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Objective Herbs and natural products are increasingly used by cancer patients for pain management, but few studies have examined their integration within conventional cancer care. This study describes the characteristics, experiences, and perspectives of cancer patients who were prescribed an herbal topical analgesic for pain management. Design and Setting Program evaluation of a pilot herbal dispensary at a National Cancer Institute–designated comprehensive cancer center. Subjects Cancer patients who were prescribed the Tibetree Pain-Relieving Plaster (PRP) by an integrative medicine physician. Methods Sociodemographic and clinical characteristics of patients were abstracted from medical records. Semistructured phone interviews were conducted 1–2 weeks after PRP prescription to evaluate patient experiences with using PRP for pain. Interviews were analyzed through thematic content analysis. Results From February 2019 to February 2020, 50 patients were prescribed PRP. Median age (range) was 63 years (21–86), 37 patients (74%) were female, 14 (28%) were non-White, and 38 (76%) were using oral analgesics. During interviews, the majority of patients reported that the PRP improved pain and health-related outcomes, was convenient to use, and addressed pain management needs that were not fulfilled by oral analgesics. However, a few patients described adverse experiences with PRP, including skin irritation. Conclusions Understanding patient experiences and perspectives is a critical step toward evidence-based integration of herbs and natural products into cancer pain management. Findings from this program evaluation will inform the design of a randomized clinical trial on the efficacy and safety of PRP for pain in patients with cancer. [ABSTRACT FROM AUTHOR]

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect that worsens quality of life and increases the risk of falls in cancer survivors. Evidence of yoga's safety and efficacy in treating CIPN is lacking. Methods In a randomized controlled study, we assigned breast and gynecological cancer survivors with persistent moderate-to-severe CIPN pain, numbness, or tingling with a score of 4 or greater (0-10 numeric rating scale [NRS]) for at least 3 months after chemotherapy to 8 weeks of usual care or yoga focused on breathwork and musculoskeletal conditioning. Primary endpoint was treatment arm differences for NRS, and secondary endpoints were Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity subscale (FACT/GOG-Ntx), and Functional Reach Test after week 8. We tested treatment arm differences for each outcome measure using linear mixed models with treatment-by-time interactions. All statistical tests were two-sided. Results We randomly assigned 41 participants into yoga (n = 21) or usual care (n = 20). At week 8, mean NRS pain decreased by 1.95 points (95% confidence interval [CI] = -3.20 to -0.70) in yoga vs 0.65 (95% CI = -1.81 to 0.51) in usual care (P =.14). FACT/GOG-Ntx improved by 4.25 (95% CI = 2.29 to 6.20) in yoga vs 1.36 (95% CI = -0.47 to 3.19) in usual care (P =.035). Functional reach, an objective functional measure predicting the risk of falls, improved by 7.14 cm (95% CI = 3.68 to 10.59) in yoga and decreased by 1.65 cm (95% CI = -5.00 to 1.72) in usual care (P =.001). Four grade 1 adverse events were observed in the yoga arm. Conclusion Among breast and gynecological cancer survivors with moderate-to-severe CIPN, yoga was safe and showed promising efficacy in improving CIPN symptoms. [ABSTRACT FROM AUTHOR]

Objective To evaluate acupuncture as a nonpharmacologic intervention for pain management in patients undergoing hematopoietic stem cell transplantation (HSCT). Methods Adult patients with multiple myeloma undergoing high-dose melphalan chemotherapy and autologous peripheral blood HSCT were randomized to receive either true (TA) or sham acupuncture (SA) once daily for five days starting on the day after chemotherapy. Use of pain medications and pain scores were assessed at baseline and at days 5, 15, and 30 after transplantation. Results Among 60 evaluable subjects, the SA group (vs TA) had greater than five times odds of increasing pain medication use from baseline. Among patients who were opioid nonusers at baseline, all 15 patients in the TA group remained free from opioid use at the end of the study. In contrast, 20% of those in the SA group (four of the 20 patients) started to use opioids after chemotherapy and stem cell infusion (day 5) and 40% (eight of the 20) had become opioid users by day 30 after HSCT (Fisher exact test P  = 0.006). Among patients who were taking opioids at baseline, 14% in the TA group vs 10% in the SA group increased opioid intake at day 5, and 21% (TA) vs 30% (SA) at day 30 (P  = 0.86). Conclusions Acupuncture appears to significantly reduce the need for pain medications during HSCT and the number of post-HSCT opioid users among baseline opioid nonusers. It warrants further studies as an opioid-sparing intervention for pain in HSCT patients. [ABSTRACT FROM AUTHOR]

Background: Insomnia is a common and debilitating disorder experienced by cancer survivors. Although cancer survivors express a preference for using nonpharmacological treatment to manage insomnia, the comparative effectiveness between acupuncture and Cognitive Behavioral Therapy for Insomnia (CBT-I) for this disorder is unknown.Methods: This randomized trial compared 8 weeks of acupuncture (n = 80) and CBT-I (n = 80) in cancer survivors. Acupuncture involved stimulating specific points on the body with needles. CBT-I included sleep restriction, stimulus control, cognitive restructuring, relaxation training, and education. We measured insomnia severity (primary outcome), pain, fatigue, mood, and quality of life posttreatment (8 weeks) with follow-up until 20 weeks. We used linear mixed-effects models for analyses. All statistical tests were two-sided.Results: The mean age was 61.5 years and 56.9% were women. CBT-I was more effective than acupuncture posttreatment (P < .001); however, both acupuncture and CBT-I produced clinically meaningful reductions in insomnia severity (acupuncture: -8.31 points, 95% confidence interval = -9.36 to -7.26; CBT-I: -10.91 points, 95% confidence interval = -11.97 to -9.85) and maintained improvements up to 20 weeks. Acupuncture was more effective for pain at the end of treatment; both groups had similar improvements in fatigue, mood, and quality of life and reduced prescription hypnotic medication use. CBT-I was more effective for those who were male (P < .001), white (P = .003), highly educated (P < .001), and had no pain at baseline (P < .001).Conclusions: Although both treatments produced meaningful and durable improvements, CBT-I was more effective and should be the first line of therapy. The relative differences in the comparative effectiveness between the two interventions for specific groups should be confirmed in future adequately powered trials to guide more tailored interventions for insomnia. [ABSTRACT FROM AUTHOR]

Objective In response to the national opioid crisis, governmental and medical organizations have called for broader insurance coverage of acupuncture to improve access to nonpharmacologic pain therapies, especially in cancer populations, where undertreatment of pain is prevalent. We evaluated whether cancer patients would be willing to use insurance-covered acupuncture for pain. Design and Setting We conducted a cross-sectional survey of cancer patients with pain at one academic center and 11 community hospitals. Methods We used logistic regression models to examine factors associated with willingness to use insurance-covered acupuncture for pain. Results Among 634 cancer patients, 304 (47.9%) reported willingness to use insurance-covered acupuncture for pain. In univariate analyses, patients were more likely to report willingness if they had severe pain (odds ratio [OR] = 1.59, 95% confidence interval [CI] = 1.03–2.45) but were less likely if they were nonwhite (OR = 0.59, 95% CI = 0.39–0.90) or had only received high school education or less (OR = 0.46, 95% CI = 0.32–0.65). After adjusting for attitudes and beliefs in multivariable analyses, willingness was no longer significantly associated with education (adjusted OR [aOR] = 0.78, 95% CI = 0.50–1.21) and was more negatively associated with nonwhite race (aOR = 0.49, 95% CI = 0.29–0.84). Conclusions Approximately one in two cancer patients was willing to use insurance-covered acupuncture for pain. Willingness was influenced by patients' attitudes and beliefs, which are potentially modifiable through counseling and education. Further research on racial disparities is needed to close the gap in utilization as acupuncture is integrated into insurance plans in response to the opioid crisis. [ABSTRACT FROM AUTHOR]

Objective To evaluate the associations between polymorphisms in two genes, catechol-O-methyltransferase and T-cell leukemia/lymphoma 1 A, and acupuncture-mediated pain reduction among breast cancer survivors with aromatase inhibitor–associated arthralgia. Design, Setting, and Subjects Biospecimens were obtained from 38 patients enrolled in a clinical trial of acupuncture for aromatase inhibitor–associated arthralgia in postmenopausal hormone receptor–positive breast cancer survivors. Methods We used polymerase chain reaction to genotype the rs4680 (Val158Met) and rs4633 (His62His) variants in the catechol-O-methyltransferase gene and rs2369049 (A > G) and rs7158782 (A > G) variants in the T-cell leukemia/lymphoma 1 A gene. Response to acupuncture was defined by 30% reduction in end-of-treatment average pain, measured by the Brief Pain Inventory. We used Fisher exact tests to evaluate associations between genotype and treatment response. Results Among participants, all six (15.8%) subjects who expressed AA in locus rs4680 responded to acupuncture. In a combined analysis, the 18 (47.4%) subjects with the responder genotype at either rs4680 (AA) or rs2369049 (GG or AG) were significantly more likely to respond to acupuncture than those without (77.8% vs 45.0%, P  = 0.039). Conclusions Specific genetic variations at loci rs4680 and rs2369049 are associated with response to acupuncture-type intervention for management of arthralgia. These results serve as a proof of concept for applying a precision medicine framework to the study of cancer pain management. [ABSTRACT FROM AUTHOR]

Abstract: Brain sizes vary substantially across vertebrate taxa, yet, the evolution of brain size appears tightly linked to the evolution of life histories. For example, larger brained species generally live longer than smaller brained species. A larger brain requires more time to grow and develop at a cost of exceeded gestation period and delayed weaning age. The cost of slower development may be compensated by better homeostasis control and increased cognitive abilities, both of which should increase survival probabilities and hence life span. To date, this relationship between life span and brain size seems well established in homoeothermic animals, especially in mammals. Whether this pattern occurs also in other clades of vertebrates remains enigmatic. Here, we undertake the first comparative test of the relationship between life span and brain size in an ectothermic vertebrate group, the anuran amphibians. After controlling for the effects of shared ancestry and body size, we find a positive correlation between brain size, age at sexual maturation, and life span across 40 species of frogs. Moreover, we also find that the ventral brain regions, including the olfactory bulbs, are larger in long‐lived species. Our results indicate that the relationship between life history and brain evolution follows a general pattern across vertebrate clades. [ABSTRACT FROM AUTHOR]

The evolution of sperm quality and quantity is shaped by various selective processes, with sperm competition generally considered the primary selective agent. Particularly in external fertilizers, however, sperm limitation through gamete dispersal can also influence gamete investments, but empirical data examining this effect are limited. Here, we studied the relative importance of sperm competition and the spawning conditions in explaining the macroevolutionary patterns of sperm size and number within two taxa with external fertilization but differences in their reproductive biology. In frogs, sperm swim slowly but for up to hours as they penetrate the gelatinous egg coating, whereas fish sperm typically swim fast, are very short-lived (seconds to minutes), and often face a relatively higher risk of being moved away from the ova by currents. Our phylogenetic models and path analyses revealed different trajectories of ejaculate evolution in these two taxa. Sperm size and number responded primarily to variation in sperm competition in the anurans, but more strongly to egg number and water turbulence in the fishes. Whereas the results across anurans align with the general expectation that sexual selection is the main driver of ejaculate evolution, our findings across the fishes suggest that sperm limitation has been underappreciated. [ABSTRACT FROM AUTHOR]

Objective To investigate the prevalence and determinants of complementary and alternative medicine (CAM) interest level among a racially diverse cohort of inner city veterans who receive primary care at the VA Medical Center. Design Cross-sectional survey study Setting Philadelphia VA Medical Center Subjects Primary care patients ( n = 258) Methods Interest in CAM was measured using a single item question. Patient treatment beliefs were assessed using validated instruments. We evaluated factors associated with patient interest in CAM using a multivariate logistic regression model. Results In this sample of 258 inner city primary care VA patients, interest in CAM was high 80% ( n = 206). Interest in CAM was strongly associated with African American race [adjusted odds ratio (AOR) 2.19, 95% Confidence Interval (CI) 1.05-4.60, P = 0.037], higher levels of education (AOR 4.33, 95% CI 1.80-10.40, P = 0.001), presence of moderate to severe pain (AOR 2.02, 95% CI 1.02-4.78, P = 0.043), and expectations of benefit from CAM use (AOR 1.21, 95% CI 1.06-1.36, P = 0.004). Conclusions CAM approaches have broad appeal within this inner city cohort of veterans, particularly among African Americans, those that experience pain and those that expect greater benefit from CAM. These findings may inform the development of patient-centered integrative pain management for veterans. [ABSTRACT FROM AUTHOR]

Members of the metallothionein (MT) family are short, cysteine-rich proteins involved in metal metabolism and detoxification, suggesting that MT proteins protect cells from damage caused by electrophilic carcinogens and thereby constitute a critical surveillance system against carcinogenesis. However, the roles of MT proteins in human hepatocellular carcinoma (HCC) are not fully understood. We identified a member of the MT family, termed MT1M. MT1M is expressed in various normal tissues with the highest level in the liver. MT1M expression can be induced by heavy metals and protect Escherichia coli from heavy metal toxicity. However, MT1M expression markedly decreased in human HCC specimens. A methylation profiling analysis indicated that the MT1M promoter is methylated in the majority of HCC tumors examined. Moreover, restored expression of MT1M in the HCC cell line Hep3B, which lacks endogenous MT1M expression, suppressed cell growth in vitro and in vivo and augmented apoptosis induced by tumor necrosis factor α. Furthermore, stable expression of MT1M in Hep3B cells blocked tumor necrosis factor α-induced degradation of IκBα and transactivation of NF-κB. We conclude that MT1M is a novel member of the MT family. Frequent downregulation of MT1M in human HCC may contribute to liver tumorigenesis by increasing cellular NF-κB activity. [ABSTRACT FROM PUBLISHER]

Nitric oxide (NO) is an important signaling molecule involved in many physiological processes in plants. Nitric oxide generation and flavonoid accumulation are two early reactions of plants to ultraviolet-B (UV-B) irradiation. However, the source of UV-B-triggered NO generation and the role of NO in UV-B-induced flavonoid accumulation are not fully understood. In order to evaluate the origin of UV-B-triggered NO generation, we examined the responses of nitrate reductase (NR) activity and the expression levels of NIA1 and NIA2 genes in leaves of Betula pendula Roth (silver birch) seedlings to UV-B irradiation. The data show that UV-B irradiation stimulates NR activity and induces up-regulation of NIA1 but does not affect NIA2 expression during UV-B-triggered NO generation. Pretreatment of the leaves with NR inhibitors tungstate (TUN) and glutamine (Gln) abolishes not only UV-B-triggered NR activities but also UV-B-induced NO generation. Furthermore, application of TUN and Gln suppresses UV-B-induced flavonoid production in the leaves and the suppression of NR inhibitors on UV-B-induced flavonoid production can be reversed by NO via its donor sodium nitroprusside. Together, the data indicate that NIA1 in the leaves of silver birch seedlings is sensitive to UV-B and the UV-B-induced up-regulation of NIA1 may lead to enhancement of NR activity. Furthermore, our results demonstrate that NR is involved in UV-B-triggered NO generation and NR-mediated NO generation is essential for UV-B-induced flavonoid accumulation in silver birch leaves. [ABSTRACT FROM PUBLISHER]

Background: Adolescent and young adult survivors of childhood cancer are a vulnerable population. Health beliefs may be related to necessary follow-up care. Purpose: This study seeks to develop a measure of health beliefs for adolescents and young adults with and without a history of cancer. Methods: Inductive and deductive methods and focus groups were used to develop the Health Competence Beliefs Inventory. Cancer survivors ( n = 138) and comparison participants ( n = 130) completed the Health Competence Beliefs Inventory and other measures. Healthcare providers reported current medical problems. Results: A series of iterative exploratory factor analyses generated a 21-item four-factor solution: (1) Health Perceptions; (2) Satisfaction with Healthcare; (3) Cognitive Competence; and (4) Autonomy. Survivors reported significantly different Health Competence Beliefs Inventory scale scores than comparisons ( p < .05). The Health Competence Beliefs Inventory was associated with beliefs, affect, quality of life, posttraumatic stress symptoms, and medical problems. Conclusions: The Health Competence Beliefs Inventory is a promising measure of adolescent and young adult perceptions of health and well-being. [ABSTRACT FROM AUTHOR]

Fungal elicitor prepared from the cell walls of Aspergillum niger induces multiple responses of Hypericum perforatum cells, including nitric oxide (NO) generation, jasmonic acid (JA) biosynthesis, and hypericin production. To determine the role of NO and JA in elicitor-induced hypericin production, we study the effects of NO scavenger 2- to 4-carboxyphenyl-4,4, 5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPITO), nitric oxide synthase inhibitor S,S′-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea, and inhibitors of the octadecanoid pathway on elicitor-induced NO generation, JA biosynthesis, and hypericin production. Pretreatment of the cells with cPITO and JA biosynthesis inhibitors suppresses not only the elicitor-induced NO generation and JA accumulation but also the elicitor-induced hypericin production, which suggests that both NO and JA are involved in elicitor-induced hypericin biosynthesis. S,S′-1,3-phenylene-bis(1,2-ethanediyl)-bis-isothiourea and cPITO inhibit both elicitor-induced NO generation and JA biosynthesis, while JA biosynthesis inhibitors do not affect the elicitor-induced NO generation, indicating that JA acts downstream of NO generation and that its biosynthesis is regulated by NO. External application of NO via its donor sodium nitroprusside induces hypericin production in the absence of fungal elicitor. Sodium-nitroprusside-induced hypericin production is blocked by JA biosynthesis inhibitors, showing that JA biosynthesis is essential for NO-induced hypericin production. The results demonstrate a causal relationship between elicitor-induced NO generation, JA biosynthesis, and hypericin production in H. perforatum cells and indicate a sequence of signaling events from NO to hypericin production, within which NO mediates the elicitor-induced hypericin biosynthesis at least partially via a JA-dependent signaling pathway. [ABSTRACT FROM AUTHOR]

Oxidative damage has long been related to carcinogenesis in human cancers and animal cancer models. Recently a rat esophageal adenocarcinoma (EAC) model was established in our laboratory by using esophagoduodenal anastomosis (EDA) plus iron supplementation. Our previous study suggested that iron supplementation enhanced inflammation and the production of reactive nitrogen species in the esophageal epithelium, which could contribute to esophageal adenocarcinogenesis. Here we further characterized oxidative damage in this model. We were particularly interested in how excess iron was deposited in the esophagus, and which cells were targeted by oxidative damage. Male Sprague–Dawley rats received iron supplementation (50 mg Fe/kg/month, i.p.) starting 4 weeks after EDA. The animals were killed at 11, 30 or 35 weeks after surgery. EAC appeared as early as week 11 after surgery, and increased over time, up to 60% at 35 weeks after surgery. All EACs were well-differentiated mucinous adenocarcinoma at the squamocolumnar junction. Iron deposition was found at the squamocolumnar junction and in the area with esophagitis. Esophageal iron overload could result from transient increase of blood iron after i.p. injection, and the overexpression of transferrin receptor in the premalignant columnar-lined esophagus (CLE) cells. Oxidative damage to DNA (8-hydroxy-2′-deoxyguanosine), protein (carbonyl content) and lipid (thiobarbituric acid reactive substance) in the esophagus was significantly higher than that of the non-operated control. CLE cells were believed to be the target cells of oxidative damage because they overexpressed heme oxygenase 1 and metallothionein, both known to be responsive to oxidative damage. We propose that oxidative damage plays an important role in the formation of EAC in the EDA model, and a similar situation may occur in humans with gastroesophageal reflux and iron over-nutrition. [ABSTRACT FROM PUBLISHER]

An editorial is presented on the study conducted by Zheng et al. on the use of acupuncture for the potential reduction of opioid administration in patients with chronic pain. Discussed are results of electroacupuncture (EA) and sham electro-acupuncture (SEA) noted in the research. Explored is the implementation of opioid use reduction on pain management's primary outcome.

Background Cancer-related cognitive impairment is an emerging public health burden. Growing research suggests that sleep disturbances contribute to poor cognition. Our study aimed to evaluate the association between insomnia and cognitive impairment in breast cancer survivors. Methods We analyzed cross-sectional data from a cohort study of postmenopausal women with stage 0–III hormone receptor-positive breast cancer on aromatase inhibitor therapy. The study was conducted between November 2011 and April 2015 at an academic cancer center (Philadelphia, PA). Insomnia was assessed with the Insomnia Severity Index. Perceived cognitive impairment was assessed with the cognitive subscale of the Breast Cancer Prevention Trial Symptom Checklist. We used linear regression to evaluate the association between insomnia and perceived cognitive impairment. Results Among 1072 patients, 556 (51.9%) reported insomnia and 847 (79.0%) were bothered by cognitive symptoms (forgetfulness, difficulty concentrating, distractibility). Greater perceived cognitive impairment was reported by patients with mild insomnia (regression coefficient [β] = 0.35, 95% confidence interval [CI] = 0.23 to 0.46, P  <  .001), moderate insomnia (β = 0.51, 95% CI = 0.36 to 0.65, P  <  .001), and severe insomnia (β = 0.94, 95% CI = 0.67 to 1.21, P  <  .001), compared with those without insomnia. Greater perceived cognitive impairment was also associated with patients younger than 55 years (β = 0.30, 95% CI = 0.15 to 0.45, P  <  .001), taxane-based chemotherapy (β = 0.11, 95% CI = 0.004 to 0.22, P  =  .04), anxiety (β = 0.47, 95% CI = 0.30 to 0.64, P  <  .001), and depression (β = 0.65, 95% CI = 0.35 to 0.94, P  <  .001). Conclusions Among postmenopausal breast cancer survivors receiving aromatase inhibitor therapy, insomnia and cognitive impairment are prevalent and characterized by a graded association, in which severity of perceived cognitive impairment increases as insomnia severity increases. Our findings warrant further research to determine whether addressing sleep is a strategy to improve management of cancer-related cognitive impairment. [ABSTRACT FROM AUTHOR]