Jacobs Institute of Women's Health
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Investigating Intensity and Percentage of p53 Nuclear Expression in Prostate Cancer: Findings from a Cohort of U.S. Military Veterans
No full textBACKGROUND: Next-generation sequencing has revealed TP53 alterations in localized prostate cancer (PCa), suggesting growing clinical potential for p53 immunohistochemistry (IHC). Prior research supports the use of IHC for the detection of p53 overexpression to predict the presence of TP53 alterations known to be associated with adverse outcomes. However, to reach a consensus definition of p53 overexpression in PCa, further insights are needed. This study aimed to compare two fundamental approaches of evaluating p53 expression across a variety of specimens regarding PCa progression. METHODS: This study included 84 patients (75% self-identified as African American) diagnosed with PCa between 1996 and 2021 at the DC VA Medical Center. Representative sections of core biopsies, radical prostatectomies, transurethral prostate resections, and metastatic deposits were examined. p53 nuclear expression was scored according to the highest intensity observed (0, 1+, 2+, 3+) and the percentage (0%, \u3c1%, 1-5%, \u3e5%) of tumor cells expressing any level of intensity in the aggregate tumor area. All slides were reviewed by two independent pathologists. Pertinent clinical data were collected. RESULTS: A total of 34 patients (40%) exhibited p53 nuclear expression, of which 18 (21%) showed the maximum (3+) intensity. The presence of maximum intensity, regardless of percentage, was found to be associated with Grade Group (p \u3c 0.001), higher PSA at biopsy (p \u3c 0.001), BCR (p \u3c 0.001) and metastasis (p \u3c 0.001). Importantly, maximum p53 intensity was identified only in patients who developed metastatic disease. CONCLUSIONS: Maximum (3+) p53 nuclear intensity of any percentage is highly associated with disease progression in PCa, suggesting that optimal determination of p53 overexpression should incorporate intensity
Innovation in the Design of Clinical Trials for Infectious Diseases: Focusing on Patients Over Pathogens
No full textMuch infectious disease research focuses on the interaction of microorganisms and drugs in the laboratory, assuming biological activity of inhibiting organism growth in vitro directly translates to improving patient outcomes in the clinic. Yet in vitro testing does not consider the important role of the human immune system in causing and response to disease. Research shows that patient outcomes are still suboptimal even with disease due to organisms that maintain in vitro susceptibility to currently available drugs. Resources and discussions have focused on antimicrobial resistance yet the majority of deaths are with susceptible organisms. Studies of new interventions do not address the questions that patients and clinicians in practice ask in order to improve patient outcomes regardless of causative pathogen in patients who would receive the drugs in the real-world setting. Research in infectious diseases should shift to refocus on improving patient outcomes. This would result in changes in the research questions evaluated, the types of patients enrolled, the comparisons made, the interventions studied, the outcomes evaluated, and the types of statistical evaluations used. In turn this would provide patients and clinicians with better evidence for patient care and justify payment for new interventions
Concurrent Control of Sodium and Bicarbonate Serum Concentrations Using a Four-Stream Hemodialysis Fluid Delivery System
No full textBACKGROUND: Previously, two reports proposed a four-stream dialysis fluid delivery system consisting of an acid concentrate, a base concentrate, a sodium chloride concentrate, and product water for correcting dysnatremias and metabolic acid-base disorders separately, by hemodialysis. METHODS: This report describes a new method for the clinical use of the previously reported four-stream dialysis fluid delivery system to treat concurrently dysnatremias and metabolic acid-base disturbances by hemodialysis. Pumps attached to each concentrate are designed to control its flow rate. Formulas were derived to determine the flow rate of each of the pumps controlling the flows of the product water (W), the base concentrate (B), and the sodium chloride concentrate (S) for any prescribed combination of sodium and bicarbonate concentrations is the final dialysis fluid. In this scheme, the flow rate of the acid concentrate (A), the concentrations of its contents in the final dialysis fluid remain constant. The flow rate ratio W:S:B:A remains also constant at 45 (i.e., 45X). RESULTS: The formulas were entered in an EXCEL flow sheet which determines the flow rate ratio W:S:B:A for any desired combination of sodium and bicarbonate concentrations in the dialysis fluid. The upper and lower limits of the concentrations of sodium and bicarbonate in the dialysis fluid were computed. The system has not been applied clinically. Measurements of any electrolyte concentrations have not been made. DISCUSSION: This system makes the treatment of profound dysnatremias, metabolic acid-base disorders, and combined dysnatremias and metabolic acid-base disorders feasible. The clinical application of the system demands prior in vitro or ex vivo studies plus fastidious and expert attention to ensure safe and dependable application
Right-Lateralization of the Visual Word Form Area after Left-Hemisphere Perinatal Stroke
No full textIn literate adults, an area along the left posterior fusiform gyrus that is often referred to as the visual word form area (VWFA) responds particularly strongly to written characters compared with other visually similar stimuli. Theoretical accounts differ in whether they attribute the strong left-lateralization of the VWFA to a left-hemisphere (LH) bias toward visual features used in script, to competition of visual word form processing with that of other visual stimuli processed in the same general cortical territory (especially faces), or to the well established left-lateralization of the language system. Here we used functional magnetic resonance imaging to test the last hypothesis by investigating lateralization of the VWFA in participants (male and female) who have right-hemisphere language due to a large LH perinatal stroke. Demographically matched controls were included for comparison. All participants had intact language skills and were proficient readers; age at testing ranged from 9.75 years to early adulthood. Activation maps contrasting activation during rapid presentation of pseudowords and pictures of places revealed left-lateralized fusiform activation in controls, as expected. In participants with left-hemisphere perinatal stroke and right-lateralized language, the VWFA was instead found in the right fusiform gyrus, despite the fact that the left-hemisphere tissue normally occupied by the VWFA was intact and responded normally to pictures of places. Region-of-interest analyses confirmed right-lateralization for visual word form processing, both relative to place stimuli and relative to a resting baseline. This provides compelling evidence that the lateralization of the VWFA indeed follows that of the frontotemporal language system
Assessing Environmental Justice in Mexico: How Polluting Industries and Healthcare Disparities Impact Congenital Heart Defects
No full textBACKGROUND: Congenital heart defects (CHDs) are the most prevalent birth defects globally and the second leading cause of death in Mexican children under five. This study examines how industrial activity and social vulnerabilities independently and jointly influence CHD incidence across 2446 Mexican municipalities from 2008 to 2019. METHODS: Using negative binomial regression models, we evaluated associations between polluting industries, healthcare access, and CHD incidence. We analyzed these factors independently, jointly, and through interaction terms to assess potential effect modification by healthcare access. Incidence rate ratios (IRRs) and 95% confidence intervals were estimated across healthcare access strata. RESULTS: Municipalities without healthcare facilities were more likely to host polluting industries, highlighting structural inequities. The presence of polluting industries was associated with increased CHD incidence, even after adjusting for healthcare access. For instance, municipalities with poor healthcare access and two or more polluting industries exhibited a 42% higher CHD incidence (IRR = 1.42, 95% CI: 1.25-1.60) compared to a 26% increase in municipalities with better healthcare access (IRR = 1.26, 95% CI: 1.02-1.57). CONCLUSIONS: These results show how environmental pollutant exposure and social vulnerabilities interact synergistically, disproportionately impacting socially vulnerable populations. Targeted policy interventions addressing both environmental pollution and healthcare inequities are crucial. Further research is also needed to clarify the mechanisms linking pollution to CHDs and to guide public health strategies aimed at reducing these disparities in Mexico
Association of Low-Calorie Sweeteners with Selected Circulating Biomarkers of Intestinal Permeability in the Cancer Prevention Study-3 Diet Assessment Substudy
No full textBACKGROUND: Low-calorie sweeteners (LCSs) are popular sugar substitutes and have been shown to alter the gut microbiota, which raises concerns about potential impacts on intestinal permeability. OBJECTIVES: This study aimed to examine cross-sectional associations between LCS consumption and circulating biomarkers of intestinal permeability. METHODS: We analyzed data from 572 United States adults participating in the Cancer Prevention Study-3 Diet Assessment Substudy who provided ≤2 fasting blood samples, collected 6 mo apart, to measure biomarkers of intestinal permeability including antibodies to flagellin (anti-flagellin), lipopolysaccharide (anti-LPS), and total antibodies; and ≤6 24-h dietary recalls, collected over the course of 12 mo, to estimate average intake of LCS including aspartame, sucralose, acesulfame-potassium, and saccharin. Multivariable linear regression, adjusted for sociodemographic characteristics, lifestyle factors, and medical history, was used to examine associations between LCS consumption and levels of intestinal permeability biomarkers by comparing mean differences in biomarkers among lower (\u3e0 to ≤50th percentile) (n = 158) and higher (\u3e50th percentile) LCS consumers (n = 157) than nonconsumers. A linear trend across nonconsumers and the 2 consumption categories was evaluated using a continuous variable based on the median LCS intake (median = 0, 11.3, and 124.2 mg/d for non-, lower, and higher consumers, respectively). RESULTS: Among the 572 study participants, the mean age was 52.5 y, 63.3% were female, 60.7% were on-Hispanic White, and 55.1% reported consuming LCS-containing products. Greater LCS consumption was not associated with anti-flagellin, anti-LPS, or total antibodies. Additionally, no associations between specific types of LCS and intestinal permeability biomarkers were observed. CONCLUSIONS: The results of our study did not demonstrate an association between LCS consumption and intestinal permeability biomarkers. Further research with larger sample sizes and randomized controlled trials is needed to confirm our findings
Factors Affecting Gastroenterologists\u27 Fear When Performing Endoscopies during the COVID Pandemic: Results of a US National Survey
No full textOBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic affected the practice of gastroenterology. Endoscopic procedures are aerosolizing procedures that carry the risk of COVID-19 transmission. Our national survey examined factors affecting gastroenterologists\u27 fear of contracting COVID-19 during endoscopy. METHODS: An institutional review board-approved multicenter cross-sectional study used a snowball sample approach to disseminate a 42-question survey to gastroenterologists during a 3-month period in 2021, during the height of the pandemic. Physician demographics, information about personal protective equipment (PPE), negative pressure rooms, and COVID-19 vaccination status was collected. Likert scales were used to evaluate gastroenterologists\u27 fear when performing endoscopy. Analysis was performed using Pearson\u27s χ, Mann-Whitney U, and Wilcoxon rank tests, with significance set at P \u3c 0.05. RESULTS: Results from 69 respondents showed that 91.3% believed that PPE was adequate, 52.2% had PPE education and training, and 47.8% reported that PPE education decreased their fear of contracting COVID-19 during endoscopy. Fear decreased from first to subsequent endoscopies (P \u3c 0.0005) and after COVID-19 vaccination (P \u3c 0.0005). Higher levels of fear were associated with having comorbid conditions (P = 0.048), being the primary caregiver for or living with a person 65 years old or older (P = 0.041), having had to quarantine during the pandemic (P = 0.017), having not performed a procedure because of infectious risks (P = 0.005), and living with someone with comorbid conditions (P = 0.001). CONCLUSIONS: Multiple factors affect gastroenterologists\u27 fear of contracting COVID-19 during endoscopic procedures. Lessons learned during the COVID-19 pandemic about mitigating gastroenterologists\u27 fear are potentially applicable to future circumstances that may be associated with significant infectious concerns
Concerns about the use of verum acupuncture points in sham acupuncture studies for pain conditions: Findings and insights from network meta-analysis
No full textBuilding a Representative Local Public Health Workforce: Progress, Promise, and Looming Challenges
No full textWhy Do They Persist? Understanding Living Kidney Donors and Persistence
No full textMany participants persist through the living kidney donation process, although it is challenging, multifaceted, and burdensome, particularly during the predonation evaluation (PDE) phase. This study uses a constructivist grounded theory approach to analyze the experiences of living kidney donors (LKDs) undergoing evaluation who shared their perspectives in blog reflections. One hundred five (105) blog posts met the inclusion criteria. They generated three overarching themes: (1) Facilitators to completing the PDE qualification process, (2) Burdens experienced during the PDE qualification process, and (3) Tools to mitigate burdens or enhance facilitators. Internal facilitators, such as the desire to help and other motivating emotions, emerged as key drivers for LKDs to persist through the donation process. Religious belief or faith, an external facilitator, is also crucial in motivating donors. Conversely, internal burdens, such as doubts, fears, financial concerns, and health risks, posed challenges to the donation process. External burdens also included recipient relationship management, delays and setbacks, poor communication, qualification testing, lack of support, and being denied as a donor. This study\u27s findings shed light on the complex interplay between burdens, facilitators, and tools in shaping the experiences of LKDs during the PDE, which enabled their persistence through the process and highlights a potential persistence spectrum. The insights gained from this research can inform interventions to better support living kidney donors throughout their donation journey, enhancing the overall donor experience and potentially increasing the number of living kidney donations