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PDF file - 63K, PCR Primer Sequences

PDF file - 7.6MB, A. Thickness of stroma surrounding each gland in different mouse postatic lobes. B. MMP7 staining in the dorsal prostatic lobes.

PDF file - 6.6MB, Immunohistochemical staining of laminin in whole prostate sections.

PDF file - 3MB, Percentages of PIN and invasive adenocarcinoma in different prostatic lobes.

BACKGROUND: Vaso-occlusive pain leads to high acute care utilization among patients with sickle cell disease (SCD). Data suggest that clinical pathways (CPWs) reduce variation in the management of vaso-occlusive pain and improve clinical outcomes. METHODS: We implemented and evaluated a CPW for vaso-occlusive pain at our institution using a before and after study design. The primary objective was to decrease acute care utilization among patients with SCD, which was assessed by the primary outcome measures of hospital length of stay (LOS), 30-day readmission rate, and total hospitalizations annually per patient. Secondary outcome measures were packed red blood cell transfusions, and acute chest syndrome incidence. Patient-controlled analgesia use and promethazine use were assessed to estimate CPW utilization. RESULTS: 344 admissions in 112 patients were analyzed, of which 193 admissions occurred pre-CPW and 151 admissions occurred post-CPW implementation. Post-CPW implementation, we observed a significant decrease in hospital admissions annually per patient, an increase in patient-controlled analgesia (PCA) use, and a decrease in intravenous (IV) promethazine use. We observed trends toward decreased 30-day readmission rate and increased ACS incidence, which were not statistically significant. No effect was found on hospital LOS. CONCLUSION: CPW implementation at our institution reduced variation in management and decreased hospital admissions for vaso-occlusive pain.

Federally qualified health centers are on the frontlines of the coronavirus disease 2019 (COVID-19) pandemic in the United States. It is essential to develop the workflows necessary to evaluate patients, perform appropriate diagnostics, make clinical recommendations, and provide public health messaging. This brief report presents findings from our COVID-19 response and compares the characteristics between the 345 patients screened between March 16 and April 10, 2020. One hundred seventeen patients tested positive for COVID-19, an overall rate of 33.9%; and Black race, increased heart rate, elevated temperature, and the use of antipyretic agents were associated with positive results.

Nutrient deficits have been repeatedly linked to cervical human papillomavirus (HPV) persistence, cervical neoplasia, and cervical cancer in case-control studies. This study sought to examine the relationship between overall diet quality and dietary components with the spontaneous resolution of cervical HPV over one year. A prospective observational cohort study was performed. Women with low-grade cervical cytology and/or positive HPV test completed a 24-hour dietary recall, from which the Healthy Eating Index (HEI)-2010, a score of overall diet quality, and scores in dietary categories were calculated. Participants were managed clinically according to national management guidelines. Those whose subsequent testing demonstrated normalization of cytology and/or HPV testing (“HPV resolution”) were compared to those whose abnormalities persisted or progressed (“HPV non-resolution”). Twenty-six women were included in the HPV resolution group and 38 in the non-resolution group. They were observed for a median of 428 and 412 days, respectively (p=0.09). There was no difference in overall diet quality between the groups. Intake of total and whole fruit, and seafood/plant protein were associated with HPV resolution in a logistic regression model (all p

OBJECTIVE Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity, and diabetes. We examined the association between hypertension, obesity, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak. RESEARCH DESIGN AND METHODS Data were collected from 287 consecutive patients with COVID-19 hospitalized at two hospitals in New Orleans, LA, from 30 March to 5 April 2020. MetS was identified per World Health Organization criteria. RESULTS Among 287 patients (mean age 61.5 years; female, 56.8%; non-Hispanic Black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR] 3.42 [95% CI 1.52–7.69]), intensive care unit requirement (ICU) (aOR 4.59 [CI 2.53–8.32]), invasive mechanical ventilation (IMV) (aOR 4.71 [95% CI 2.50–8.87]), and acute respiratory distress syndrome (ARDS) (aOR 4.70 [95% CI 2.25–9.82]) compared with non-MetS. Multivariable analyses of hypertension, obesity, and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR 2.18 [95% CI 1.25–3.81]), ARDS (aOR 2.44 [95% CI 1.28–4.65]), and IMV (aOR 2.36 [95% CI 1.33–4.21]). Diabetes was associated with ICU (aOR 2.22 [95% CI 1.24–3.98]) and IMV (aOR 2.12 [95% CI 1.16–3.89]). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, CRP and lactate dehydrogenase (LDH), were associated with mortality (CRP [aOR 3.66] [95% CI 1.22–10.97] and LDH [aOR 3.49] [95% CI 1.78–6.83]). CONCLUSIONS In predominantly Black patients hospitalized for COVID-19, the clustering of hypertension, obesity, and diabetes as MetS increased the odds of mortality compared with these comorbidities individually.

Background Aging is the most important risk factor for prostate cancer (PCa), but how age contributes to PCa is poorly understood. Aging is characterized by low-grade systemic inflammation (i.e., inflammaging) that is often attributed to the progressive activation of immune cells over time, which may play an important role in prostate carcinogenesis. Th17 response is elevated in aging humans and mice, but it remains unknown whether it is increased in prostate tissue or contributes to prostate carcinogenesis during aging. In this study, we aimed to determine the role of age-related Th17 response in PCa cell growth, migration, and invasion. Methods C57BL/6J (B6) mouse was used as an aging animal model and the prostate histopathology during aging was analyzed. Splenic CD4+ T cells were isolated from young (16-20 weeks old) and aged (96-104 weeks old) mice, and cultured in the presence of plate-bound anti-CD3/anti-CD28, with or without Th17 differentiation conditions. The cells were collected and used for subsequent flow cytometry or quantitative reverse transcription polymerase chain reaction. The supernatant was collected and used to treat PCa cell lines. The treated PCa cells were analyzed for cell viability, migration, invasion, and nuclear factor kappa B (NF-κB) signaling. Results Aged mice had enlarged prostate glands and increased morphological alterations, with not only increased inflammatory cell infiltration but also increased Th17 cytokines in prostate tissue, compared to young mice. Naive CD4+ T cells from aged mice differentiated increased interleukin (IL)-17-expressing cells. CD4+ T cells from aged mice spleen had increased Th17 cells, Th17 cytokines and Th17/Treg ratio compared to young mice. Factors secreted from aged CD4+ T cells, especially from ex vivo differentiated Th17 cells, not only promoted PCa cell viability, migration, and invasion but also activated the NF-κB signaling in PCa cells compared to young mice. Conclusions These results indicate that age-related CD4+ T cells, especially Th17 cells-secreted factors have the potential to contribute to prostate carcinogenesis. Our work could prompt further research using autochthonous PCa mouse models at different ages to elucidate the functional role of Th17 response in prostate carcinogenesis during aging.

Background Obesity remains a relative contraindication for heart transplantation, and hence, obese patients with advanced heart failure receive ventricular assist devices (VADs) either as a destination or “bridge to weight loss” strategy. However, impact of obesity on clinical outcomes after VAD implantation is largely unknown. We sought to determine the clinical outcomes of obese patients with body mass index (BMI) ≥ 35 kg/m2) following contemporary VAD implantation. Methods The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) registry was queried for patients who underwent VAD implantation. Patients were categorized into BMI groups based on World Health Organization classification. Results Of 17,095 patients, 2620 (15%) had a BMI ≥ 35 kg/m2. Obese patients were likely to be young, non-white, females with dilated cardiomyopathy and undergo device implantation as destination. Survival was similar amongst BMI groups (P = .058). Obese patients had significantly higher risk for infection (hazard ratio [HR]: 1.215; P = .001), device malfunction or thrombosis (HR: 1.323; P ≤ .001), cardiac arrhythmia (HR: 1.188; P = .001) and hospital readmissions (HR: 1.073; P = .022), but lower risk of bleeding (HR: 0.906; P = .018). Significant weight loss (≥10%) during VAD support was achieved only by a small proportion (18.6%) of patients with BMI ≥ 35 kg/m2. Significant weight loss rates observed in obese patients with VAD implantation as destination and bridge to transplant strategy were comparable. Obese patients with significant weight loss were more likely to undergo cardiac transplantation. Weight loss worsened bleeding risk without altering risk for infection, cardiac arrhythmia, and device complications. Conclusions Obesity alone should not be considered a contraindication for VAD therapy in contemporary era. Given durability of heart transplantation, strategies should be developed to promote weight loss, which occurs infrequently in obese patients. Impact of weight loss on clinical outcome of obese patients warrants further investigation.

Serologic testing of residual blood samples from 812 children from a hospital in New Orleans, LA, between March and May 2020, demonstrated a SARS-CoV-2 seroprevalence of 6.8% based on S and N protein IgG; Black and Hispanic children, and children living in zip codes with lower household incomes were over-represented.

BACKGROUND/STUDY CONTEXT. Adaptation to normative age-related declines in memory is an important but understudied aspect of successful aging. The purpose of the present study was to shed new light on memory self-efficacy and beliefs about memory and aging as two integral aspects of adult cognition with relevance to successful aging. METHODS. Young (19 to 27 years) and community-dwelling older adults (60 to 94 years) from the Louisiana Healthy Aging Study (LHAS) completed an adapted Memory Functioning Questionnaire (MFQ) which includes a memory self-efficacy subscale, the Memory Controllability Inventory (MCI), and the Aging Concerns Scale (ACS). RESULTS. Nonagenarians’ self-reported memory and beliefs about memory and aging were of central interest. We compared their responses to three younger reference groups to examine hypothesized differences in self-reported memory and beliefs about memory and aging in very late life. Results yielded age effects for most of the MFQ and MCI subscales demonstrating more positive subjective views about memory functioning and control over memory for the young adults. Correlation and regression analyses were conducted to isolate factors that may be associated with memory self-efficacy. Age, symptoms of depression, and memory control beliefs accounted for approximately half of the variance in memory self-efficacy ratings. CONCLUSION. These data indicate that although memory self-efficacy may be age sensitive, we detected no differences in subjective views across the three older groups. Implications for cognitive adaptability and successful aging are considered.

Preeclampsia is a pregnancy-related hypertensive disorder accounting for 14% of global maternal deaths annually. Preeclampsia — maternal hypertension and proteinuria — is promoted by placental ischemia resulting from reduced uteroplacental perfusion. Here, we assess longitudinal changes in placental oxygenation during preeclampsia using spectral photoacoustic imaging. Spectral photoacoustic images were acquired of the placenta of normal pregnant (NP) and preeclamptic reduced uterine perfusion pressure (RUPP) Sprague Dawley rats on gestational days (GD) 14, 16, and 18, corresponding to mid- to late gestation (n = 10 per cohort). Two days after implementation of the RUPP surgical model, placental oxygen saturation decreased 12% in comparison with NP. Proteinuria was determined from a 24-hour urine collection prior to imaging on GD18. Blood pressure measurements were obtained on GD18 after imaging. Placental hypoxia in the RUPP was confirmed with histological staining for hypoxia-inducible factor (HIF)-1α, a cellular transcription regulator which responds to local oxygen levels. Using in vivo, longitudinal imaging methods we determined that the placenta in the reduced uterine perfusion pressure rat model of preeclampsia is hypoxic, and that this hypoxia is maintained through late gestation. Future work will utilize these methods to assess the impact of novel therapeutics on placental ischemia and the progression of preeclampsia.

In vitro studies indicate IFNγ is central to Chlamydia trachomatis (Ct) eradication, but its function may be compromised by anaerobes typically associated with bacterial vaginosis (BV), a frequent co-morbidity in women with Ct. Here we investigated the associations between natural clearance of cervical Ct infection, the vaginal microbiome, and the requirements for IFNγ by evaluating the vaginal microbial and cytokine composition of Ct treatment visit samples from women who cleared Ct infection in the interim between their Ct screening and Ct treatment visit. The pilot cohort was young, predominantly African American, and characterized by a high rate of BV that was treated with metronidazole at the Ct screening visit. The rate of natural Ct clearance was 23.6% by the Ct treatment visit (median 9 days). 16S rRNA gene sequencing revealed that metronidazole-treated women who had a Lactobacillus spp.-dominant vaginal microbiota (CST 2 or 3) at the Ct treatment visit, were more prevalent in the Ct clearing population than the non-clearing population (86% v. 50%). L. iners (CST2) was the major Lactobacillus spp. present in Ct clearers, and 33% still remained anaerobe-dominant (CST1). Vaginal IFNγ levels were not significantly different in Ct clearers and non-clearers and were several logs lower than that required for killing Ct in vitro. An expanded panel of IFNγ-induced and proinflammatory cytokines and chemokines also did not reveal differences between Ct clearers and non-clearers, but, rather, suggested signatures better associated with specific CSTs. Taken together, these findings suggest that BV-associated bacteria may impede Ct clearance, but a Lactobacillus spp.-dominant microbiome is not an absolute requirement to clear. Further, IFNγ may be required at lower concentrations than in vitro modeling indicates, suggesting it may act together with other factors in vivo. Data also revealed that the vaginal bacteria-driven inflammation add complexity to the genital cytokine milieu, but changes in this microbiota may contribute to, or provide cytokine biomarkers, for a shift to Ct clearance.

Light has been a crucial part of everyday life since the beginning of time. Most recently, light-emitting diode (LED) light enriched in the blue-appearing portion of the visible spectrum (465 to 485 nm), which is more efficient in energy use, is becoming the normal lighting technology in facilities around the world. Previous reports revealed that blue-enriched LED light at day (bLAD) enhances animal health and wellbeing as compared with cool white fluorescent (CWF) lighting. We hypothesized that bLAD, compared with CWF light, has a positive influence on basic physiologic indices such as food consumption, water consumption, weight gain, nesting behavior, complete blood count, and blood chemistry profile. To test this, we allocated 360 mice into equal-sized groups by sex, strain (C3H/HeNCrl, C57BL/6NCrl, BALB/cAnNCrl), lighting conditions, and 6 blood collection time points (n = 5 mice/sex/strain/lighting condition/time point). Food consumption, water consumption, body weight, nest location, and nest type were recorded every 3 d. At the end of the study, all mice were anesthetized over a period of 1 wk and blood was collected via cardiocentesis at 6 different time points. Overall, male C3H/HeNCrl consumed more food under bLAD conditions as compared with CWF conditions; male C3H/HeNCrl had lower cholesterol levels under bLAD conditions than under CWF conditions; female BALB/cAnNCrl mice had higher serum total protein under bLAD conditions than under CWF conditions; female C57BL/6NCrl mice had higher phosphorus levels under bLAD conditions than under CWF conditions, and female C3H/HeNCrl mice had a higher neutrophil count under bLAD conditions as compared with CWF conditions. Although sex and strain differences were found in various physiologic parameters under bLAD as compared with CWF lighting conditions, the differences were minimal. Thus, this study suggests that for these strains of mice, bLAD and CWF are largely equivalent with regard to indices of health and wellbeing, although some differences could affect research outcomes.

Purpose: To compare the dietary quality among adolescents who skip lunch and those who do not and explore associations between school-level variables, demographic variables and lunch skipping. Design: Cross-sectional Setting: Public schools in New Orleans, Louisiana (n = 21) Participants: 718 adolescents Methods: Adolescents participated in a 24-hour dietary recall using the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Tool early in 2013. Data were converted into Healthy Eating Index (HEI-2010) scores. Mean scores were compared between students who skipped lunch and those who did not. A multilevel analysis was conducted to assess relationships between school environment, demographics, and lunch skipping. Results: Of the 718 respondents, 88.3% were Black and 15.3% skipped lunch. Students who ate lunch had a mean HEI score of 46.6 compared to a mean score of 41.7 for students who skipped lunch (p < .001). Students who skipped lunch also had significantly lower intake of total vegetables (p = .02), whole fruits (p < .001), total dairy (p = .003), total protein (p < .001). Conclusions: Skipping lunch was associated with lower quality diet, though diet quality was low among all students. Considering over 15% of the sample did not eat lunch in a closed-campus school setting, further research should consider how to encourage students to participate in the National School Lunch Program, which has the ability to increase diet quality in adolescents.

Biological age captures some of the variance in life expectancy for which chronological age is not accountable, and it quantifies the heterogeneity in the presentation of the aging phenotype in various individuals. Among the many quantitative measures of biological age, the mathematically uncomplicated frailty/deficit index is simply the proportion of the total health deficits in various health items surveyed in different individuals. We used 3 different statistical methods that are popular in machine learning to select 17–28 health items that together are highly predictive of survival/mortality, from independent study cohorts. From the selected sets, we calculated frailty indexes and Klemera–Doubal’s biological age estimates, and then compared their mortality prediction performance using Cox proportional hazards regression models. Our results indicate that the frailty index outperforms age and Klemera–Doubal’s biological age estimates, especially among the oldest old who are most prone to biological aging-caused mortality. We also showed that a DNA methylation index, which was generated by applying the frailty/deficit index calculation method to 38 CpG sites that were selected using the same machine learning algorithms, can predict mortality even better than the best performing frailty index constructed from health, function, and blood chemistry.

BACKGROUNDChildren (≤18 years) account for ∼20% of the US population but currently represent METHODSDuring the March 18th-May 15th 2020 Louisiana Stay At Home Order, 1690 blood samples from 812 individuals from a Children’s Hospital were tested for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein. Demographics, COVID-19 testing, and clinical presentation abstracted from medical records were compared with local COVID-19 cases.RESULTSIn total, 62 subjects (7.6%) were found to be seropositive. The median age was 11 years with 50.4% female. The presenting complaint of seropositive patients was chronic illness (43.5%). Only 18.2% had a previous positive COVID-19 PCR or antibody test. Seropositivity was significantly associated with parish (counties), race, and residence in a low-income area. Importantly, seropositivity was linearly correlated with cumulative COVID-19 case number for all ages by parish.CONCLUSIONIn a large retrospective study, the seropositivity prevalence for SARS-CoV-2 in children in Louisiana during the mandated Stay At Home Order was 7.6%. Residence location, race, and lower socioeconomic factors were linked to more frequent seropositivity in children and correlated to regional COVID-19 case rates. Thus, a significant number of children in Louisiana had SARS-CoV-2 infections that went undetected and unreported and may have contributed to virus transmission.

Background Burnout is an occupational syndrome that leads to mental health problems, job turnover, and patient safety events. Those caring for critically ill patients are especially susceptible due to high patient mortality, long hours, and regular encounters with trauma and ethical issues. Interventions to prevent burnout in this population are needed. Preliminary studies suggest debriefing sessions may reduce burnout. This study aims to assess whether participation in regular debriefing can prevent burnout in intensive care unit (ICU) clinicians. Methods A randomized controlled trial will be conducted in two large academic medical centers. Two hundred ICU clinicians will be recruited with target enrollment of 100 physicians and 100 non-physicians (nurses, pharmacists, therapists). Participants must have worked in the ICU for the equivalent of at least 1 full time work week in the preceding 4 weeks. Enrolled subjects will be randomized to virtually attend biweekly debriefing sessions facilitated by a psychotherapist for 3 months or to a control arm without sessions. Our debriefs are modeled after Death Cafés, which are informal discussions focusing on death, dying, loss, grief, and illness. These sessions allow for reflection on distressing events and offer community and collaboration among hospital employees outside of work. The primary outcome is clinician burnout as measured by the Maslach Burnout Inventory (MBI) Score. Secondary outcomes include depression and anxiety, as measured by the Patient Health Questionnaire 8 (PHQ-8) and Generalized Anxiety Disorder 7-item scale (GAD-7), respectively. Questionnaires will be administered prior to the intervention, at 1 month, at 3 months, and at 6 months after enrollment. These values will be compared between groups temporally. Qualitative feedback will also be collected and analyzed. Discussion With ICU clinician burnout rates exceeding 50%, Death Café debriefing sessions may prove to be an effective tool to avert this debilitating syndrome. With COVID-19 limiting social interactions and overloading ICUs worldwide, the virtual administration of the Death Café for ICU clinicians provides an innovative strategy to potentially mitigate burnout in this vulnerable population. Trial registration ClinicalTrials.gov NCT04347811. Registered on 15 April 2020

Introduction: A healthy diet is key in preventing chronic diseases and black adults have higher rates of hypertension, obesity, and heart disease death rates compared to their white counterparts. Because dietary habits track from adolescence to adulthood, it is important to understand dietary habits of adolescents. This study aimed to examine the dietary quality among adolescents who skip lunch compared to those who do not. Methods: Data were collected in 2012 from 718 adolescents attending schools in New Orleans, Louisiana. Schools were high-poverty and closed-campus. Adolescents participated in a 24-hour dietary recall using the Automated Self-Administered 24-Hour (ASA24) Dietary Assessment Tool and data were converted into Healthy Eating Index (HEI-10) scores (range 0-100; higher scores reflect higher quality diet). Mean scores were compared between students who skipped lunch and those who did not. Results: Of the 718 respondents, 88.3% were black and 15.3% of students skipped lunch. Students who ate lunch had a mean HEI score of 46.6 compared to a mean score of 41.7 for students who skipped lunch (p Conclusions: Skipping lunch was associated with lower quality diet, though diet quality was low among all students. Students who skip lunch are less likely to consume vegetables, whole fruits, whole grains, and proteins and have higher intake of SoFASS. Considering over 15% of the sample did not eat lunch in a closed-campus school setting, further research should consider how to encourage students to participate in the National School Lunch Program. Table 1. HEI score comparisons between those who skip and do not skip lunch.

BACKGROUND. Aging is the most important risk factor for prostate cancer (PCa), but how age contributes to PCa is poorly understood. Aging is characterized by low-grade systemic inflammation (i.e., inflammaging) that is often attributed to the progressive activation of immune cells over time, which may play an important role in prostate carcinogenesis. Th17 response is elevated in aging humans and mice, but it remains unknown whether it is increased in prostate tissue or contributes to prostate carcinogenesis during aging. In this study, we aimed to determine the role of age-related Th17 response in PCa cell growth, migration, and invasion. METHODS. C57BL/6J (B6) mouse was used as an aging animal model and the prostate histopathology during aging was analyzed. Splenic CD4(+) T cells were isolated from young (16–20 weeks old) and aged (96–104 weeks old) mice, and cultured in the presence of plate-bound anti-CD3/anti-CD28, with or without Th17 differentiation conditions. The cells were collected and used for subsequent flow cytometry or qRT-PCR. The supernatant was collected and used to treat PCa cell lines. The treated PCa cells were analyzed for cell viability, migration, invasion, and NF-κB signaling. RESULTS. Aged mice had enlarged prostate glands and increased morphological alterations, with not only increased inflammatory cell infiltration but also increased Th17 cytokines in prostate tissue, compared to young mice. Naïve CD4(+) T cells from aged mice differentiated increased interleukin (IL)-17-expressing cells. CD4(+) T cells from aged mice spleen had increased Th17 cells, Th17 cytokines and Th17/Treg ratio compared to young mice. Factors secreted from aged CD4(+) T cells, especially from ex vivo differentiated Th17 cells, not only promoted PCa cell viability, migration, and invasion, but also activated the NF-κB signaling in PCa cells compared to young mice. CONCLUSIONS. These results indicate that age-related CD4(+) T cells, especially Th17 cells-secreted factors have the potential to contribute to prostate carcinogenesis. Our work could prompt further research using autochthonous PCa mouse models at different ages to elucidate the functional role of Th17 response in prostate carcinogenesis during aging.

Human cytomegalovirus (HCMV) is a large DNA herpesvirus that is highly prevalent in the human population. HCMV can result in severe direct and indirect pathologies under immunosuppressed conditions and is the leading cause of birth defects related to infectious disease. Currently, the effect of HCMV infection on host cell metabolism as an increase in glycolysis during infection has been defined. We have observed that oxidative phosphorylation is also increased. We have identified morphological and functional changes to host mitochondria during HCMV infection. The mitochondrial network undergoes fission events after HCMV infection. Interestingly, the network does not undergo fusion. At the same time, mitochondrial mass and membrane potential increase. The electron transport chain (ETC) functions at an elevated rate, resulting in the release of increased reactive oxygen species. Surprisingly, despite the stress applied to the host mitochondria, the network is capable of responding to and meeting the increased bioenergetic and biosynthetic demands placed on it. When mitochondrial DNA is depleted from the cells, we observed severe impairment of viral replication. Mitochondrial DNA encodes many of the ETC components. These findings suggest that the host cell ETC is essential to HCMV replication. Our studies suggest the host cell mitochondria may be a therapeutic target. IMPORTANCE Human cytomegalovirus (HCMV) is a herpesvirus present in up to 85% of some populations. Like all herpesviruses, HCMV infection is for life. No vaccine is currently available, neutralizing antibody therapies are ineffective, and current antivirals have limited long-term efficacy due to side effects and potential for viral mutation and resistance. The significance of this research is in understanding how HCMV manipulates the host mitochondria to support bioenergetic and biosynthetic requirements for replication. Despite a large genome, HCMV relies exclusively on host cells for metabolic functions. By understanding the dependency of HCMV on the mitochondria, we could exploit these requirements and develop novel antivirals.

Prostate cancer (PCa) is associated with advanced age. To better understand how age impacts PCa, it is critical to use PCa animal models generated at different ages (aged vs. non-aged). The PB-Cre4 driven phosphatase and tensin homolog (Pten) conditional knockout mouse model, which closely imitates human PCa initiation and progression. However, the Pten deletion is triggered in a 2-week-old prostate, when comparing the extent of PCa between aged and non-aged mice, it is difficult to distinguish the extent to which the onset and progression of PCa are due to the acceleration of the normal aging process or due to the manifestation of PCa pathologies over time. We present here a protocol to inject Cre-expressing adenovirus with luciferin tag intraductally into the prostate anterior lobes of Pten floxed mice, thus, the Pten-loss will be triggered at different ages post-Cre expression. The in vivo imaging of luciferin signals following viral infection was conducted to confirm the Cre expression and activity. Immunohistochemical staining was performed to confirm the Cre expression, Pten loss, and p-Akt and p-S6 activation. Prostate weight and histopathology were compared between aged and non-aged mice. The results showed that the virus infection was limited in the prostate glands and aged mice had significantly increased PCa onset and progression compared to young mice. Although technical skill is required to carry out this procedure and the success rate of viral infection is about 80%, this model of PCa is of great use to all investigators in the aging and cancer research field.

PURPOSE Patients undergoing breast augmentation are treated with multiple combinations of medications for pain control including ketorolac, liposomal bupivacaine, bupivacaine, and intravenous and oral narcotics. There is no current consensus on the optimal combination; therefore, all are used at the discretion of the surgeon. METHODS This was a single-center, retrospective study. The total number of patients included was 132. Comparisons were made between 4 groups: bupivacaine only (B); bupivacaine and liposomal bupivacaine (BL); bupivacaine and liposomal bupivacaine plus intraoperative ketorolac (BLKi); and bupivacaine and liposomal bupivacaine plus postoperative ketorolac (BLKp). Average pain scores immediately postoperative and before discharge were recorded and correlated to percentage of patients who received narcotic in the post-anesthesia care unit (PACU). Additional end points noted were side effects including nausea and time spent in PACU postoperatively. RESULTS Those receiving intraoperative ketorolac had the lowest pain on discharge (P < 0.0001) and the lowest percentage of patients receiving narcotics (P = 0.009) out of all 4 groups. There was no significant difference between the 4 groups in terms of time spent in PACU, pain immediately after the procedure, or amount of antiemetic given. No bleeding complications were noted for those who did or did not receive ketorolac. CONCLUSIONS When given options for pain control in breast augmentation, intraoperative ketorolac should be considered, because its inclusion was significant in decreasing use of narcotics and pain upon discharge. Addition of other costly drugs such as liposomal bupivacaine may not provide additional benefit in the immediate postoperative setting for procedures with a short recovery period such as breast augmentation.

A big problem associated with aging is thought to be impaired microvascular growth or angiogenesis. However, to link the evidence for impaired angiogenesis to microvascular dysfunction in aged tissues, we must compare adult vs. aged microvascular networks in unstimulated scenarios. The objective of this study was to test the hypothesis that aged microvascular networks are characterized by both fewer vessels and the impaired ability to undergo angiogenesis. Mesentery tissues from adult (9-mo) and aged (24-mo) male Fischer 344 rats were harvested and immunolabeled for platelet/endothelial cell adhesion molecule (an endothelial cell marker) according to two scenarios: unstimulated and stimulated. For unstimulated groups, tissues harvested from adult and aged rats were compared. For stimulated groups, tissues were harvested 3 or 10 days after compound 48/80-induced mast cell degranulation stimulation. Unstimulated aged microvascular networks displayed larger mean vascular area per tissue area compared with the unstimulated adult networks. The lack of a decrease in vessel density was supported at the gene expression level with RNA-Seq analysis and with comparison of vessel densities in soleus muscle. Following stimulation, capillary sprouting and vessel density were impaired in aged networks at 3 and 10 days, respectively. Our results suggest that aging associated with impaired angiogenesis mechanisms might not influence normal microvascular function, since unstimulated aged microvascular networks can display a “normal adult-like” vessel density and architecture. NEW & NOTEWORTHY Using a multidimensional approach, we present evidence supporting that aged microvascular networks display vessel density and patterning similar to adult networks despite also being characterized by a decreased capacity to undergo angiogenesis. Thus, vessel loss is not necessarily a characteristic of aging.

The measurement of biological age as opposed to chronological age is important to allow the study of factors that are responsible for the heterogeneity in the decline in health and function ability among individuals during aging. Various measures of biological aging have been proposed. Frailty indices based on health deficits in diverse body systems have been well studied, and we have documented the use of a frailty index (FI34) composed of 34 health items, for measuring biological age. A different approach is based on leukocyte DNA methylation. It has been termed DNA methylation age, and derivatives of this metric called age acceleration difference and age acceleration residual have also been employed. Any useful measure of biological age must predict survival better than chronological age does. Meta-analyses indicate that age acceleration difference and age acceleration residual are significant predictors of mortality, qualifying them as indicators of biological age. In this article, we compared the measures based on DNA methylation with FI34. Using a well-studied cohort, we assessed the efficiency of these measures side by side in predicting mortality. In the presence of chronological age as a covariate, FI34 was a significant predictor of mortality, whereas none of the DNA methylation age-based metrics were. The outperformance of FI34 over DNA methylation age measures was apparent when FI34 and each of the DNA methylation age measures were used together as explanatory variables, along with chronological age: FI34 remained significant but the DNA methylation measures did not. These results indicate that FI34 is a robust predictor of biological age, while these DNA methylation measures are largely a statistical reflection of the passage of chronological time.

No single biomarker can reliably represent the complexity of aging. One way to overcome this shortcoming is to aggregate multiple biomarkers into a composite index. The frailty index (FI), which is simply the proportion of accumulated deficits among a set of various health markers, reflects functional abilities and risks of adverse outcomes. Furthermore, the FI accounts for the variation in mortality among individuals of the same chronological age (CA). Thus, the FI is a reliable measure of biological age (BA). Unlike the FI, other popular BA-estimating algorithms use CA directly as a biomarker or indirectly to derive model parameters. However, genetic, pharmaceutical, and intervention studies have shown that aging is delayable or reversible, indicating that CA is not the direct cause of aging. The popular Klemera-Doubal (K-D) method proposes two equations for BA estimation: BE uses CA to derive equation parameters, and BEC directly incorporates CA as an additional biomarker. BA estimates by the K-D method, especially by BEC, have been shown to outperform CA. Using Louisiana Healthy Aging Study (LHAS) data, we constructed an FI from a battery of health items selected using machine learning methods for their ability to predict mortality. We compared the FI with CA and the two K-D BA estimates and found that the FI was the better predictor of mortality, especially among nonagenarians. The results were replicable with the FI calculated from different sets of selected health items using NHANES and HRS datasets. These results demonstrate the FI as the best-performing measure of BA.

Rapid-start, immediate antiretroviral therapy (ART) initiation is a novel intervention that leads to earlier viral suppression. Longer-term data is essential before supporting this strategy more widely. CrescentCare, a federally qualified health center in New Orleans, followed 195 patients who received same-day ART; here we present a continuum of care for immediate ART intervention.

Parks can be an important, low-cost neighborhood resource to increase physical activity and reduce overweight and obesity. The quality of parks, however, may impact use. This study used observational data to examine the relationships between park quality, park usage and levels of physical activity among users in 31 parks within low-income, African American neighborhoods. Relationships between park use and park characteristics (signs of disorder, attractiveness, and number of activity settings) varied by gender and user activity level. No variables of interest were significant for overall number of male users, whereas, disorder and attractiveness were significant for overall number of female users. Parks with signs of disorder were associated with 49% fewer female users (IRR = 0.51, 95% CI = (0.34&ndash, 0.77)) and attractive parks with 146% more female users (IRR = 2.46, 95% CI = (1.39&ndash, 4.33)). Similar significant relationships were found among active but not sedentary female users. Communities may consider increasing park maintenance and addressing attractiveness in existing parks as a relatively low-cost environmental strategy to encourage park use, increase physical activity, and reduce the burden of obesity, especially among women in low-income, African-American communities.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity and diabetes mellitus, yet a plausible mechanism remains unknown We examined the association between hypertension, obesity, hyperlipidemia, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak METHODS: This was a retrospective, observational study of consecutive COVID-19 patients hospitalized at two academic tertiary hospitals in New Orleans from March 30th to April 5th, 2020 Patients were identified as MetS using WHO criteria and compared to patients without MetS The primary outcome for all analyses was hospital mortality Secondary outcomes included need for ICU, invasive mechanical ventilation (IMV), a diagnosis of ARDS as defined by Berlin Criteria, hospital length of stay (LOS), and hospital readmission after initial discharge Multivariable regression models included age, sex, race, individual hospital site and Charlson Comorbidity Index as covariates RESULTS: Among 287 patients (mean age, 61 5 years;female, 56 8%;non-Hispanic Black, 85 4%), MetS was present in 188 (66%) MetS was significantly associated with mortality (adjusted odds ratio [aOR]: 3 42, 95% confidence interval [CI]: 1 52-7 69), ICU (aOR: 4 59, CI: 2 53-8 32), IMV (aOR: 4 71, CI: 2 50-8 87) and ARDS (aOR: 4 70, CI: 2 25-9 82), compared with non-MetS Multivariable analyses of hypertension, obesity and diabetes individually showed no association with mortality Obesity was associated with ICU (aOR, 2 18, CI, 1 25-3 81), ARDS (aOR, 2 44, CI, 1 28-4 65), and IMV (aOR, 2 36, CI, 1 33-4 21) Diabetes was associated with ICU (aOR, 2 22, CI, 1 24-3 98) and IMV (aOR, 2 12, CI, 1 16-3 89) Hypertension was not significantly associated with any outcome Inflammatory biomarkers associated with MetS, C-reactive protein (CRP) and lactate dehydrogenase (LDH) were associated with mortality [CRP (aOR, 3 66, CI, 1 22-10 97), LDH (aOR, 3 49, CI, 1 78-6 83)] CONCLUSIONS: In predominantly Black patients hospitalized for COVID-19, the clustering of hypertension, obesity and diabetes as MetS increased the odds of mortality compared with non-MetS These findings suggest that MetS may be a composite predictor of COVID-19 lethal outcome

Chronic inflammation has been associated with a variety of human cancers including prostate cancer. Interleukin-17 (IL-17) is a critical pro-inflammatory cytokine, which has been demonstrated to promote development of prostate cancer, colon cancer, skin cancer, breast cancer, lung cancer, and pancreas cancer. IL-17 promotes prostate adenocarcinoma with a concurrent increase of matrix metalloproteinase 7 (MMP7) expression in mouse prostate. Whether MMP7 mediates IL-17’s action and the underlying mechanisms remain unknown. We generated Mmp7 and Pten double knockout (Mmp7−/− in abbreviation) mouse model and demonstrated that MMP7 promotes prostate adenocarcinoma through induction of epithelial-to-mesenchymal transition (EMT) in Pten-null mice. MMP7 disrupted E-cadherin/β-catenin complex to up-regulate EMT transcription factors in mouse prostate tumors. IL-17 receptor C and Pten double knockout mice recapitulated the weak EMT characteristics observed in Mmp7−/− mice. IL-17 induced MMP7 and EMT in human prostate cancer LNCaP, C4-2B, and PC-3 cell lines, while siRNA knockdown of MMP7 inhibited IL-17-induced EMT. Compound III, a selective MMP7 inhibitor, decreased development of invasive prostate cancer in Pten single knockout mice. In human normal prostates and prostate tumors, IL-17 mRNA levels were positively correlated with MMP7 mRNA levels. These findings demonstrate that MMP7 mediates IL-17’s function in promoting prostate carcinogenesis through induction of EMT, indicating IL-17-MMP7-EMT axis as potential targets for developing new strategies in the prevention and treatment of prostate cancer.

Sickle cell disease (SCD) is the most common inherited hematologic disorder in the United States. Patients with SCD are at increased risk of invasive pneumococcal disease (IPD) and are reliant on both early penicillin prophylaxis and anti-pneumococcal vaccination for prevention of infection. Although studies examining vaccine response have demonstrated a drop off of titer response after 3 years, an optimal vaccination regimen has not been identified. Our study sought to assess the immunogenicity of our center's pneumococcal vaccination strategy which included Prevnar® (PCV-7) (prior to the introduction of PCV-13) followed by Pneumovax® (PPV-23) given routinely at 2 and 5 years of age and then every 5 years thereafter. Our goal was to assess vaccine response in a population of patients with SCD who had received vaccines according to this regimen using multiplex bead analysis. Our study demonstrated a significant percentage of persons with SCD do not maintain a sufficient vaccination response to PPV-23 for 5 years. Our study revealed that only 36% of patients had protective levels of anti-pneumococcal antibody titers at an average of 37 months following vaccination. Most alarmingly, within the group of patients with sub-therapeutic titers, 64% demonstrated vaccine response to less than 25% of the tested serotypes. These findings were significantly associated with duration of time since last vaccine administration but the mean age of lack of response was below the 3-year window where vaccine response was previously reported to wane. Our results indicate anti-pneumococcal immunity may not be optimally maintained using this vaccination strategy in patients with SCD leaving them vulnerable to IPD. Many pediatric hematologists stop prophylactic penicillin at 5 years of age making these results alarming. We recommend further investigation into an optimal vaccine schedule and monitoring of anti-pneumococcal titers in at risk patients.

// Sen Liu 1, * , Qiuyang Zhang 1, * , Chong Chen 1 , Dongxia Ge 1 , Yine Qu 1 , Rongyi Chen 2 , Yi-Ming Fan 2 , Nan Li 2 , Wendell W. Tang 3 , Wensheng Zhang 4 , Kun Zhang 4 , Alun R. Wang 5 , Brian G. Rowan 1, 6, 7 , Steven M. Hill 1, 6 , Oliver Sartor 6, 8, 9 , Asim B. Abdel-Mageed 6, 8 , Leann Myers 10 , Qishan Lin 11 , Zongbing You 1, 6, 7, 12 1 Department of Structural and Cellular Biology, Tulane University, New Orleans, LA 70112, USA 2 Department of Dermatology, Affiliated Hospital of Guangdong Medical College, Zhanjiang, Guangdong 524001, China 3 Department of Pathology, Ochsner Clinic Foundation, New Orleans, LA 70130, USA 4 Department of Computer Science and Biostatistics Facility of RCMI Cancer Research Center, Xavier University of Louisiana, New Orleans, LA 70125, USA 5 Department of Pathology and Laboratory Medicine, Tulane University, New Orleans, LA 70112, USA 6 Tulane Cancer Center, Louisiana Cancer Research Consortium, Tulane University, New Orleans, LA 70112, USA 7 Tulane Center for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, LA 70112, USA 8 Department of Urology, Tulane University, New Orleans, LA 70112, USA 9 Department of Medicine, Tulane University, New Orleans, LA 70112, USA 10 Department of Biostatistics and Bioinformatics, Tulane University, New Orleans, LA 70112, USA 11 Proteomics/Mass Spectrometry Facility, University at Albany, Rensselaer, NY 12144, USA 12 Department of Orthopaedic Surgery and Tulane Center for Aging, Tulane University, New Orleans, LA 70112, USA * These authors contributed equally to this work Correspondence to: Zongbing You, e-mail: zyou@tulane.edu Keywords: hyperinsulinemia, obesity, prostate cancer, interleukin-17, GSK3 Received: December 02, 2015 Accepted: January 29, 2016 Published: February 10, 2016 ABSTRACT Interleukin-17 (IL-17) plays important roles in inflammation, autoimmune diseases, and some cancers. Obese people are in a chronic inflammatory state with increased serum levels of IL-17, insulin, and insulin-like growth factor 1 (IGF1). How these factors contribute to the chronic inflammatory status that promotes development of aggressive prostate cancer in obese men is largely unknown. We found that, in obese mice, hyperinsulinemia enhanced IL-17-induced expression of downstream proinflammatory genes with increased levels of IL-17 receptor A (IL-17RA), resulting in development of more invasive prostate cancer. Glycogen synthase kinase 3 (GSK3) constitutively bound to and phosphorylated IL-17RA at T780, leading to ubiquitination and proteasome-mediated degradation of IL-17RA, thus inhibiting IL-17-mediated inflammation. IL-17RA phosphorylation was reduced, while the IL-17RA levels were increased in the proliferative human prostate cancer cells compared to the normal cells. Insulin and IGF1 enhanced IL-17-induced inflammatory responses through suppressing GSK3, which was shown in the cultured cell lines in vitro and obese mouse models of prostate cancer in vivo . These findings reveal a mechanism underlying the intensified inflammation in obesity and obesity-associated development of aggressive prostate cancer, suggesting that targeting GSK3 may be a potential therapeutic approach to suppress IL-17-mediated inflammation in the prevention and treatment of prostate cancer, particularly in obese men.

Background Racial disparities in birth outcomes are mirrored in cardiovascular health. Recently there have been calls for more attention to preconception and interconceptional health in order to improve birth outcomes, including as a strategy to reduce black-white disparities. Methods As part of a larger study of cardiovascular and reproductive health (“Bogalusa Babies”), female participants were linked to their children’s birth certificates for Louisiana, Mississippi, and Texas births from 1982 to 2009. Three thousand and ninety-five women were linked to birth certificate data. Birth outcomes were defined as low birthweight (LBW) birthweight 3 weeks early; small for gestational age (SGA), 90th percentile for gestational age]. Cardiovascular measures (blood pressure, lipids, glucose, insulin) at the visit closest in time but prior to the pregnancy was examined as predictors of birth outcomes using logistic models adjusted for covariates. Results Only a few cardiovascular risk factors were associated with birth outcomes. Triglycerides were associated with higher risk of LBW among whites (aOR 1.05, 95% 1.01–1.10). Higher glucose was associated with a reduction in risk of SGA for black women (aOR 0.85, 95% CI 0.76–0.95), but not whites (p for interaction = 0.02). Clear racial disparities were found, but they were reduced modestly (LBW/SGA) or not at all (PTB/LGA) after CVD risk factors were adjusted for. Conclusions This analysis does not provide evidence for preconception cardiovascular risk being a strong contributor to racial disparities. Electronic supplementary material The online version of this article (10.1186/s12884-018-1959-y) contains supplementary material, which is available to authorized users.

Vaso-occlusive pain, a primary feature of sickle cell disease (SCD), leads to high acute care utilization, including frequent hospital admission. Though limited by a paucity of high quality evidence, guideline recommendations for the inpatient management of vaso-occlusive pain include rapid and continual pain assessment, early and individualized pain control, and intravenous fluid resuscitation (Yawn et. al. JAMA). However, research suggests that inpatient vaso-occlusive pain management varies significantly within institutions (Co et. al. Jt Comm J Qual Saf). Clinical pathways, which are a mechanism for increasing evidence-based management within an institution to standardize and improve quality of care, have been shown to reduce variation in vaso-occlusive pain management (Morrisey et. al. Pediatr Blood Cancer). We developed and implemented a clinical pathway for the management of vaso-occlusive pain using evidence-based interventions and expert consensus guidelines and hypothesized that it would improve clinical outcomes. The pathway was implemented as an electronic orderset and providers were educated on its use, which was voluntary. A retrospective chart review was then performed of adult patients admitted to Tulane Hospital for vaso-occlusive pain during one year prior to and following pathway implementation (344 total admissions, 112 total patients). Outcome measures were hospital length of stay (LOS), rate of 30-day readmission, median number of hospitalizations over one year prior to and after pathway implementation, and incidence of acute chest syndrome. Use of patient-controlled analgesia (PCA) and intravenous (IV) promethazine were used as surrogate measures of pathway utilization. Data were summarized in terms of medians (IRQ) for continuous outcomes (analyzed with the Wilcoxon Rank Sum Test) and percentages for categorical variables (analyzed with the Pearson's Chi-Squared Test). Following pathway implementation, we observed a statistically significant decrease in median number of admissions per patient (2 vs. 1, p=0.0027), an increase in PCA use (3.6% vs. 87.3%, p Increased PCA use and decreased IV promethazine use suggest high pathway utilization among providers. We suspect the decrease in median admissions occurred due to improved discharge planning, primarily arranging close followup, given that lack of an outpatient provider is a known risk factor for hospital admission for vaso-occlusive pain (Brodsky Am J Med). Despite the reduction in median admissions, the observed decrease in readmission rates was not statistically significant, possibly due to insufficient study power. A nonsignificant change in readmission rates may also suggest that additional interventions need to be developed and evaluated to address socioeconomic barriers to outpatient healthcare access, such as financial insecurity and missed appointments, which have also been identified as modifiable risk factors for readmission (Cronin et. al. Hematology). The lack of an effect on hospital LOS may be due to the confounding variable of pain episode severity, which is difficult to control for given the absence of a biomarker for vaso-occlusive disease severity. Thus, we suggest 30-day readmission and total hospital days be used as primary outcome measures in future studies. By increasing evidence-based and expert consensus management of vaso-occlusive pain, clinical pathways may decrease hospital admissions for SCD patients. More research is needed to evaluate interventions to mitigate socioeconomic risk factors for readmission, which may then be incorporated into future clinical pathways to reduce readmission rates. Disclosures Debord: Stryker Orthopaedics: Consultancy, Other: ceives salary as well as is a stock holder with Stryker.