Self-managed dietary changes and functional gut symptoms in endometriosis: A qualitative interview study.

Objective: Endometriosis is a chronic gynaecological condition, often causing gastrointestinal symptoms and misdiagnosed as irritable bowel syndrome (IBS). Endometriosis guidelines do not formally endorse dietary changes and little is known about how they are self-managed. The objective of this study is to understand nutritional practices and management of gut symptoms in people with endometriosis. Study design: Participants were recruited as part of a larger survey study via endometriosis support groups on social media. Eligibility criteria were: a self-reported physician-led diagnosis of endometriosis, over 18 years old and residing in the United Kingdom (UK). Semi-structured interviews were undertaken virtually via Zoom using a predefined interview guide. All interviews were transcribed and analysed using thematic analysis. Results: 10 people with endometriosis were interviewed. All had made individual dietary changes to manage their gut-related endometriosis symptoms. Dietary changes were made based on advice from social media support, books, websites or professionals other than dietitians. Changes included the restriction and exclusion of multiple essential food groups, including dairy, grains (primarily gluten), vegetables, fruits, and animal products. These changes impacted participants' weight, nutritional status and relationship with food. Four strong themes were identified: 1) impact of pain 2) severe and unpredictable gut symptoms 3) dietary changes and their impact 4) seeking support for dietetic intervention. A common thread underlying and linking these four main themes was the feeling of being dismissed, care being delayed and lack of support. Overall the long delay waiting for a diagnosis, surgery and, at times, the re-occurrence of symptoms post-surgery led to unsupported trial and error with modifiable lifestyle factors, including diet. Conclusion: Overall, participants demonstrated some patterns of restrictive eating behaviour and wanted more professional support to help manage their endometriosis-related gut symptoms. This highlights the need for dietitians to be involved in endometriosis care to help alleviate gut symptoms, whilst ensuring nutritional adequacy and offering weight management support where required.

Nutritional practices and dietetic provision in the endometriosis population, with a focus on functional gut symptoms.

BACKGROUND: Endometriosis is a common condition causing chronic pain, fatigue and gut symptoms. Research suggests that dietary changes may improve symptoms; however, evidence is lacking. The present study aimed to investigate the nutritional practices and needs of individuals with endometriosis (IWE) and the management of endometriosis by dietitians in the UK, focusing on gut symptoms. METHODS: Two online questionnaires were distributed via social media: a survey of dietitians working with IWE and functional gut symptoms and a survey of IWE. RESULTS: All respondents to the dietitian survey (n = 21) used the low fermentable oligosaccharides disaccharides monosaccharides and polyols (FODMAP) diet in IWE, with the majority 69.3% (n = 14), reporting positive adherence and patient benefit. Dietitians recommended more training (85.7%, n = 18) and resources (81%, n = 17) for IWE. Of those who completed the IWE questionnaire (n = 1385), 38.5% (n = 533) had coexisting irritable bowel syndrome. Only 24.1% (n = 330) had satisfactory relief of gut symptoms. The most common symptoms were tiredness, bloating and abdominal pain, experienced by 85.5% (n = 1163), 75.3% (n = 1025) and 67.3% (n = 917), respectively. Some 52.2% (n = 723) had tried dietary modifications to relieve their gut symptoms; 36.7% (n = 500) ate a restricted diet at present; 13.5% (n = 184) experienced recent unintentional weight loss and 29.8% (n = 407) a decreased appetite Some 13.2% (n = 183) had seen a dietitian regarding their gut symptoms. Of those who had not seen a dietitian, 57.7% (n = 693) would find it useful to. CONCLUSIONS: Gut symptoms and dietary restriction are very common in IWE; however, dietetic input is not. More research on the role of nutrition and dietetics in the management of endometriosis is recommended.

Investigating Relations between the NICU Speech Environment and Weight Gain in Infants Born Very Preterm.

OBJECTIVE: Children born preterm, especially those born very preterm (<32 weeks of gestational age [GA]) are at risk for poor growth and adverse neurodevelopmental outcomes. Adverse growth and neurodevelopmental outcomes in preterm children have been attributed, in part, to the aversive sounds and relative speech paucity of the neonatal intensive care unit (NICU). Experimental studies that directly expose preterm infants to speech sounds in the NICU find significant improvements in health factors relevant to neurodevelopment. Few studies have examined whether natural variations in the speech environment of the NICU are related to short-term health outcomes in preterm infants. Such data are important for optimizing the sound environment of the NICU. Our objective was to examine relations between the NICU speech environment and the rate of weight gain during hospitalization. STUDY DESIGN: Participants were infants born very preterm (n = 20). The speech environment of each infant was assessed at 32 to 36 weeks of postmenstrual age using an automatic speech-counting device. Average rates of weight gain (g/kg/d) were ascertained over the same period. Calories were derived from charted intake (kcals/kg/d). Linear regressions examined caloric intake and speech counts as predictors of infant weight gain. RESULTS: Infant weight gain was significantly predicted by caloric intake and speech exposure, each uniquely accounting for approximately 27% variance (total R 2 = 60.2%; p < 0.001). Speech counts were uncorrelated with rates of family visitation, time in incubator, or health acuity. CONCLUSION: While future research should establish causality and direction of effects, enhancing speech exposure in the NICU may be beneficial for physical growth. NICU care plans should consider opportunities to increase speech exposure. KEY POINTS: · Preterm infants who experienced greater amounts of speech in the NICU gained significantly more weight than preterm infants who were exposed to lower amounts of speech during the same developmental period (32-36 weeks of postmenstrual age).. · Caloric intake and speech counts accounted for almost 60% of variance in infant weight gain between 32 and 36 weeks of postmenstrual age.. · Speech counts were not significantly correlated with family visitation, how long infants resided in incubators, or health acuity.. · Findings suggest that the NICU speech environment may play an important role in the physical health of preterm infants; however, more studies are needed to determine the directionality of the observed associations..

Development of a nutrition screening tool to identify need for dietetic intervention in female infertility.

BACKGROUND: One in seven couples are impacted by infertility in the UK, and female infertility is often associated with several health conditions impacted by nutrition. Despite many studies aimed at identifying the critical role of nutrition in infertility, there is currently no screening tool that identifies nutritional risk factors for infertility. AIM: To propose a self-administered screening tool to identify women who would benefit from nutritional intervention to promote fertility. METHODS: A narrative review was carried out to identify and summarise modifiable nutritional risk factors that can influence female fertility, including comorbidities that can influence nutrition intake, absorption, and metabolism. KEY FINDINGS: A nutrition screening tool outlining modifiable nutrition risk factors potentially improving female fertility has been proposed, comprising of BMI, medical history and quality of diet and lifestyle which would aid in designing evidence based dietetic services for female infertility.

Hypertrophic Pachymeningitis Presenting as "Eyebrows" Sign on 18 F FDG PET/CT.

Hypertrophic pachymeningitis refers to linear or nodular thickening of the dura mater covering the brain and spinal cord following various inflammatory/infective processes. Usually, magnetic resonance imaging brain shows uniform thickening with enhancement of involved meninges. Fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) findings of pachymeningitis are rarely reported in literature. We describe the PET/CT findings of a patient with hypertrophic pachymeningitis involving the bilateral supraorbital regions depicting as "eyebrows" on brain maximum intensity projection image.

Risk of preterm birth and neonatal outcomes after cerclage placement in triplet pregnancies.

BACKGROUND: The number of triplet pregnancies in the United States has increased significantly. Perinatal morbidity and mortality are higher in these pregnancies mainly due to higher preterm birth rates. Interventions to decrease the risk of preterm delivery in this population are needed. Evidence regarding cerclage placement in triplets is limited. We performed a population-based, retrospective cohort study to study the risk of preterm birth and neonatal outcomes after cerclage placement in triplet pregnancies. METHODS: All U.S. triplet deliveries from 2006 to 2013 with risk factors for cervical insufficiency were selected, excluding cases with indicated preterm delivery. Cases were categorized according to cerclage placement status. The risk of preterm birth and adverse neonatal outcomes were calculated using propensity score analysis, generalized linear, and logistic regression models. RESULTS: From ∼33 million deliveries, 43,000 were triplets, and 7308 fulfilled eligibility criteria. There was no difference in the gestational age at delivery between the cerclage and noncerclage groups, aOR (95% CI) = 1.0(0.9-1.0). The difference between the risk of preterm delivery at <34 weeks and <32 weeks was not statistically significant. The risk of the composite outcome of neonatal complications was higher in the cerclage compared to the noncerclage group, aOR (95% CI) = 1.5 (1.1-2.2). CONCLUSIONS: Cerclage placement in triplet pregnancies does not appear to decrease preterm birth rates and seems to increase the risk of neonatal complications.

Catalytic Conversion of Glucose into Levulinic Acid Using 2-Phenyl-2-Imidazoline Based Ionic Liquid Catalyst.

Levulinic acid (LA) is an industrially important product that can be catalytically valorized into important value-added chemicals. In this study, hydrothermal conversion of glucose into levulinic acid was attempted using Brønsted acidic ionic liquid catalyst synthesized using 2-phenyl-2-imidazoline, and 2-phenyl-2-imidazoline-based ionic liquid catalyst used in this study was synthesized in the laboratory using different anions (NO3, H2PO4, and Cl) and characterized using 1H NMR, TGA, and FT-IR spectroscopic techniques. The activity trend of the Brønsted acidic ionic liquid catalysts synthesized in the laboratory was found in the following order: [C4SO3HPhim][Cl] > [C4SO3HPhim][NO3] > [C4SO3HPhim][H2PO4]. A maximum 63% yield of the levulinic acid was obtained with 98% glucose conversion at 180 °C and 3 h reaction time using [C4SO3HPhim][Cl] ionic liquid catalyst. The effect of different reaction conditions such as reaction time, temperature, ionic liquid catalyst structures, catalyst amount, and solvents on the LA yield were investigated. Reusability of [C4SO3HPhim][Cl] catalyst up to four cycles was observed. This study demonstrates the potential of the 2-phenyl-2-imidazoline-based ionic liquid for the conversion of glucose into the important platform chemical levulinic acid.

Addressing Racial Disparities in Live Donor Kidney Transplantation Through Education and Advocacy Training.

BACKGROUND: The Live Donor Champion (LDC) program trains kidney transplant (KT) candidates and their family/friends ("champions") as educator-advocates for live donor KT (LDKT). This program was created to empower patients and champions, particularly African American (AA) waitlist candidates that historically had lower access to LDKT. We assessed changes in knowledge about and comfort discussing live donation and donor referral associated with LDC participation, both overall and by participant race. METHODS: We compared 163 adult KT candidates who were LDC participants from October 2013 to May 2016 with 489 matched controls, both overall and by race. We compared changes in comfort and knowledge post-LDC using rank-sum tests among participants by race. We compared time to first live donor referral for participants versus controls, by race, using Cox regression. RESULTS: Post-LDC versus pre-LDC, participants had higher median knowledge (83% versus 63% on 12-question quiz; P < 0.001) and comfort (1.8 versus 1 on 4-point Likert scale; P < 0.001). Among participants, AAs had similar baseline and final knowledge (P = 0.9 and P = 0.1, respectively) and baseline comfort (P > 0.9) as non-AAs but higher final comfort (2 versus 1.4; P = 0.005) than non-AAs. LDC participants were 5.8 times as likely as controls to have a live donor referral (aHR 3.765.788.89; P < 0.001); the impact of LDC participation was similar among non-AAs and AAs (p-interaction = 0.6). CONCLUSIONS: The LDC program increased knowledge, comfort, and live donor referral for non-AA and AA participants, underscoring the effectiveness in the program in promoting LDKT in a population with historically lower access to LDKT.

Willingness to Donate Organs Among People Living With HIV.

BACKGROUND: With passage of the HIV Organ Policy Equity (HOPE) Act, people living with HIV (PLWH) can donate organs to PLWH awaiting transplant. Understanding knowledge and attitudes regarding organ donation among PLWH in the United States is critical to implementing the HOPE Act. METHODS: PLWH were surveyed regarding their knowledge, attitudes, and beliefs about organ donation and transplantation at an urban academic HIV clinic in Baltimore, MD, between August 2016 and October 2016. Responses were compared using Fisher exact and χ tests. RESULTS: Among 114 survey respondents, median age was 55 years, 47.8% were female, and 91.2% were African American. Most were willing to be deceased donors (79.8%) or living donors (62.3%). Most (80.7%) were aware of the US organ shortage; however, only 24.6% knew about the HOPE Act, and only 21.1% were registered donors. Respondents who trusted the medical system or thought their organs would function adequately in recipients were more likely to be willing to be deceased donors (P < 0.001). Respondents who were concerned about surgery, worse health postdonation, or need for changes in HIV treatment because of donation were less likely to be willing to be living donors (P < 0.05 for all). Most believed that PLWH should be permitted to donate (90.4%) and that using HIV+ donor organs for transplant would reduce discrimination against PLWH (72.8%). CONCLUSIONS: Many of the PLWH surveyed expressed willingness to be organ donors. However, knowledge about the HOPE Act and donor registration was low, highlighting a need to increase outreach.

Racial differences in completion of the living kidney donor evaluation process.

Racial disparities in living donor kidney transplantation (LDKT) persist but the most effective target to eliminate these disparities remains unknown. One potential target could be delays during completion of the live donor evaluation process. We studied racial differences in progression through the evaluation process for 247 African American (AA) and 664 non-AA living donor candidates at our center between January 2011 and March 2015. AA candidates were more likely to be obese (38% vs 22%: P < .001), biologically related (66% vs 44%: P < .001), and live ≤50 miles from the center (64% vs 37%: P < .001) than non-AAs. Even after adjusting for these differences, AAs were less likely to progress from referral to donation (aHR for AA vs non-AA: 0.26 0.47 0.83; P = .01). We then assessed racial differences in completion of each step of the evaluation process and found disparities in progression from medical screening to in-person evaluation (aHR: 0.41 0.620.94; P = .02) and from clearance to donation (aHR: 0.28 0.510.91; P = .02), compared with from referral to medical screening (aHR: 0.78 1.021.33; P = .95) and from in-person evaluation to clearance (aHR: 0.59 0.931.44; P = .54). Delays may be a manifestation of the transplant candidate's social network, thus, targeted efforts to optimize networks for identification of donor candidates may help address LDKT disparities.

Racial/ethnic disparities in magnesium sulfate neuroprotection: a subgroup analysis of a multicenter randomized controlled trial.

OBJECTIVE: Despite known racial disparities in obstetrics, as well as differences in magnesium pharmacodynamics according to race, the effect of race/ethnicity in magnesium sulfate (MgSO4) use during pregnancy has not been studied. Whether some mothers are at increased risk of side effects, or infants at decreased neuroprotective effects is unknown. We analyze the effect of race/ethnicity in maternal/infant outcomes after MgSO4 neuroprotection. STUDY DESIGN: Subgroup analysis of a multicenter clinical trial (BEAM trial) where pregnant women at risk of preterm birth were randomized to either MgSO4 or placebo. For this study, nonanomalous singleton pregnancies were studied. The effect of race in maternal/neonatal outcomes after MgSO4 was analyzed with Breslow-Day and multifactorial ANOVA. Logistic regression was used to calculate odds ratios (OR) of complications according to race. RESULTS: 922 MgSO4 and 972 placebo cases were included (45.0% African-American, 36.2% Caucasian, 17.8% Hispanics, and 1.0% Asians). Interaction analysis showed a significant effect of race/ethnicity (p = .043). Hispanics presented the highest frequency (88.3%, p < .001), as well as the highest odds of MgSO4 side effects [OR(95%CI) = 6.6 (1.3-33.8)]. CONCLUSION: Hispanics present increased risk of magnesium toxicity compared to other racial/ethnic groups. Whether specific racial/ethnic groups require closer surveillance for early signs of magnesium toxicity needs to be further explored.

Risk of Expectant Management and Optimal Timing of Delivery in Low-Risk Term Pregnancies: A Population-Based Study.

OBJECTIVE: The benefits of the 39-week rule have been questioned and concerns of increased stillbirth after adoption of this rule have been raised. Whether expectant management risks outweigh the benefits of awaiting 39 weeks has not been studied. We analyze the risks of expectant management at term and the optimal timing for delivery. STUDY DESIGN: All U.S. nonanomalous singleton term deliveries in 2013 were selected, excluding diabetes/hypertension, and low birth weight. Maternal/neonatal complications and stillbirth/infant death were compared among expectant management versus deliveries at each term gestational age. Logistic regression was used to calculate adjust odds ratios of complications according to delivery plan at each gestational age. RESULTS: From approximately 3 million deliveries, maternal complications during expectant management were lower at early term, and became higher at 39 weeks, relative risk [RR] (95% confidence interval [CI]) = 1.18 (1.16-1.19). Neonatal complications during expectant management were lower during early term, and became higher at ≥39 weeks, RR (95% CI) = 1.09 (1.08-1.09). The risk of perinatal mortality in the expectant management group was lower during early term, and became higher at ≥39 weeks, 18.93 (17.83-20.10) versus 17.37 (16.61-18.16), p = 0.010. CONCLUSION: Complications during expectant management occurring while awaiting full term do not outweigh the benefits of better outcomes from reaching 39 weeks. However, extending beyond 39 weeks may put these pregnancies at an increased risk.

Persistent regional and racial disparities in nondirected living kidney donation.

Nondirected living donors (NDLDs) are an important and growing source of kidneys to help reduce the organ shortage. In its infancy, NDLD transplantation was clustered at a few transplant centers and rarely benefited African American (AA) recipients. However, NDLDs have increased 9.4-fold since 2000, and now are often used to initiate kidney paired donation chains. Therefore, we hypothesized that the initial geographic clustering and racial disparities may have improved. We used Scientific Registry of Transplant Recipients data to compare NDLDs and their recipients between 2008-2015 and 2000-2007. We found that NDLD increased an average of 12% per year, from 20 in 2000 to 188 in 2015 (IRR: 1.12, 95% CI: 1.11-1.13, P < .001). In 2000-2007, 18.3% of recipients of NDLD kidneys were AA; this decreased in 2008-2015 to 15.7%. NDLD transplants initially became more evenly distributed across centers (Gini 0.91 in 2000 to Gini 0.69 in 2011), but then became more clustered at fewer transplant centers (Gini 0.75 in 2015). Despite the increased number of NDLDs, racial disparities have worsened and the center-level distribution of NDLD transplants has narrowed in recent years.

Contemporary epidemiology and novel predictors of uterine rupture: a nationwide population-based study.

PURPOSE: In spite of several policies aiming to decrease cesarean rates and related complications such as uterine rupture, data show that uterine rupture and associated morbidity are increasing along the years. Whether previously unidentified risk factors are currently playing an important role on these trends is unknown. We analyze current risks of uterine rupture and main preceding factors from more recent years compared to former data. METHODS: All uterine rupture cases in the US from 2011-2012 were selected, with matched non-uterine rupture cases selected as controls. Variables considered for analysis included demographics, maternal morbidity, and obstetric complications. Likelihood forward selection was used to identify main risk factors of uterine rupture. Medians of main factors identified were used to simulate groups at risk and calculate odds ratios of uterine rupture. RESULTS: From ~8 million births, 1925 presented uterine rupture. In patients with no prior cesarean delivery, multiple gestation, chronic hypertension and chorioamnionitis presented the highest odds of uterine rupture, with the combination of these factors increasing the odds of rupture 59 times (~1%). In women with prior cesarean delivery, induction/augmentation and chorioamnionitis were the most significant predictors, with the combination increasing the odds 33 times (~3%). CONCLUSIONS: Despite policies implemented and changes in clinical practice, uterine rupture remains an important issue. Previously unidentified risk factors are playing now an important role, information that should be considered during patient counseling and clinical practice. Combinations of some of these factors may increase the risk of uterine rupture significantly enough to modify clinical care.

Is mean platelet volume a better biomarker in pre-eclampsia?

AIM: Platelet activation and destruction is a well recognized feature of pre-eclampsia, but the current literature is contradictory regarding the role of mean platelet volume (MPV) in the diagnosis of this condition. We investigated whether MPV, compared with other routine laboratory markers such as platelet count, is a more significant biomarker of pre-eclampsia, giving special attention to the intrapartum period. METHODS: Biochemical and hematological markers along pregnancy including MPV were compared retrospectively between pre-eclampsia and matched controls. Laboratory marker data were compared using independent t-test. A logistic regression model was used to compare the strength of the associations of MPV and other routine markers such as platelet count with pre-eclampsia. Receiver operating characteristic curves were plotted. RESULTS: There were a total of 150 cases of pre-eclampsia and 297 controls. In the pre-eclampsia group, there were 60 cases of mild pre-eclampsia (40.0%); 84, severe (56.0%); and six of eclampsia (4.0%). MPV was significantly higher in the pre-eclampsia than in the control group (11.3 ± 1.0 vs 10.1 ± 0.8 fL, P = 0.002). On multivariate analysis, MPV was the only statistically significant biomarker of pre-eclampsia (OR, 4.5; 95%CI: 1.5-13.7), and severe pre-eclampsia (OR, 6.2; 95%CI: 1.6-24.6); performing superiorly to platelet count. CONCLUSIONS: Mean platelet volume is a more significant biomarker of pre-eclampsia. It is more significantly associated with this condition than other routinely measured laboratory markers such as platelet count. MPV is routinely obtained on complete blood cell count and its utilization in the assessment of pre-eclampsia in a clinical setting should continue to be evaluated.

Contemporary analysis of maternal and neonatal morbidity after uterine rupture: A nationwide population-based study.

AIM: Uterine rupture is a rare but feared perinatal event. Despite abundant research and changes to guidelines implemented to reduce this complication, evaluation of whether uterine rupture still engenders significant maternal/neonatal morbidity has not been conducted. We analyzed recent cases of maternal/neonatal morbidity after uterine rupture. METHODS: Deliveries complicated by uterine rupture from 2011 to 2012 in the United States were selected. Comparison cases without uterine rupture were used as controls. Measures of maternal/neonatal complications were compared with χ2 test, and relative risks were calculated. Logistic regression was used to identify the most significant complications. P < 0.05 indicated statistical significance. RESULTS: From 7 922 016 births, 1925 cases of uterine rupture and 3765 controls were identified. Regression models retained four maternal outcomes; blood transfusion was the most common (~15%) and unplanned hysterectomy had the highest odds (~97-fold). For newborns, the model retained three measures of morbidity; neonatal intensive care unit admission was the most common (~35%) and seizures had the highest odds (~20-fold). CONCLUSIONS: Despite efforts to reduce complications, mothers remain at significant risk of unplanned hysterectomy and intensive care unit admission. Neonates are at sizeable risk for neonatal intensive care unit admission and seizures, recognized markers of long-term neurobehavioral abnormality. Uterine rupture remains a major risk for mothers and babies.

Outcomes of Live Kidney Donors Who Develop End-Stage Renal Disease.

BACKGROUND: Kidney donors can develop end-stage renal disease (ESRD) after donation, but the outcomes of those who do remain poorly characterized. METHODS: Using United States Renal Data System and Scientific Registry for Transplant Research data, we compared access to kidney transplantation (KT), time from ESRD to listing, time from listing to KT, and post-KT graft failure and death between donors and matched nondonors with ESRD. RESULTS: Among 99 donors between April 1994 and November 2011 who developed ESRD, 78 initially received dialysis (of whom 37 listed for KT, 2 received live donor KT without listing, and 39 never listed for or received a KT), 20 listed preemptively (of whom 19 were subsequently transplanted), and 1 received a preemptive live donor KT without listing or ever receiving dialysis. Donors were listed earlier (median time to listing, 17 months vs 120 for nondonors; P < 0.001), received KT earlier (median waiting time, 2.8 months vs 21.5 for nondonors; P < 0.001), and received 13% live donor, 87% standard criteria, and 0% expanded criteria deceased donor KT (39%, 50%, and 11% in nondonors). Post-KT graft (adjusted hazard ratio, 1.9; 95% confidence interval, 0.9 to 4.1; P = 0.1) and patient (adjusted hazard ratio, 0.7; 95% confidence interval, 0.2 to 2.4; P = 0.5) survival were comparable in donors and nondonors. CONCLUSIONS: Our finding that 39 of 99 donors who developed ESRD never listed for a transplant warrants further study to ascertain why these donors with ESRD never gained access to the waiting list.

Coexpression of hyperactivated AKT1 with additional genes activated in leukemia drives hematopoietic progenitor cells to cell cycle block and apoptosis.

The phosphatidylinositol 3-kinase/AKT pathway is an integral component of signaling involved in the development of many cancers, including myeloid leukemias such as chronic myeloid leukemia and acute myeloid leukemia (AML). Increased AKT1 activity is frequently seen in AML patients, providing leukemic cells with growth and survival promoting signals. An important aspect of AKT1 function is its involvement in cellular metabolism and energy production. Under some circumstances, strong activation of AKT1 increases oxidative stress, which can cause apoptosis when cells progressively build up excess free radicals. This has been described in hematopoietic cells overexpressing activated AKT1; however, whether this is true in cells coexpressing other genetic events involved in leukemia is not known. This prompted us to investigate the effect of constitutively active AKT1 (myristoylated AKT1) in hematopoietic progenitor cells expressing constitutively active signal transducer and activator of transcription 5, Fms-related tyrosine kinase 3-internal tandem duplication, or antiapoptotic B-cell lymphoma 2. Surprisingly, myristoylated AKT1 was incompatible with proliferation driven by both signal transducer and activator of transcription 5 and Fms-related tyrosine kinase 3-internal tandem duplication, which triggered cell cycle block and apoptosis. Moreover, transplantable cells of B-cell lymphoma 2-transgenic mice were impaired in their engraftment ability to recipient mice when expressing hyperactivated AKT1. This was linked to AKT1-mediated proapoptotic functions and not to impairment in homing to the bone marrow. Although cells expressing hyperactivated AKT1 displayed higher levels of reactive oxygen species both in vitro and in vivo, the addition of the antioxidant N-acetyl-L-cysteine significantly reduced apoptosis. Taken together, the results indicate that constitutive AKT1 activity is incompatible with growth- and survival-promoting ability of other activated genes in AML.

Perceptions about hemodialysis and transplantation among African American adults with end-stage renal disease: inferences from focus groups.

BACKGROUND: Disparities in access to kidney transplantation (KT) remain inadequately understood and addressed. Detailed descriptions of patient attitudes may provide insight into mechanisms of disparity. The aims of this study were to explore perceptions of dialysis and KT among African American adults undergoing hemodialysis, with particular attention to age- and sex-specific concerns. METHODS: Qualitative data on experiences with hemodialysis and views about KT were collected through four age- and sex-stratified (males <65, males ≥65, females <65, and females ≥65 years) focus group discussions with 36 African American adults recruited from seven urban dialysis centers in Baltimore, Maryland. RESULTS: Four themes emerged from thematic content analysis: 1) current health and perceptions of dialysis, 2) support while undergoing dialysis, 3) interactions with medical professionals, and 4) concerns about KT. Females and older males tended to be more positive about dialysis experiences. Younger males expressed a lack of support from friends and family. All participants shared feelings of being treated poorly by medical professionals and lacking information about renal disease and treatment options. Common concerns about pursuing KT were increased medication burden, fear of surgery, fear of organ rejection, and older age (among older participants). CONCLUSIONS: These perceptions may contribute to disparities in access to KT, motivating granular studies based on the themes identified.