Patterns and predictors of anxiety and depression symptom trajectories in patients diagnosed with primary brain tumors.

BACKGROUND: Patients with primary brain tumors (pPBTs) often exhibit heightened distress. This study assesses how symptoms of anxiety and depression change over time in pPBTs and identifies factors that may predict patients' symptom trajectories. METHODS: Ninety-nine adult pPBTs completed psychosocial assessments at neuro-oncology appointments over 6-18 months. Quality of life was assessed with the Functional Assessment of Cancer Therapy-Brain; symptoms of anxiety and depression were assessed with the Patient-Reported Outcomes Measurement Information System short forms. The prevalence of patients with clinically elevated symptoms and those who experienced clinically meaningful changes in symptoms throughout follow-up were examined. Linear mixed-effects models evaluated changes in symptoms over time at the group level, and latent class growth analysis (LCGA) evaluated changes in symptoms over time at the individual level. RESULTS: At enrollment, 51.5% and 32.3% of patients exhibited clinically elevated levels of anxiety and depression, respectively. Of patients with follow-up data (n = 74), 54.1% and 50% experienced clinically meaningful increases in anxiety and depression scores, respectively. There were no significant changes in anxiety or depression scores over time, but better physical, functional, and brain-cancer well-being predicted lower levels of anxiety and depression (p < 0.001). Five sub-groups of patients with distinct symptom trajectories emerged via LCGA. CONCLUSIONS: pPBTs commonly experience elevated symptoms of anxiety and depression that may fluctuate in clinically meaningful manners throughout the disease. Routine screening for elevated symptoms is needed to capture clinically meaningful changes and identify factors affecting symptoms to intervene on.

Effect of Out-of-Hospital Sodium Nitrite on Survival to Hospital Admission After Cardiac Arrest: A Randomized Clinical Trial.

Importance: Therapeutic delivery of sodium nitrite during resuscitation improved survival in animal models of cardiac arrest, but efficacy has not been evaluated in clinical trials in humans. Objective: To determine whether parenteral administration of sodium nitrite given by paramedics during resuscitation for out-of-hospital cardiac arrest improved survival to hospital admission. Design, Setting, and Participants: Double-blind, placebo-controlled, phase 2 randomized clinical trial including 1502 adults in King County, Washington, with out-of-hospital cardiac arrest from ventricular fibrillation or nonventricular fibrillation. Patients underwent resuscitation by paramedics and were enrolled between February 8, 2018, and August 19, 2019; follow-up and data abstraction were completed by December 31, 2019. Interventions: Eligible patients with out-of-hospital cardiac arrest were randomized (1:1:1) to receive 45 mg of sodium nitrite (n = 500), 60 mg of sodium nitrite (n = 498), or placebo (n = 499), which was given via bolus injection by the paramedics as soon as possible during active resuscitation. Main Outcomes and Measures: The primary outcome was survival to hospital admission and was evaluated with 1-sided hypothesis testing. The secondary outcomes included out-of-hospital variables (rate of return of spontaneous circulation, rate of rearrest, and use of norepinephrine to support blood pressure) and in-hospital variables (survival to hospital discharge; neurological outcomes at hospital discharge; cumulative survival to 24 hours, 48 hours, and 72 hours; and number of days in the intensive care unit). Results: Among 1502 patients with out-of-hospital cardiac arrest who were randomized (mean age, 64 years [SD, 17 years]; 34% were women), 99% completed the trial. Overall, 205 patients (41%) in the 45 mg of sodium nitrite group and 212 patients (43%) in the 60 mg of sodium nitrite group compared with 218 patients (44%) in the placebo group survived to hospital admission; the mean difference for the 45-mg dose vs placebo was -2.9% (1-sided 95% CI, -8.0% to ∞; P = .82) and the mean difference for the 60-mg dose vs placebo was -1.3% (1-sided 95% CI, -6.5% to ∞; P = .66). None of the 7 prespecified secondary outcomes were significantly different, including survival to hospital discharge for 66 patients (13.2%) in the 45 mg of sodium nitrite group and 72 patients (14.5%) in the 60 mg of sodium nitrite group compared with 74 patients (14.9%) in the placebo group; the mean difference for the 45-mg dose vs placebo was -1.7% (2-sided 95% CI, -6.0% to 2.6%; P = .44) and the mean difference for the 60-mg dose vs placebo was -0.4% (2-sided 95% CI, -4.9% to 4.0%; P = .85). Conclusions and Relevance: Among patients with out-of-hospital cardiac arrest, administration of sodium nitrite, compared with placebo, did not significantly improve survival to hospital admission. These findings do not support the use of sodium nitrite during resuscitation from out-of-hospital cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT03452917.

Blending genetics and sociocultural historical inquiry: ethics, culture, and human subjects protection in international cross cultural research.

In this paper, we examine the implementation and difficulties when conducting genetics research in a rural, traditional West African culture within the frame of the United States' grounded research ethics. Research challenges are highlighted by Western researchers following U.S. Institutional Review Board (IRB) guidelines and practices in a non-Western country. IRB concepts are culture bound in Western ideals that may not have synchronicity and compatibility with non-Western cultures. Differences in sociocultural norms, traditions, language, and geography were influencing factors that can affect application of IRB principles. Suggestions for change are offered, which will potentially aid researchers considering application of IRB requirements when conducting research in non-Westernized, non-industrialized countries.

Effects of parity on blood pressure among West African Dogon women.

OBJECTIVE: This study examined the effect of parity on blood pressure (BP) readings and BMI among rural West African Dogon women. DESIGN: Correlational research design. SETTING: Sangha, West Africa PARTICIPANTS: 133 West African Dogon Women METHODS: Demographic survey including age, number of children, history of hypertension, and village affiliation. BP readings were taken in accordance with JNC-7 guidelines. BMI was calculated from height and weight. RESULTS: Women with BP readings diagnostic of hypertension were typically older (M = 55.72 years) than those who were normotensive (M = 42.40). However, BMI, on average, was within normal range for both groups (22.81 and 22.15, respectively). A statistically significant difference was found between number of children and systolic BP (SBP), P = .015, with those having 5 or more children with higher SBP than those with one to three children. A statistically significant difference, P = .001, was found between hypertension and normotensive diagnostic groups. CONCLUSIONS: This study shows that increased parity of five or more children may contribute to West African Dogon women's risk factors for hypertension in terms of increased SBP. Because BMI was within normal range for both groups of women, it was not shown to be an independent risk factor for hypertension in this sample. Further studies, with larger samples followed throughout their childbearing years (before, during, and after each pregnancy), are needed before more definitive conclusions can be made regarding the effects of parity on BMI and BP among rural West African Dogon women.

Alliances of cooperation: negotiating New Hampshire nurse practitioners' prescribing practice.

Nurse practitioner legislation varies among states, particularly in relation to practice without physician oversight, altering the legal environment within which nurse practitioners can use knowledge and skills to meet patient needs. Using New Hampshire as a case study, this historical analysis of nurse practitioners' negotiations over time for independent practice, defined in state practice acts, illuminates the complex social and economic factors affecting nurses' struggle to gain legal rights over their own professional practice without supervision and intervention from another profession. In New Hampshire, not only did organized medicine oppose nurses rights to practice, but pharmacists demanded the right to control all aspects of medication management, including who could prescribe and under what circumstances prescribing could occur. Shifting social and political terrain as well as changes in legislative and state professional board leadership affected the environment and negotiations of a small group of nurses who were ultimately successful in obtaining the right to define their own professional practice.

Origin of the old testament plagues: explications and implications.

Analyses of past disasters may supply insights to mitigate the impact of recurrences. In this context, we offer a unifying causative theory of Old Testament plagues, which has present day public health implications. We propose the root cause to have been an aberrant El Niño-Southern Oscillation teleconnection that brought unseasonable and progressive climate warming along the ancient Mediterranean littoral, including the coast of biblical Egypt, which, in turn, initiated the serial catastrophes of biblical sequence - in particular arthropod-borne and arthropod-caused diseases. Located beyond the boundary of focal climate change, inland Goshen would not have been similarly affected. Implicit in this analysis is a framework to consider a possibility of present day recurrence of similar catastrophes and their impact upon essential public services.

Focusing on feedback: how nurse practitioners can use focus group interviews to build a patient-centered practice.

PURPOSE: The success or failure of clinical interventions often rests upon the degree of insight nurse practitioners (NPs) have into their patients' preferences for receiving their care. Therefore, NPs have a vested interest in understanding the perspective of their patients, which can be derived by conducting practice-specific focus groups. This article offers NPs practice guidelines for conducting focus groups to improve practice and quality and making practice-related decisions. DATA SOURCES: An extensive review of the scholarly databases and scientific literature. CONCLUSIONS: Focus groups can generate valuable data for NPs in clinical practice settings. Currently, focus groups are rarely used for this purpose; however, data gathered from the population served could be invaluable for improving practice, quality, and decisions made regarding the types of services that NPs provide for their patients. IMPLICATIONS FOR PRACTICE: The benefits of an NP clinician conducting focus groups are that they provide a forum for listening to the people they serve and learning from them. The knowledge gained from patients allows the NP to tailor their interventions and care to meet the patient's needs, and may be required to make the practice thrive.

Genetic and BMI risks for predicting blood pressure in three generations of West African Dogon women.

The study of genetic polymorphisms and body mass index (BMI) among African women in Africa and in the United States contributes to our understanding of the genetic and environmental risk factors for hypertension. African American women have the highest prevalence of hypertension and obesity compared to other ethnic groups in the United States. Using a cross-sectional research design, we examined the effects of genetic and environmental risks of single nucleotide polymorphisms (SNPs) and BMI on blood pressure (BP) among three generations of West African Dogon women (N = 199). We genotyped six SNPs located in the candidate genes known to be related to hypertension. We tested the associations between these SNPs and systolic BP (SBP) and diastolic BP (DBP) with Fisher's exact tests, chi-square tests for independence, and multivariable linear mixed models. The SNP rs8179526 (SLC4A5) was significantly associated with SBP adjusted for age, age(2), and BMI (p = .02). The "C" allele variant of rs8179526 (allele frequency of 0.445) was associated with higher SBP. This SNP did not deviate from the Hardy-Weinberg equilibrium (HWE) with p value of .772. The SNP × BMI interaction effects associated with SBP and DBP were not significant. rs8179526 is located on the SLC4A5 gene on chromosome 2. SLC4A5 encodes a protein that transports sodium and bicarbonate across cell membranes while regulating cellular pH and contains several SNPs linked to elevated BP. Knowledge of the SNP's effect on hypertension among West African women can help health practitioners educate their patients about genetic risks of developing hypertension.

A literature review on community-acquired methicillin-resistant Staphylococcus aureus in the United States: clinical information for primary care nurse practitioners.

PURPOSE: To analyze the state of the science of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in the United States to support the integration of current knowledge for primary care nurse practitioners' (PCNP) practice. DATA SOURCES: Published research limited to U.S. studies in MEDLINE, CINAHL, and Cochrane Review from 1950 to the week of September 4, 2008. Investigations were identified through electronic search engines and databases. Manual searches were done of hard copy references in journal articles. Citations and reference lists for English language research studies of CA-MRSA in the United States were reviewed to identify additional research that fit evaluation criteria for this analysis. CONCLUSIONS: Until the late 1990s, healthcare-associated MRSA (HA-MRSA) was the predominant cause of serious infections. Recently, CA-MRSA has caused infections in previously healthy nonhospitalized people. Major demographic and epidemiological differences exist between the two types of resistant bacteria; the emergence of CA-MRSA suggests new implications for primary care. IMPLICATIONS FOR PRACTICE: PCNPs will undoubtedly treat MRSA infections and need a comprehensive understanding of the pathogenicity, diagnosis, and management of CA-MRSA to ensure expedient and appropriate treatment. This will help to prevent invasive disease as a result of improperly treated infections.

Neuroblastoma survival and death: an in vitro model of hypoxia and metabolic stress.

Heterogeneous oxygen tension and access to metabolites in solid tumors may produce variability in response to adjuvant therapy. To better understand these microenvironmental features, we examined survival and proliferation of neuroblastoma (NB) cells in an in vitro model of hypoxia and metabolite deprivation. Human NB cells (SH-SY5Y) were subjected to a "self-generated" diffusion gradient of nutrient and oxygen deprivation in a modified in vitro "sandwich model." In this model, the extent of both hypoxia and metabolite deprivation were individually altered, and the effects of each were studied. Cellular proliferation was confirmed by proliferating cell nuclear antigen (PCNA) immunocytochemistry and morphology and hypoxia by vascular endothelial growth factor (VEGF) and pimonidazole immunocytochemistry. We examined apoptotic cell death using TUNEL analysis, assaying for plasma membrane transfer of phosphotidylserine and the presence of the anti-apoptotic protein Bcl-2 using immunocytochemistry. As predicted, cellular survival diminished with increasing duration and severity of hypoxia and metabolite deprivation; oxygen deprivation was determined to be the more important contributory factor to early survival and proliferation. PCNA immunocytochemistry confirmed decreasing fractions of proliferating cells as a function of distance from oxygen and metabolites. VEGF and Bcl-2 immunoreactivity increased with prolonged exposure and increased extent of oxygen/metabolite deprivation. TUNEL analysis and phosphotidylserine transfer demonstrated cellular death of hypoxic and metabolite-deprived NB cells in a manner consistent with a mitochondrial apoptotic pathway. This in vitro model demonstrates that increasing the severity of hypoxia and metabolite deprivation results in diminished proliferation and greater apoptotic death, observations analogous to that of clinical NB tumors.

Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1.

E2 enzymes catalyze attachment of ubiquitin and ubiquitin-like proteins to lysine residues directly or through E3-mediated reactions. The small ubiquitin-like modifier SUMO regulates nuclear transport, stress response, and signal transduction in eukaryotes and is essential for cell-cycle progression in yeast. In contrast to most ubiquitin conjugation, the SUMO E2 enzyme Ubc9 is sufficient for substrate recognition and lysine modification of known SUMO targets. Crystallographic analysis of a complex between mammalian Ubc9 and a C-terminal domain of RanGAP1 at 2.5 A reveals structural determinants for recognition of consensus SUMO modification sequences found within SUMO-conjugated proteins. Structure-based mutagenesis and biochemical analysis of Ubc9 and RanGAP1 reveal distinct motifs required for substrate binding and SUMO modification of p53, IkappaBalpha, and RanGAP1.