Community-Based Yoga for Women Undergoing Substance Use Disorder Treatment: A Descriptive Study.

BACKGROUND: Women with substance use disorders (SUD) receive medication-assisted treatment (MAT) with behavioral interventions and counseling for recovery. Evidence supports the use of yoga for SUD; however few studies specifically feature women. OBJECTIVES: Community-based yoga may add to health promotion through preferable physical activity for women in recovery. The aims of this study are to explore demographics and quantitative measures relevant to recovery and capture and understand the subjective experience of one session of yoga. STUDY DESIGN: The study design involves Descriptive/Cross-sectional. METHODOLOGY: Women in an inpatient SUD center attending weekly optional off-site yoga for recovery were recruited to capture first-time attendance. Survey data included Medical Outcomes Survey 12-item short-form (SF-12), Toronto Mindfulness Scale (TMS), and Brief Resilience Scale (BRS), demographics, and narrative reflections. Recruitment opportunities occurred weekly during ongoing hour-long classes. RESULTS: Twenty-nine women (average age 36.6) with primarily opiate-based addictions completed surveys. SF-12 was below the normative value of 50 for both subscales. BRS scores showed averages on the low end of normal resiliency. The frequency of responses to writing prompts confirmed physical and mental well-being through yoga intervention. Women shared potential relapse prevention specifically attributed to the mindfulness component of the intervention. CONCLUSION: The SF-12, BRS, and TMS are brief, valid, and reliable and can be easily incorporated in clinical practice or future research. Suboptimal SF-12 scores were found in women with SUD and, therefore important to note in the context of recovery to optimize treatment. Subjective reports from the participants find community-based yoga an enjoyable and beneficial type of physical activity. Yoga may be a viable option for comprehensive mind-body intervention for this population.

Yoga for Substance Use Disorder in Women: A Systematic Review.

It has been suggested that yoga may be an effective adjunct intervention in the management of substance use disorders (SUD). Additionally, women with SUD require different treatment approaches than men. The objective of this study was to critically evaluate the evidence for the effectiveness of yoga, specifically for women, as part of treatment for SUD. Nine electronic databases were searched from inception to January 2020. Randomized controlled trials (RCT) that evaluated any type of yoga, including yoga as a component of mindfulness-based treatment, against any type of control in individuals with any type of addiction were eligible. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Checklist and Statement, methodological quality was appraised using Physiotherapy Evidence Database (PE Dro) criteria. Ten RC Ts (eight mixed-gender and two female-focused) met the eligibility criteria. Most of these RCTs were small to medium-sized, with various methodological and analytical flaws and deficits. The types of addictions included in these studies were alcohol, drug, and nicotine addiction. Most RCTs suggested that various types of yoga, primarily Hatha Yoga and its components, led to favorable or equivalent results for SUD as an adjunct to control or treatment-as-usual interventions. There are limited results on the impact of yoga for SUD specifically focused on women and their unique needs. Although the results of mixed-gender articles are encouraging, large RCTs with gender-specific subanalyses are required to better determine the benefits specific to women incorporating yoga for SUD.

Association of breast cancer with MRI background parenchymal enhancement: the IMAGINE case-control study.

BACKGROUND: Background parenchymal enhancement (BPE) on breast magnetic resonance imaging (MRI) may be associated with breast cancer risk, but previous studies of the association are equivocal and limited by incomplete blinding of BPE assessment. In this study, we evaluated the association between BPE and breast cancer based on fully blinded assessments of BPE in the unaffected breast. METHODS: The Imaging and Epidemiology (IMAGINE) study is a multicenter breast cancer case-control study of women receiving diagnostic, screening, or follow-up breast MRI, recruited from three comprehensive cancer centers in the USA. Cases had a first diagnosis of unilateral breast cancer and controls had no history of or current breast cancer. A single board-certified breast radiologist with 12 years' experience, blinded to case-control status and clinical information, assessed the unaffected breast for BPE without view of the affected breast of cases (or the corresponding breast laterality of controls). The association between BPE and breast cancer was estimated by multivariable logistic regression separately for premenopausal and postmenopausal women. RESULTS: The analytic dataset included 835 cases and 963 controls. Adjusting for fibroglandular tissue (breast density), age, race/ethnicity, BMI, parity, family history of breast cancer, BRCA1/BRCA2 mutations, and other confounders, moderate/marked BPE (vs minimal/mild BPE) was associated with breast cancer among premenopausal women [odds ratio (OR) 1.49, 95% CI 1.05-2.11; p = 0.02]. Among postmenopausal women, mild/moderate/marked vs minimal BPE had a similar, but statistically non-significant, association with breast cancer (OR 1.45, 95% CI 0.92-2.27; p = 0.1). CONCLUSIONS: BPE is associated with breast cancer in premenopausal women, and possibly postmenopausal women, after adjustment for breast density and confounders. Our results suggest that BPE should be evaluated alongside breast density for inclusion in models predicting breast cancer risk.

Indirect cholinergic activation slows down pancreatic cancer growth and tumor-associated inflammation.

BACKGROUND: Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine. METHODS: We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/-physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival. RESULTS: We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves. CONCLUSION: For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy.

Effectiveness of Somatic Yoga and Meditation: A Pilot Study in a Multicultural Cancer Survivor Population with Chemotherapy-Induced Peripheral Neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) causes significant pain and is an adverse effect of treatment with chemotherapeutic agents. We explored a somatic yoga and meditation intervention in a predominantly minority population. Goals included describing strategies for minority inclusion and testing feasibility and effectiveness. Eight individuals with CIPN enrolled in a single-arm feasibility trial. Somatic yoga and meditation were provided weekly for 8 weeks, with an additional home program component. The primary outcomes were Sit and Reach, Functional Reach, and Timed Up and Go. Secondary outcomes were Patient Neurotoxicity Questionnaire, FACT-GOG-Ntx (for addressing patient concerns associated with neurological symptoms), Brief Pain Inventory, Perceived Stress Scale, Pittsburgh Sleep Quality Index, and Falls Efficacy Scale. Sensitivity to vibration was measured via biothesiometer. Participants with a mean age of 65 (49-73) years self-reported as 63% African-American and 37% Caucasian. They attended 81% of the sessions, and no adverse events we re re p o rted. CIPN symptoms (FAC T- G O G - N t x ) improved significantly (from 88.88 to 106.88, standard deviation = 20.03; p = 0.039). Fear of falling improved, approaching significance (from 39.26 to 34.38, standard deviation = 6.081; p = 0.058). Other measures showed improvement trends, with a slight increase in Brief Pain Inventory pain severity (from 3.50 to 3.75, p = 0.041) possibly reflecting comorbidities. Four qualitative themes emerged: (1) CIPN symptom variability, with musculoskeletal comorbidities; (2) utility of learned skills; (3) improvement in self-confidence, balance, and stability; and (4) social support, with CIPN experience validation and increasing health literacy. Challenges of recruitment and retention require specific outreach, community trust, and health literacy. Preliminary data suggest that somatic yoga and meditation may affect fear of falling and quality of life in cancer survivors with CIPN. A randomized controlled trial using inclusive recruitment and retention methods is indicated to establish the intervention's efficacy.

Impact of Somatic Yoga and Meditation on Fall Risk, Function, and Quality of Life for Chemotherapy-Induced Peripheral Neuropathy Syndrome in Cancer Survivors.

OBJECTIVE: Chemotherapy-induced peripheral neuropathy (CIPN) syndrome causes significant pain as an adverse effect of treatment, with few nonpharmacological interventions tested. A somatic yoga and meditation (SYM) intervention on functional outcomes and quality of life (QOL) was investigated. DESIGN AND METHODS: Individuals diagnosed with CIPN were enrolled in an open-label, single-arm, mixed-methods feasibility trial. PARTICIPANTS AND SETTING: In an outpatient rehabilitation center, ten participants with median age 64.4 years (47-81) attended 61% of the sessions with no adverse events. INTERVENTION: SYM twice a week for 8 weeks for 1.5 hours, with home program and journaling. MAIN OUTCOME MEASURES: Primary functional outcomes included Sit and Reach (SR), Functional Reach (FR), and Timed Up and Go (TUG). Self-reported Patient Neurotoxicity Questionnaire (PNQ) and Functional Assessment of Cancer Therapy-Neurotoxicity (FACT-GOG-NTX) were secondary CIPN outcomes. Biomarkers included salivary cortisol (stress) and bioesthesiometer (vibration). RESULTS: Quantitative findings. Significant improvements were found in flexibility (SR; P = .006); balance (FR; P = .001) and fall risk (TUG; P = .004). PNQ improved significantly ( P = .003) with other measures improving non-significantly. Qualitative findings. Five themes emerged: (1) vacillation of CIPN pain perception over time; (2) transferability of skills to daily activities; (3) improvement in physical function; (4) perceived relaxation as an effect of SYM; and (5) group engagement provided a social context for not feeling isolated with CIPN. CONCLUSION: Preliminary data suggest SYM may improve QOL, flexibility, and balance in cancer survivors with CIPN, with a fully powered randomized controlled trial indicated. TRIAL REGISTRATION: NCT03786055.

Discovery of tricyclic 5,6-dihydro-1H-pyridin-2-ones as novel, potent, and orally bioavailable inhibitors of HCV NS5B polymerase.

A novel series of non-nucleoside small molecules containing a tricyclic dihydropyridinone structural motif was identified as potent HCV NS5B polymerase inhibitors. Driven by structure-based design and building on our previous efforts in related series of molecules, we undertook extensive SAR studies, in which we identified a number of metabolically stable and very potent compounds in genotype 1a and 1b replicon assays. This work culminated in the discovery of several inhibitors, which combined potent in vitro antiviral activity against both 1a and 1b genotypes, metabolic stability, good oral bioavailability, and high C(12) (PO)/EC(50) ratios.

Mammalian lignans and genistein decrease the activities of aromatase and 17beta-hydroxysteroid dehydrogenase in MCF-7 cells.

Estrogen plays a major role in breast cancer development and progression. Breast tissue and cell lines contain the necessary enzymes for estrogen synthesis, including aromatase and 17beta-hydroxysteroid dehydrogenase (17beta-HSD). These enzymes can influence tissue exposure to estrogen and therefore have become targets for breast cancer treatment and prevention. This study determined whether the isoflavone genistein (GEN) and the mammalian lignans enterolactone (EL) and enterodiol (ED) would inhibit the activity of aromatase and 17beta-HSD type 1 in MCF-7 cancer cells, thereby decreasing the amount of estradiol (E2) produced and consequently cell proliferation. Results showed that 10 microM EL, ED and GEN significantly decreased the amount of estrone (E1) produced via the aromatase pathway by 37%, 81% and 70%, respectively. Regarding 17beta-HSD type 1, 50 microM EL and GEN maximally inhibited E2 production by 84% and 59%, respectively. The reduction in E1 and E2 production by EL and the reduction in E2 production by GEN were significantly related to a reduction in MCF-7 cell proliferation. 4-Hydroxyandrostene-3,17-dione (50 microM) did not inhibit aromatase but inhibited the conversion of E1 to E2 by 78%, suggesting that it is a 17beta-HSD type 1 inhibitor. In conclusion, modulation of local E2 synthesis is one potential mechanism through which ED, EL and GEN may protect against breast cancer.

Supplementation with flaxseed alters estrogen metabolism in postmenopausal women to a greater extent than does supplementation with an equal amount of soy.

BACKGROUND: Phytoestrogens, which are abundant in flaxseed and soy, have chemical structures resembling those of endogenous estrogens and have been shown to exert hormonal effects, thereby affecting chronic diseases. OBJECTIVE: We compared the effects of consuming equal amounts of flaxseed or soy on estrogen metabolism and biochemical markers of bone metabolism in postmenopausal women. DESIGN: In a parallel design, the diet of postmenopausal women (n = 46) was supplemented with either a placebo, soy (25 g soy flour), or flaxseed (25 g ground flaxseed) muffin for 16 wk. Blood and 24-h urine samples were collected at baseline and at the endpoint. Urine samples were analyzed for phytoestrogens, estrogen metabolites (2-hydroxyestrone, 16alpha-hydroxyestrone), and serum hormones (estradiol, estrone, estrone sulfate). Serum and urine samples were also analyzed for biochemical markers of bone metabolism. RESULTS: Urinary concentrations of 2-hydroxyestrone, but not of 16alpha-hydroxyestrone, increased significantly in the flaxseed group (P = 0.05). In the flaxseed group, the ratio of 2-hydroxyestrone to 16alpha-hydroxyestrone was positively correlated with urinary lignan excretion (r = 0.579, P = 0.02). In the soy and placebo groups, no significant correlation was observed. No significant change in serum hormones or biochemical markers of bone metabolism was observed within or between the treatment groups. CONCLUSIONS: Supplementation with flaxseed modifies urinary estrogen metabolite excretion to a greater extent than does supplementation with an equal amount of soy. This modification by flaxseed is associated with an increase in urinary lignan excretion. Despite the shift in estrogen metabolism to favor the less biologically active estrogens, a negative effect on bone cell metabolism was not observed.