ownership Interests: Myriad Genetic LaboratoriesSusan DomchekHonoraria: AstraZeneca, Clovis Oncology, Bristol Myers Squibb Research Funding: AstraZeneca (Inst), Clovis Oncology (Inst) Open Payments Link: https://openpaymentsdata.cms.gov/physician/917904Judy GarberConsulting or Advisory Role: Novartis (I), GTx (I), Helix BioPharma, Konica Minolta, Aleta BioTherapeutics (I), H3 Biomedicine (I), Kronos Bio (I) Research Funding: Novartis (I), Ambry Genetics, Invitae Genetics, Myriad Genetics Other Relationship: Susan G. Komen for the Cure (I), American Association for Cancer Research, Diane Helis Henry Medical Foundation, James P. Wilmot Foundation (I), Adrienne Helis Malvin Medical Research Foundation (I), Breast Cancer Research Foundation, Facing our Risk of Cancer EmpoweredJohnathan LancasterEmployment: Myriad Genetics, Regeneron Stock and Other Ownership Interests: Myriad Genetics, RegeneronJeffrey WeitzelSpeakers' Bureau: AstraZenecaAllison W. KurianResearch Funding: Myriad Genetics (Inst) Other Relationship: Ambry Genetics, Color Genomics, GeneDx/BioReference, InVitae, GenentechJerry S. LanchburyEmployment: Myriad Genetics Leadership: Myriad Genetics Stock and Other Ownership Interests: Myriad Genetics Patents, Royalties, Other Intellectual Property: I am an inventor on multiple patents filed by Myriad Genetics Travel, Accommodations, Expenses: Myriad GeneticsAlexander GutinEmployment: Myriad Genetics, Myriad Genetics (I) Stock and Other Ownership Interests: Myriad Genetics, Myriad Genetics (I), Gilead SciencesMark RobsonHonoraria: AstraZeneca Consulting or Advisory Role: Change Health Care Research Funding: AstraZeneca (Inst), Myriad Genetics (Inst), InVitae (Inst), AbbVie (Inst), Tesaro (Inst), Medivation (Inst), Pfizer (Inst) Travel, Accommodations, Expenses: AstraZeneca, Pfizer Other Relationship: Research to Practice, Clinical Care Options, Physician Education Resource Uncompensated Relationships: Merck, Pfizer, Daiichi Sankyo Open Payments Link: https://openpaymentsdata.cms.gov/physician/612669/summary No other potential conflicts of interest were reported., (© 2020 by American Society of Clinical Oncology.)

The remnants of colonialism manifesting as structural violence, racism, and oppression continue to plague our society as evidenced by the persistence of health inequities, particularly for minority populations in the United States. As a profession bound by moral and ethical mandates, nursing must resist and deconstruct oppression in all its forms. Nurses, informed by critical race theory, intersectionality, and historical trauma, can become formidable allies with marginalized populations in the fight for social justice and health equity.

Colostrum provides high amounts of nutritive and non-nutritive substrates, which are essential for calf nutrition and passive immunization. Colostral growth factors and hormones have beneficial effects on postnatal maturation and may affect substrate utilization and energy expenditure in neonatal calves. We tested the hypothesis that energy metabolism and its endocrine regulation differ during the first 10 d of life in calves fed either colostrum or a milk-based formula with a similar nutrient composition to colostrum, but largely depleted of bioactive substances, for the first 2 d postnatum. Male Holstein calves (n = 18) were fed either pooled colostrum (COL; n = 9) or a milk-based formula (FOR; n = 9) for the first 2 d of life. From d 3 on, all calves received same milk replacer. On d 2 and 7 of life, calves were placed in a respiration chamber for indirect calorimetric measurements to calculate heat production, fat (FOX) and carbohydrate oxidation (COX), as well as respiratory quotient. Blood was sampled on d 1 before first colostrum intake and on d 2, 3, 7, 8, 9, and 10 before morning feeding, to measure plasma concentrations of immunoglobulins, metabolites, and hormones. Additional postprandial blood samples were taken on d 1 and 9 at 30, 60, 120, 240, and 420 min after milk feeding. Liver samples were collected on d 10 of life to determine gene expression related to energy metabolism. Formula-fed calves showed lower plasma concentrations of total protein, immunoglobulins, haptoglobin, leptin, adiponectin, and insulin-like growth factor (IGF) binding protein (IGFBP)-4 during the whole study but temporarily higher plasma concentrations of urea, insulin, glucagon, triglyceride, and cholesterol on the first day after feeding, compared with concentrations in COL. The temporary increase in glucagon, triglyceride, and cholesterol on d 1 reversed on d 2 or 3, showing higher concentrations in COL than in FOR calves. In FOR, IGF-I, IGFBP-2, and IGFBP-3 were lower on d 3 than in COL. Interestingly, FOR calves had higher heat production during respiratory measurements on d 2 and higher body temperature on d 2, 3, and 5 than those of COL. The hepatic mRNA abundance of cytosolic phosphoenolpyruvate carboxykinase was higher in FOR than in COL. Our results indicate that first milk feeding after birth influenced whole-body energy expenditure but not FOX and COX in neonatal calves, and the absorption of colostral leptin and adiponectin might affect insulin sensitivity on d 1 of life., (Copyright © 2020 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Background Generic drug exchange is common practice in most healthcare systems. While generics certainly contribute to economic savings, the altered drug formulation might be associated with potential therapeutic problems. Given the narrow therapeutic windows in neurologic indications, any detrimental effect on the therapy can lead to significant consequences. Aim of the review This review aims to investigate potential problems related to a switch from brand-name to generic or from generic to generic drug products in patients with neurologic diseases. Method The review was conducted following the PICO framework and the PRISMA guidelines. MEDLINE and Scopus databases were searched for articles published in English and German language between January 1, 1995 and October 17, 2018. Studies included in this review were randomized controlled studies, reviews, systematic reviews, overviews, cohort studies and case-control studies. Studies excluded were letters, comments, authors view, congress or seminar papers and studies with a focus on economic impact or costs. Results were synthesized qualitatively. The primary outcomes were pharmacokinetic parameters such as the area under the curve (AUC), the peak serum concentration (c max ) or the time at which c max is observed (t max ). Results The search identified 67 studies with a great variety of endpoints and study designs. The leading indication was epilepsy. Two small RCTs were found on lamotrigine switch. Analysis of the other studies found no significant differences in pharmacokinetic parameters when switching to generic drugs. A more heterogeneous picture was revealed regarding hospitalizations, breakthrough seizures, failure of therapy, adherence and patient concerns. Conclusion While most reports were of poor quality, lamotrigine was the drug with the best available data. Summarizing the results of the available studies, pharmacokinetic parameters of antiepileptic drugs show low deviation. In contrast, data on clinical parameters are less consistent. Some studies found increased seizure frequencies and adverse-drug events, while others showed no complications. Adherence and patient satisfaction seemed to be impaired. In daily practice, generic exchange in epilepsy should be a carefully balanced decision, conducted with great caution. Further research is needed, especially regarding neurologic indications other than epilepsy.

Objective(s): Prenatal home visiting programs are a strategy to promote positive birth outcomes. Ongoing evaluations of these programs are important to promote fidelity and quality. The goal of this program evaluation was to gain clients' perspectives of their experiences in one Wisconsin Health Department's Prenatal Care Coordination program including: (a) why clients entered the program, (b) whether client expectations were met, and (c) how expectations impacted client retention., Design: A Health Department in Wisconsin undertook a three-part program evaluation of their Prenatal Care Coordination program in 2014-2015. Highlighted here is the final phase of this evaluation. The evaluation was guided by the CDC's (1999) Framework for Program Evaluation in Public Health., Sample: Clients meeting eligibility criteria were divided into representative clusters using k-means clustering model. Twenty semi-structured interviews with former clients of the Wisconsin Health Department's Prenatal Care Coordination program were conducted., Results: Most clients had no expectations coming into the program and were satisfied with the services they received. Participants named the nurse-client relationship and support from this relationship as a key benefit of the program, while a secondary benefit was the information and resources received. The Health Department used these findings for program improvement and strategic planning., (© 2019 Wiley Periodicals, Inc.)

Next-generation sequencing (NGS) hereditary pan-cancer panel testing can identify somatic variants, which exhibit lower allele frequencies than do germline variants and may confound hereditary cancer predisposition testing. This analysis examined the prevalence and characteristics of likely-somatic variants among 348,543 individuals tested using a clinical NGS hereditary pan-cancer panel. Variants showing allele frequencies between 10% and 30% were interpreted as likely somatic and identified in 753 (0.22%) individuals. They were most frequent in TP53, CHEK2 and ATM, commonly as C-to-T transitions. Among individuals who carried a likely-somatic variant and reported no personal cancer history, 54.2% (78/144) carried a variant in TP53, CHEK2 or ATM. With a reported cancer history, this percentage increased to 81.1% (494/609), predominantly in CHEK2 and TP53. Their presence was associated with age (OR=3.1, 95% CI 2.5, 3.7; p<0.001) and personal history of cancer (OR=3.3, 95% CI 2.7, 4.0; p<0.001), particularly ovarian cancer. Germline ATM pathogenic variant carriers showed significant enrichment of likely-somatic variants (OR=2.8, 95% CI 1.6, 4.9; p = 0.005), regardless of cancer status. The appearance of likely-somatic variants is consistent with clonal hematopoiesis, possibly influenced by cancer treatment. These findings highlight the precision required of diagnostic laboratories to deliver accurate germline testing results., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Breast cancer is a partially heritable trait and genome-wide association studies (GWAS) have identified over 180 common genetic variants associated with breast cancer. We have previously performed breast cancer GWAS in Latinas and identified a strongly protective single nucleotide polymorphism (SNP) at 6q25, with the protective minor allele originating from indigenous American ancestry. Here we report on fine mapping of the 6q25 locus in an expanded sample of Latinas., Methods: We performed GWAS in 2385 cases and 6416 controls who were either US Latinas or Mexican women. We replicated the top SNPs in 2412 cases and 1620 controls of US Latina, Mexican, and Colombian women. In addition, we validated the top novel variants in studies of African, Asian and European ancestry. In each dataset we used logistic regression models to test the association between SNPs and breast cancer risk and corrected for genetic ancestry using either principal components or genetic ancestry inferred from ancestry informative markers using a model-based approach., Results: We identified a novel set of SNPs at the 6q25 locus associated with genome-wide levels of significance (p = 3.3 × 10 - 8 - 6.0 × 10 - 9 ) not in linkage disequilibrium (LD) with variants previously reported at this locus. These SNPs were in high LD (r 2  > 0.9) with each other, with the top SNP, rs3778609, associated with breast cancer with an odds ratio (OR) and 95% confidence interval (95% CI) of 0.76 (0.70-0.84). In a replication in women of Latin American origin, we also observed a consistent effect (OR 0.88; 95% CI 0.78-0.99; p = 0.037). We also performed a meta-analysis of these SNPs in East Asians, African ancestry and European ancestry populations and also observed a consistent effect (rs3778609, OR 0.95; 95% CI 0.91-0.97; p = 0.0017)., Conclusion: Our study adds to evidence about the importance of the 6q25 locus for breast cancer susceptibility. Our finding also highlights the utility of performing additional searches for genetic variants for breast cancer in non-European populations.

The purpose of the study was to develop an understanding of how nursing students gained perspective on nursing care of diverse populations through watching documentaries in a cultural diversity course. The basis of this paper is our analyses of students' written responses and reactions to documentaries viewed in class. The guiding theoretical frameworks for the course content and the study included postcolonial feminism, Foucauldian thought, and cultural safety. Krathwohl's Taxonomy of the Affective Domain was used to identify themes and determine how undergraduate nursing students were progressing in achieving learning outcomes. Our findings suggest that while the use of documentaries serves as a tool for deepening students' understanding of the realities of various populations, this activity, in the absence of critical reflection, may inadvertently promote stereotypes and further marginalize different people groups. Even though nursing students reflected on the importance of cultural safety in nursing, our findings indicate that their actions may not reflect this, especially since these students are in the early stages of the nursing program. Students need to be provided with a space where they can explore implicit biases evoked by exposure to new information about different people groups as a way of enhancing culturally safe care., (© 2018 John Wiley & Sons Ltd.)

Nurses teach, work, and conduct research in an increasingly hostile sociopolitical climate where health inequities persist among marginalized communities. Current approaches to cultural competency do not adequately equip nurses to address these complex factors and risk perpetuating stereotypes and discrimination. A theory-driven emancipatory approach to cultural competency will instead lead to lasting change and uphold the core nursing value of commitment to social justice. This article explicates key tenets of critical race, postcolonial feminist, and intersectionality theories and then applies them, using an emancipatory approach to cultural competency that can reshape nursing education, research, and practice.

This descriptive, qualitative study was conducted to gain insight into how pre-clinical nursing students' worldviews about people different from themselves are formed, changed, and expanded. 90 mid-term and 87 end- of-term reflection papers in a cultural diversity course were analyzed. Krathwohl's taxonomy of learning guided the evaluation of students' development. Our findings showed that the course content supported most students' in their affective development. It was also evident that students' perspectives, which were influenced by past experiences, changed as the course progressed. However, while a positive change in perspective towards providing culturally safe care was evident, this was not the case for all students. Our findings have implications for informing the development of undergraduate nursing courses that prepare future nurses for their professional role in providing culturally safe care., (Copyright © 2017 Elsevier Inc. All rights reserved.)

[This corrects the article DOI: 10.1371/journal.pone.0187630.].