Multiplex array analysis of serum cytokines offers minimal predictive value for cognitive function in the subacute phase after stroke.

Objective: The effects of inflammation on post-stroke cognitive function are still unclear. This study investigated the correlation between the Th17-related cytokines in peripheral blood and post-stroke cognitive function after ischemic stroke in the subacute phase. Design: A retrospective cohort study. Setting: Academic acute inpatient rehabilitation facility. Participants: One hundred and fourteen patients with first ischemic stroke were categorized as the poor cognitive recovery group (n = 58) or good cognitive recovery group (n = 56) based on their cognitive MRFS efficiency. Interventions: All subjects received routine physical, occupational, and speech-language pathology therapy. Main outcome measures: Serum cytokines/chemokine (IL-1 ß, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12p70, IL-13, IL-15, IL-17A, IL-17E, IL-17F, IL-21, IL-22, IL-23, IL-27, IL-28A, IL-31, IL-33, GM-CSF, IFN-γ, MIP-3 α, TNF-α, and TNF-ß) levels were measured in duplicate using Human Th17 magnetic bead panel and multiplex array analysis (Luminex-200 system). The primary functional outcome was a gain in functional independence measure (FIM) cognitive subscore at discharge. The secondary outcome measures were FIM total score at discharge, length of stay in the hospital, and discharge destination. Cognitive Montebello Rehabilitation Factor Score (MRFS) and cognitive MRFS efficiency were calculated. Demographic and clinical characteristics were obtained from the medical record. Results: The good cognitive recovery group had an interesting trend of higher IL-13 than the poor cognitive recovery group (good cognitive recovery group 257.82 ± 268.76 vs. poor cognitive recovery group 191.67 ± 201.82, p = 0.049, unit: pg/ml). However, Pearson's correlation analysis showed no significant correlation between cytokine levels and gain of cognition, cognitive MRFS, or cognitive MRFS efficiency. Receiver operating characteristic (ROC) analysis of cytokines also suggested a low accuracy of prediction as a predictor for post-stroke cognitive recovery improvement. Conclusion: Our preliminary findings suggested that the level of serum cytokines had minimal predictive value for the recovery of cognitive function during the subacute inpatient rehabilitation after stroke.

Application of Network Analysis to Uncover Variables Contributing to Functional Recovery after Stroke.

To estimate network structures to discover the interrelationships among variables and distinguish the difference between networks. Three hundred and forty-eight stroke patients were enrolled in this retrospective study. A network analysis was used to investigate the association between those variables. A Network Comparison Test was performed to compare the correlation of variables between networks. Three hundred and twenty-five connections were identified, and 22 of these differed significantly between the high- and low-Functional Independence Measurement (FIM) groups. In the high-FIM network structure, brain-derived neurotrophic factor (BDNF) and length of stay (LOS) had associations with other nodes. However, there was no association with BDNF and LOS in the low-FIM network. In addition, the use of amantadine was associated with shorter LOS and lower FIM motor subscores in the high-FIM network, but there was no such connection in the low-FIM network. Centrality indices revealed that amantadine use had high centrality with others in the high-FIM network but not the low-FIM network. Coronary artery disease (CAD) had high centrality in the low-FIM network structure but not the high-FIM network. Network analysis revealed a new correlation of variables associated with stroke recovery. This approach might be a promising method to facilitate the discovery of novel factors important for stroke recovery.

Co-occurring Fatigue and Lymphatic Pain Incrementally Aggravate Their Negative Effects on Activities of Daily Living, Emotional Distress, and Overall Health of Breast Cancer Patients.

BACKGROUND: Fatigue and lymphatic pain are the most common and debilitating long-term adverse effects of breast cancer treatment. Fatigue and pain independently have negative effects on quality of life, physical functions, and cancer recurrence-free survival. The interactions between fatigue and pain may aggravate their negative effects. OBJECTIVES: Examine the effects of co-occurring fatigue and lymphatic pain on activities of daily living (ADLs), emotional distress, and overall health of breast cancer patients. METHODS: A cross-sectional and observational design was used to enroll 354 breast cancer patients. Valid and reliable instruments were used to assess fatigue, lymphatic pain, ADLs, emotional distress, and overall health. Descriptive statistics and multivariable regression models were used for data analysis. RESULTS: After controlling for demographic and clinical factors, patients with co-occurring fatigue and lymphatic pain had higher odds of having impaired ADLs (OR = 24.43, CI = [5.44-109.67], P < .001) and emotional distress (OR = 26.52, CI = [9.64-72.90], P < .001) compared to patients with only fatigue and only lymphatic pain. Patients with co-occurring fatigue and lymphatic pain had 179% increase in impaired ADL scores (B = 8.06, CI = [5.54-10.59]) and 211% increase in emotional distress scores (B = 9.17, CI = [5.52-12.83]) compared to those without co-occurring fatigue and lymphatic pain. Patients with co-occurring fatigue and lymphatic pain had a 34% decrease (B = -26.29, CI = [-31.90 to -20.69]) and patients with only fatigue had a 33% decrease in overall health scores (B = -25.74, 95% CI = [-34.14 to -17.33]), indicating poor overall health. CONCLUSIONS: Fatigue and lymphatic pain affected 66.4% of breast cancer patients. Findings from this study suggest that co-occurring fatigue and lymphatic pain have negative effects on breast cancer patients' ADLs, emotional distress, and overall health. The synergistic interactions between fatigue and lymphatic pain incrementally aggravated their negative effects on ADLs and emotional distress. Findings of the study highlight the need to evaluate the underlying mechanisms for co-occurring fatigue and lymphatic pain and develop interventions that target both fatigue and lymphatic pain to improve breast cancer patients' the quality of life.

Lymphatic Pain in Breast Cancer Survivors.

Background: Breast cancer survivors who report chronic pain in the affected ipsilateral upper limb or body are nearly twice as likely to develop lymphedema. Little is known about lymphatic pain, defined as co-occurring pain and swelling in the affected ipsilateral upper limb or body. The study aimed to examine the predictors and effects of lymphatic pain on breast cancer survivors' activities of daily living (ADLs). Materials and Methods: A sample of 568 patients was recruited in a metropolitan cancer center in the United States. Demographic and clinical data were collected. Body mass index (BMI) and limb volume were measured using infra-red perometer. Lymphatic pain and ADLs were measured by the Lymphedema and Breast Cancer Symptom Experience Index. Parametric and nonparametric tests and generalized linear models were used to analyze data. Results: Lymphatic pain affected 33% of survivors. Significant predictors of lymphatic pain included younger age, higher BMI, financial hardship, and a diagnosis of lymphedema. Patients with a diagnosis of lymphedema had 9.68 odds (confidence interval [CI]: 5.78-16.63; p < 0.001) and those with financial hardship had 4.64 odds (CI: 1.99-11.32; p = 0.001) of experiencing lymphatic pain. Patients with lymphatic pain had more impairments in ADLs (p < 0.001) compared to patients with only pain, only swelling, and no symptoms. Significantly more patients with lymphatic pain had a limb volume difference of >5% and >10% compared to patients with only pain and no symptom. Conclusion: This study is the first to report that in a large sample of patients, 33.1% experienced lymphatic pain and that lymphatic pain was associated with significant impairments in ADLs. Findings suggest that lymphatic pain may be due to abnormal accumulation of lymph fluid. Research is needed to ascertain the physiological mechanisms that underlie lymphatic pain and determine whether strategies to prevent and treat lymphedema can decrease lymphatic pain.

Glyphosate-Based Herbicides Alter the Reproductive Morphology of Rosa acicularis (Prickly Rose).

Glyphosate is a broad-spectrum herbicide that is widely used in many different commercial formulations. Glyphosate-based herbicides (GBH) are used in forestry operations to reduce populations of plants that compete with merchantable conifers. Past research has found that low-dose GBH applications caused male sterility in agriculturally relevant plants, sparking a need to determine the potential impacts of forestry-related GBH applications on understory plants. We investigated the effects of GBH on the reproductive morphology of Rosa acicularis, a highly prevalent understory shrub within British Columbia, Canada, growing on three operational forestry cutblocks treated with 1.782 kg a.i./ha of glyphosate, in the Omineca Region, and also in a controlled experiment. We analyzed floral and pollen morphology from treated plants and compared these with untreated plants in both scenarios. Pollen viability of treated plants was reduced by an average of 66%, and >30% of anthers were non-dehiscent compared to controls across our three field sites and experimental plants. We also found alterations in pollen and petal morphology in flowers from treated sites and glyphosate residues present in floral tissues 2 years after GBH applications. It is important to fully understand how long GBH-induced change will impact forest vegetation, to preserve natural forest biodiversity and reduce anthropogenic influences on boreal forest ecosystems.

Topographical data analysis to identify high-density clusters in stroke patients undergoing post-acute rehabilitation.

BACKGROUND: During acute stroke rehabilitation, the recovery of motor and cognitive function is highly variable: while some patients regain function, others do not. OBJECTIVE: Our objective was to identify data-driven subgroups of stroke patients undergoing acute rehabilitation using topological data analysis (TDA), compare TDA with K-means clustering, and to assess inter-group demographic and clinical differences among the subgroups. METHODS: This is a secondary data analysis of clinical, functional outcomes, and demographic data collected from 339 stroke patients undergoing acute rehabilitation post-stroke. We identified stroke recovery sub-groups using TDA on the point cloud, persistent homology, and finally, density clustering. We assessed inter-group differences in demographic and clinical characteristics using one-way ANOVA, Kruskal-Wallis, or χ2 tests. RESULTS: TDA revealed three high-density clusters among 137 subjects in the point cloud- poor-recoverers (G1(n = 34)), intermediate-recoverers (G2 (n = 88)) and good-recoverers (G3(n = 15)).Significant differences across clusters were observed for amantadine use (p = .009), number of stroke risk factors (p = .047), creatinine (p = .015), length of stay (p < .001), discharge destination (p < .001), FIM motor, FIM cognition, and FIM total on admission and discharge (all p < .001), and motor, cognition, and total MRFS scores (all p < .001). CONCLUSION: This study revealed that in addition to functional status on admission, stroke risk factors are associated with recovery outcomes. Future studies using TDA to analyze omic data, including clinical, biological, and sociodemographic factors, will accelerate the development of personalized treatment plans in post-acute stroke rehabilitation patients.

Exploring Factors Associated With Long-Term Opioid Therapy in Cancer Survivors: An Integrative Review.

CONTEXT: The prevalence of chronic pain in cancer survivors is double that of the general U.S. POPULATION: Opioids have been the foundation of cancer pain management for decades; however, there is a paucity of literature on long-term opioid therapy (LTOT) in cancer survivors. An understanding of factors related to LTOT use in cancer survivors is needed to address chronic pain and balance opioid harms in the expanding population of cancer survivors. OBJECTIVES: To analyze the research of LTOT utilization and factors associated with persistent opioid use in cancer survivors. METHODS: A five-stage integrative review process was adapted from Whittemore and Knafl. Data sources searched included Web of Science, PubMed, Embase, Cochrane, and Google Scholar. Quantitative research studies from 2010 to present related to cancer survivors managed on LTOT were included. Editorials, reviews, or abstracts were excluded. RESULTS: After reviewing 315 articles, 21 articles were included. We found that there were several definitions of LTOT in the reviewed studies, but the duration of opioid use (i.e., more than three months after completion of curative treatment) was the most common. The reviewed literature describes a relationship between LTOT and important biopsychosocial factors (cancer type, socioeconomic factors, and comorbidities). CONCLUSION: The studies in this review shed light on the factors associated with LTOT in cancer survivors. LTOT was common in certain populations of cancer survivors and those with a collection of patient-specific characteristics. This review suggests that there is a critical need for specialized research on chronic cancer pain and opioid safety in cancer survivors.

Symptom Clusters and Functional Impairment in Individuals Treated for Lyme Borreliosis.

Context: Persistent fatigue, pain, and neurocognitive impairment are common in individuals following treatment for Lyme borreliosis (LB). Poor sleep, depression, visual disturbance, and sensory neuropathies have also been reported. The cause of these symptoms is unclear, and widely accepted effective treatment strategies are lacking. Objectives: To identify symptom clusters in people with persistent symptoms previously treated for LB and to examine the relationship between symptom severity and perceived disability. Methods: This was a retrospective chart review of individuals with a history of treatment of LB referred to The Dean Center for Tick-Borne Illness at Spaulding Rehabilitation Hospital between 2015 and 2018 (n = 270) because of persistent symptoms. Symptoms and functional impairment were collected using the General Symptom Questionnaire-30 (GSQ-30), and the Sheehan Disability Scale. Clinical tests were conducted to evaluate for tick-borne co-infections and to rule out medical disorders that could mimic LB symptomatology. Exploratory factor analysis was performed to identify symptom clusters. Results: Five symptom clusters were identified. Each cluster was assigned a name to reflect the possible underlying etiology and was based on the majority of the symptoms in the cluster: the neuropathy symptom cluster, sleep-fatigue symptom cluster, migraine symptom cluster, cognitive symptom cluster, and mood symptom cluster. Symptom severity for each symptom cluster was positively associated with global functional impairment (p < 0.001). Conclusion: Identifying the interrelationship between symptoms in post-treatment LB in a cluster can aid in the identification of the etiological basis of these symptoms and could lead to more effective symptom management strategies. Key Message: This article describes symptom clusters in individuals with a history of Lyme borreliosis. Five clusters were identified: sleep-fatigue, neuropathy, migraine-like, cognition, and mood clusters. Identifying the interrelationship between symptoms in each of the identified clusters could aid in more effective symptom management through identifying triggering symptoms or an underlying etiology.

Acceptability and feasibility of using actigraphy to assess habitual physical activity and sleep parameters in men and women living in rural communities in conflict-affected Eastern Democratic Republic of Congo.

BACKGROUND: The goals of this study were to (1) determine the feasibility and acceptability of using actigraphy to objectively measure sleep quality and habitual physical activity in rural Democratic Republic of Congo (DRC) and (2) examine the relationship between sleep parameters, self-report symptoms, daytime physical activity, and physical function, including the ability to work. METHOD: Thirty individuals were asked to wear a wrist-worn accelerometer for 5 nights and 4 days. Nighttime sleep parameters derived were average and intra-individual variability (IIV) in total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), and wake after sleep onset (WASO). Daytime habitual physical data derived were average and peak activity and daytime napping. RESULTS: Ninety-three percent (n = 28) of participants completed the study. All participants who wore the device marked sleep and wake cycles and periods of non-wear using the marker. Trauma-related symptoms were not associated with mean or IIV in TST, SE, SOL, or WASO (p > 0.01). Those with higher levels of bodily pain slept longer (ß = 0.633, p = 0.003, adjusted R 2 = 0.279), were more likely to report that their physical health limited their physical activities (ß = 0.71, p < 0.001, adjusted R 2 = 0.679) and had greater difficulty doing daily work (ß = 0.84, p = 0.001, adjusted R 2 = 0.665). CONCLUSION: The use of actigraphy to collect objective measures of activity and sleep quality in rural post-conflict settings is feasible and acceptable. Our preliminary findings suggest that bodily pain and not trauma-related symptoms have a significant impact on sleep and functional outcomes in men and women survivors of prolonged conflict in the DRC.

The Serum BDNF Level Offers Minimum Predictive Value for Motor Function Recovery After Stroke.

Brain-derived neurotrophic factor (BDNF) plays an important role in neuroplasticity and neurogenesis following ischemic and non-ischemic brain injury. The predictive value of BDNF for short-term outcome after stroke is controversial. The objective of this study was to investigate the relationship among serum BDNF level, fractional anisotropy (FA), and functional outcome during post-acute stroke rehabilitation. Serum BDNF levels were measured on admission to an acute inpatient rehabilitation hospital. The primary functional outcome was functional independence measure (FIM) motor subscore at discharge. The secondary outcome measures were FIM total score at discharge, FIM motor subscore on admission, length of stay in the hospital, and discharge destination. We investigated the relationship among the level of serum BDNF and FA as well as functional outcome measures. Three hundred forty-eight consecutive stroke subjects were included in the analysis. Serum BDNF levels on admission were statistically but not clinically correlated with FIM motor subscore at discharge (r = 0.173, P = 0.001) and FIM total score at discharge (r = 0.155, P = 0.004). Receiver operating characteristic (ROC) analysis of BDNF as a predictor for FIM motor subscore improvement showed low accuracy of prediction with an area under the curve (AUC) of 0.581 (P = 0.026). Serum BDNF significantly correlated with FA in the high FIM motor group (n = 10, r = 0.609, P = 0.031) but not in the low FIM motor group (n = 11, r = - 0.132, P = 0.349). The serum BDNF level alone offers minimum predictive value for recovery of motor function during post-acute rehabilitation. Our findings suggest that serum BDNF level may be correlated with FA.

Homeless health care: meeting the challenges of providing primary care.

People experiencing homelessness have multiple complex health conditions yet are typically disengaged from primary health care services and place a significant burden on the acute health system. Barriers preventing people who are homeless from accessing primary care can be both personal and practical and include competing needs and priorities, illness and poor health, physical access to health services, difficulty in contacting services, medication security, and the affordability of health care. Differences in social status and perceptions of being judged can lead to relationship barriers to accessing primary care. Key solutions include prioritising access to stable housing, continuity of health care, specialised homeless general practice, hospital inreach, discharge planning and coordinated care, general practice outreach, and medical recovery centres.

Impaired Cognitive Performance in Endothelial Nitric Oxide Synthase Knockout Mice After Ischemic Stroke: A Pilot Study.

OBJECTIVES: Cognitive dysfunction and dementia are common following ischemic stroke. Endothelial nitric oxide synthase (eNOS) has been found to play an important role in neurologic function and cognition. The purpose of the present study was to assess the specific role of eNOS in cognitive performance after stroke. DESIGN: Male wild-type and mice lacking eNOS (eNOS) underwent middle cerebral artery occlusion or sham-surgery. Primary outcomes were repeated measures of neurologic score, limb asymmetry, sensory/motor function, and spatial memory/learning assessed at intervals up to 28 days postsurgery. Group differences in brain microglia activation and infiltration and levels of interferon-gamma were examined. RESULTS: There was no genotype × surgery interaction effect on the pattern of change in neurologic score, limb asymmetry, or sensory motor function across the 28 days postsurgery. In the Morris water maze, eNOS-/- middle cerebral artery occlusion mice displayed learning and memory deficits not evident in wild-type middle cerebral artery occlusion mice. Poorer spatial memory and learning in eNOS-/- middle cerebral artery occlusion mice was associated with a reduction in the number of activated microglia in the striatum on the lesion side and decreased brain tissue levels of interferon-gamma. CONCLUSIONS: This study's data support a role for eNOS in cognitive performance after stroke. This finding may lead to the development of novel interventions to treat poststroke cognitive deficits.

Dexamethasone exacerbates cytotoxic chemotherapy induced lethargy and weight loss in female tumor free mice.

Cytotoxic chemotherapy can induce a systemic inflammatory response which has been proposed to be an underlying mechanism of cancer treatment related fatigue. Dexamethasone, a synthetic glucocorticoid that has potent anti-inflammatory effects, is incorporated into chemotherapy regimens to prevent chemotherapy-induced nausea and vomiting (CINV). The purpose of this study was to determine whether by suppressing cytotoxic chemotherapy-induced inflammation, dexamethasone could ameliorate chemotherapy induced fatigue/lethargy in tumor free mice. The effect of dexamethasone (DEX) on Cytoxan-Adriamycin (CA)-induced inflammation was assessed by measuring circulating levels of IL-1ß, TNF-α, IL-6, GCSF, KC, and MCP-1 twenty-four-hours post CA injection. Decline in voluntary wheel running activity (VWRA) from baseline (used as a proxy for fatigue/lethargy), body weight and composition, and food intake were monitored in mice administered four cycles of CA every two weeks with or without DEX. CA increased circulating levels of IL-6, GCSF, KC, and MCP-1 and caused a rapid decline in VWRA and body weight immediately following CA-injection. Although the acute CA-induced decline in VWRA and body weight was not evident in mice administered CA + DEX, DEX alone had a suppressive effect on VWRA, and body weight continued to decline in mice administered both CA and DEX while it returned to baseline in CA-treated mice. CA or DEX alone had no long term impact on VWRA but DEX exacerbated lethargy and weight loss in CA-treated mice. Despite dampening the systemic inflammatory response to chemotherapy, dexamethasone failed to ameliorate acute or long term chemotherapy related fatigue/lethargy. Our pre-clinical findings suggest that supportive therapies like dexamethasone used to acutely control nausea and vomiting in cancer patients may actually contribute to overall symptom burden in cancer patients.

The Effects of Resistance Exercise on Biomarkers of Breast Cancer Prognosis: A Pooled Analysis of Three Randomized Trials.

Background: Using a secondary data analysis from randomized controlled trials comparing one year of resistance exercise (n = 109) to a placebo control condition (n = 106) in postmenopausal, posttreatment breast cancer survivors, we investigated the influence of resistance training and changes in body composition on markers associated with cancer progression.Methods: Measures included serum levels of insulin, IGF-1, IGFBP1-3, leptin, serum amyloid A (SAA), adiponectin, C-reactive protein (CRP), IL1ß, TNFα, IL6, and IL8, and body composition (total, lean and fat mass in kg) by DXA at baseline, 6, and 12 months. Linear mixed effects models were used to examine the association between group, biomarkers, and body composition and whether or not changes in muscle strength or body composition influenced the effect of exercise on biomarkers.Results: CRP decreased over time among women participating in resistance training compared with increases in controls (P = 0.045). In stratified analyses and compared with increases in controls, women who gained strength reduced CRP (P = 0.003) and maintained levels of IL1ß and IL6. Among exercisers who lost weight (≥2 kg), CRP (P = 0.045), leptin (P < 0.01), and SAA (P = 0.029) decreased, whereas IGF-BP1 (P = 0.036) increased compared with controls.Conclusions: Resistance training may lower inflammation and improve insulin pathway profiles, but the magnitude and degree of benefit from exercise may depend upon whether or not women gained strength, a possible marker of compliance with training, and/or lost weight during exercise.Impact: Future resistance training trials should consider these potential influencing factors as they may determine how well exercise can slow cancer progression and prevent disease recurrence. Cancer Epidemiol Biomarkers Prev; 27(2); 146-53. ©2017 AACR.

Auricular Point Acupressure to Manage Aromatase Inhibitor-Induced Arthralgia in Postmenopausal Breast Cancer Survivors: A Pilot Study.

PURPOSE/OBJECTIVES: To assess the feasibility of auricular point acupressure to manage aromatase inhibitor-induced arthralgia.
. DESIGN: Wait list control design.
. SETTING: Outpatient clinics and oncology center.
. SAMPLE: 20 women with aromatase inhibitor-induced arthralgia.
. METHODS: After baseline data were collected, participants waited one month before they received acupressure once per week for four weeks at a convenient time. The baseline data served as the control comparison. Self-reported measures and blood samples were obtained at baseline, at preintervention, weekly during the intervention, and at post-intervention.
. MAIN RESEARCH VARIABLES: The primary outcomes included pain intensity, pain interference, stiffness, and physical function. Inflammatory cytokines and chemokines were tested.
. FINDINGS: After the four-week intervention, participants reported decreases in worst pain and pain interference, and improvements in physical function, cancer-related symptom severity, and interference. The proinflammatory cytokines and chemokines displayed a trend of a mean percentage reduction. The anti-inflammatory cytokine interleukin-13 increased from pre- to postintervention.
. CONCLUSIONS: Auricular point acupressure is feasible and may be effective in managing arthralgia in breast cancer survivors.
. IMPLICATIONS FOR NURSING: Nurses can administer acupressure in clinical settings, which could enhance the management of aromatase inhibitor-induced arthralgia and contribute to a shift from traditional disease-based biomedical models to a broader, integrative, medical paradigm for managing aromatase inhibitor-induced arthralgia.

Lysosomal Proteolysis Is Associated With Exercise-Induced Improvement of Mitochondrial Quality Control in Aged Hippocampus.

Exercise improves cognitive function in older adults, but the underlying mechanism is largely unknown. Both lysosomal degradation and mitochondrial quality control decline with age. We hypothesized that exercise ameliorates age-related cognitive decline through the improvement of mitochondrial quality control in aged hippocampus, and this effect is associated with lysosomal proteolysis. Sixteen to eighteen-month old male Sprague Dawley rats underwent swim exercise training for 10 weeks. The exercise regimen prevented cognitive decline in aged rats, reduced oxidative stress, and rejuvenated mitochondria in the aged hippocampus. Exercise training promoted mitochondrial biogenesis, increased mitochondrial fusion and fission, and activated autophagy/mitophagy in aged hippocampal neurons. Lysosomal inhibitor chloroquine partly blocked beneficial effects of exercise on cognitive function, oxidative stress, autophagy/mitophagy, and mitochondrial quality control in aged rats. These results suggest that preservation of cognitive function by long-term exercise is associated with improvement of mitochondrial quality control in aged hippocampus and that lysosomal degradation is required for this process. Our findings suggest that exercise training or pharmacological regulation of mitochondrial quality control and lysosomal degradation may be effective strategies for slowing down age-related cognitive decline.

Lung inflammation caused by inhaled toxicants: a review.

Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials) and those of heavy metals (from paint) are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles) or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7) may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections.