The transition to family caregiving and its effect on biomarkers of inflammation.

Chronic stress has been widely proposed to increase systemic inflammation, a pathway that may link stress with a heightened risk for many diseases. The chronic stress-inflammation relationship has been challenging to study in humans, however, and family caregiving has been identified as one type of stressful situation that might lead to increased inflammation. Previous studies of caregiving and inflammation have generally used small convenience samples, compared caregivers with poorly characterized control participants, and assessed inflammation only after caregivers provided care for extended periods of time. In the current project, changes over a 9-y period were examined on six circulating biomarkers of inflammation for 480 participants from a large population-based study. All participants reported no involvement in caregiving prior to the first biomarker assessment, and 239 participants then took on extensive and prolonged family caregiving responsibilities at some point prior to the second biomarker assessment. Incident caregivers were individually matched on multiple demographic and health history variables with participants who reported no caregiving responsibilities. Of the six biomarkers examined, only tumor necrosis factor alpha receptor 1 showed a significantly greater increase in caregivers compared with controls. This effect was small (d = 0.14), and no effects were found for a subset of 45 caregivers who were living with a spouse with dementia. These results are consistent with recent meta-analytic findings and challenge the widespread belief that caregiving is a substantial risk factor for increased inflammation. Future research is warranted on factors that may account for stress resilience in family caregivers.

Pediatric Cardiology Fellowship Standards for Training in Exercise Medicine and Curriculum Outline.

Over the past 2 decades, fundamentals of exercise medicine, including clinical exercise testing, assessment and promotion of physical activity, exercise prescription, and supervised exercise training/rehabilitation programming have demonstrated considerable clinical value in the management of children and adolescents with congenital and acquired heart disease. Although the principles of exercise medicine have become an integral component in pediatric cardiology, there are no standardized training recommendations for exercise physiology during pediatric cardiology fellowship at this time. Thus, the Pediatric Cardiology Exercise Medicine Curriculum Committee (PCEMCC) was formed to establish core and advanced exercise physiology training recommendations for pediatric cardiology trainees. The PCEMCC includes a diverse group of pediatric cardiologists, exercise physiologists, and fellowship program directors. The expert consensus training recommendations are by no means a mandate and are summarized herein, including suggestions for achieving the minimum knowledge and training needed for general pediatric cardiology practice.

Racial differences in persistence to secondary prevention medication regimens after ischemic stroke.

BACKGROUND: Prior stroke is one of the biggest risk factors for future stroke events. Effective secondary prevention medication regimens can dramatically reduce recurrent stroke risk. Guidelines recommend the use of antithrombotic, antihypertensive and lipid-lowering medications after stroke. Medication adherence is known to be better in the presence of a caregiver but long-term adherence after stroke is unknown and disparities may persist. METHODS: We examined the effects of race and sex on baseline prescription and maintenance of secondary prevention regimens in the presence of a caregiver using the Caring for Adults Recovering from the Effects of Stroke (CARES) study, an ancillary study of the national REasons for Geographic and Racial Differences in Stroke (REGARDS). RESULTS: Incident ischemic stroke survivors (N = 172; 36% Black) with family caregivers had medications recorded at hospital discharge and on average 9.8 months later during a home visit. At discharge, antithrombotic prescription (95.9%), lipid-lowering medications (78.8%) and antihypertensives (89.9%) were common and there were no race or sex differences in discharge prescription rates. One year later, medication persistence had fallen to 86.6% for antithrombotics (p = 0.002) and 69.8% for lipid lowering (p = 0.008) but increased to 93.0% for antihypertensives (p = 0.30). Blacks were more likely to have discontinued antithrombotics than Whites (18.3% v 7.7%, p = 0.04). No significant differences in persistence were seen with age, sex, income, depression, or cognitive impairment. CONCLUSIONS: Medication persistence was high in this sample, likely due to the presence of a caregiver. In our cohort, despite similar prescription rates at the time of hospital discharge, Black stroke survivors were more than twice as likely to stop antithrombotics than Whites. The effect of changes in patterns of medication usage on health outcomes in Black stroke survivors warrants continued investigation.

Continuous cardiac rhythm monitoring post-stroke: A feasibility study in REGARDS.

OBJECTIVES: Cardiac rhythm monitoring is increasingly used after stroke. We studied feasibility of telephone guided, mail-in ambulatory long-term cardiac rhythm monitoring in Black and White stroke survivors. MATERIALS AND METHODS;: We contacted 28 participants of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who had an ischemic stroke during follow-up. After obtaining informed consent by telephone, a noninvasive 14-day cardiac rhythm monitoring device (ZIO® XT patch; iRhythm Technologies, San Francisco, CA) was mailed to each participant. We evaluated the results of telephone consent, follow-up calls, compliance and wear time as the primary objective. Secondarily, we reported prevalence of atrial and ventricular arrhythmias. RESULTS: The majority of those contacted (20/28 = 71%) agreed to enroll in the monitoring study. Non-participation was nominally more common in Black than White participants; 6/16 (37.5%) vs. 2/12 (17%). Of those who agreed, 15 participants (75%, 6 Black, 9 White) completed ambulatory monitoring with mean wear time 12.9 ± 2.5 days. Arrhythmias were observed in two-thirds of the 15 participants: AF in 2, brief atrial tachycardia in 12, NSVT in 2, premature ventricular contractions in 3, and pause or atrioventricular block in 2. CONCLUSIONS: Non-invasive rhythm monitoring was feasible in this pilot from a large, national cohort study of stroke survivors that employed a telephone guided, mail-in monitoring system, and these preliminary results suggest a high prevalence of arrhythmias. Increased emphasis on recruitment strategies for Black stroke survivors may be required. We demonstrated a high yield of significant cardiac arrhythmias among post-stroke participants who completed monitoring.

Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis.

BACKGROUND: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterized by a 'cytokine storm' and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID-19. METHODS: Narrative review. RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P = 0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin-converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID-19 severity but it is all indirect. Community-based placebo-controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID-19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile, vitamin D supplementation should be strongly advised for people likely to be deficient.

Depressive Symptoms After Ischemic Stroke: Population-Based Comparisons of Patients and Caregivers With Matched Controls.

Background and Purpose- Persistent depression after ischemic stroke is common in stroke survivors and may be even higher in family caregivers, but few studies have examined depressive symptom levels and their predictors in patient and caregiver groups simultaneously. Methods- Stroke survivors and their family caregivers (205 dyads) were enrolled from the national REGARDS study (Reasons for Geographic and Racial Differences in Stroke) into the CARES study (Caring for Adults Recovering from the Effects of Stroke) ≈9 months after a first-time ischemic stroke. Demographically matched stroke-free dyads (N=205) were also enrolled. Participants were interviewed by telephone, and depressive symptoms were assessed with the 20-item Center for Epidemiological Studies-Depression scale. Results- Significant elevations in depressive symptoms (Ps<0.03) were observed for stroke survivors (M=8.38) and for their family caregivers (M=6.42) relative to their matched controls (Ms=5.18 and 4.62, respectively). Stroke survivors reported more symptoms of depression than their caregivers (P=0.008). No race or sex differences were found, but differential prediction of depressive symptom levels was found across patients and caregivers. Younger age and having an older caregiver were associated with more depressive symptoms in stroke survivors while being a spouse caregiver and reporting fewer positive aspects of caregiving were associated with more depressive symptoms in caregivers. The percentage of caregivers at risk for clinically significant depression was lower in this population-based sample (12%) than in previous studies of caregivers from convenience or clinical samples. Conclusions- High depressive symptom levels are common 9 months after first-time ischemic strokes for stroke survivors and family caregivers, but rates of depressive symptoms at risk for clinical depression were lower for caregivers than previously reported. Predictors of depression differ for patients and caregivers, and standards of care should incorporate family caregiving factors.

Association Between Patients' Self-Reported Gaps in Care Coordination and Preventable Adverse Outcomes: a Cross-Sectional Survey.

BACKGROUND: Whether patients' reports of gaps in care coordination reflect clinically significant problems is unclear. OBJECTIVE: To determine any association between patient-reported gaps in care coordination and patient-reported preventable adverse outcomes. DESIGN AND PARTICIPANTS: We administered a cross-sectional survey on experiences with healthcare to participants in the national Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were ≥ 65 years old. Of the 15,817 participants in REGARDS at the time of our survey (August 2017-November 2018), 11,138 completed the survey. We restricted the sample to participants who reported ≥ 2 ambulatory visits and ≥ 2 ambulatory providers in the past year (N = 7568). MAIN MEASURES: We considered 7 gaps in ambulatory care coordination, elicited with previously validated questions. We considered 4 outcomes: (1) a test that was repeated because the doctor did not have the result of the first test, (2) a drug-drug interaction that occurred due to multiple prescribers, (3) an emergency department visit that could have been prevented by better communication among providers, and (4) a hospital admission that could have been prevented by better communication among providers. We used logistic regression to determine the association between ≥ 1 gap in care coordination and ≥ 1 preventable outcome, adjusting for potential confounders. KEY RESULTS: The average age of the sample was 77.0 years; 55% were female, and 34% were African-American. More than one-third of participants (38.1%) reported ≥ 1 gap in care coordination and nearly one-tenth (9.8%) reported ≥ 1 preventable outcome. Having ≥ 1 gap in care coordination was associated with an increased odds of ≥ 1 preventable outcome (adjusted odds ratio 1.55; 95% confidence interval 1.33, 1.81). CONCLUSIONS: Participants' reports of gaps in care coordination were associated with an increased odds of preventable adverse outcomes. Future interventions should leverage patients' observations to detect and resolve gaps in care coordination.

Multiple Sclerosis Performance Test: validation of self-administered neuroperformance modules.

BACKGROUND AND PURPOSE: The purpose was to determine the test-retest reliability, practice effects, convergent validity and sensitivity to multiple sclerosis (MS) disability of neuroperformance subtests from the patient self-administered Multiple Sclerosis Performance Test (MSPT) designed to assess low contrast vision (Contrast Sensitivity Test, CST), upper extremity motor function (Manual Dexterity Test, MDT) and lower extremity motor function (Walking Speed Test, WST) and to introduce the concept of regression-based norms to aid clinical interpretation of performance scores using the MSPT cognition test (Processing Speed Test, PST) as an example. METHODS: Substudy 1 assessed test-retest reliability, practice effects and convergent validity of the CST, MDT and WST in 30 MS patients and 30 healthy controls. Substudy 2 examined sensitivity to MS disability in over 600 MS patients as part of their routine clinic assessment. Substudy 3 compared performance on the PST in research volunteers and clinical samples. RESULTS: The CST, MDT and WST were shown to be reliable, valid and sensitive to MS outcomes. Performance was comparable to technician-administered testing. PST performance was poorer in the clinical sample compared with the research volunteer sample. CONCLUSIONS: The self-administered MSPT neuroperformance modules produce reliable, objective metrics that can be used in clinical practice and support outcomes research. Published studies which require patient voluntary consent may underestimate the rate of cognitive dysfunction observed in a clinical setting.

Transitions to family caregiving: enrolling incident caregivers and matched non-caregiving controls from a population-based study.

BACKGROUND AND AIM: Providing care to an older adult with a disability has been associated with increased risk to the caregiver's health, but most previous studies of caregiving and health compare persons who are already caregivers with poorly matched non-caregiving controls and are often based on convenience samples. In this report, we describe the enrollment of persons who transitioned into a family caregiving role while participating in a national epidemiological study. METHODS: Participants in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study were asked on two occasions 9-14 years apart if they were providing care on an ongoing basis to a family member with a chronic illness or disability. Those who answered "no" and "yes", respectively, to this caregiving question and reported sufficient caregiving responsibilities after their transitions were enrolled in the present study as incident caregivers (N = 251). Participants matched on multiple demographic and health history variables and who reported no history of caregiving were enrolled as non-caregiving controls (N = 251). RESULTS: Among eligible participants, 84% agreed to participate, and 47% of caregivers reported caring for a person with dementia. Descriptive analyses confirmed the success of the matching procedures for balancing the groups on multiple demographic and pre-caregiving health variables. Depressive symptoms and perceived stress increased significantly after the transition to caregiving. CONCLUSION: Comparable, population-based samples of incident caregivers and matched non-caregivers have been enrolled. Future analyses will examine within-person changes in health and circulating biomarkers as a function of the transition to caregiving.

Vitamin D and Inflammation: Potential Implications for Severity of Covid-19.

Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways. We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality. Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection. Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection. Covid-19 infection and mortality data was gathered from the World Health Organisation. Results Counter-intuitively, lower latitude and typically 'sunny' countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency. These countries have also been experiencing the highest infection and death rates in Europe. The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates. The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0.046) by Spearman's Rank Correlation. Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19. There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19.

Does Natural Mentoring Matter? A Multilevel Meta-analysis on the Association Between Natural Mentoring and Youth Outcomes.

In this meta-analytic review, we examined the relation between natural mentoring and youth outcomes in four domains: academic and vocational functioning, social-emotional development, physical health, and psychosocial problems. Natural mentoring relationships are thought to foster positive youth development and buffer against the risks associated with the tumultuous years of adolescence. Two separate meta-analyses were conducted on the presence of a natural mentor and the quality of the natural mentoring relationship, including thirty studies from 1992 to present. The findings indicated that the presence of a natural mentor was significantly associated with positive youth outcomes (r = .106). A larger effect size was found for the quality of the natural mentoring relationship in terms of relatedness, social support, and autonomy support (r = .208). The largest effect sizes were found for social-emotional development and academic and vocational functioning. Risk-status (e.g., teenage mothers, homeless youth, youth in foster care, and youth of alcoholic parents) did not moderate the relation between presence and quality of natural mentoring relationships and youth outcomes, which may indicate that natural mentors are generally beneficial for all youth regardless of risk-status. Implications for theory and practice concerning the quality of the natural mentoring relationship are discussed.

Psychosis and sexual abuse: An interpretative phenomenological analysis.

OBJECTIVES: This study aimed to investigate the first-person perspective of psychosis sufferers who survived childhood sexual abuse. METHODS: Interpretative phenomenological analysis was employed to explore the experiences of 7 women with a history of sexual abuse and psychosis. RESULTS: Analysis generated six themes: (a) degradation of self, interlinking shame, guilt, and sometimes disgust; (b) body-self entrapment, experiencing bodily constraint and distortion; (c) a sense of being different to others, involving interpersonal problems; (d) unending struggle and depression, a pervasive sense of defeat; (e) psychotic condemnations and abuse, describing psychotic phenomena related to harm and sexual abuse; and (f) perception of links to the past, the links made from past abuse to current functioning. CONCLUSION: Participants suffered extreme psychological, physical, and interpersonal difficulties past and present. Psychotic experiences reported exhibited themes of condemnation by external entities and reflected the topic of sexual abuse. Participants did not generally link psychosis to their past abusive experiences.

Medical therapy following hospitalization for heart failure with reduced ejection fraction and association with discharge to long-term care: a cross-sectional analysis of the REasons for Geographic And Racial Differences in Stroke (REGARDS) population.

BACKGROUND: Less intensive treatment for heart failure with reduced ejection fraction (HFrEF) may be appropriate for patients in long-term care settings because of limited life expectancy, frailty, comorbidities, and emphasis on quality of life. METHODS: We compared treatment patterns between REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants discharged to long-term care versus home following HFrEF hospitalizations. We examined medical records and Medicare pharmacy claims for 147 HFrEF hospitalizations among 80 participants to obtain information about discharge disposition and medication prescriptions and fills. RESULTS: Discharge to long-term care followed 22 of 147 HFrEF hospitalizations (15%). Participants discharged to long-term care were more likely to be prescribed beta-blockers and less likely to be prescribed aldosterone receptor antagonists and hydralazine/isosorbide dinitrate (96%, 14%, and 5%, respectively) compared to participants discharged home (81%, 22%, and 23%, respectively). The percentages of participants discharged to long-term care and home who had claims for filled prescriptions were similar for beta-blockers (68% versus 66%) and angiotensin converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARBs) (45% versus 47%) after 1 year. Smaller percentages of participants discharged to long-term care had claims for filled prescriptions of other medications compared to participants discharged home (diuretics: long-term care-50%, home-72%; hydralazine/isosorbide dinitrate: long-term care-5%, home-23%; aldosterone receptor antagonists: long-term care-5%, home-23%). CONCLUSIONS: Differences in medication prescriptions and fills among individuals with HFrEF discharged to long-term care versus home may reflect prioritization of some medical therapies over others for patients in long-term care.

'Many die in the hurricane': An Interpretative Phenomenological Analysis of Adults with Psychosis and a History of Childhood Physical Abuse.

The study aimed to investigate the experience of adults with a diagnosis of psychosis and who have survived childhood physical abuse. We interviewed eight participants and used interpretative phenomenological analysis to generate themes. The main themes were of perceiving an everyday world of aggression and contempt by others, pervasive mistrust, feeling isolated and for some, attacking oneself with hate. Most participants were also able to reflect on what they saw as 'paranoia' or 'voices'. Paranoia was described as a fluctuating compulsive 'thread' of meaning, feeling and sometimes a transformation of the self. The paranoia and voices experienced often involved a dread of murderous obliteration. The discussion considers the relevance of altered consciousness, psychotic states of self and the contribution of mutating narrative and meaning. Our findings point to the importance of therapy for interpersonal difficulties and the long-term effects of trauma. Copyright © 2016 John Wiley & Sons, Ltd.

Bayesian latent class estimation of the incidence of chest radiograph-confirmed pneumonia in rural Thailand.

Pneumonia is a leading cause of mortality and morbidity worldwide with radiographically confirmed pneumonia a key disease burden indicator. This is usually determined by a radiology panel which is assumed to be the best available standard; however, this assumption may introduce bias into pneumonia incidence estimates. To improve estimates of radiographic pneumonia incidence, we applied Bayesian latent class modelling (BLCM) to a large database of hospitalized patients with acute lower respiratory tract illness in Sa Kaeo and Nakhon Phanom provinces, Thailand from 2005 to 2010 with chest radiographs read by both a radiology panel and a clinician. We compared these estimates to those from conventional analysis. For children aged <5 years, estimated radiographically confirmed pneumonia incidence by BLCM was 2394/100 000 person-years (95% credible interval 2185-2574) vs. 1736/100 000 person-years (95% confidence interval 1706-1766) from conventional analysis. For persons aged ⩾5 years, estimated radiographically confirmed pneumonia incidence was similar between BLCM and conventional analysis (235 vs. 215/100 000 person-years). BLCM suggests the incidence of radiographically confirmed pneumonia in young children is substantially larger than estimated from the conventional approach using radiology panels as the reference standard.

Early Changes in Brain Oxygen Tension May Predict Outcome Following Severe Traumatic Brain Injury.

We report on the change in brain oxygen tension (PbtO2) over the first 24 h of monitoring in a series of 25 patients with severe traumatic brain injury (TBI) and relate this to outcome. The trend in PbtO2 for the whole group was to increase with time (mean PbtO2 17.4 [1.75] vs 24.7 [1.60] mmHg, first- vs last-hour data, respectively; p = 0.002). However, a significant increase in PbtO2 occurred in only 17 patients (68 %), all surviving to intensive care unit discharge (p = 0.006). Similarly, a consistent increase in PbtO2 with time occurred in only 13 patients, the correlation coefficient for PbtO2 versus time being ≥0.5 for all survivors. There were eight survivors and four non-survivors, with low correlation coefficients (<0.5). Significantly more patients with a correlation coefficient ≥0.5 for PbtO2 versus time survived in intensive care (p = 0.039). The cumulative length of time that PbtO2 was <20 mmHg was not significantly different among these three groups. In conclusion, although for the cohort as a whole PbtO2 increased over the first 24 h, the individual trends of PbtO2 were related to outcome. There was a significant association between improving PbtO2 and survival, despite these patients having cumulative durations of hypoxia similar to those of non-survivors.

Stroke Symptoms as a Predictor of Future Hospitalization.

BACKGROUND: Stroke symptoms in the general adult population are common and associated with stroke risk factors, lower physical and mental functioning, impaired cognitive status, and future stroke. Our objective was to determine the association of stroke symptoms with self-reported hospitalization or emergency department (ED) visit. METHODS: Lifetime history of stroke symptoms (sudden weakness, numbness, unilateral or general loss of vision, loss of ability to communicate or understand) was assessed at baseline in a national, population-based, longitudinal cohort study of 30,239 blacks and whites younger than 45 years, enrolled from 2003 to 2007. Self-reported hospitalization or ED visit and reason were collected during follow-up through March 2013. The symptom-hospitalization association was assessed by proportional hazards analysis in persons who were stroke/transient ischemic attack-free at baseline (27,126) with adjustment for sociodemographics and further adjustment for risk factors. RESULTS: One or more stroke symptoms were reported by 4758 (17.5%). After adjustment for sociodemographics, stroke symptoms were most strongly associated with greater risk of hospitalization/ED for cardiovascular disease (CVD) (hazard ratio [HR] = 1.87, 95% confidence interval [CI]: 1.78-1.96), stroke (HR = 1.69, 95% CI: 1.55-1.85), and any reason (HR = 1.39, 95% CI: 1.34-1.44). These associations remained significant and only modestly reduced after risk factor adjustment. CONCLUSIONS: Stroke symptoms are a marker for future hospitalization and ED visit not only for stroke but also for CVD in general. Findings suggest a role for stroke symptom assessment as a novel and simple approach for identifying individuals at high risk for CVD including stroke in whom preventive strategies could be implemented.

Increased adult hippocampal neurogenesis is not necessary for wheel running to abolish conditioned place preference for cocaine in mice.

Recent evidence suggests that wheel running can abolish conditioned place preference (CPP) for cocaine in mice. Running significantly increases the number of new neurons in the hippocampus, and new neurons have been hypothesised to enhance plasticity and behavioral flexibility. Therefore, we tested the hypothesis that increased neurogenesis was necessary for exercise to abolish cocaine CPP. Male nestin-thymidine kinase transgenic mice were conditioned with cocaine, and then housed with or without running wheels for 32 days. Half of the mice were fed chow containing valganciclovir to induce apoptosis in newly divided neurons, and the other half were fed standard chow. For the first 10 days, mice received daily injections of bromodeoxyuridine (BrdU) to label dividing cells. On the last 4 days, mice were tested for CPP, and then euthanized for measurement of adult hippocampal neurogenesis by counting the number of BrdU-positive neurons in the dentate gyrus. Levels of running were similar in mice fed valganciclovir-containing chow and normal chow. Valganciclovir significantly reduced the numbers of neurons (BrdU-positive/NeuN-positive) in the dentate gyrus of both sedentary mice and runner mice. Valganciclovir-fed runner mice showed similar levels of neurogenesis as sedentary, normal-fed controls. However, valganciclovir-fed runner mice showed the same abolishment of CPP as runner mice with intact neurogenesis. The results demonstrate that elevated adult hippocampal neurogenesis resulting from running is not necessary for running to abolish cocaine CPP in mice.

Circulating galectins -2, -4 and -8 in cancer patients make important contributions to the increased circulation of several cytokines and chemokines that promote angiogenesis and metastasis.

BACKGROUND: Circulating concentrations of the cytokines interleukin-6 (IL-6), granulocyte colony-stimulating factor (G-CSF) and chemokines monocyte chemotatic protein 1 (MCP-1)/CCL2 and growth-regulator oncogene α (GROα)/chemokine C-X-C motif ligand 1 are commonly increased in cancer patients and they are increasingly recognised as important promoters, via divergent mechanisms, of cancer progression and metastasis. METHODS: The effect of galectins-2, -4 and -8, whose circulating levels are highly increased in cancer patients, on endothelial secretion of cytokines was assessed in vitro by cytokine array and in mice. The relationship between serum levels of galectins and cytokines was analysed in colon and breast cancer patients. RESULTS: Galectins-2, -4 and -8 at pathological concentrations induce secretion of G-CSF, IL-6, MCP-1 and GROα from the blood vascular endothelial cells in vitro and in mice. Multiple regression analysis indicates that increased circulation of these galectins accounts for 41∼83% of the variance of these cytokines in the sera of colon and breast cancer patients. The galectin-induced secretion of these cytokines/chemokines is shown to enhance the expression of endothelial cell surface adhesion molecules, causing increased cancer-endothelial adhesion and increased endothelial tubule formation. CONCLUSION: The increased circulation of galectins -2, -4 and -8 in cancer patients contributes substantially to the increased circulation of G-CSF, IL-6 and MCP-1 by interaction with the blood vascular endothelium. These cytokines and chemokines in turn enhance endothelial cell activities in angiogenesis and metastasis.