Impact of recurrence on employment, finances, and productivity for early-stage cancer patients and caregivers: US survey.

Background: Following an early-stage cancer diagnosis, recurrences can occur. To quantify financial impacts of a first recurrence, we surveyed patients and caregivers.

Methods: The survey was self-administered online to patients ( = 202) with early-stage bladder, gastric, head and neck, melanoma, non-small cell lung, renal cell, and triple-negative breast cancers that recurred and caregivers ( = 100) of such patients.

Upregulated pexophagy limits the capacity of selective autophagy.

Selective autophagy is an essential process to maintain cellular homeostasis through the constant recycling of damaged or superfluous components. Over a dozen selective autophagy pathways mediate the degradation of diverse cellular substrates, but whether these pathways can influence one another remains unknown. We address this question using pexophagy, the autophagic degradation of peroxisomes, as a model.

Arf1-PI4KIIIβ positive vesicles regulate PI(3)P signaling to facilitate lysosomal tubule fission.

Formation and fission of tubules from autolysosomes, endolysosomes, or phagolysosomes are required for lysosome reformation. However, the mechanisms governing these processes in these different lysosomal organelles are poorly understood. Thus, the role of phosphatidylinositol-4-phosphate (PI(4)P) is unclear as it was shown to promote the formation of tubules from phagolysosomes but was proposed to inhibit tubule formation on autolysosomes because the loss of PI4KIIIβ causes extensive lysosomal tubulation.

Fyn and TOM1L1 are recruited to clathrin-coated pits and regulate Akt signaling.

The epidermal growth factor (EGF) receptor (EGFR) controls many aspects of cell physiology. EGF binding to EGFR elicits the membrane recruitment and activation of phosphatidylinositol-3-kinase, leading to Akt phosphorylation and activation. Concomitantly, EGFR is recruited to clathrin-coated pits (CCPs), eventually leading to receptor endocytosis.

Glycogen synthase downregulation rescues the amylopectinosis of murine RBCK1 deficiency.

Longer glucan chains tend to precipitate. Glycogen, by far the largest mammalian glucan and the largest molecule in the cytosol with up to 55 000 glucoses, does not, due to a highly regularly branched spherical structure that allows it to be perfused with cytosol. Aberrant construction of glycogen leads it to precipitate, accumulate into polyglucosan bodies that resemble plant starch amylopectin and cause disease.

Determinant of Prenatal Diagnostic Testing among Women with Increased Risk of Fetal Aneuploidy and Genetic Disorders.

Objective: This study aimed to assess factors that influence patients' decisions in accepting prenatal diagnostic testing following genetic counseling for increased risk of fetal aneuploidy.

Methods: This is a retrospective cohort study of women at increased risk of fetal aneuploidy and genetic disorders who had genetic counseling from January 2012 to December 2016 at a single academic center. Demographics, indications for genetic counseling, and rates of diagnostic testing were collected and compared between those who accepted diagnostic testing and those who chose cell free DNA.

Pharmacokinetics of 17 alpha hydroxyprogesterone caproate in singleton pregnancy and its influence of maternal body size measures.

Background: Reducing spontaneous preterm deliveries is a worldwide public health priority. Although many interventions have been studied, 1 of the most effective treatments to decrease recurrent preterm birth is the use of weekly 17 alpha hydroxy progesterone caproate. Previous studies on the influence of excessive adipose tissue and obesity on the use of 17 alpha hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm deliveries have shown conflicting findings.

Maintaining social contacts: The physiological relevance of organelle interactions.

Membrane-bound organelles in eukaryotic cells form an interactive network to coordinate and facilitate cellular functions. The formation of close contacts, termed "membrane contact sites" (MCSs), represents an intriguing strategy for organelle interaction and coordinated interplay. Emerging research is rapidly revealing new details of MCSs.

Longitudinal outcomes with cancer multigene panel testing in previously tested BRCA1/2 negative patients.

Although multigene panel testing (MGPT) is increasingly utilized in clinical practice, there remain limited data on patient-reported outcomes. BRCA 1/2 negative patients were contacted and offered MGPT. Patients completed pre- and posttest counseling, and surveys assessing cognitive, affective and behavioral outcomes at baseline, postdisclosure and 6 and 12 months.

Research participants' experiences with return of genetic research results and preferences for web-based alternatives.

Background: While there is increasing interest in sharing genetic research results with participants, how best to communicate the risks, benefits and limitations of research results remains unclear.

Methods: Participants who received genetic research results answered open and closed-ended questions about their experiences receiving results and interest in and advantages and disadvantages of a web-based alternative to genetic counseling.

Results: 107 BRCA1/2 negative women with a personal or family history of breast cancer consented to receive genetic research results and 82% completed survey items about their experience.

A Case of Massive Hepatic Infarction in a Patient with HELLP Syndrome.

 Hepatic infarction is an exceedingly rare complication of hemolysis, elevated liver enzymes, and low platelets syndrome. Few cases have been described in the medical literature and the true incidence remains unknown. It can lead to fulminant liver failure, liver transplant, or death if not promptly addressed.

Pearls in clinical obstetrics: challenges in anticoagulation in pregnancy.

Women are at increased risk for venous thromboembolism (VTE) during both pregnancy and in the post-partum period. We have conducted a comprehensive literature review of the use of anticoagulation in pregnancy for pregnant women at increased risk for VTE. Multiple factors, including physiologic and pharmacokinetic changes make the treatment and prevention of VTE complicated in pregnancy.

Risk factors for sexual dysfunction in BRCA mutation carriers after risk-reducing salpingo-oophorectomy.

Objective: The aim of the study was to identify risk factors for sexual dysfunction in BRCA mutation carriers who have undergone risk-reducing salpingo-oophorectomy (RRSO).

Methods: A cross-sectional study was performed. BRCA1/2 mutation carriers with and without RRSO were surveyed to determine sexual function (Female Sex Function Index [FSFI]), demographics, medical history, sleep quality, depression, and anxiety scores.

Cervical cerclage for singleton pregnant patients on vaginal progesterone with progressive cervical shortening.

Background: Premature cervical ripening plays a significant role in spontaneous preterm birth. Vaginal progesterone is the recommended treatment in singleton pregnancy with incidental short cervix. There is lack of evidence on whether it is beneficial to reinforce the cervix with cerclage when the cervical length becomes progressively shortened <10 mm while on vaginal progesterone.

Returning Individual Genetic Research Results to Research Participants: Uptake and Outcomes Among Patients With Breast Cancer.

Purpose: Understanding the outcomes of returning individual genetic research results to participants is critical because some genetic variants are found to be associated with health outcomes and have become available for clinical testing.

Materials And Methods: -negative women with early-onset breast cancer, multiple primary cancers, or a family history of breast cancer who participated in a gene discovery cancer registry were offered the opportunity to learn their individual genetic research results of 24 breast cancer susceptibility genes with a genetic counselor after predisclosure genetic counseling. Outcomes included uptake of research results, knowledge, informed choice, psychosocial adjustment, uncertainty, satisfaction, and uptake of clinical confirmation testing.

Reproductive Decision-Making in Women with BRCA1/2 Mutations.

Expanded genetic testing of BRCA mutations has led to identification of more reproductive-aged women who test positive for the mutation which might impact attitudes and decisions about relationships, childbearing and the use of preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND). A cross-sectional survey was administered to 1081 self-reported BRCA carriers to investigate how knowledge of BRCA status influences these issues. The mean age at BRCA test disclosure was 44 years and 36 % reported a personal history of cancer.

Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.

Purpose Massively parallel sequencing allows simultaneous testing of multiple genes associated with cancer susceptibility. Guidelines are available for variant classification; however, interpretation of these guidelines by laboratories and providers may differ and lead to conflicting reporting and, potentially, to inappropriate medical management. We describe conflicting variant interpretations between Clinical Laboratory Improvement Amendments-approved commercial clinical laboratories, as reported to the Prospective Registry of Multiplex Testing (PROMPT), an online genetic registry.

Huntingtin N17 domain is a reactive oxygen species sensor regulating huntingtin phosphorylation and localization.

The N17 domain of the huntingtin protein is post-translationally modified and is the master regulator of huntingtin intracellular localization. In Huntington's disease (HD), mutant huntingtin is hypo-phosphorylated at serines 13 and 16 within N17, and increasing N17 phosphorylation has been shown to be protective in HD mouse models. Thus, N17 phosphorylation is defined as a sub-target of huntingtin for potential therapeutic intervention.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

Background: Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer.

Dose-response effects of aerobic exercise on estrogen among women at high risk for breast cancer: a randomized controlled trial.

Unlabelled: Medical and surgical interventions for elevated breast cancer risk (e.g., BRCA1/2 mutation, family history) focus on reducing estrogen exposure.

Patient feedback and early outcome data with a novel tiered-binned model for multiplex breast cancer susceptibility testing.

Purpose: The risks, benefits, and utilities of multiplex panels for breast cancer susceptibility are unknown, and new counseling and informed consent models are needed. We sought to obtain patient feedback and early outcome data with a novel tiered-binned model for multiplex testing.

Methods: BRCA1/2-negative and untested patients completed pre- and posttest counseling and surveys evaluating testing experiences and cognitive and affective responses to multiplex testing.

A hybrid effectiveness-implementation trial of an evidence-based exercise intervention for breast cancer survivors.

Background: The primary aims of this hybrid Type 1 effectiveness-implementation trial were to quantitatively assess whether an evidence-based exercise intervention for breast cancer survivors, Strength After Breast Cancer, was safe and effective in a new setting and to qualitatively assess barriers to implementation.

Methods: A cohort of 84 survivors completed measurements related to limb volume, muscle strength, and body image at baseline, 67 survivors completed measurements 12 months later. Qualitative methods were used to understand barriers to implementation experienced by referring oncology clinicians and physical therapists who delivered the program.

Women In Steady Exercise Research (WISER) Sister: study design and methods.

Purpose: Women at elevated risk for breast cancer are motivated to reduce their risk. Current approaches rely primarily on hormonal intervention. A preventive exercise intervention might address the same hormonal issues, yet have fewer serious side effects and less negative impact on quality of life as compared to prophylactic mastectomy.

Evaluation of ethics education in obstetrics and gynecology residency programs.

Objective: The objective of the study was to assess the current status of ethics education in obstetrics-gynecology residency programs.

Study Design: A cross-sectional, web-based survey was designed in conjunction with a professional survey laboratory at the University of Chicago. The survey was piloted with a convenience sample of clinical medical ethics fellows to assess question content and clarity.