Empowering STEM students: A university-wide mentorship program fostering retention and belonging.

In the face of a challenging climate STEM (Science, Technology, Engineering and Mathematics) higher education that is resistant to Diversity, Equity, and Inclusion efforts aimed to increase and retain students from historically excluded groups (HEGs), there is a critical need for a support structure to ensure students from HEGs continue to be recruited retained. The Biology Undergraduate and Master's Mentorship Program (BUMMP) embodies this commitment to fostering scientific identity, efficacy, and a sense of belonging for first-generation and historically underserved undergraduate and master's students at UC San Diego. The mission of BUMMP is to cultivate a sense of belonging, instill confidence, and nurture a strong scientific identity amongst all its participants. At its core, the three pillars of BUMMP are (1) mentorship, (2) professional development, and (3) research. Quality mentorship is provided where students receive personal guidance from faculty, graduate students, postdocs, and industry leaders in navigating their career pathways. Complementing mentorship, BUMMP provides paid research opportunities and prioritizes professional development by offering workshops designed to enhance students' professional skills. These three pillars form the backbone of BUMMP, empowering students from all backgrounds and ensuring their retention and persistence in STEM. So far, we've served over 1350 mentees, collaborated with 809 mentors, and had over 180 mentees actively engaged in BUMMP-sponsored research activities. The primary focus of this paper is to provide a programmatic guideline for the three pillars of BUMMP: mentorship, professional development, and research. This will offer a blueprint for other institutions to establish similar mentorship programs. Additionally, the paper highlights the impact of the BUMMP program and surveyed mentees who have participated in the mentorship and research component of BUMMP. We showed that mentorship and research experience enhance students' sense of belonging, science identity, and science efficacy, which are key predictors of retention and persistence in pursuing a STEM career. Overall, BUMMP's expansive efforts have made a tremendous impact at UC San Diego and will continue to foster a community of future leaders who will be prepared to make meaningful contributions to the scientific community and beyond.

Repeated Administration of 2-Hydroxypropyl-ß-Cyclodextrin (HPßCD) Attenuates the Chronic Inflammatory Response to Experimental Stroke.

Globally, more than 67 million people are living with the effects of ischemic stroke. Importantly, many stroke survivors develop a chronic inflammatory response that may contribute to cognitive impairment, a common and debilitating sequela of stroke that is insufficiently studied and currently untreatable. 2-Hydroxypropyl-ß-cyclodextrin (HPßCD) is an FDA-approved cyclic oligosaccharide that can solubilize and entrap lipophilic substances. The goal of the present study was to determine whether the repeated administration of HPßCD curtails the chronic inflammatory response to stroke by reducing lipid accumulation within stroke infarcts in a distal middle cerebral artery occlusion mouse model of stroke. To achieve this goal, we subcutaneously injected young adult and aged male mice with vehicle or HPßCD 3 times per week, with treatment beginning 1 week after stroke. We evaluated mice at 7 weeks following stroke using immunostaining, RNA sequencing, lipidomic, and behavioral analyses. Chronic stroke infarct and peri-infarct regions of HPßCD-treated mice were characterized by an upregulation of genes involved in lipid metabolism and a downregulation of genes involved in innate and adaptive immunity, reactive astrogliosis, and chemotaxis. Correspondingly, HPßCD reduced the accumulation of lipid droplets, T lymphocytes, B lymphocytes, and plasma cells in stroke infarcts. Repeated administration of HPßCD also preserved NeuN immunoreactivity in the striatum and thalamus and c-Fos immunoreactivity in hippocampal regions. Additionally, HPßCD improved recovery through the protection of hippocampal-dependent spatial working memory and reduction of impulsivity. These results indicate that systemic HPßCD treatment following stroke attenuates chronic inflammation and secondary neurodegeneration and prevents poststroke cognitive decline.SIGNIFICANCE STATEMENT Dementia is a common and debilitating sequela of stroke. Currently, there are no available treatments for poststroke dementia. Our study shows that lipid metabolism is disrupted in chronic stroke infarcts, which causes an accumulation of uncleared lipid debris and correlates with a chronic inflammatory response. To our knowledge, these substantial changes in lipid homeostasis have not been previously recognized or investigated in the context of ischemic stroke. We also provide a proof of principle that solubilizing and entrapping lipophilic substances using HPßCD could be an effective strategy for treating chronic inflammation after stroke and other CNS injuries. We propose that using HPßCD for the prevention of poststroke dementia could improve recovery and increase long-term quality of life in stroke sufferers.

Glial scars are permeable to the neurotoxic environment of chronic stroke infarcts.

Following stroke, the damaged tissue undergoes liquefactive necrosis, a stage of infarct resolution that lasts for months although the exact length of time is currently unknown. One method of repair involves reactive astrocytes and microglia forming a glial scar to compartmentalize the area of liquefactive necrosis from the rest of the brain. The formation of the glial scar is a critical component of the healing response to stroke, as well as other central nervous system (CNS) injuries. The goal of this study was to evaluate the toxicity of the extracellular fluid present in areas of liquefactive necrosis and determine how effectively it is segregated from the remainder of the brain. To accomplish this goal, we used a mouse model of stroke in conjunction with an extracellular fluid toxicity assay, fluorescent and electron microscopy, immunostaining, tracer injections into the infarct, and multiplex immunoassays. We confirmed that the extracellular fluid present in areas of liquefactive necrosis following stroke is toxic to primary cortical and hippocampal neurons for at least 7 weeks following stroke, and discovered that although glial scars are robust physical and endocytic barriers, they are nevertheless permeable. We found that molecules present in the area of liquefactive necrosis can leak across the glial scar and are removed by a combination of paravascular clearance and microglial endocytosis in the adjacent tissue. Despite these mechanisms, there is delayed atrophy, cytotoxic edema, and neuron loss in regions adjacent to the infarct for weeks following stroke. These findings suggest that one mechanism of neurodegeneration following stroke is the failure of glial scars to impermeably segregate areas of liquefactive necrosis from surviving brain tissue.

Feasibility of Project Mentor: A Mentoring Program Based on Self-Determination Theory for Adolescents Classified as Overweight.

Purpose: This study examined the feasibility of Project Mentor, a mentoring program based on self-determination theory (SDT) for youth classified as overweight or obese. Methods: In Study 1, youth (N = 23) ranging from 12-18 years of age were randomly assigned to a mentoring intervention or wait-list control condition. Study 2 served as a replication sample and consisted of N = 38 youth who participated in the mentoring program. As part of a process evaluation, attendance and exercise heart rate were monitored to assess whether participants exercised at a moderate-to-vigorous level as intended. Mentees also rated whether mentors created a need-supportive environment. For outcome evaluation, basic need satisfaction, behavioral regulation, fitness, and body composition were assessed at pre, post, and follow-up. Results: Across both studies, participants attended over 80% of the exercise sessions and exercised at a moderate to vigorous intensity level. Mentees also perceived that mentors created a need-supportive environment. Post-test and follow-up basic need scores were higher than baseline values and autonomous motivation increased for mentoring program participants. Effect sizes were generally moderate to large in magnitude based on partial eta-squared and Cohen d. Aerobic fitness (i.e., Vo2peak) showed a moderate to large increase at post-test that was partially maintained at follow-up. Body composition changes were nonsignificant and small in magnitude. Participants in the wait-list control reported showed small changes or decreases across SDT related constructs, fitness, and body composition across both studies. Conclusions: Results across both studies support the feasibility of a mentoring program focused on CARE (competence, autonomy, relatedness, and enjoyment).

Gender-based differences in assessment and management of acute abdominal pain in the emergency department: A retrospective audit.

BACKGROUND: Previous research has identified gender-based differences in acute pain management in the emergency department [ED]. The aim of this study was to compare pharmacological management of acute abdominal pain in the ED by gender. METHODS: A retrospective chart audit was conducted at one private metropolitan ED including adult patients (18-80 years) who presented with acute abdominal pain in 2019. Exclusion criteria included: pregnancy, repeat presentation within the study period, pain-free at initial medical review or documented refusal of analgesia, and oligo-analgesia. Comparisons by gender included: (1) analgesia type and (2) time to analgesia. Bivariate analysis was undertaken using SPSS. RESULTS: There were 192 participants: 61 (31.6 %) men and 131 (67.9 %) women. Men were more likely to get combined opioid and non-opioid medication as first line analgesia (men: 26.2 % n = 16; women: 14.5 % n = 19, p = .049). Median time from ED presentation to analgesia was 80 min for men (IQR: 60) versus 94 min for women (IQR: 58), (p = .119). Women (25.2 % n = 33) were more likely to receive their first analgesic after 90 min from ED presentation compared to men versus men (11.5 %, n = 7 p = .029). In addition, women waited longer before receiving second analgesia (women: 94, men: 30 min, p = .032). CONCLUSION: Findings confirm there are differences in pharmacological management of acute abdominal pain in the ED. Larger studies are required to further explore differences observed in this study.

[18F](R)-5-chloro-1-(1-cyclopropyl-2-methoxyethyl)-3-(4-(2-fluoroethoxy)-2,5-dimethyl phenylamino)pyrazin-2(1H)-one: introduction of N3-phenylpyrazinones as potential CRF-R1 PET imaging agents.

Based on a favorable balance between CRF-R1 affinity, lipophilicity and metabolic stability, compound 10 was evaluated for potential development as PET radioligand. Compound [(18)F]10 was prepared with high radiochemical purity and showed promising binding properties in rat brain imaging experiments.

Positive Human Contact and Housing Systems Impact the Responses of Piglets to Various Stressors.

This experiment studied the effects of lactation housing systems and human interaction on piglets' responses to routine stressors. Forty litters of piglets were reared in either a standard farrowing crate (FC) or a loose farrowing and lactation pen (LP; PigSAFE pen) and received either routine contact with humans (C) or regular opportunities for positive human contact (+HC; 3 min of patting, stroking and scratching 5 times/week). Behavioural and physiological responses to routine husbandry procedures, weaning, novelty and humans were studied in addition to effects on piglet growth, injuries and survival. Compared to C piglets, +HC piglets vocalised for shorter durations (p = 0.018) during husbandry procedures and showed a lower intensity of escape behaviour during iron injection (p = 0.042) and oral vaccination (p = 0.026) at 3 d of age, capture at 2 wk of age (p < 0.001), and intramuscular vaccination (p = 0.005) at 3 wk of age. +HC piglets at 2 wk of age were faster than C piglets to approach (p = 0.048) and interact (p = 0.042) with a stationary unfamiliar human. Compared to LP piglets, FC piglets showed a lower intensity of escape behaviour during capture and iron administration by a stockperson at 3 d of age (p = 0.043). FC piglets at 2 wk of age were faster than LP piglets to approach (p = 0.005) and interact (p = 0.027) with a novel object and approach (p = 0.009) and interact (p = 0.008) with an unfamiliar human. FC piglets had fewer injuries than LP piglets at 2 wk of age (p = 0.004). +HC pigs had fewer injuries than C pigs after weaning (p = 0.003). After weaning there were more pigs from LP than FC observed to be upright (both stationary, p = 0.002 and walking, p = 0.024), vocalizing (p = 0.004), nosing another pig (p = 0.035) and nosing the pen floor (p = 0.038). There were no significant effects on neutrophil:lymphocyte ratios or plasma cortisol concentrations 1.5 h after weaning. However, 25 h after weaning +HC pigs had higher haptoglobin concentrations than C pigs (p = 0.002), and C/LP pigs had higher cortisol concentrations than +HC/LP and C/FC pigs (p = 0.012). There were no significant effects on piglet growth, the number of piglets born alive or the number stillborn, however there were more piglets weaned from FC than LP (p = 0.035). The results from this experiment raise questions that require further research on the ability of pigs reared in loose pens to cope with stressors such as exposure to humans, novelty, husbandry procedures and weaning. This experiment also provides evidence that regular positive human interaction reduces pigs' fear of humans and husbandry procedures imposed by stockpeople. More research is required to determine if any of these effects are sustained long-term.

Effects of Positive Human Contact during Gestation on the Behaviour, Physiology and Reproductive Performance of Sows.

Previous positive interactions with humans may ameliorate the stress response of farm animals to aversive routine practices such as painful or stressful procedures, particularly those associated with stockpeople. We studied the effects of positive handling by providing younger (parity 1-2) and older (parity 3-8) sows housed in pens of fifteen (n = 24 pens in total) with either positive human contact (+HC) or routine human contact (control) during gestation. The +HC treatment involved a familiar stockperson patting and scratching sows and was imposed at a pen-level for 2 min daily. Measurements studied included behavioural, physiological and productivity variables. The +HC sows showed reduced avoidance of the stockperson conducting pregnancy testing and vaccination in the home pens, however the behavioural and cortisol responses of sows in a standard unfamiliar human approach test did not differ. There were no effects of +HC on aggression between sows, serum cortisol or serum brain-derived neurotrophic factor concentrations during gestation, or on the behavioural and cortisol response to being moved to farrowing crates. There were also no effects of +HC on the maternal responsiveness of sows, farrowing rate or the number of piglets born alive, stillborn or weaned. Sows in the +HC pens reduced their physical interaction with the stockpeople imposing the treatment after 2 weeks, which suggests the sows may have habituated to the novel or possible rewarding elements of the handling treatment. This experiment shows that regular positive interaction with stockpeople does reduce sows' fear of stockpeople, but does not always confer stress resilence.

The association between clinical parameters recorded at vet gates during Fédération Equestre Internationale endurance rides and the imminent risk of elimination.

BACKGROUND: Endurance competitions over distances of 80-160 km are required by Fédération Equestre Internationale (FEI) rules to be divided into a number of stages between three and six. These stages are also known as "loops". Veterinary inspections, designed to ensure horse welfare, are conducted at the end of each loop, with details recorded on a separate "vet card" for each horse. OBJECTIVES: To identify risk factors recorded on vet cards that were associated with elimination at subsequent loops. STUDY DESIGN: Retrospective cohort study. METHODS: Data relating to 3213 horse starts worldwide in international (CEI) events during 2014 were analysed. Univariable logistic regression was used to identify risk factors for potential inclusion in a final multivariable logistic regression model. Models were constructed stepwise using backwards-removal and assessed using the Bayesian information criterion. RESULTS: Risk factors were identified, which would allow an "in-ride" risk profile to be constructed for each horse which evolves as the horse progresses through the ride. Some risk factors such as abnormal gait and high heart rate were found to be repeatedly associated with imminent failure to qualify. MAIN LIMITATIONS: This is a relatively small study in terms of cohort size, based on the data that were available at the time of the study. Although comprehensive ride history data were also available for each horse via the main FEI database, training data were not. CONCLUSIONS: By identifying risk factors observed during the veterinary inspections at the end of a loop that are strongly associated with elimination at the end of the next or subsequent loops, these results provide an evidence-base for educational initiatives and regulatory changes that will inform the way veterinary delegates use veterinary inspections to help identify horses at risk of imminent FTQ.

Assessment of 18F-labeled mitochondrial complex I inhibitors as PET myocardial perfusion imaging agents in rats, rabbits, and primates.

PURPOSE: Myocardial extractions of mitochondria complex I (MC-I) inhibitors were high and well correlated with flow. This study assessed the potential of MC-I inhibitors to be developed as myocardial perfusion imaging (MPI) agents. METHODS: RP1003, RP1004, and RP1005 representing three classes of MC-I inhibitor were synthesized and radio-labeled with (18)F. These agents were evaluated for IC(50) values, tissue biodistribution, and cardiac PET imaging. (18)F-RP1004 was further examined for first-pass extraction and by imaging in non-human primates (NHP) and rats following coronary ligation. RESULTS: RP1003, RP1004, and RP1005 exhibited high MC-I inhibitory activity with IC(50) of 3.7, 16.7, and 14.4 nM. Heart uptakes in rats (percent injected dose per gram tissue) at 15 and 60 min after injection were 3.52 +/- 0.36 and 2.68 +/- 0.20 for (18)F-RP1003, 2.40 +/- 0.21 and 2.67 +/- 0.27 for (18)F-RP1004, and 2.28 +/- 0.12 and 1.81 +/- 0.17 for (18)F-RP1005. The heart to lung and liver uptake ratios were favorable for cardiac imaging with these agents. In isolated perfused rabbit hearts, the uptake of (18)F-RP1004 increased from 0.74 +/- 0.19 to 1.68 +/- 0.39 mL/min/g at flow rates of 1.66 to 5.06 mL/min/g. These values were higher than or similar to that of (99m)Tc-sestamibi. Cardiac imaging with these agents in rats and rabbits allowed visualization of the heart with minimal lung interference and rapid liver activity clearance. Imaging with (18)F-RP1004 also showed clear myocardium and marked liver activity washout in the NHP and clear detection of the perfusion-deficit area associated with left coronary artery ligation in the rat. CONCLUSION: MC-I inhibitors have the potential to be a new class of MPI agent.

Synthesis and biological evaluation of pyridazinone analogues as potential cardiac positron emission tomography tracers.

A series of fluorinated pyridazinone derivatives with IC50 values ranging from 8 to 4000 nM for the mitochondrial complex 1 (MC1) have been prepared. Structure-activity relationship (SAR) assessment indicated preference of the fluorine label to be incorporated on an alkyl side chain rather than directly on the pyridazinone moiety. Tissue distribution studies of a series of analogues ([18F] 22-28) in Sprague-Dawley (SD) rats identified [18F]27 as the most promising radiotracer with high uptake in cardiac tissue (3.41%ID/g; 30 min post injection) in addition to favorable heart to nontarget organ distribution ratios. MicroPET images of SD rats and nonhuman primates after [18F]27 administration allowed easy assessment of the myocardium through 60 min with minimal lung or liver interference.

Alzheimer's associated amyloid and tau deposition co-localizes with a homeostatic myelin repair pathway in two mouse models of post-stroke mixed dementia.

The goal of this study was to determine the chronic impact of stroke on the manifestation of Alzheimer's disease (AD) related pathology and behavioral impairments in mice. To accomplish this goal, we used two distinct models. First, we experimentally induced ischemic stroke in aged wildtype (wt) C57BL/6 mice to determine if stroke leads to the manifestation of AD-associated pathological ß-amyloid (Aß) and tau in aged versus young adult wt mice. Second, we utilized a transgenic (Tg) mouse model of AD (hAPP-SL) to determine if stroke leads to the worsening of pre-existing AD pathology, as well as the development of pathology in brain regions not typically expressed in AD Tg mice. In the wt mice, there was delayed motor recovery and an accelerated development of cognitive deficits in aged mice compared to young adult mice following stroke. This corresponded with increased brain atrophy, increased cholinergic degeneration, and a focal increase of Aß in areas of axonal degeneration in the ipsilateral hemisphere of the aged animals. By contrast, in the hAPP-SL mice, we found that ischemia induced aggravated behavioral deficits in conjunction with a global increase in Aß, tau, and cholinergic pathology compared to hAPP-SL mice that underwent a sham stroke procedure. With regard to a potential mechanism, in both models, we found that the stroke-induced Aß and tau deposits co-localized with increased levels of ß-secretase 1 (BACE1), along with its substrate, neuregulin 1 (NGR1) type III, both of which are proteins integral for myelin repair. Based on these findings, we propose that the chronic sequelae of stroke may be ratcheting-up a myelin repair pathway, and that the consequent increase in BACE1 could be causing an inadvertent cleavage of its alternative substrate, AßPP, resulting in greater Aß seeding and pathogenesis.

Liquefaction of the Brain following Stroke Shares a Similar Molecular and Morphological Profile with Atherosclerosis and Mediates Secondary Neurodegeneration in an Osteopontin-Dependent Mechanism.

Here we used mouse models of heart and brain ischemia to compare the inflammatory response to ischemia in the heart, a protein rich organ, to the inflammatory response to ischemia in the brain, a lipid rich organ. We report that ischemia-induced inflammation resolves between one and four weeks in the heart compared to between eight and 24 weeks in the brain. Importantly, we discovered that a second burst of inflammation occurs in the brain between four and eight weeks following ischemia, which coincided with the appearance of cholesterol crystals within the infarct. This second wave shares a similar cellular and molecular profile with atherosclerosis and is characterized by high levels of osteopontin (OPN) and matrix metalloproteinases (MMPs). In order to test the role of OPN in areas of liquefactive necrosis, OPN-/- mice were subjected to brain ischemia. We found that at seven weeks following stroke, the expression of pro-inflammatory proteins and MMPs was profoundly reduced in the infarct of the OPN-/- mice, although the number of cholesterol crystals was increased. OPN-/- mice exhibited faster recovery of motor function and a higher number of neuronal nuclei (NeuN) positive cells in the peri-infarct area at seven weeks following stroke. Based on these findings we propose that the brain liquefies after stroke because phagocytic cells in the infarct are unable to efficiently clear cholesterol rich myelin debris, and that this leads to the perpetuation of an OPN-dependent inflammatory response characterized by high levels of degradative enzymes.

Synthesis and biological evaluation of the mitochondrial complex 1 inhibitor 2-[4-(4-fluorobutyl)benzylsulfanyl]-3-methylchromene-4-one as a potential cardiac positron emission tomography tracer.

A series of fluorinated chromone analogs with IC50 values ranging from 9 to 133 nM for the mitochondrial complex 1 (MC-I) has been prepared. A structure-activity relationship (SAR) study of the most potent fluorinated chromone analog 10 demonstrated the linkage heteroatom preference of the side chain region of the molecule while maintaining potent MC-I inhibitory activity. Tissue distribution studies 30 min after [(18)F]10 administration to Sprague-Dawley (SD) rats demonstrated high uptake of the radiotracer from the blood pool into the myocardium (2.24% ID/g), kidney (1.93% ID/g), and liver (2.00% ID/g). After 2 h about 66% of the activity in the myocardium at 30 min had been retained, whereas approximately 70% had been cleared from the liver and kidney. MicroPET images of SD rats after [(18)F]10 administration allowed easy assessment of the myocardium through 60 min with minimal lung or liver interference.

Amino Acid derived enamides: synthesis and aminopeptidase activity.

Recently developed copper-catalyzed coupling methodology has been applied to the synthesis of amino acid derived enamides. Bond formation proved to be strongly influenced by protection strategy and vinyl iodide substitution while tolerant of limited side chain functionality. Assessment of aminopeptidase activity revealed a preference for (E)-1,2-disubstituted constructs.

Mechanism of uptake and retention of F-18 BMS-747158-02 in cardiomyocytes: a novel PET myocardial imaging agent.

BACKGROUND: BMS-747158-02 is a novel fluorine 18-labeled pyridazinone derivative designed for cardiac imaging. The uptake and retention mechanisms of F-18 BMS-747158-02 in cardiac myocytes were studied in vitro, and the biodistribution of F-18 BMS-747158-02 was studied in vivo in mice. METHODS AND RESULTS: Fluorine 19 BMS-747158-01 inhibited mitochondrial complex I (MC-I) in bovine heart submitochondrial particles with an IC(50) of 16.6 +/- 3 nmol/L that was comparable to the reference inhibitors of MC-1, rotenone, pyridaben, and deguelin (IC(50) of 18.2 +/- 6.7 nmol/L, 19.8 +/- 2.6 nmol/L, and 23.1 +/- 1.5 nmol/L, respectively). F-18 BMS-747158-02 had high uptake in monolayers of neonatal rat cardiomyocytes (10.3% +/- 0.7% of incubated drug at 60 minutes) that was inhibited by 200 nmol/L of rotenone (91% +/- 2%) and deguelin (89% +/- 3%). In contrast, an inactive pyridaben analog, P-070 (IC(50) value >4 micromol/L in MC-1 assay), did not inhibit the binding of F-18 BMS-747158-02 in cardiomyocytes. Uptake and washout kinetics for F-18 BMS-747158-02 in rat cardiomyocytes indicated that the time to half-maximal (t((1/2))) uptake was very rapid (approximately 35 seconds), and washout t((1/2)) for efflux of F-18 BMS-747158-02 was greater than 120 minutes. In vivo biodistribution studies in mice showed that F-18 BMS-747158-02 had substantial myocardial uptake (9.5% +/- 0.5% of injected dose per gram) at 60 minutes and heart-to-lung and heart-to-liver ratios of 14.1 +/- 2.5 and 8.3 +/- 0.5, respectively. Positron emission tomography imaging in the mouse allowed clear cardiac visualization and demonstrated sustained myocardial uptake through 55 minutes. CONCLUSIONS: F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.

Multiplex immunoassay characterization and species comparison of inflammation in acute and non-acute ischemic infarcts in human and mouse brain tissue.

This study provides a parallel characterization of the cytokine and chemokine response to stroke in the human and mouse brain at different stages of infarct resolution. The study goal was to address the hypothesis that chronic inflammation may contribute to stroke-related dementia. We used C57BL/6 and BALB/c mice to control for strain related differences in the mouse immune response. Our data indicate that in both mouse strains, and humans, there is increased granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin-6 (IL-6), interleukin-12 p70 (IL-12p70), interferon gamma-induced protein-10 (IP-10), keratinocyte chemoattractant/interleukin-8 (KC/IL-8), monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α), macrophage inflammatory protein-1ß (MIP-1ß), regulated on activation, normal T cell expressed and secreted (RANTES), and Tumor necrosis factor-α (TNF-α) in the infarct core during the acute time period. Nevertheless, correlation and two-way ANOVA analyses reveal that despite this substantial overlap between species, there are still significant differences, particularly in the regulation of granulocyte colony-stimulating factor (G-CSF), which is increased in mice but not in humans. In the weeks after stroke, during the stage of liquefactive necrosis, there is significant resolution of the inflammatory response to stroke within the infarct. However, CD68+ macrophages remain present, and levels of IL-6 and MCP-1 remain chronically elevated in infarcts from both mice and humans. Furthermore, there is a chronic T cell response within the infarct in both species. This response is differentially polarized towards a T helper 1 (Th1) response in C57BL/6 mice, and a T helper 2 (Th2) response in BALB/c mice, suggesting that the chronic inflammatory response to stroke may follow a different trajectory in different patients. To control for the fact that the average age of the patients used in this study was 80 years, they were of both sexes, and many had suffered from multiple strokes, we also present findings that reveal how the chronic inflammatory response to stroke is impacted by age, sex, and multiple strokes in mice. Our data indicate that the chronic cytokine and chemokine response to stroke is not substantially altered in 18-month old compared to 3-month old C57BL/6 mice, although T cell infiltration is attenuated. We found a significant correlation in the chronic cytokine response to stroke in males and females. However, the chronic cytokine response to stroke was mildly exacerbated by a recurrent stroke in both C57BL/6 and BALB/c mice.

Patients' adherence to aspects of haemodialysis regimens in tropical north Queensland, Australia.

BACKGROUND: Patients with end-stage kidney disease often have difficulty in adhering to aspects of their haemodialysis regimens. OBJECTIVES: This study aimed to quantify the number of patients who attended 100% of their scheduled haemodialysis sessions, and the number of patients who gained no more than one kilogram per day between dialysis sessions, over a three-month period. DESIGN: Retrospective chart audit PARTICIPANTS: Patients undergoing haemodialysis at an in-hospital centre in tropical Australia. METHODS: A renal nurse audited the 72 charts pertaining to a 12-week period in 2013. RESULTS: Patients attended 90.1% of all scheduled dialysis sessions. Forty-one patients attended all sessions, with the remaining 31 missing at least one scheduled session. One patient missed 16 scheduled sessions. The following were statistically less likely to attend all their scheduled sessions: Aboriginal and Torres Strait Islander patients; patients on a three times per week dialysis schedule; patients who had relocated from rural or regional towns and younger patients. The average daily weight gain ranged from 0.414 kg to 1.017 kg (mean = 0.885 kg). Younger patients were statistically less likely to adhere to fluid restrictions; patients without diabetes were more likely to adhere to the fluid allowances. CONCLUSIONS AND APPLICATIONS TO PRACTICE: Renal services need to assist patients to adhere to their regimens. Initially, this service will examine strategies to maximise the likelihood of patients attending all of their dialysis sessions. Such an outcome will help to delay deterioration in the patients' health status, while minimising additional strain on the health service.

Synthesis and Cardiac Imaging of (18)F-Ligands Selective for ß1-Adrenoreceptors.

A series of potent and selective ß1-adrenoreceptor ligands were identified (IC50 range, 0.04-0.25 nM; ß1/ß2 selectivity range, 65-450-fold), labeled with the PET radioisotope fluorine-18 and evaluated in normal Sprague-Dawley rats. Tissue distribution studies demonstrated uptake of each radiotracers from the blood pool into the myocardium (0.48-0.62% ID/g), lung (0.63-0.97% ID/g), and liver (1.03-1.14% ID/g). Dynamic µPET imaging confirmed the in vivo dissection studies.