The Effects of an Online Positive Psychology Course on Happiness, Health, and Well-Being.

This study investigated the effects of an 8-week online positive psychology course on happiness, health, and well-being. There were 65 undergraduate students in the course and a comparison group of 63 undergraduates taking other online psychology courses. The participants were assessed on positive mental health (e.g., happiness, positive emotions), negative mental health (e.g., anxiety, depression), general health, and personal characteristics (e.g., hope, resilience) during the first and last week of the courses. The anxiety and depression measures had cut-offs for clinically significant symptoms. The hypotheses were that the positive psychology students would have significant improvements on all measures and a reduction in the percent anxious and depressed relative to the comparison group. The hypotheses were supported with large effect sizes for positive and negative mental health (mean ds = 0.907 and - 0.779, respectively) and medium-to-large effects for general health and personal characteristics (d = 0.674 and mean ds = 0.590, respectively). There was a reduction from 49.2 to 23.1% percent anxious and from 18.6 to 6.2% percent depressed with no change in the comparison group. In addition, improvements in the online positive psychology course were compared with a previous study of a similar face-to-face positive psychology course (Smith et al., 2021) showing the effect sizes for improvements relative to the comparison groups were larger in the online vs. face-to-face course (mean ds = 0.878. vs. 0.593). Possible explanations for these differences are discussed along with the implications for maximizing the benefits of positive psychology courses in the future.

Comparison of Toxicity and Treatment Outcomes in HIV-positive Versus HIV-negative Patients With Squamous Cell Carcinoma of the Anal Canal.

PURPOSE: To compare the toxicity and treatment outcomes in human immunodeficiency virus (HIV)-positive versus HIV-negative patients with squamous cell carcinoma of the anal canal who underwent definitive concurrent chemoradiation at a single institution. MATERIALS AND METHODS: Fifty-three consecutive HIV-positive patients treated between 1987 and 2013 were compared with 205 consecutive HIV-negative patients treated between 2003 and 2013. All patients received radiotherapy at a single regional facility. The median radiation dose was 54 Gy (range, 28 to 60 Gy). Concurrent chemotherapy consisted of 2 cycles 5-FU with mitomycin-C given on day 1±day 29). After treatment, patients were closely followed with imaging studies, clinical examinations, and rigid proctoscopies. Outcomes assessed were toxicity rates, progression-free survival, colostomy-free survival, cancer-specific survival, and overall survival. RESULTS: Median follow-up was 34 months. Compared with HIV-negative patients, HIV-positive patients were younger (median age, 48 vs. 62 y) and predominantly male sex (98% of HIV-positive patients were male vs. 22% of HIV-negative patients). Of the HIV-positive patients, 37 (70%) were on highly active antiretroviral therapy, 26 (65%) had an undetectable viral load at the time of treatment, and 36 (72%) had a CD4 count>200 (mean CD4 count, 455). There were no significant differences in acute or late nonhematologic or hematologic toxicity rates between the 2 groups. At 3 years, there was no significant difference between HIV-positive and HIV-negative patients in regards to progression-free survival (75% vs. 76%), colostomy-free survival (85% vs. 85%), or cancer-specific survival (79% vs. 88%, P=0.36), respectively. On univariate analysis, there was a trend toward worse overall survival in HIV-positive patients (72% vs. 84% at 3 y, P=0.06). For the entire cohort, on multivariate analysis only male sex and stage were predictive of worse survival outcomes. HIV status was not associated with worse outcomes in Cox models. CONCLUSIONS: In the highly active antiretroviral therapy era, HIV-positive patients with anal cancer treated with standard definitive chemoradiation have equivalent toxicity and cancer-specific survival compared with HIV-negative patients.

Problem-solving strategies of women undergoing chemotherapy for breast cancer.

BACKGROUND: Many women undergoing chemotherapy for breast cancer experience side effects that make it difficult to perform daily occupations. PURPOSE: To summarize the types of challenges, goals, and adaptive strategies identified by women with stage 1-3 breast cancer participating in a pilot study of Problem-solving Treatment-Occupational Therapy (PST-OT). METHODS: Content analysis of 80 PST-OT sessions. FINDINGS: Women addressed 11 types of challenging activities, with exercise and instrumental activities of daily living (IADL) being the most common. Most women set a goal to adapt a current activity, but also set goals to find a new activity, plan the steps of a current activity, or gather information about a possible activity change in the future. The adaptive strategies generated by the women were grouped into five types. Most often they found ways to add a new step to an activity, but they also brainstormed about when, how, where, and with whom they could do activities. IMPLICATIONS: The women were usually trying to adapt familiar activities but also were looking for ways to include new, healthy occupations into their routines.

Long-term outcomes and patterns of tumor progression after gamma knife radiosurgery for benign meningiomas.

OBJECT: To characterize the timing and patterns of long-term treatment failure after Gamma Knife radiosurgery (GKRS) for benign meningiomas. METHODS: Data were retrospectively reviewed in 116 patients who underwent 136 GKRS treatments for benign intracranial meningiomas from 1996 to 2004. Patients with atypical or malignant meningiomas were excluded. Surgical resection preceded GKRS in 72 patients (62%). The median tumor volume was 3.4 cm, and the median prescription dose to the 50% isodose line was 16 Gy. RESULTS: The median follow-up time was 75 months (range, 4-146 months). Overall tumor control was achieved in 128 of 136 lesions (94%), of which tumor size was stable in 68% and decreased in 26%. Seven patients experienced disease progression in 8 tumors, occurring at a mean time of 90 months. The overall 5-year and 10-year actuarial tumor control rate was 98.9% and 84%, respectively. Characteristics corresponding to tumor progression included insufficient tumor coverage (98% vs 93%, P = .007), cavernous sinus lesions, and meningiomatosis. Complications after GKRS developed in 8% of patients, in whom the mean tumor volume was nearly double that in patients with no adverse effects (11 vs 5.7 cm3, P = .003). CONCLUSIONS: GKRS demonstrates excellent long-term tumor control in the management of benign meningiomas. Tumor progression occurred at a mean time of 7.5 years after GKRS, reinforcing the need for long-term surveillance despite initial tumor control. Treatment failure was related to undercoverage of lesions in the majority of cases, with the remainder demonstrating evidence of abnormal tumor biology.

CyberKnife enhanced conventionally fractionated chemoradiation for high grade glioma in close proximity to critical structures.

INTRODUCTION: With conventional radiation technique alone, it is difficult to deliver radical treatment (>or= 60 Gy) to gliomas that are close to critical structures without incurring the risk of late radiation induced complications. Temozolomide-related improvements in high-grade glioma survival have placed a higher premium on optimal radiation therapy delivery. We investigated the safety and efficacy of utilizing highly conformal and precise CyberKnife radiotherapy to enhance conventional radiotherapy in the treatment of high grade glioma. METHODS: Between January 2002 and January 2009, 24 patients with good performance status and high-grade gliomas in close proximity to critical structures (i.e. eyes, optic nerves, optic chiasm and brainstem) were treated with the CyberKnife. All patients received conventional radiation therapy following tumor resection, with a median dose of 50 Gy (range: 40 - 50.4 Gy). Subsequently, an additional dose of 10 Gy was delivered in 5 successive 2 Gy daily fractions utilizing the CyberKnife image-guided radiosurgical system. The majority of patients (88%) received concurrent and/or adjuvant Temozolmide. RESULTS: During CyberKnife treatments, the mean number of radiation beams utilized was 173 and the mean number of verification images was 58. Among the 24 patients, the mean clinical treatment volume was 174 cc, the mean prescription isodose line was 73% and the mean percent target coverage was 94%. At a median follow-up of 23 months for the glioblastoma multiforme cohort, the median survival was 18 months and the two-year survival rate was 37%. At a median follow-up of 63 months for the anaplastic glioma cohort, the median survival has not been reached and the 4-year survival rate was 71%. There have been no severe late complications referable to this radiation regimen in these patients. CONCLUSION: We utilized fractionated CyberKnife radiotherapy as an adjunct to conventional radiation to improve the targeting accuracy of high-grade glioma radiation treatment. This technique was safe, effective and allowed for optimal dose-delivery in our patients. The value of image-guided radiation therapy for the treatment of high-grade gliomas deserves further study.

Radical cyberknife radiosurgery with tumor tracking: an effective treatment for inoperable small peripheral stage I non-small cell lung cancer.

OBJECTIVE: Curative surgery is not an option for many patients with clinical stage I non-small-cell lung carcinoma (NSCLC), but radical radiosurgery may be effective. METHODS: Inoperable patients with small peripheral clinical stage I NSCLC were enrolled in this study. Three-to-five fiducial markers were implanted in or near tumors under CT guidance. Gross tumor volumes (GTVs) were contoured using lung windows. The GTV margin was expanded by 5 mm to establish the planning treatment volume (PTV). A dose of 42-60 Gy was delivered to the PTV in 3 equal fractions in less than 2 weeks using the CyberKnife radiosurgery system. The 30-Gy isodose contour extended at least 1 cm from the GTV. Physical examination, CT imaging and pulmonary function testing were completed at 6 months intervals for three years following treatment. RESULTS: Twenty patients with an average maximum tumor diameter of 2.2 cm (range, 1.1 - 3.5 cm) and a mean FEV1 of 1.08 liters (range, 0.53 - 1.71 L) were treated. Pneumothorax requiring tube thoracostomy occurred following CT-guided fiducial placement in 25% of the patients. All patients completed treatment with few acute side effects and no procedure-related mortality. Transient chest wall discomfort developed in 8 of the 12 patients with lesions within 5 mm of the pleura. The mean percentage of the total lung volume receiving a minimum of 15 Gy was 7.3% (range, 2.4% to 11.3%). One patient who received concurrent gefitinib developed short-lived, grade III radiation pneumonitis. The mean percent predicted DLCO decreased by 9% and 11% at 6 and 12 months, respectively. There were no local failures, regional lymph node recurrences or distant metastases. With a median follow-up of 25 months for the surviving patients, Kaplan-Meier overall survival estimate at 2 years was 87%, with deaths due to COPD progression. CONCLUSION: Radical CyberKnife radiosurgery is a well-tolerated treatment option for inoperable patients with small, peripheral stage I NSCLC. Effective doses and adequate margins are likely to have contributed to the optimal early local control seen in this study.

Radical stereotactic radiosurgery with real-time tumor motion tracking in the treatment of small peripheral lung tumors.

BACKGROUND: Recent developments in radiotherapeutic technology have resulted in a new approach to treating patients with localized lung cancer. We report preliminary clinical outcomes using stereotactic radiosurgery with real-time tumor motion tracking to treat small peripheral lung tumors. METHODS: Eligible patients were treated over a 24-month period and followed for a minimum of 6 months. Fiducials (3-5) were placed in or near tumors under CT-guidance. Non-isocentric treatment plans with 5-mm margins were generated. Patients received 45-60 Gy in 3 equal fractions delivered in less than 2 weeks. CT imaging and routine pulmonary function tests were completed at 3, 6, 12, 18, 24 and 30 months. RESULTS: Twenty-four consecutive patients were treated, 15 with stage I lung cancer and 9 with single lung metastases. Pneumothorax was a complication of fiducial placement in 7 patients, requiring tube thoracostomy in 4. All patients completed radiation treatment with minimal discomfort, few acute side effects and no procedure-related mortalities. Following treatment transient chest wall discomfort, typically lasting several weeks, developed in 7 of 11 patients with lesions within 5 mm of the pleura. Grade III pneumonitis was seen in 2 patients, one with prior conventional thoracic irradiation and the other treated with concurrent Gefitinib. A small statistically significant decline in the mean % predicted DLCO was observed at 6 and 12 months. All tumors responded to treatment at 3 months and local failure was seen in only 2 single metastases. There have been no regional lymph node recurrences. At a median follow-up of 12 months, the crude survival rate is 83%, with 3 deaths due to co-morbidities and 1 secondary to metastatic disease. CONCLUSION: Radical stereotactic radiosurgery with real-time tumor motion tracking is a promising well-tolerated treatment option for small peripheral lung tumors.

Botulinum toxin type A targets RhoB to inhibit lysophosphatidic acid-stimulated actin reorganization and acetylcholine release in nerve growth factor-treated PC12 cells.

Botulinum toxin type A (BoNT/A) produced by Clostridium botulinum inhibits Ca2+-dependent acetylcholine (ACh) release (neuroexocytosis) at peripheral neuromuscular junctions, sometimes causing neuromuscular paralysis. This inhibitory effect is attributed to its metalloprotease activity to cleave the 25-kDa synaptosomal-associated protein, which is essential for the exocytotic machinery. However, deletion of this protein does not result in a complete block of neuroexocytosis, suggesting that botulinum-mediated inhibition may occur via another mechanism. Rho GTPases, a class of small GTP-binding proteins (G proteins), control actin cytoskeletal organization, thereby regulating a variety of cellular functions in various cells, including neuronal cells. We have shown that the G protein activator lysophosphatidic acid (LPA) triggered actin reorganization followed by Ca2+-dependent ACh release in nerve growth factor-treated PC12 cells and that BoNT/A blocked both events through degradation of RhoB by the proteasome. Overexpression of wild-type RhoB caused actin reorganization and enhanced the release of ACh by LPA to overcome toxin's inhibitory effect on actin reorganization/exocytosis stimulated by LPA, whereas overexpression of a dominant negative RhoB inhibited ACh release, regardless of LPA and/or toxin treatment. Finally, a knockdown of the RhoB gene via sequence-specific, post-transcriptional gene silencing reduced RhoB expression in PC12 cells, resulting in total inhibition of both actin reorganization and ACh release induced by LPA. We conclude that the RhoB signaling pathway regulates ACh release via actin cytoskeletal reorganization and that botulinum toxin inhibits neuroexocytosis by targeting RhoB pathway.