Spillover of highly pathogenic avian influenza H5N1 virus to dairy cattle.

The highly pathogenic avian influenza (HPAI) H5N1 virus clade 2.3.4.4b has caused the death of millions of domestic birds and thousands of wild birds in the USA since January 2022 (refs. 1-4). Throughout this outbreak, spillovers to mammals have been frequently documented5-12. Here we report spillover of the HPAI H5N1 virus to dairy cattle across several states in the USA. The affected cows displayed clinical signs encompassing decreased feed intake, altered faecal consistency, respiratory distress and decreased milk production with abnormal milk. Infectious virus and viral RNA were consistently detected in milk from affected cows. Viral distribution in tissues via immunohistochemistry and in situ hybridization revealed a distinct tropism of the virus for the epithelial cells lining the alveoli of the mammary gland in cows. Whole viral genome sequences recovered from dairy cows, birds, domestic cats and a raccoon from affected farms indicated multidirectional interspecies transmissions. Epidemiological and genomic data revealed efficient cow-to-cow transmission after apparently healthy cows from an affected farm were transported to a premise in a different state. These results demonstrate the transmission of the HPAI H5N1 clade 2.3.4.4b virus at a non-traditional interface, underscoring the ability of the virus to cross species barriers.

Integrating causal pathway diagrams into practice facilitation to address colorectal cancer screening disparities in primary care.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause of cancer death and the second most common cancer diagnosis among the Hispanic population in the United States. However, CRC screening prevalence remains lower among Hispanic adults than among non-Hispanic white adults. To reduce CRC screening disparities, efforts to implement CRC screening evidence-based interventions in primary care organizations (PCOs) must consider their potential effect on existing screening disparities. More research is needed to understand how to leverage existing implementation science methodologies to improve health disparities. The Coaching to Improve Colorectal Cancer Screening Equity (CoachIQ) pilot study explores whether integrating two implementation science tools, Causal Pathway Diagrams and practice facilitation, is a feasible and effective way to address CRC screening disparities among Hispanic patients. METHODS: We used a quasi-experimental, mixed methods design to evaluate feasibility and assess initial signals of effectiveness of the CoachIQ approach. Three PCOs received coaching from CoachIQ practice facilitators over a 12-month period. Three non-equivalent comparison group PCOs received coaching during the same period as participants in a state quality improvement program. We conducted descriptive analyses of screening rates and coaching activities. RESULTS: The CoachIQ practice facilitators discussed equity, facilitated prioritization of QI activities, and reviewed CRC screening disparities during a higher proportion of coaching encounters than the comparison group practice facilitator. While the mean overall CRC screening rate in the comparison PCOs increased from 34 to 41%, the mean CRC screening rate for Hispanic patients did not increase from 30%. In contrast, the mean overall CRC screening rate at the CoachIQ PCOs increased from 41 to 44%, and the mean CRC screening rate for Hispanic patients increased from 35 to 39%. CONCLUSIONS: The CoachIQ program merges two implementation science methodologies, practice facilitation and causal pathway diagrams, to help PCOs focus quality improvement efforts on improving CRC screening while also reducing screening disparities. Results from this pilot study demonstrate key differences between CoachIQ facilitation and standard facilitation, and point to the potential of the CoachIQ approach to decrease disparities in CRC screening.

Assessment of a community pharmacist remote monitoring service in patients using continuous glucose monitors.

BACKGROUND: Diabetes is the eighth leading cause of death and has a substantial impact on the U.S. health care system. Recent changes to major insurance formularies allow for increased access to continuous glucose monitors (CGMs). Community pharmacists routinely assist and educate patients about diabetes care, including usage of CGM. OBJECTIVES: The purpose of this study was to evaluate the clinical impact of a community pharmacist remote CGM monitoring service on patients' glycemic metrics. Patient completion of comprehensive diabetes standards of care and pharmacist interventions and recommendations were assessed as secondary objectives. METHODS: This study was a prospective, feasibility study conducted at two pharmacies within 1 regional division of a large community pharmacy chain between November 2022 and June 2023. A pharmacist conducted patient enrollment visits and remotely monitored CGM glycemic metrics via cloud-based platforms per the study protocol. CGM glycemic metrics were evaluated for each patient 3 months pre- and post-study enrollment, including time above range (TAR), time in range (TIR), time below range, glucose management indicator, average glucose, CGM utilization rate, and glucose variability. Metrics were evaluated for statistical significance using the Wilcoxon signed-rank test and descriptive statistics. RESULTS: Pharmacists enrolled 36 patients in this study with 20 patients completing the full 3-month study period per protocol. There was a statistically significant improvement in three of eight glycemic metrics (very high TAR, TIR, and average glucose). Specifically, TIR had the largest improvement from 61.8% pre-enrollment to 69.9% (P < 0.006) postenrollment. All other pertinent glycemic metrics displayed improvements but were not statistically significant. CONCLUSION: The results demonstrate clinically and statistically significant improvements in several glycemic metrics for patients who participated in the community pharmacist-led remote CGM monitoring service, which may result in improved diabetes control and fewer long-term diabetes-related health complications.

The N-linker region of hERG1a upregulates hERG1b potassium channels.

A major physiological role of hERG1 (human Ether-á-go-go-Related Gene 1) potassium channels is to repolarize cardiac action potentials. Two isoforms, hERG1a and hERG1b, associate to form the potassium current IKr in cardiomyocytes. Inherited mutations in hERG1a or hERG1b cause prolonged cardiac repolarization, long QT syndrome, and sudden death arrhythmia. hERG1a subunits assemble with and enhance the number of hERG1b subunits at the plasma membrane, but the mechanism for the increase in hERG1b by hERG1a is not well understood. Here, we report that the hERG1a N-terminal region expressed in trans with hERG1b markedly increased hERG1b currents and increased biotin-labeled hERG1b protein at the membrane surface. hERG1b channels with a deletion of the N-terminal 1b domain did not have a measurable increase in current or biotinylated protein when coexpressed with hERG1a N-terminal regions, indicating that the 1b domain was required for the increase in hERG1b. Using a biochemical pull-down interaction assay and a FRET hybridization experiment, we detected a direct interaction between the hERG1a N-terminal region and the hERG1b N-terminal region. Using engineered deletions and alanine mutagenesis, we identified a short span of amino acids at positions 216 to 220 within the hERG1a "N-linker" region that were necessary for the upregulation of hERG1b. We propose that direct structural interactions between the hERG1a N-linker region and the hERG1b 1b domain increase hERG1b at the plasma membrane. Mechanisms regulating hERG1a and hERG1b are likely critical for cardiac function, may be disrupted by long QT syndrome mutants, and serve as potential targets for therapeutics.

A Retrospective Analysis of Preclinical and Clinical Pharmacokinetics from Administration of Long-Acting Aqueous Suspensions.

Administration of long-acting injectable suspensions is an increasingly common approach to increasing patient compliance and improving therapeutic efficacy through less frequent dosing. While several long-acting suspensions have recently been marketed, parameters modulating drug absorption from suspension-based formulations are not well understood. Further, methods for predicting clinical pharmacokinetic data from preclinical studies are not well established. Together, these limitations hamper compound selection, formulation design and formulation selection through heavy reliance on iterative optimization in preclinical and clinical studies. This article identifies key parameters influencing absorption from suspension-based formulations through compilation and analysis of preclinical and clinical pharmacokinetic data of seven compounds marketed as suspensions; achievable margins for predicting the clinical dose and input rate from preclinical studies as a function of the preclinical species, the clinical injection location and the intended therapeutic duration were also established.

Creating research-ready partnerships: the initial development of seven implementation laboratories to advance cancer control.

BACKGROUND: In 2019-2020, with National Cancer Institute funding, seven implementation laboratory (I-Lab) partnerships between scientists and stakeholders in 'real-world' settings working to implement evidence-based interventions were developed within the Implementation Science Centers in Cancer Control (ISC3) consortium. This paper describes and compares approaches to the initial development of seven I-Labs in order to gain an understanding of the development of research partnerships representing various implementation science designs. METHODS: In April-June 2021, members of the ISC3 Implementation Laboratories workgroup interviewed research teams involved in I-Lab development in each center. This cross-sectional study used semi-structured interviews and case-study-based methods to collect and analyze data about I-Lab designs and activities. Interview notes were analyzed to identify a set of comparable domains across sites. These domains served as the framework for seven case descriptions summarizing design decisions and partnership elements across sites. RESULTS: Domains identified from interviews as comparable across sites included engagement of community and clinical I-Lab members in research activities, data sources, engagement methods, dissemination strategies, and health equity. The I-Labs use a variety of research partnership designs to support engagement including participatory research, community-engaged research, and learning health systems of embedded research. Regarding data, I-Labs in which members use common electronic health records (EHRs) leverage these both as a data source and a digital implementation strategy. I-Labs without a shared EHR among partners also leverage other sources for research or surveillance, most commonly qualitative data, surveys, and public health data systems. All seven I-Labs use advisory boards or partnership meetings to engage with members; six use stakeholder interviews and regular communications. Most (70%) tools or methods used to engage I-Lab members such as advisory groups, coalitions, or regular communications, were pre-existing. Think tanks, which two I-Labs developed, represented novel engagement approaches. To disseminate research results, all centers developed web-based products, and most (n = 6) use publications, learning collaboratives, and community forums. Important variations emerged in approaches to health equity, ranging from partnering with members serving historically marginalized populations to the development of novel methods. CONCLUSIONS: The development of the ISC3 implementation laboratories, which represented a variety of research partnership designs, offers the opportunity to advance understanding of how researchers developed and built partnerships to effectively engage stakeholders throughout the cancer control research lifecycle. In future years, we will be able to share lessons learned for the development and sustainment of implementation laboratories.

The evaluation of mandatory alerts on long-acting opioid prescriptions and the use of a community pharmacy naloxone protocol.

BACKGROUND: Opioid overdose deaths accounted for approximately 69.5% of the total drug overdoses in the United States in 2018. In the same year, the Centers for Disease Control and Prevention estimates that around 9 million opportunities to dispense naloxone to high-risk patients were missed. Community pharmacists are equipped to help all patients obtain naloxone to prevent opioid-related overdoses. OBJECTIVES: The purpose of this study was to determine the impact of mandatory alerts on the dispensing of naloxone by pharmacists using a physician-approved protocol. The primary objective of this study was to evaluate the change in the number of dispensed naloxone prescriptions via physician-approved protocol compared with the same time period in the previous year. The secondary objective was to evaluate the pharmacists' knowledge and confidence dispensing naloxone via physician-approved protocol. PRACTICE DESCRIPTION: A system-generated mandatory alert that prompted pharmacists to assess the need for naloxone and initiate and dispense as appropriate via a physician-approved protocol was implemented in 5 pharmacies of a large community pharmacy chain between June and July 2020. PRACTICE INNOVATION: A technology enhancement was designed that automatically created a mandatory alert in the pharmacy management system for all patients who were dispensed a long-acting opioid medication to prompt pharmacists to initiate and dispense naloxone as appropriate. EVALUATION METHODS: The impact of the mandatory alert was evaluated by assessing patients' medication fill history in the pharmacy management system to determine the change in naloxone prescriptions dispensed. RESULTS: During the intervention period, pharmacists initiated and dispensed 34 incremental naloxone prescriptions via a physician-approved protocol compared with the same time period in the previous year. CONCLUSION: The results illustrated that system-generated mandatory alerts prompting pharmacist intervention can effectively increase pharmacist utilization of a physician-approved protocol, resulting in increased naloxone prescriptions dispensed to high-risk patients.

Gestational gut microbial remodeling is impaired in a rat model of preeclampsia superimposed on chronic hypertension.

Preeclampsia is a progressive hypertensive disorder of pregnancy affecting 2%-8% of pregnancies globally. Preexisting chronic hypertension is a major risk factor associated with developing preeclampsia, and growing evidence suggests a role for the gut microbiome in the development of preeclampsia. However, neither alterations in the gut microbiome associated with preeclampsia nor the mechanisms involved are fully understood. In this study, we tested the hypothesis that normal gestational maternal gut microbiome remodeling is impaired in the Dahl salt-sensitive (Dahl S) rat model of superimposed preeclampsia. Gut microbiome profiles of pregnant Dahl S, normal pregnant Sprague-Dawley (SD), and matched virgin controls were assessed by 16S rRNA gene sequencing at baseline; during early, middle, and late pregnancy; and 1-wk postpartum. Dahl S rats had significantly higher abundance in Proteobacteria, and multiple genera were significantly different from SD rats at baseline. The pregnant SD displayed a significant increase in Proteobacteria and genera such as Helicobacter, but these were not different between pregnant and virgin Dahl S rats. By late pregnancy, Dahl S rats had significantly lower α-diversity and Firmicutes compared with their virgin Dahl S controls. ß-diversity was significantly different among groups (P < 0.001). KEGG metabolic pathways including those associated with short-chain fatty acids were different in Dahl S pregnancy but not in SD pregnancy. These results reveal an association between chronic hypertension and gut microbiome dysbiosis which may hinder pregnancy-specific remodeling in the gut microbial composition during superimposed preeclampsia.

Nephron-deficient HSRA rats exhibit renal injury with age but have limited renal damage from streptozotocin-induced hyperglycemia.

Hypertension and diabetes are the greatest factors influencing the progression of chronic kidney disease (CKD). Investigation into the role of nephron number in CKD alone or with hypertension has revealed a strong inverse relationship between the two; however, not much is known about the connection between nephron number and diabetic kidney disease. The heterogeneous stock-derived model of unilateral renal agenesis (HSRA) rat, a novel model of nephron deficiency, provides a unique opportunity to study the association between nephron number and hypertension and diabetes on CKD. HSRA rats exhibit failure of one kidney to develop in 50-75% of offspring, whereas the remaining offspring are born with two kidneys. Rats born with one kidney (HSRA-S) develop significant renal injury with age compared with two-kidney littermates (HSRA-C). The induction of hypertension as a secondary stressor leads to significantly more renal injury in HSRA-S compared with HSRA-C rats and nephrectomized HSRA-C (HSRA-UNX) rats. The present study sought to address the hypothesis that nephron deficiency in the HSRA rat would hasten renal injury in the presence of a secondary stressor of hyperglycemia. HSRA animals did not exhibit diabetes-related traits at any age; thus, streptozotocin (STZ) was used to induce hyperglycemia in HSRA-S, HSRA-C, and HSRA-UNX rats. STZ- and vehicle-treated animals were followed for 15 wk. STZ-treated animals developed robust hyperglycemia, but in contrast to the response to hypertension, neither HSRA-S nor HSRA-UNX animals developed proteinuria compared with vehicle treatment. In total, our data indicate that hyperglycemia from STZ alone does not have a significant impact on the onset or progression of injury in young one-kidney HSRA animals.NEW & NOTEWORTHY The HSRA rat, a novel model of nephron deficiency, provides a unique opportunity to study the association between nephron number and confounding cardiovascular complications that impact kidney health. Although hypertension was previously shown to exacerbate renal injury in young HSRA animals, diabetic hyperglycemia did not lead to worse renal injury, suggesting that nephron number has limited impact on kidney injury, at least in this model.

Implementation of a depression screening as part of a holistic adherence assessment in a large community pharmacy chain.

BACKGROUND: Medication nonadherence is associated with increased morbidity and mortality, higher rates of hospital admissions, and increased health care costs. Nearly half of patients do not take their medications as prescribed leading to poor outcomes. Patients with chronic conditions, especially those with depression, demonstrate lower adherence to their medications. Community pharmacists routinely address demographic and sociocultural barriers and are equipped to screen for and assist with behavioral barriers to medication adherence. OBJECTIVES: The purpose of this study was to assess the feasibility and impact of conducting a depression screening as part of a holistic adherence assessment. The primary objective of this project was to evaluate the impact of a holistic adherence assessment on medication adherence. The secondary objectives evaluated patients' barriers to adherence, Patient Health Questionnaires 2 and 9 (PHQ-2 and 9) results, and pharmacist interventions. PRACTICE DESCRIPTION: Pharmacists conducted a holistic adherence assessment and performed a depression screening for patients who were nonadherent or at risk of becoming nonadherent to their chronic medications. PRACTICE INNOVATION: A pharmacist-led holistic adherence assessment implemented in 2 pharmacies of a large community pharmacy chain between January and May 2020. EVALUATION METHODS: The impact on medication adherence was evaluated by assessing if patients received the next fill of their chronic medication on time after the holistic adherence assessment. RESULTS: During the study period, 69 patients completed the holistic adherence assessment and were screened for depression. A total of 12 patients (17.4%) screened positive on the PHQ-2, and 6 patients (8.7%) screened positive on the PHQ-9. After the intervention, 42 patients (60.9%) received the next fill of their targeted chronic medication on time, and 27 patients (39.1%) were late to pick up their next fill. CONCLUSION: The results illustrated that community pharmacists can incorporate a depression screening into a holistic adherence assessment effectively to screen for behavioral barriers that may affect medication adherence.

Whole genome sequencing and novel candidate genes for CAKUT and altered nephrogenesis in the HSRA rat.

The HSRA rat is a model of congenital abnormalities of the kidney and urogenital tract (CAKUT). Our laboratory has used this model to investigate the role of nephron number (functional unit of the kidney) in susceptibility to develop kidney disease as 50-75% offspring are born with a single kidney (HSRA-S), while 25-50% are born with two kidneys (HSRA-C). HSRA-S rats develop increased kidney injury and hypertension with age compared with nephrectomized two-kidney animals (HSRA-UNX), suggesting that even slight differences in nephron number can be an important driver in decline in kidney function. The HSRA rat was selected and inbred from a family of outbred heterogeneous stock (NIH-HS) rats that exhibited a high incidence of CAKUT. The HS model was originally developed from eight inbred strains (ACI, BN, BUF, F344, M520, MR, WKY, and WN). The genetic make-up of the HSRA is therefore a mosaic of these eight inbred strains. Interestingly, the ACI progenitor of the HS model exhibits CAKUT in 10-15% of offspring with the genetic cause being attributed to the presence of a long-term repeat (LTR) within exon 1 of the c-Kit gene. Our hypothesis is that the HSRA and ACI share this common genetic cause, but other alleles in the HSRA genome contribute to the increased penetrance of CAKUT (75% HSRA vs. 15% in ACI). To facilitate genetic studies and better characterize the model, we sequenced the whole genome of the HSRA to a depth of ~50×. A genome-wide variant analysis of high-impact variants identified a number of novel genes that could be linked to CAKUT in the HSRA model. In summary, the identification of new genes/modifiers that lead to CAKUT/loss of one kidney in the HSRA model will provide greater insight into association between kidney development and susceptibility to develop cardiovascular disease later in life.

Altered renal hemodynamics is associated with glomerular lipid accumulation in obese Dahl salt-sensitive leptin receptor mutant rats.

The present study examined whether development of renal injury in the nondiabetic obese Dahl salt-sensitive leptin receptor mutant (SSLepRmutant) strain is associated with elevations in glomerular filtration rate and renal lipid accumulation. Baseline mean arterial pressure at 6 wk of age was similar between Dahl salt-sensitive wild-type (SSWT) and SSLepRmutant rats. However, by 18 wk of age, the SSLepRmutant strain developed hypertension, while the elevation in mean arterial pressure was not as severe in SSWT rats (192 ± 4 and 149 ± 6 mmHg, respectively). At baseline, proteinuria was fourfold higher in SSLepRmutant than SSWT rats and remained elevated throughout the study. The early development of progressive proteinuria was associated with renal hyperfiltration followed by a decline in renal function over the course of study in the SSLepRmutant compared with SSWT rats. Kidneys from the SSLepRmutant strain displayed more glomerulosclerosis and glomerular lipid accumulation than SSWT rats. Glomeruli were isolated from the renal cortex of both strains at 6 and 18 wk of age, and RNA sequencing was performed to identify genes and pathways driving glomerular injury. We observed significant increases in expression of the influx lipid transporters, chemokine (C-X-C motif) ligand 16 (Cxcl16) and scavenger receptor and fatty acid translocase (Cd36), respectively, and a significant decrease in expression of the efflux lipid transporter, ATP-binding cassette subfamily A member 2 (Abca2; cholesterol efflux regulatory protein 2), in SSLepRmutant compared with SSWT rats at 6 and 18 wk of age, which were validated by RT-PCR analysis. These data suggest an association between glomerular hyperfiltration and glomerular lipid accumulation during the early development of proteinuria associated with obesity.

Localization and functional consequences of a direct interaction between TRIOBP-1 and hERG proteins in the heart.

Reduced levels of the cardiac human (h)ERG ion channel protein and the corresponding repolarizing current IKr can cause arrhythmia and sudden cardiac death, but the underlying cellular mechanisms controlling hERG surface expression are not well understood. Here, we identified TRIOBP-1, an F-actin-binding protein previously associated with actin polymerization, as a putative hERG-interacting protein in a yeast-two hybrid screen of a cardiac library. We corroborated this interaction by performing Förster resonance energy transfer (FRET) in HEK293 cells and co-immunoprecipitation in HEK293 cells and native cardiac tissue. TRIOBP-1 overexpression reduced hERG surface expression and current density, whereas reducing TRIOBP-1 expression via shRNA knockdown resulted in increased hERG protein levels. Immunolabeling in rat cardiomyocytes showed that native TRIOBP-1 colocalized predominantly with myosin-binding protein C and secondarily with rat ERG. In human stem cell-derived cardiomyocytes, TRIOBP-1 overexpression caused intracellular co-sequestration of hERG signal, reduced native IKr and disrupted action potential repolarization. Ca2+ currents were also somewhat reduced and cell capacitance was increased. These findings establish that TRIOBP-1 interacts directly with hERG and can affect protein levels, IKr magnitude and cardiac membrane excitability.

Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp.

Without an approved vaccine or treatments, Ebola outbreak management has been limited to palliative care and barrier methods to prevent transmission. These approaches, however, have yet to end the 2014 outbreak of Ebola after its prolonged presence in West Africa. Here we show that a combination of monoclonal antibodies (ZMapp), optimized from two previous antibody cocktails, is able to rescue 100% of rhesus macaques when treatment is initiated up to 5 days post-challenge. High fever, viraemia and abnormalities in blood count and blood chemistry were evident in many animals before ZMapp intervention. Advanced disease, as indicated by elevated liver enzymes, mucosal haemorrhages and generalized petechia could be reversed, leading to full recovery. ELISA and neutralizing antibody assays indicate that ZMapp is cross-reactive with the Guinean variant of Ebola. ZMapp exceeds the efficacy of any other therapeutics described so far, and results warrant further development of this cocktail for clinical use.

The Perinatal Mental Health of Indigenous Women: A Systematic Review and Meta-Analysis.

OBJECTIVE: Although Indigenous women are exposed to high rates of risk factors for perinatal mental health problems, the magnitude of their risk is not known. This lack of data impedes the development of appropriate screening and treatment protocols, as well as the proper allocation of resources for Indigenous women. The objective of this systematic review and meta-analysis was to compare rates of perinatal mental health problems among Indigenous and non-Indigenous women. METHODS: We searched Medline, EMBASE, PsycINFO, CINAHL, and Web of Science from their inceptions until February 2019. Studies were included if they assessed mental health in Indigenous women during pregnancy and/or up to 12 months postpartum. RESULTS: Twenty-six articles met study inclusion criteria and 21 were eligible for meta-analysis. Indigenous identity was associated with higher odds of mental health problems (odds ratio [OR] 1.62; 95% confidence interval [CI], 1.25 to 2.11). Odds were higher still when analyses were restricted to problems of greater severity (OR 1.95; 95% CI, 1.21 to 3.16) and young Indigenous women (OR 1.86; 95% CI, 1.51 to 2.28). CONCLUSION: Indigenous women are at increased risk of mental health problems during the perinatal period, particularly depression, anxiety, and substance misuse. However, resiliency among Indigenous women, cultural teachings, and methodological issues may be affecting estimates. Future research should utilize more representative samples, adapt and validate diagnostic and symptom measures for Indigenous groups, and engage Indigenous actors, leaders, and related allies to help improve the accuracy of estimates, as well as the well-being of Indigenous mothers, their families, and future generations. TRIAL REGISTRATION: PROSPERO-CRD42018108638.

"I just might kill myself": Suicide expressions on Twitter.

In order to examine how Twitter can be a significant indicator of how suicidal thoughts occur and spread, we used content analysis to analyze 4524 Twitter messages. Although expressions of "wanting to die" occurred frequently, most of the tweets appeared to be non-threatening. In addition, discussions about suicide on Twitter mostly involved sharing suicide prevention resources with fellow users. This finding suggests that Twitter could offer an efficient way to circulate suicide awareness materials across geographical bounds.

Spontaneous superimposed preeclampsia: chronology and expression unveiled by temporal transcriptomic analysis.

Preeclampsia (PE), a multifactorial pregnancy-specific syndrome accounting for up to 8% of pregnancy complications, is a leading cause of maternal and fetal morbidity and mortality. PE is also associated with long-term risk of hypertension and stroke for both mother and fetus. Currently, the only "cure" is delivery of the baby and placenta, largely because the pathogenesis of PE is not yet fully understood. PE is associated with impaired vascular remodeling at the maternal-fetal interface and placental insufficiency; however, specific factors contributing to this impairment have not been identified. To identify molecular pathways involved in PE, we examined temporal transcriptomic changes occurring within the uterus, uterine implantation sites, and placentae from the Dahl salt-sensitive (Dahl S) rat model of superimposed PE compared with Sprague Dawley (SD) rats. We hypothesized that targeted gene analysis and whole transcriptome analysis would identify genetic factors that contribute to development of the preeclamptic phenotype in the Dahl S rat and unveil novel biomarkers, therapeutic targets, and mechanistic pathways in PE. Quantitative real-time PCR (qRT-PCR) and whole genome microarray analysis were performed on isolated total RNA from uterus (day 0), uterine implantation sites (days 7 and 10), and placenta (days 14 and 20). We found 624, 332, 185, and 366 genes to be differentially expressed between Dahl S (PE) and SD (normal pregnancy) on days 0, 7, 10, and 14, respectively. Our data revealed numerous pathways that may play a role in the pathophysiology of spontaneous superimposed PE and allow for further investigation of novel therapeutic targets and biomarker development.

Impact of obesity as an independent risk factor for the development of renal injury: implications from rat models of obesity.

Diabetes and hypertension are the major causes of chronic kidney disease (CKD). Epidemiological studies within the last few decades have revealed that obesity-associated renal disease is an emerging epidemic and that the increasing prevalence of obesity parallels the increased rate of CKD. This has led to the inclusion of obesity as an independent risk factor for CKD. A major complication when studying the relationship between obesity and renal injury is that cardiovascular and metabolic disorders that may result from obesity including hyperglycemia, hypertension, and dyslipidemia, or the cluster of these disorders [defined as the metabolic syndrome, (MetS)] also contribute to the development and progression of renal disease. The associations between hyperglycemia and hypertension with renal disease have been reported extensively in patients suffering from obesity. Currently, there are several obese rodent models (high-fat diet-induced obesity and leptin signaling dysfunction) that exhibit characteristics of MetS. However, the available obese rodent models currently have not been used to investigate the impact of obesity alone on the development of renal injury before hypertension and/or hyperglycemia. Therefore, the aim of this review is to describe the incidence and severity of renal disease in these rodent models of obesity and determine which models are suitable to study the independent effects obesity on the development and progression of renal disease.

Assessment of community pharmacists' confidence, foundational knowledge, and coordination of care activities in patients with cancer as a chronic condition.

OBJECTIVES: To develop and deliver a series of structured educational programs to community pharmacists to build on current foundational knowledge of cancer and cancer therapy. The specific objectives were to: 1) develop and provide an educational program focused on oncology pharmacy practice in the community; and 2) measure the program impact on participants' confidence, foundational knowledge, and coordination of cancer care activities. PRACTICE INNOVATION: A structured, in-person, 6-hour educational program tailored for community pharmacists was developed and delivered along with two 20-minute online webinar sessions. The topics identified for the webinars were based on solicited feedback from participants attending the live educational program. EVALUATION: A pre- and post-survey was used to evaluate the participant's assessment of the live educational program, and a retrospective survey was used to evaluate the education sessions. RESULTS: Twenty-one pharmacists attended the in-person session. Participants indicated that they were more confident and able to coordinate care after the educational intervention. There was a nonsignificant improvement in foundational knowledge. CONCLUSION: The educational sessions provided current relevant information for community pharmacists to build on knowledge of oncology pharmacy practice and resources. This increased the pharmacists' confidence to address needs and facilitate coordination of care for individuals with cancer. Delivery of education tailored to community pharmacy is important as the advancing cancer care model continues to adapt with new medications and innovations.