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Biomedical subjects

Susan L Woods

Publications and source records attributed to Susan L Woods.

9 recordsLinked to original sources
PubMed2026

Selective Macrocyclic WEE1 Kinase Inhibitors with Strong Efficacy against Patient-Derived Colorectal Cancer Organoids.

Macrocyclization can enhance the selectivity of acyclic compounds toward structurally similar biological targets such as kinases. WEE1 regulates cellular homeostasis and is a promising target in oncology. The clinical candidate AZD1775 (1) failed to progress past Phase II trials because of patient tolerability issues, likely due to off-target inhibition of polo-like kinase 1 (PLK1). Herein, a computer-aided drug design approach was conducted to develop a macrocycle based on the 1-WEE1 X-ray cocrystal structure. Significantly enhanced WEE1 inhibitory selectivity over PLK1 was determined for leading macrocycle 2, which also demonstrated broader kinome-wide selectivity. Patient-derived organoids from colorectal cancer (CRC) peritoneal and liver metastases, treated with 2, demonstrated comparably strong or enhanced anticancer efficacy compared to that of 1. Against patient-matched normal colon vs primary CRC organoids, 2 potently and selectively treated CRC, as well as enhanced DNA damage compared to 1. Finally, the X-ray cocrystal structure of 2 bound to WEE1 validated its computationally predicted bioactive binding mode.

Humans↗
PubMed2006

Cerebrovascular dynamics with head-of-bed elevation in patients with mild or moderate vasospasm after aneurysmal subarachnoid hemorrhage.

BACKGROUND: In patients with aneurysmal subarachnoid hemorrhage, elevation of the head of the bed during vasospasm has been limited in an attempt to minimize vasospasm or its sequelae or both. Consequently, some patients have remained on bed rest for weeks. OBJECTIVES: To determine how elevations of the head of the bed of 20 degrees and 45 degrees affect cerebrovascular dynamics in adult patients with mild or moderate vasospasm after aneurysmal subarachnoid hemorrhage and to describe the response of mild or moderate vasospasm to head-of-bed elevations of 20 degrees and 45 degrees with respect to variables such as grade of subarachnoid hemorrhage and degree of vasospasm. METHODS: A within-patient repeated-measures design was used. The head of the bed was positioned in the sequence of 0 degrees -20 degrees -45 degrees -0 degrees in 20 patients with mild or moderate vasospasm between days 3 and 14 after aneurysmal subarachnoid hemorrhage. Continuous transcranial Doppler recordings were obtained for 2 to 5 minutes after allowing approximately 2 minutes for stabilization in each position. RESULTS: No patterns or trends indicated that having the head of the bed elevated increases vasospasm. As a group, there were no significant differences within patients at the different positions of the head of the bed. Utilizing repeated-measures analysis of variance, P values ranged from .34 to .97, well beyond .05. No neurological deterioration occurred. CONCLUSIONS: In general, elevation of the head of the bed did not cause harmful changes in cerebral blood flow related to vasospasm.

Adolescent↗
PubMed2005

Depression and heart failure in patients with a new myocardial infarction.

BACKGROUND: Heart failure (HF) is a disabling chronic illness that is increasing in prevalence. Despite advances in its medical treatment, little is known about its psychosocial correlates. This investigation compared the prevalence of depression in patients with and without HF who were hospitalized with myocardial infarction (MI) and also at high psychosocial risk. METHODS: Baseline data from the 2444 participants in the ENRICHD clinical trial were used. Within 28 days of the MI, all patients were assessed for depression using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria, for HF based upon left ventricular dysfunction or history of HF and for demographic and medical confounders. RESULTS: Eight hundred forty-seven patients (34.7%) met the criteria for HF. Major depression was observed in 43% in the HF group compared with 36% in the non-HF group (P < .001). Multivariate modeling showed a 38% increase in odds of HF for patients with major depression, after adjustment for sociodemographic factors and medical comorbidities (adjusted OR 1.38, 95% CI 1.09-1.76). CONCLUSIONS: These findings suggest that in patients with new MI who are at psychosocial risk, major depression is more prevalent in those who also have HF. Because major depression undermines adherence and lowers quality of life, special efforts to diagnose and treat it in post-MI patients with HF appear warranted.

Aged↗
PubMed2005

Gender differences in symptom experiences of patients with acute coronary syndromes.

To compare the symptom experiences between men and women with acute coronary syndromes (ACS), we surveyed a convenience sample of 112 subjects with a final diagnosis of ACS in four hospitals. Our study found that after adjusting for cardiac diagnosis, diabetes, and age, women were more likely than men to experience chest discomfort rather than chest pain; pain/discomfort only in areas of the body other than the chest; pain/discomfort that started first either in the arm(s) or in areas of the body other than the chest; and unexplained anxiety. Women were less likely than men to experience chest pain/discomfort, pain/discomfort in the left side of the chest, and chest pain/discomfort as the most worrisome symptom. Significant gender differences were observed in the reports of several symptoms associated with ACS. This study is the first to identify different pain/discomfort referral patterns between men and women that require further validation.

Adult↗
PubMed2005

Infants who have undergone cardiac surgery: what can we learn about lengths of stay in the hospital and presence of complications?

The purpose of this study was to describe a population of infants undergoing cardiac surgery at a regional tertiary medical center and the relationship between age, weight, number of other diagnoses, and length of stay in the hospital and presence of complications. Nearly two thirds of the infants in the sample (n = 551; age, birth to 365 days) were younger than 28 days with a modal weight of 3.2 kg. There were 56 defects in the infants and 152 operative procedures studied. Fifty percent of the infants had one primary defect and were discharged in 2 to 10 days; 63.7% had no complications after surgery and were discharged in 4 to 15 days after surgery. Operative weight significantly predicted length of stay (p = .046; R(2) = .046). Operative age (p = .0011) and number of other diagnoses other than a child's primary defect (p = .0099) significantly predicted presence of fatal and nonfatal complications. As the number of other diagnoses increased by one, the odds of complications increased by 28%. As operative age increased by 1 day, the odds of complications decreased by 0.63%. The findings from this study can be used as evidence to support care that nurses give to neonates and infants undergoing cardiac surgery. These findings provide support for integration of this information into the informed consent process.

Age Distribution↗
PubMed2002

Differential activities of murine single minded 1 (SIM1) and SIM2 on a hypoxic response element. Cross-talk between basic helix-loop-helix/per-Arnt-Sim homology transcription factors.

The basic helix-loop-helix/Per-Arnt-Sim homology (bHLH/PAS) protein family comprises a group of transcriptional regulators that often respond to a variety of developmental and environmental stimuli. Two murine members of this family, Single Minded 1 (SIM1) and Single Minded 2 (SIM2), are essential for postnatal survival but differ from other prototypical family members such as the dioxin receptor (DR) and hypoxia-inducible factors, in that they behave as transcriptional repressors in mammalian one-hybrid experiments and have yet to be ascribed a regulating signal. In cell lines engineered to stably express SIM1 and SIM2, we show that both are nuclear proteins that constitutively complex with the general bHLH/PAS partner factor, ARNT. We report that the murine SIM factors, in combination with ARNT, attenuate transcription from the hypoxia-inducible erythropoietin (EPO) enhancer during hypoxia. Such cross-talk between coexpressed bHLH/PAS factors can occur through competition for ARNT, which we find evident in SIM repression of DR-induced transcription from a xenobiotic response element reporter gene. However, SIM1/ARNT, but not SIM2/ARNT, can activate transcription from the EPO enhancer at normoxia, implying that the SIM proteins have the ability to bind hypoxia response elements and affect either activation or repression of transcription. This notion is supported by co-immunoprecipitation of EPO enhancer sequences with the SIM2 protein. SIM protein levels decrease with hypoxia treatment in our stable cell lines, although levels of the transcripts encoding SIM1 and SIM2 and the approximately 2-h half-lives of each protein are unchanged during hypoxia. Inhibition of protein synthesis, known to occur in cells during hypoxic stress in order to decrease ATP utilization, appears to account for the fall in SIM levels. Our data suggest the existence of a hypoxic switch mechanism in cells that coexpress hypoxia-inducible factor and SIM proteins, where up-regulation and activation of hypoxia-inducible factor-1alpha is concomitant with attenuation of SIM activities.

Adenosine Triphosphate↗
PubMedDate not supplied

Gender differences in symptoms associated with acute myocardial infarction: a review of the research.

Recognizing similarities and differences in symptom experiences of acute myocardial infarction (AMI) between men and women has implications for both health care providers and the general public. Rapid accurate diagnosis is necessary to implement timely lifesaving treatment. The purpose of this article is to critically review and evaluate studies that have compared symptoms of AMI between men and women. Research to date has demonstrated that during AMI, women are more likely than men to report shortness of breath, nausea, vomiting, back pain, jaw pain, neck pain, cough, and fatigue, but less likely than men to report chest pain and sweating. However, the findings were inconsistent across studies. These inconsistent findings could be attributable to methodological issues such as collecting data from medical records, small sample sizes, and controversial eligibility criteria for studies. More studies are needed to confirm gender differences in symptom experiences of AMI.

Biomedical Research↗
PubMedDate not supplied

Essential qualifications for nursing students.

Course objectives do not always support grading or evaluation decisions when a student demonstrates poor judgment or disrespectful interactions with others in clinical settings, classrooms, and program-related activities. Instructor attempts to help a student identify, reflect upon, and correct an inappropriate behavior are often awkward, avoided altogether, or lack an articulated set of standards to which both student and instructor can refer. Yet qualifications such as sound judgment and sensitive communication skills are essential in the provision of quality nursing care. The Essential Qualifications documents at the University of Washington School of Nursing offer a structure within which students, instructors, and administrators can identify, assess, and document action plans for student success. This article describes the legal basis and process for the formulation and use of an educational tool for assessing and guiding, outside the realm of course objectives, essential qualifications in applicants and students of nursing programs.

Clinical Competence↗