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OBJECTIVES/SPECIFIC AIMS: The study aimed at assessing whether M. bovis BCG infection and inflammation exacerbates the development of atherosclerosis in Ldlr-/- mice. METHODS/STUDY POPULATION: Twelve-week old male Ldlr-/- mice (n=10) were infected with M. bovis BCG (0.3–3.0x10^6 colony-forming units (CFUs)) via the intranasal route, to simulate a natural respiratory route of infection. Mice were subsequently fed a western-type diet (WD) containing 21% fat and 0.2% cholesterol for 16 weeks. Age-matched uninfected Ldlr-/- mice (n=10) fed with an identical WD served as controls. Mice were euthanized after 16 weeks of WD to examine atherosclerotic lesions in aortic root sections and en face aorta using Oil Red O staining. Plasma cholesterol and triglyceride levels were measured by enzymatic assays and lipoprotein distribution was assessed using fast protein liquid chromatography. Because of the important role of T cells and monocytes in atherosclerosis development, we assessed these cell subsets in blood using flow cytometry at 8 and 16 weeks. Experiments were conducted in duplicate. We used unpaired Student’s t-test for group comparisons of numeric variables and flow cytometry data. RESULTS/ANTICIPATED RESULTS: M. bovis BCG infection significantly increased atherosclerotic lesions in en face aorta (plaque size per aorta area ratio; 0.15±0.13 vs. 0.06±0.02; P<0.01), but not in the aortic root. There were no significant differences in plasma cholesterol (1,160 mg/dL vs. 1,278 mg/dL; P = 0.36), triglycerides (340 mg/dL vs. 413 mg/dL; P = 0.28), or lipoprotein profiles between infected vs. uninfected mice at 16 weeks. M. bovis BCG increased circulating T lymphocytes (1,490 cells/uL vs. 1,227 cells/uL; P = 0.03) and monocytes (901 cells/uL vs. 414 cells/uL; P<0.01) within 8 weeks post-infection. When we assessed T lymphocyte subsets, M. bovis BCG infection increased total CD4+ T cell counts (556 cells/uL vs. 416 cells/uL; P<0.01) but not CD8+ T cells. No differences in the proportion of CD44+CD25+ activated T lymphocytes were noted between groups. When we assessed monocyte subsets, M. bovis BCG infection increased the numbers of Ly6Chigh (709 cells/uL vs. 362 cells/uL; P<0.01) and Ly6Clow (145 cells/uL vs. 35 cells/uL; P<0.01) monocytes. Infection was associated with an increased proportion of Ly6Clow monocytes at week 8 (17% vs. 8%; P<0.01) and week 16 (19% vs. 5%; P<0.01), compared to uninfected mice. DISCUSSION/SIGNIFICANCE OF IMPACT: M. bovis BCG infection increased the extent of atherosclerosis formation in the aortas of WD-fed hyperlipidemic Ldlr-/- mice after 16 weeks. Lipid profiles were similar between infected and uninfected mice, and therefore do not explain the observed differences in atherosclerosis. Compared to uninfected controls, M. bovis BCG-infected mice exhibited increased CD4+ T cell and monocyte driven inflammation. Interestingly, M. bovis BCG-infected mice had a higher proportion of non-classical Ly6Clow monocytes, suggesting a pro-atherogenic contribution of these cells in our model. Overall, our results support a pathogenic role of mycobacterial infection in atherosclerosis development and ASCVD.
Spirituality is what gives people meaning and purpose in life, and it has been recognized as a critical factor in patients’ well-being, particularly at the ends of their lives. Studies have demonstrated relationships between spirituality and patient-reported outcomes such as quality of life and mental health. Although a number of studies have suggested that spiritual belief can be associated with mortality, the results are inconsistent. We aimed to determine whether spirituality was related to survival in advanced cancer inpatients in Korea.
For this multicenter study, we recruited adult advanced cancer inpatients who had been admitted to seven palliative care units with estimated survival of <3 months. We measured spirituality at admission using the Korean version of the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-sp), which comprises two subscales: meaning/peace and faith. We calculated a Kaplan-Meier curve for spirituality, dichotomized at the predefined cutoffs and medians for the total scale and each of the two subscales, and performed univariate regression with a Cox proportional hazard model.
We enrolled a total of 204 adults (mean age: 64.5 ± 13.0; 48.5% female) in the study. The most common primary cancer diagnoses were lung (21.6%), colorectal (18.6%), and liver/biliary tract (13.0%). Median survival was 19.5 days (95% confidence interval [CI95%]: 23.5, 30.6). Total FACIT-sp score was not related to survival time (hazard ratio [HR] = 0.981, CI95% = 0.957, 1.007), and neither were the scores for its two subscales, meaning/peace (HR = 0.969, CI95% = 0.932, 1.008) and faith (HR = 0.981, CI95% = 0.938, 1.026).
Significance of results
Spirituality was not related to survival in advanced cancer inpatients in Korea. Plausible mechanisms merit further investigation.
Caregiver symptom assessment is not part of regular clinical cancer care. The ESAS (Edmonton Symptom Assessment System) is a multidimensional tool regularly used to measure symptom burden in patients but not caregivers. The objectives of the present study were to determine the feasibility of the ESAS in caregiver completion (defined as ≥ 9 of 12 items) and determine its concurrent validity with the Zarit Burden Interview–12 (ZBI–12).
We conducted a prospective study on 90 patient–primary caregiver dyads seen in an outpatient supportive care center in a cancer center. The 12 item ESAS–FS (financial–spiritual) was completed by the dyads along with other clinical and psychosocial measures.
The caregiver ESAS was found to be feasible (90/90 caregivers, 100% completed ≥ 9/12 items) and useful (66/90 caregivers, 73%) by caregivers to report their symptom burden. Some 68 of 90 (76%) caregivers had symptom distress scores ≥ 4 on at least one symptom. A significant association was found between the ESAS scores of caregivers and patients for fatigue (0.03), depression (<0.01), anxiety (<0.01), sleep (0.05), well-being (<0.01), financial distress (<0.01), spiritual pain (<0.01), and total ESAS score (<0.01). Concurrent validity with the ZBI–12 was not achieved (r = 0.53, p = 0.74). A significant correlation was found between caregiver ESAS scores and time spent feeding, housekeeping, total combined caregiver activities, and total ZBI–12 scores.
Significance of results:
The caregiver ESAS is a feasible tool and was found useful by our caregivers. Further research is needed to modify the ESAS based on caregivers' recommendations, and further psychometric studies need to be conducted.
Brief cognitive–behavioural therapy (CBT) is an emerging treatment for
schizophrenia in community settings; however, further trials are needed,
especially in non-Western countries.
To test the effects of brief CBT for Chinese patients with schizophrenia
in the community (trial registration: ChiCTR-TRC-13003709).
A total of 220 patients with schizophrenia from four districts of Beijing
were randomly assigned to either brief CBT plus treatment as usual (TAU)
or TAU alone. Patients were assessed at baseline, post-treatment and at
6- and 12-month follow-ups by raters masked to group allocation.
At the post-treatment assessment and the 12-month follow-up, patients who
received brief CBT showed greater improvement in overall symptoms,
general psychopathology, insight and social functioning. In total, 37.3%
of those in the brief CBT plus TAU group experienced a clinically
significant response, compared with only 19.1% of those in the TAU alone
group (P = 0.003).
Brief CBT has a positive effect on Chinese patients with schizophrenia in
Experimental observations have shown that carbon nanotubes (CNTs)/Al nanocomposites with high level ordered nanolaminates exhibit greatly improved plasticity. The increased plasticity is mainly attributed to enhanced dislocation storage capability and two-dimensional alignment of the reinforcement. Here a theoretical model is proposed with interactions between aligned CNTs and grain boundary dislocations emitted from a crack tip taken into consideration to investigate crack blunting and fracture toughness in nanocrytalline metal matrix composites (MMCs). The critical shear stress for emission of first dislocation from intersections between a long, flat crack and aligned CNTs is quantitatively characterized. The final equilibrium positions and maximum numbers of emitted dislocations for different orientation angles and microstructures of aligned reinforcement are evaluated. In addition, the dependence of enhanced fracture toughness on effective gliding distance of emitted dislocations is also determined. The results show that the existence of aligned CNTs can lead to an increase of critical crack intensity factor by 77% than that in dislocation free case under certain conditions. The model may provide a basis understanding of ductility in aligned CNTs-reinforced nanocrystalline MMCs on respective of emission and motion of dislocations.
There is no standardized and universally accepted pain classification system for the assessment and management of cancer pain in both clinical practice and research studies. The Edmonton Classification System for Cancer Pain (ECS–CP) is an assessment tool that has demonstrated value in assessing pain characteristics and response. The purpose of our study was to determine the relationship between negative ECS–CP features and some pain-related variables like pain intensity and opioid use. We also explored whether the number of negative ECS–CP features was associated with higher pain intensity.
The electronic charts of 100 patients at an outpatient supportive care clinic in a comprehensive cancer center were reviewed for variables like patient characteristics, initial ECS–CP assessment, morphine equivalent daily dose (MEDD), opioid rotation, Edmonton Symptom Assessment Score (ESAS), and use of adjuvant analgesics.
Some 91 of the 100 charts were eligible for analysis. The most common primary cancer type was gastrointestinal (22.1%). The median pain intensity was 6, and the median MEDD was 45 mg. Neuropathic pain was associated with higher median pain intensity (7 vs. 5, p = 0.007) and median MEDD requirement (83 vs. 30, p = 0.013). Psychological distress was associated with higher median pain intensity (7 vs. 5, p = 0.042). Incident pain was also associated with a trend toward higher pain intensity (6 vs. 5, p = 0.06). A higher number of negative ECS–CP features was associated with higher pain intensity (p = 0.01).
Significance of Results:
The ECS–CP was successfully completed in the majority of patients, demonstrating its utility in routine clinical practice. Neuropathic pain and psychological distress were associated with higher pain intensity. Also, neuropathic pain was associated with a higher MEDD. A higher sum of negative ECS–CP features was associated with higher pain intensity. Further studies will be needed to verify and explore these observations.
Although “fatigue” and “depression” are well-accepted clinical terms in the English language, they are ill defined in many other languages, including Portuguese. We aimed to investigate the most appropriate words to describe cancer-related fatigue (CRF) and depression in Brazilian cancer patients.
The interviewers read to patients two clinical vignettes describing fatigued patients and two others describing depressed patients. Participants were asked to choose from among “fatigue,” “tiredness,” “weakness,” “depression,” and “sadness” the best and worst terms to explain the vignettes. In addition, they were administered an instrument containing numeric rating scales (NRSs), addressing common symptoms, including the aforementioned terms. Pearson correlation analysis and accuracy diagnostic tests were conducted using the Hospital Anxiety and Depression Scale (HADS) and the Functional Assessment of Cancer Treatment–Fatigue (FACIT–F) as references.
Among the 80 participants, 40% reported that the best term to explain the concept of CRF was “tiredness,” and 59% chose “sadness” as the best descriptor of depression. Regarding diagnostic accuracy, the areas under the curve (AUCs) for “fatigue,” “weakness,” and “tiredness” were 0.71, 0.81, and 0.76, respectively; the AUCs for “depression” and “sadness” ranged from 0.81 to 0.91 and 0.73 to 0.83, respectively. Negative correlations were found among FACIT–F fatigue subscale scores and NRS scores for “fatigue” (r = –0.58), “tiredness” (r = –0.67), and “weakness” (r = –0.62). Regarding depression, there were positive correlations between HADS–D scores and both NRS for “depression” (r = 0.61) and “sadness” (r = 0.54).
Significance of results:
“Tiredness” was considered the best descriptor of CRF. Taking into consideration the clinical correlation with depression scores, the term “depression” was accepted as the best term to explain the concept of depression.
The evolution of arid environments in northern China was a major environmental change during the Quaternary. Here we present the dating and environmental proxy results from a 35 m long core (A-WL10ZK-1) collected from the Ulan Buh Desert (UBD), along with supplemental data from four other cores. The UBD is one of the main desert dune fields in China and our results indicate the UBD has undergone complex evolution during the late Quaternary. Most of the present UBD was covered by a Jilantai-Hetao Mega-paleolake lasting until ~ 90 ka ago. A sandy desert environment prevailed throughout the UBD during the last glacial period and early Holocene. A wetland environment characterized by the formation of numerous interdunal ponds in the northern UBD occurred at ~ 8–7 ka, although a dune field persisted in the southern UBD. The modern UBD landscape formed after these wetlands dried up. During the last 2000 years, eolian sand from the Badain Jaran Desert has invaded the northern UBD, while farming and overgrazing resulted in the formation of the eastern UBD. We suggest that the formation of UBD landforms is related to the disintegration of the megalake Jilantai-Hetao and to summer monsoon changes during the last glaciation and Holocene.
The purpose of this case series was to describe patients with aberrant drug-related behaviors and similar patterns of dose escalation in whom interdisciplinary assessment revealed different bases for their dose increases.
During the period from December 26 to December 30, 2011, the medical records of two patients with opioid-related aberrant behaviors were reviewed.
We described two patients with a significant cancer history and different comorbidities who presented with different aberrant drug-related behaviors and opioid requirements.
Significance of Results:
Opioid-related aberrant behaviors can be interpreted in different ways, and two of the more common syndromes in cancer patients are chemical coping and pseudoaddiction. In advanced cancer patients, the boundaries between these conditions are not as clear, and diagnosis is often made retrospectively. Furthermore, there have been relatively limited studies describing these two syndromes. Thus, they continue to pose a diagnostic and treatment challenge that requires different approaches for effective management of symptoms. The key characteristic between the two syndromes is that the behaviors displayed in chemical coping are motivated by obtaining opioids to relieve psychosocial distress, while in pseudoaddiction these behaviors are motivated by uncontrolled nociceptive input. Close monitoring of the pain syndromes, aberrant behaviors, and opioid requirements over several visits is usually necessary to distinguish the two syndromes.
Advanced cancer patients often develop severe physical and psychological symptom clusters (SCs), but limited data exist on their consistency or severity after an outpatient interdisciplinary team consultation led by palliative care specialists. The primary aim of the study was to determine the consistency and severity of SCs in advanced cancer patients in this setting.
A total of 1373 patients with advanced cancer who were referred to The University of Texas MD Anderson Cancer Center's Outpatient Supportive Care Center between January 2003 and October 2008 with a complete Edmonton Symptom Assessment Scale (ESAS; 0–10 scale) occurred at initial and first follow-up visit were reviewed (median 14 days, range 1–4 weeks). We used a Wilcoxon signed-rank test to determine whether symptoms changed over time, and a principal components factor analysis with varimax rotation to determine SCs at baseline and at first follow-up. The number of factors calculated was determined based upon the number of eigenvalues.
The patients' ratings of the following symptoms (mean, SD) at the initial and follow-up visits, respectively, were: fatigue 6.2 (2.3) and 5.7 (2.5, p < 0.0001), pain 5.4 (2.9) and 4.6 (3, p < 0.0001), nausea 2.2 (2.8) and 2.0 (2.6, p < 0.0001), depression 3.0 (2.9) and 2.5 (2.7, p < 0.0001), anxiety 3.4 (3.0) and 2.8 (2.8, p < 0.0001), drowsiness 4.8 (3.1) and 4.4 (3.1, p < 0.0001), dyspnea 3.0 (2.9) and 2.7 (2.8), p < 0.0001), loss of appetite 4.2 (2.7) and 3.9 (2.7, p < 0.0001), sleep disturbances 4.2 (2.6) and 3.8 (2.6, P < 0.0001), and well-being 4.3 (2.5) and 3.9 (2.3, p < 0.0001). Cluster composition differentiated into physical (fatigue, pain, nausea, drowsiness, dyspnea, and loss of appetite) and psychological (anxiety and depression) components at the initial visit, and these two SCs were consistent upon follow-up.
Significance of results:
We conclude that SCs remain constant between baseline and near-term follow-up but that the severity of those symptoms lessened during that interval. This knowledge may allow palliative care teams to provide more targeted and higher-quality care, but further studies are needed.