What about the men? Perinatal experiences of men of color whose partners were at risk for preterm birth, a qualitative study.

BACKGROUND:Preterm birth in the United States is associated with maternal clinical factors such as diabetes, hypertension and social factors including race, ethnicity, and socioeconomic status. In California, 8.7% of all live births are preterm, with African American and Black families experiencing the greatest burden. The impact of paternal factors on birth outcomes has been studied, but little is known about the experience of men of color (MOC). The purpose of this study was to explore the experiences of MOC who are partners to women at medical and social risk for preterm birth. METHODS:This study used a qualitative research design and focus group methods. The research was embedded within an existing study exploring experiences of women of color at risk for preterm birth conducted by the California Preterm Birth Initiative. RESULTS:Twelve MOC participated in the study and among them had 9 preterm children. Four themes emerged from thematic analysis of men's experiences: (1) "Being the Rock": Providing comfort and security; (2) "It's a blessing all the way around": Keeping faith during uncertainty; (3) "Tell me EVERYTHING": Unmet needs during pregnancy and delivery; (4) "Like a guinea pig": Frustration with the healthcare system. Participants identified many barriers to having a healthy pregnancy and birth including inadequate support for decision making, differential treatment, and discrimination. CONCLUSIONS:This study shows novel and shared narratives regarding MOC experiences during pregnancy, birth, and postpartum periods. Healthcare providers have an essential role to acknowledge MOC, their experience of discrimination and mistrust, and to assess needs for support that can improve birth outcomes. As MOC and their families are at especially high social and medical risk for preterm birth, their voice and experience should be central in all future research on this topic

Armed conflict and fisheries in the Lake Victoria basin

Civil conflict is the most prevalent form of armed conflict in the world today, but this significant driver of food and income security has been largely missing from studies of fisheries. Fisheries conflict is an example of complex dynamics operating in social-ecological systems. We theorize and document the existence of such a feedback loop between conflict in Uganda and fisheries in Lake Victoria. Civil war in northern Uganda resulted in mass human population displacement, which corresponded in time with increases in fishing effort in Lake Victoria. Subsequent changes in catch of Nile perch, the dominant commercial fishery, sparked armed conflict in the lake itself, at Migingo Island, between Uganda and Kenya. From this case study, we draw seven main conclusions. First, these correlation-based relationships are illustrative but not conclusive and we call for further empirical investigation. Second, the couplings between conflict and fishing subsystems are spatially asymmetric: conflict effects are diffuse in their links to broad changes in the fishery, whereas fishery effects may produce more localized conflict events. Third, and most relevant to conflict scholars, the drivers of fishing effort and catch may originate in different subsystems, but their changes and effects must be analyzed in concert. Fourth, the complex and path-dependent impacts of conflicts on natural resources in general, and fisheries in particular, highlights the urgent need for targeted surveys and more mechanistic understanding. Fifth, the open access nature of fisheries in Lake Victoria may exacerbate instabilities not present in other systems. Sixth, the diffuse and context-specific effects of conflicts on fisheries means models of fisheries management (e.g., stock assessment) should not incorporate conflict as a driver at this time. Finally, countries and their stakeholders should focus on diversification in employment for short term coping mechanisms during conflict as a means of short-circuiting the conflict-fisheries feedback loop.U.S. Army Research Office under the Minerva Initiative of the U.S. Department of Defense [W911NF-09-1-007]; National Science Foundation Dynamics of Coupled Natural and Human Systems [1358861]Open Access JournalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Mobile-enhanced Family Integrated Care for preterm infants: A qualitative study of parents views.

OBJECTIVE: The Family Integrated Care (FICare) model improves outcomes for preterm infants and parents compared with family-centered care (FCC). FICare with mobile technology (mFICare) may improve uptake and impact. Research on FICare in the United States (US) is scarce and little is known about parents experience. METHODS: We conducted qualitative interviews with nine parents, exploring their NICU experiences, participation in and perceptions of the mFICare program. A directed content analysis approach was used, and common themes were derived from the data. RESULTS: Overall, parents had positive NICU experiences and found mFICare helpful in meeting three common parenting priorities: actively caring for their infant, learning how to care for their infant, and learning about the clinical status of their infant. They described alignment and misalignment with mFICare components relative to their personal parenting priorities and offered suggestions for improvement. Nurses were noted to play key roles in providing or facilitating parent support and encouragement to participate in mFICare and parenting activities. CONCLUSION: The mFICare program showed potential for parental acceptance and participation in US NICUs. INNOVATION: The mFICare model is an innovation in neonatal care that can advance the consistent delivery of NICU family-centered care planning and caregiving.Clinical Trial Registration:NCT03418870 01/02/2018

Maternal mental health after infant discharge: a quasi-experimental clinical trial of family integrated care versus family-centered care for preterm infants in U.S. NICUs.

BACKGROUND: Involvement in caregiving and tailored support services may reduce the risk of mental health symptoms for mothers after their preterm infants neonatal intensive care unit (NICU) discharge. We aimed to compare Family-Centered Care (FCC) with mobile-enhanced Family-Integrated Care (mFICare) on post-discharge maternal mental health symptoms. METHOD: This quasi-experimental study enrolled preterm infant (≤ 33 weeks)/parent dyads from three NICUs into sequential cohorts: FCC or mFICare. We analyzed post-discharge symptoms of perinatal post-traumatic stress disorder (PTSD) and depression using intention-to-treat and per protocol approaches. RESULTS: 178 mothers (89 FCC; 89 mFICare) completed measures. We found no main effect of group assignment. We found an interaction between group and stress, indicating fewer PTSD and depression symptoms among mothers who had higher NICU-related stress and received mFICare, compared with mothers who had high stress and received FCC (PTSD: interaction β=-1.18, 95% CI: -2.10, -0.26; depression: interaction β=-0.76, 95% CI: -1.53, 0.006). Per protocol analyses of mFICare components suggested fewer PTSD and depression symptoms among mothers who had higher NICU stress scores and participated in clinical team rounds and/or group classes, compared with mothers who had high stress and did not participate in rounds or classes. CONCLUSION: Overall, post-discharge maternal mental health symptoms did not differ between the mFICare and FCC groups. However, for mothers with high levels of stress during the NICU stay, mFICare was associated with fewer post-discharge PTSD and depression symptoms

Neonatal outcomes from a quasi-experimental clinical trial of Family Integrated Care versus Family-Centered Care for preterm infants in U.S. NICUs

BackgroundFamily Integrated Care (FICare) benefits preterm infants compared with Family-Centered Care (FCC), but research is lacking in United States (US) Neonatal Intensive Care Units (NICUs). The outcomes for infants of implementing FICare in the US are unknown given differences in parental leave benefits and health care delivery between the US and other countries where FICare is used. We compared preterm weight and discharge outcomes between FCC and mobile-enhanced FICare (mFICare) in the US.MethodsIn this quasi-experimental study, we enrolled preterm infant (≤ 33 weeks)/parent dyads from 3 NICUs into sequential cohorts: FCC or mFICare. Our primary outcome was 21-day change in weight z-scores. Our secondary outcomes were nosocomial infection, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), and human milk feeding (HMF) at discharge. We used intention-to-treat analyses to examine the effect of the FCC and mFICare models overall and per protocol analyses to examine the effects of the mFICare intervention components.Findings253 infant/parent dyads participated (141 FCC; 112 mFICare). There were no parent-related adverse events in either group. In intention-to-treat analyses, we found no group differences in weight, ROP, BPD or HMF. The FCC cohort had 2.6-times (95% CI: 1.0, 6.7) higher odds of nosocomial infection than the mFICare cohort. In per-protocol analyses, we found that infants whose parents did not receive parent mentoring or participate in rounds lost more weight relative to age-based norms (group-difference=-0.128, CI: -0.227, -0.030; group-difference=-0.084, CI: -0.154, -0.015, respectively). Infants whose parents did not participate in rounds or group education had 2.9-times (CI: 1.0, 9.1) and 3.8-times (CI: 1.2, 14.3) higher odds of nosocomial infection, respectively.ConclusionWe found indications that mFICare may have direct benefits on infant outcomes such as weight gain and nosocomial infection. Future studies using implementation science designs are needed to optimize intervention delivery and determine acute and long-term infant and family outcomes.Clinical trial registrationNCT03418870 01/02/2018

Maternal mental health after infant discharge: a quasi-experimental clinical trial of family integrated care versus family-centered care for preterm infants in U.S. NICUs

Abstract Background Involvement in caregiving and tailored support services may reduce the risk of mental health symptoms for mothers after their preterm infant’s neonatal intensive care unit (NICU) discharge. We aimed to compare Family-Centered Care (FCC) with mobile-enhanced Family-Integrated Care (mFICare) on post-discharge maternal mental health symptoms. Method This quasi-experimental study enrolled preterm infant (≤ 33 weeks)/parent dyads from three NICUs into sequential cohorts: FCC or mFICare. We analyzed post-discharge symptoms of perinatal post-traumatic stress disorder (PTSD) and depression using intention-to-treat and per protocol approaches. Results 178 mothers (89 FCC; 89 mFICare) completed measures. We found no main effect of group assignment. We found an interaction between group and stress, indicating fewer PTSD and depression symptoms among mothers who had higher NICU-related stress and received mFICare, compared with mothers who had high stress and received FCC (PTSD: interaction β=-1.18, 95% CI: -2.10, -0.26; depression: interaction β=-0.76, 95% CI: -1.53, 0.006). Per protocol analyses of mFICare components suggested fewer PTSD and depression symptoms among mothers who had higher NICU stress scores and participated in clinical team rounds and/or group classes, compared with mothers who had high stress and did not participate in rounds or classes. Conclusion Overall, post-discharge maternal mental health symptoms did not differ between the mFICare and FCC groups. However, for mothers with high levels of stress during the NICU stay, mFICare was associated with fewer post-discharge PTSD and depression symptoms

Context-Dependent Role of Vinculin in Neutrophil Adhesion, Motility and Trafficking.

Neutrophils are innate immune effector cells that traffic from the circulation to extravascular sites of inflammation. β2 integrins are important mediators of the processes involved in neutrophil recruitment. Although neutrophils express the cytoskeletal protein vinculin, they do not form mature focal adhesions. Here, we characterize the role of vinculin in β2 integrin-dependent neutrophil adhesion, migration, mechanosensing, and recruitment. We observe that knockout of vinculin attenuates, but does not completely abrogate, neutrophil adhesion, spreading, and crawling under static conditions. However, we also found that vinculin deficiency does not affect these behaviors in the presence of forces from fluid flow. In addition, we identify a role for vinculin in mechanosensing, as vinculin-deficient neutrophils exhibit attenuated spreading on stiff, but not soft, substrates. Consistent with these findings, we observe that in vivo neutrophil recruitment into the inflamed peritoneum of mice remains intact in the absence of vinculin. Together, these data suggest that while vinculin regulates some aspects of neutrophil adhesion and spreading, it may be dispensable for β2 integrin-dependent neutrophil recruitment in vivo

Context-Dependent Role of Vinculin in Neutrophil Adhesion, Motility and Trafficking.

Neutrophils are innate immune effector cells that traffic from the circulation to extravascular sites of inflammation. β2 integrins are important mediators of the processes involved in neutrophil recruitment. Although neutrophils express the cytoskeletal protein vinculin, they do not form mature focal adhesions. Here, we characterize the role of vinculin in β2 integrin-dependent neutrophil adhesion, migration, mechanosensing, and recruitment. We observe that knockout of vinculin attenuates, but does not completely abrogate, neutrophil adhesion, spreading, and crawling under static conditions. However, we also found that vinculin deficiency does not affect these behaviors in the presence of forces from fluid flow. In addition, we identify a role for vinculin in mechanosensing, as vinculin-deficient neutrophils exhibit attenuated spreading on stiff, but not soft, substrates. Consistent with these findings, we observe that in vivo neutrophil recruitment into the inflamed peritoneum of mice remains intact in the absence of vinculin. Together, these data suggest that while vinculin regulates some aspects of neutrophil adhesion and spreading, it may be dispensable for β2 integrin-dependent neutrophil recruitment in vivo

Epigenetic Profiling Of Leukemia Stem Cells In a Model Of TET2/FLT3-Mutant AML

Specific combinations of Acute Myeloid Leukemia (AML) somatic mutations are associated with distinct clinical and biologic features. However, in vivo models do not exist for the majority of common, poor-prognosis genotypes. Concurrent mutations in FLT3 and TET2 are associated with adverse outcome. We hypothesized that activating mutations in FLT3 would cooperate with inactivating mutations in TET2to induce AML in vivo, and that we could investigate AML pathogenesis and therapeutic response using a genetic model of this poor-risk AML genotype. To understand how these genes cooperate to induce AML, we generated Vav+Tet2fl/flFlt3-ITD mice, which resulted in fully penetrant, lethal disease in all recipient mice. Flow cytometric analysis revealed expansion of mac1+ cells in the peripheral blood, with progressive expansion of a c-Kit+, blast population which was apparent in the blood and bone marrow at 28 days, leading to lethal AML in all Vav+Tet2fl/flFlt3-ITD mice with a median survival of 12 months. Consistent with genetic data demonstrating most AML patients have monoallelic TET2 mutations, Vav+Tet2fl/+Flt3-ITD mice also develop AML, suggesting haploinsufficiency for Tet2 is sufficient to cooperate with the Flt3-ITD mutation to induce AML. All mice developed leukocytosis (median 85K/uL), splenomegaly (median 554mg) and hepatomegaly (median 2900mg) with evidence of extramedullary disease cell infiltration by leukemic blasts. Flow cytometric analysis of stem/progenitor populations revealed expansion of the granulocyte-macrophage progenitor (GMP) population and the lin- sca+ kit+ (LSK) stem cell population. Detailed analysis of the LSK population revealed a decrease in the LT-HSC population (LSK CD150+ CD48-) that was replaced by a monomorphic CD48+ CD150- multipotent progenitor population. Given previous studies have shown that LSK and GMP cells can contain leukemia stem cells (LSC) in other models of AML, we performed secondary transplant studies with LSK and GMP populations. LSK (CD48+ CD150-) cells, but not GMP cells, were able to induce disease in secondary and tertiary recipients in vivo. In order to assess the sensitivity of Tet2/Flt3-mutant AML and specifically the LSCs, to targeted therapies, we treated primary and transplanted mice with chronic administration of AC220, a FLT3 inhibitor in late-stage clinical trials. AC220 treatment inhibited FLT3 signaling in vivo, and reduced peripheral blood counts/splenomegaly. However, FLT3 inhibition did not reduce the proportion of AML cells in the bone marrow and peripheral blood. AC220 therapy in vivo reduced the proportion of GMP cells, but not LSK cells, demonstrating LSCs in this model are resistant to FLT3-targeted anti-leukemic therapy. We hypothesized that Tet2/Flt3-mutant LSCs possess a distinct epigenetic/transcriptional signature that contributes to leukemic cell self-renewal and therapeutic resistance. We performed RNA-seq using the Lifetech Proton sequencer to profile the expression landscape of Vav+Tet2fl/flFlt3-ITD mutant LSKs compared to normal stem cells. We were able to obtain an average of 62 million reads per sample. We identified over 400 genes differentially expressed in LSCs relative to normal hematopoietic stem cells (FC>2.5, padj <0.05). Of note, we found that genes involved in normal myelo-erythroid differentiation, including GATA1, GATA2, and EPOR, were transcriptionally silenced in LSCs relative to normal stem cells, consistent with their the impaired differentiation and increased self-renewal observed in LSCs. Enhanced representation bisulfite sequencing revealed a subset of these genes were marked by increased promoter methylation. The number of hyper differentially methylated regions (HyperDMRs, 10% methylation difference, FDR<0.2) was significantly greater in Vav+Tet2fl/flFlt3-ITD cells (787 HyperDMRs) compared to Vav+Tet2fl/fl cells (76 DMRs) suggesting FLT3 activation and TET2 loss cooperate to alter the epigenetic landscape in hematopoietic cells. Our data demonstrate that TET and FLT3 mutations can cooperate to induce AML in vivo, with a defined LSC population that is resistant to targeted therapies and characterized by site-specific changes in DNA methylation and gene expression. Current studies are aimed to assess the functional role of specific gene targets in LSC survival, and at defining therapeutic liabilities that can be translated to the clinical context. Disclosures: No relevant conflicts of interest to declare