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BACKGROUNDThe inclusion of adolescents in TB drug trials is essential for the development of safe, child-friendly regimens for the prevention and treatment of TB. TB Trials Consortium Study 31/AIDS Clinical Trials Group A5349 (S31/A5349) enrolled adolescents as young as 12 years old. We assessed investigator and coordinator described facilitators and barriers to adolescent recruitment, enrollment, and retention.METHODSInterviews were conducted with six investigators from sites that enrolled adolescent participants and six investigators from non-enrolling sites. Additionally, two focus groups were conducted with study coordinators from enrolling sites and two focus groups with non-enrolling sites. Discussions were transcribed, analyzed, summarized, and summaries were reviewed by Community Research Advisors Group members and research group representatives for content validity.RESULTSInvestigators and coordinators attributed the successful enrollment of adolescents to the establishment and cultivation of external partnerships, flexibility to accommodate adolescents' schedules, staff engagement, recruitment from multiple locations, dedicated recruitment staff working onsite to access potential participants, creation of youth-friendly environments, and effective communications. Non-enrolling sites were mainly hindered by regulations. Suggestions for improvement in future trials focused on study planning and site preparations.CONCLUSIONProactive partnerships and collaboration with institutions serving adolescents helped identify and reduce barriers to their inclusion in this trial..

It has been previously shown that the cytokine interleukin 33 is required for two processes, i.e., autophagic digestion of granulosa cells and recruitment of macrophages into atretic follicles, for full disposal of atretic follicles. Now, this study shows that activation of interleukin 33-suppression of tumorigenicity 2-Nuclear Factor ĸB (NFκB) axis in granulosa in early atretic follicles may regulate those two events. Injection of human chorionic gonadotropin has been shown to induce a transient peak of interleukin 33 expression with synchronized atresia. In this model, interleukin 33-independent expression of suppression of tumorigenicity 2 in granulosa cells was detected in early atretic follicles before macrophage invasion. The activation of NFκB pathway in ovaries was further demonstrated in vivo in Tg mice with luciferase-reporter for NFκB activation; the activation was microscopically localized to granulosa cells in early atretic follicles. Importantly, antibody blockage of interleukin 33 or interleukin 33 Knock-out (KO) (Il33-/-) not only inhibited NFκB activity in ovaries, but it also altered expression of two key genes, i.e., reduction in proinflammatory interleukin6 (IL6) expression, and a surge of potential autophagy-inhibitory mammalian target of rapamycin (mTOR) expression in atretic follicles. By contrast, apoptosis and other genes, such as interleukin1β (IL1β) were not affected. In conclusion, in parallel to apoptosis, atresia signals also trigger activation of the interleukin 33-suppression of tumorigenicity 2-NFκB pathway in granulosa, which leads to (1) down-regulated expression of mTOR that is a negative regulator of autophagy and (2) up-regulated expression of proinflammatory IL6., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Understanding the effects of family-based lifestyle intervention beyond the treated adolescent is important, given that obesity is a familial disease and there are likely bidirectional relations between an adolescent's treatment success and broader household changes. However, it is unknown if recommended household-wide changes are adopted or if untreated family members experience weight-related benefits., Methods: TEENS + REACH leverages our ongoing randomized clinical trial of TEENS+, a family-based lifestyle intervention for adolescents with obesity, to determine: 1) if household-wide changes to the shared home environment are implemented, 2) if ripple effects to untreated family members are observed, and 3) whether these changes are predictive of adolescents' weight management success. TEENS + REACH will expand trial assessments to include comprehensive assessments of the shared home feeding, weight, and physical activity environment of the target adolescents. Specifically, we will enroll untreated children (8-17yrs) and caregivers living in the same household as the target parent/adolescent dyad (N = 60 families). At 0, 2, 4 (primary endpoint), and 8-months, the target parent/adolescent dyad and other untreated children and caregivers in the home will complete anthropometric assessments., Discussion: Results will determine the familial reach of TEENS+ and reveal potential mediators of treatment response, which can inform future efforts to optimize family-based lifestyle interventions., Trial Registration: TEENS + REACH was retrospectively registered in Clinicaltrials.gov March 22, 2023 (NCT05780970) as an observational study ancillary to the TEENS + clinical trial, registered February 22, 2019 (NCT03851796)., Competing Interests: 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., (© 2024 The Authors.)

Conditional gene regulation in Drosophila through binary expression systems like the LexA-LexAop system provides a superb tool for investigating gene and tissue function. To increase the availability of defined LexA enhancer trap insertions, we present molecular, genetic, and tissue expression studies of 301 novel Stan-X LexA enhancer traps derived from mobilization of the index SX4 line. This includes insertions into distinct loci on the X, II, and III chromosomes that were not previously associated with enhancer traps or targeted LexA constructs, an insertion into ptc, and seventeen insertions into natural transposons. A subset of enhancer traps was expressed in CNS neurons known to produce and secrete insulin, an essential regulator of growth, development, and metabolism. Fly lines described here were generated and characterized through studies by students and teachers in an international network of genetics classes at public, independent high schools, and universities serving a diversity of students, including those underrepresented in science. Thus, a unique partnership between secondary schools and university-based programs has produced and characterized novel resources in Drosophila, establishing instructional paradigms devoted to unscripted experimental science., Competing Interests: Conflicts of interest statement The author(s) declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

The Centers for Disease Control and Prevention works to eliminate tuberculosis (TB) disease by finding and treating cases of TB disease and expanding latent tuberculosis infection (LTBI) testing and treatment to prevent TB disease. Approximately 70% of reported TB cases in the United States occur among non-U.S.-born persons. We conducted 15 focus groups with U.S. residents born in the six most common countries of birth among non-U.S.-born TB patients: Mexico, the Philippines, India, Vietnam, China and Guatemala. Participants reacted to 39 messages on LTBI and TB disease risk factors, the Bacille Calmette-Guérin (BCG) vaccine, and LTBI testing and treatment. There was low awareness of LTBI, the TB blood test, and how the TB blood test is not affected by prior BCG vaccination. Several participants thought TB disease is contracted by sharing kitchenware. Some felt negatively targeted when presented with information about countries where TB disease is more common than the U.S. Findings highlight the need for communication aimed at increasing LTBI testing and treatment to include messages framed in ways that will be resonant and actionable to populations at risk. Focus groups revealed LTBI misconceptions which highlight areas for targeted education to decrease TB stigma and increase LTBI testing and treatment.

Background: Phosphorodiamidate morpholino oligomer (PMO)-mediated exon skipping is currently used in clinical development to treat Duchenne muscular dystrophy (DMD), with four exon-skipping drugs achieving regulatory approval. Exon skipping elicits a truncated, but semi-functional dystrophin protein, similar to the truncated dystrophin expressed in patients with Becker Muscular dystrophy (BMD) where the disease phenotype is less severe than DMD. Despite promising results in both dystrophic animal models and DMD boys, restoration of dystrophin by exon skipping is highly variable, leading to contradictory functional outcomes in clinical trials., Objective: To develop optimal PMO dosing protocols that result in increased dystrophin and improved outcome measures in preclinical models of DMD., Methods: Tested effectiveness of multiple chronic, high dose PMO regimens using biochemical, histological, molecular, and imaging techniques in mdx mice., Results: A chronic, monthly regimen of high dose PMO increased dystrophin rescue in mdx mice and improved specific force in the extensor digitorum longus (EDL) muscle. However, monthly high dose PMO administration still results in variable dystrophin expression localized throughout various muscles., Conclusions: High dose monthly PMO administration restores dystrophin expression and increases muscle force; however, the variability of dystrophin expression at both the inter-and intramuscular level remains. Additional strategies to optimize PMO uptake including increased dosing frequencies or combination treatments with other yet-to-be-defined therapies may be necessary to achieve uniform dystrophin restoration and increases in muscle function.

This study aimed to determine barriers to accepting mental health care among depressed cancer patients. Cancer patients who screened positive for depression were referred for mental health treatment and sent a validated questionnaire designed to assess barriers to receiving mental health care. Responses were compared between patients who accepted their referral and those who did not. Among 75 patients who agreed to participate, 51 (68%) completed the questionnaire. Reported barriers to accessing mental healthcare were not significantly different between the two groups but patients residing within 50 miles of the clinic had increased odds of attending their appointment.

Introduction: Distress related to disease burden has been defined and described among people with chronic diseases including diabetes and cancer. In these populations, disease-specific distress is associated with health outcomes. Haemophilia-related distress is less understood., Aim: To identify qualitative features of haemophilia-related distress among affected adults to ultimately inform the creation of a measurement tool., Methods: Adults with haemophilia A or B associated with a large haemophilia treatment centre in the south-eastern U.S. were recruited to participate in this qualitative study. Fifteen participants completed semi-structured telephone interviews. Interviews lasted 1-2 hours and explored experiences of distress related to various aspects of haemophilia. Interviews were audio taped, transcribed and coded using NVIVO, software for organizing, managing and analysing qualitative data. Coding was deductive and inductive, and the analysis was thematic., Results: Haemophilia-related distress was broadly related to feelings of isolation and vulnerability which incorporated health system factors, physical functioning, caretaker roles and psychological considerations. Specific features associated with haemophilia-related distress included lack of trust in the knowledge of haemophilia and care provided by staff in community healthcare settings, concerns about the future such as health insurance access and ageing/disability, long-standing feelings of being different from others and feeling like an outsider, treatment burdens and fear of acute bleeds. Protective factors included supportive relationships with family, friends and haemophilia care teams through which participants received practical and emotional support., Conclusion: Features of haemophilia-related distress were identified. Results will facilitate distress measurement and intervention efforts to reduce distress in adults with haemophilia., (© 2019 John Wiley & Sons Ltd.)

Purpose/objectives: To examine how the eHealth literacy of partners of patients with newly diagnosed prostate cancer affects their involvement in decision making, and to identify the factors that influence their eHealth literacy.
., Design: Cross-sectional exploratory study.
., Setting: North Carolina.
., Sample: 142 partners of men with newly diagnosed localized prostate cancer. 
., Methods: A telephone survey and descriptive and multiple linear regression analyses were used.
., Main Research Variables: The partners' eHealth literacy, involvement in treatment decision making, and demographics, and the health statuses of the patients and their partners. 
., Findings: Higher levels of eHealth literacy among partners were significantly associated with their involvement in getting a second opinion, their awareness of treatment options, and the size of the social network they relied on for additional information and support for treatment decision making for prostate cancer. The factor influencing eHealth literacy was the partners' access to the Internet for personal use, which explained some of the variance in eHealth literacy.
., Conclusions: This study described how partners' eHealth literacy influenced their involvement in treatment decision making for prostate cancer and highlighted the influencing factors (i.e., partners' access to the Internet for personal use).
., Implications for Nursing: When helping men with prostate cancer and their partners with treatment decision making, nurses need to assess eHealth literacy levels to determine whether nonelectronically based education materials are needed and to provide clear instructions on how to use eHealth resources.

Purpose/objectives: To examine partner involvement in treatment decision making for localized prostate cancer, congruence between partner involvement and patient preference, reasons for partner noninvolvement, and partner satisfaction with patient treatment
., Design: Cross-sectional exploratory study., Setting: 100 counties in North Carolina., Sample: 281 partners of men with newly diagnosed localized prostate cancer., Methods: Participants completed a phone survey. Logistic regression analyses were used., Main Research Variables: Partners' involvement in treatment decision making, partner satisfaction with treatment, activities of partner involvement, and reasons for noninvolvement., Findings: Of the 228 partners (81%) related to decision making, 205 (73%) were very satisfied with the treatment the patients received, and partner involvement was congruent with patient preference in 242 partners (86%). Partners reported several reasons for noninvolvement., Conclusions: Most partners engaged in multiple activities during treatment decision making for localized prostate cancer and were satisfied with the patient's treatment. Partner involvement was mostly congruent with patient preference., Implications for Nursing: Partners' active involvement in treatment decision making for localized prostate cancer (e.g., being involved in patients' conversations with doctors) should be encouraged and facilitated for those who prefer this type of decision making. 
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Background: Many types of glomerulonephritis (GN) undergo tandem connected phases: inflammation and fibrosis. Fibrosis in human GNs leads to irreversible end-stage disease. This study investigated how these 2 phases were controlled., Methods: Using a rat anti-glomerular basement membrane GN model, we established bone marrow (BM) chimeras between GN-resistant Lewis (LEW) and GN-susceptible Wistar Kyoto (WKY) rats. Glomerular inflammation and fibrosis were compared between chimeras., Results: LEW's BM to WKY chimeras with or without co-transfer of host WKY's T cells were GN-resistant. On the other hand, WKY's BM to LEW (LEW(WKY)) chimeras developed glomerular inflammation and albuminuria upon immunization. Quantitative analysis showed that the number and composition of inflammatory cells in glomeruli of immunized LEW(WKY) chimeras were similar to those in immunized WKY rats at their inflammatory peak. Thus, glomerular inflammation was controlled by BM-derived non-T cell populations. However, unlike WKY rats, LEW(WKY) rats did not develop fibrosis until the end of experiments (84 days) in spite of persistent inflammation and albuminuria., Conclusion: Inflammation alone was not sufficient to trigger fibrosis, suggesting a critical role of glomerular cells in the fibrotic process. As LEW(WKY) chimera allows us to separate glomerular inflammation from fibrosis, this model provides a useful tool to study how fibrosis is initiated following inflammation., (© 2015 S. Karger AG, Basel)

Ovaries are among the most active organs. Frequently occurring events such as ovulation and ovarian atresia are accompanied with tissue destruction and repairing. Critical roles of immune cells or molecules in those events have been well recognized. IL-33 is a new member of the IL-1 cytokine gene family. Recent studies suggest its roles beyond immune responses. We systemically examined its expression in ovaries for its potential roles in ovarian functions. During ovulation, a high level of IL-33 was transiently expressed, making it the most significantly upregulated immune gene. During estrous cycle, IL-33 expression levels fluctuated along with numbers of ovarian macrophages and atresia wave. Cells with nuclear form of IL-33 (nIL-33(+) cells) were mostly endothelial cells of veins, either in the inner layer of theca of ovulating follicles during ovulation, or surrounding follicles during estrous cycle. Changes in number of nIL-33(+) cells showed a tendency similar to that in IL-33 mRNA level during estrous cycle. However, the cell number sharply declined before a rapid increase of macrophages and a surge of atresia. The decline in nIL-33(+) cell number was coincident with detection of higher level of the cytokine form of IL-33 by Western blot, suggesting a release of cytokine form of IL-33 before the surge of macrophage migration and atresia. However, IL-33 Ab, either by passive transfer or immunization, showed a limited effect on ovulation or atresia. It raises a possibility of IL-33's role in tissue homeostasis after ovarian events, instead of a direct involvement in ovarian functions., (Copyright © 2014 by The American Association of Immunologists, Inc.)

A descriptive, correlational study design was used to determine if a customized clinical education for orientation based on knowledge weaknesses identified from a prehire screening examination would reduce the length of orientation and improve the critical thinking ability of newly hired nurses. Results of the study demonstrated significant evidence that customized education based on this prehire assessment has a positive effect on both the length of orientation and critical thinking.

This first part of a 2-phase study examined the relationship between general pediatric nursing knowledge, critical thinking (CT) ability of newly hired nurse, as determined by a custom Health Education System Inc exam and the length of orientation necessary to meet the required clinical competencies. A descriptive correlational study design was used to administer the customized computer-based examination to 98 nurses at the beginning of employment at a large pediatric healthcare organization. The examination results were statistically significant in the determination of CT ability and a correlation to the ability to provide clinically competent patient care. The custom examination provided an objective measurement of CT ability in the nurse's specific domain of knowledge.

Dedicated education units (DEUs) teach nursing students how to provide professional, competent, and safe nursing care using staff nurses as educators and reduce the number of adjunct clinical faculty required by schools of nursing. The authors describe a collaborative clinical partnership between a pediatric healthcare system and a school of nursing to pilot the use of a DEU for one-on-one clinical education of students with expert pediatric nurses.

ABSTRACT Lysobacter enzymogenes produces extracellular lytic enzymes capable of degrading the cell walls of fungi and oomycetes. Many of these enzymes, including beta-1,3-glucanases, are thought to contribute to the biological control activity expressed by several strains of the species. L. enzymogenes strain C3 produces multiple extracellular beta-1,3-glucanases encoded by the gluA, gluB, and gluC genes. Analysis of the genes indicates they are homologous to previously characterized genes in the related strain N4-7, each sharing >95% amino acid sequence identity to their respective counterparts. The gluA and gluC gene products encode enzymes belonging to family 16 glycosyl hydrolases, whereas gluB encodes an enzyme belonging to family 64. Mutational analysis indicated that the three genes accounted for the total beta-1,3-glucanase activity detected in culture. Strain G123, mutated in all three glucanase genes, was reduced in its ability to grow in a minimal medium containing laminarin as a sole carbon source. Although strain G123 was not affected in antimicrobial activity toward Bipolaris sorokiniana or Pythium ultimum var. ultimum using in vitro assays, it was significantly reduced in biological control activity against Bipolaris leaf spot of tall fescue and Pythium damping-off of sugar beet. These results provide direct supportive evidence for the role of beta-1,3-glucanases in biocontrol activity of L. enzymogenes strain C3.

Objective: Our purpose was to evaluate cardiac variables, including right and left end-diastolic and end-systolic dimensions by use of M-mode echocardiography during fetal, neonatal (transitional), and infancy periods to understand hemodynamic adaptation during these periods., Study Design: Fifty-three fetuses were enrolled in this study. Echocardiography evaluations were started as early as the sixteenth week of gestation and were repeated every 4 to 6 weeks until term, on postnatal days 1 and 2, and at 6 weeks, 6 months, and 12 months of age. End-diastolic and end-systolic measurements were made according to published standards. Mean and SEM for each of the end-diastolic and end-systolic measurements were calculated for each of 11 study periods. Data were analyzed by one-way analysis of variance, corrected for repeated measures, and in the case of right and left ventricular differences paired t tests were used for significance., Results: Left ventricular end-diastolic and end-systolic correlated positively with advancing age (R2 = 0.93, p < 0.0001), right ventricular end-diastolic also correlated with advancing age (R2 = = 0.361, p < 0.05), and right ventricular end-diastolic was significantly larger than left ventricular end-diastolic in utero (p < 0.01), whereas the opposite was true after birth (p < 0.0001). Heart rate significantly decreased with advancing age (p < 0.001), whereas ejection fraction for either the right or the left ventricle did not change significantly with advancing age., Conclusion: This suggests that under basal conditions the ventricles can meet the increased demands in cardiac output by increasing ventricular dimensions without having to increase contractility reserve.

Objective: Our purpose was to longitudinally quantify human fetal renal blood flow., Study Design: Twenty-two normal fetuses underwent a color-pulsed Doppler evaluation of the renal artery. The Doppler waveforms were digitized to assess the velocity-time integral. The size of the vessel was determined during systole with color high-resolution two-dimensional ultrasonography. Renal blood flow was estimated by multiplying the time-velocity integral (i.e., area under the curve) by the area of the renal artery. The combined cardiac output was calculated by adding right and left inflow Doppler-derived volumes., Results: Renal artery size, peak flow velocity, time-velocity integral, and renal blood flow significantly increased with advancing gestational age. The resistivity indexes, such as the systolic/diastolic ratio or the Pourcelot index of the fetal renal artery, did not significantly change with advancing gestational age. The pulsatility index, however, was correlated with gestational age. The percentage of the combined cardiac output to the fetal kidney remained constant throughout gestation., Conclusions: Color pulsed Doppler can be used to visualize small and deep vascular structures in the human fetus. Renal blood flow increased with advancing gestational age. This increase seems to be related to the increase in the combined cardiac output.

Objectives: We attempted to quantify noninvasively blood flow of the middle cerebral artery in human fetuses during five distinct periods., Study Design: Twenty normal fetuses had color pulsed Doppler ultrasonography of the middle cerebral artery. A total of 68 studies were successfully done and are reported. The Doppler sample was placed as parallel to the direction of the vessel flow as possible. All waveforms were recorded on a strip chart at a preset speed of 100 mm/sec. Six Doppler waveforms were digitized for the time velocity integral (area under the curve is equal to time velocity integral) and averaged. Middle cerebral blood flow was obtained by multiplying the time velocity integral of the Doppler curve by the cross-sectional area of the vessel. The combined cardiac output was obtained by adding the right and left ventricular outputs, which were obtained by multiplying the time velocity integrals by the area of the corresponding annuli. Analysis of variance for repeated measurements was used to determine significance., Results: The diameter of the middle cerebral artery, the time velocity integral, and the peak flow velocity of the Doppler waveform increased significantly with advancing gestational age. Blood flow to the middle cerebral artery ranged from 23 ml/min at 19 weeks to 133 ml/min at term. Resistivity index values were not correlated with advancing gestational age. The percent of the cardiac output to one of the two middle cerebral arteries remained constant throughout gestation with a range between 3% and 7%., Conclusions: (1) Time velocity integral, peak flow velocity, diameter, and blood flow of the middle cerebral artery increased significantly with gestational age; (2) the percent of the total cardiac output to the middle cerebral artery does not significantly change with gestational age.