Developing a model for decision-making around antibiotic prescribing for patients with COVID-19 pneumonia in acute NHS hospitals during the first wave of the COVID-19 pandemic: qualitative results from the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients (PEACH Study).

OBJECTIVE: To explore and model factors affecting antibiotic prescribing decision-making early in the pandemic. DESIGN: Semistructured qualitative interview study. SETTING: National Health Service (NHS) trusts/health boards in England and Wales. PARTICIPANTS: Clinicians from NHS trusts/health boards in England and Wales. METHOD: Individual semistructured interviews were conducted with clinicians in six NHS trusts/health boards in England and Wales as part of the Procalcitonin Evaluation of Antibiotic use in COVID-19 Hospitalised patients study, a wider study that included statistical analysis of procalcitonin (PCT) use in hospitals during the first wave of the pandemic. Thematic analysis was used to identify key factors influencing antibiotic prescribing decisions for patients with COVID-19 pneumonia during the first wave of the pandemic (March to May 2020), including how much influence PCT test results had on these decisions. RESULTS: During the first wave of the pandemic, recommendations to prescribe antibiotics for patients with COVID-19 pneumonia were based on concerns about secondary bacterial infections. However, as clinicians gained more experience with COVID-19, they reported increasing confidence in their ability to distinguish between symptoms and signs caused by SARS-CoV-2 viral infection alone, and secondary bacterial infections. Antibiotic prescribing decisions were influenced by factors such as clinician experience, confidence, senior support, situational factors and organisational influences. A decision-making model was developed. CONCLUSION: This study provides insight into the decision-making process around antibiotic prescribing for patients with COVID-19 pneumonia during the first wave of the pandemic. The importance of clinician experience and of senior review of decisions as factors in optimising antibiotic stewardship is highlighted. In addition, situational and organisational factors were identified that could be optimised. The model presented in the study can be used as a tool to aid understanding of the complexity of the decision-making process around antibiotic prescribing and planning antimicrobial stewardship support in the context of a pandemic. TRIAL REGISTRATION NUMBER: ISRCTN66682918.

Margin of exposure to free formaldehyde in personal care products containing formaldehyde-donor preservatives: Evidence for consumer safety.

Formaldehyde has been classified as carcinogenic to humans by International Agency for Research on Cancer and found in personal care (PC) products containing formaldehyde-donor (FD) preservatives. However, the cancer risk associated with the use of FD-containing PC products has not been well established. Our study provides the quantitative cancer risk assessment of formaldehyde in FD-containing PC products. The carbon-13 nuclear magnetic resonance (13C-NMR) spectroscopy was used in this risk assessment to provide reliable exposure information to formaldehyde in PC products and aqueous solutions containing sodium hydroxymethylglycinate. The risk assessment was conducted using the margin of exposure (MOE) approach with benchmark doses (BMDs) for 10% effect. For hemolymphoreticular neoplasias in male rats, a BMD of 28.03 mg/kg/day and a BMD lower confidence limit (BMDL) of 2.52 mg/kg/day were calculated from available long-term animal experiments. The worst-case consumer exposure to formaldehyde from FD-containing PC products was 0.007 µg/kg/day. Comparing the consumer exposure with BMDL, the resulting MOE was 360,000 for the worst-case scenario. The consumer exposure to formaldehyde (0.007 µg/kg/day) from using FD-containing PC products represents less than 1.0 × 10-6 % of background level endogenous formaldehyde (878-1310 mg/kg/day). The cancer risk from formaldehyde to consumers using FD-containing PC products is negligible.

Validation of Immunotherapy Response Score as Predictive of Pan-solid Tumor Anti-PD-1/PD-L1 Benefit.

Immunotherapy response score (IRS) integrates tumor mutation burden (TMB) and quantitative expression biomarkers to predict anti-PD-1/PD-L1 [PD-(L)1] monotherapy benefit. Here, we evaluated IRS in additional cohorts. Patients from an observational trial (NCT03061305) treated with anti-PD-(L)1 monotherapy were included and assigned to IRS-High (-H) versus -Low (-L) groups. Associations with real-world progression-free survival (rwPFS) and overall survival (OS) were determined by Cox proportional hazards (CPH) modeling. Those with available PD-L1 IHC treated with anti-PD-(L)1 with or without chemotherapy were separately assessed. Patients treated with PD-(L)1 and/or chemotherapy (five relevant tumor types) were assigned to three IRS groups [IRS-L divided into IRS-Ultra-Low (-UL) and Intermediate-Low (-IL), and similarly assessed]. In the 352 patient anti-PD-(L)1 monotherapy validation cohort (31 tumor types), IRS-H versus IRS-L patients had significantly longer rwPFS and OS. IRS significantly improved CPH associations with rwPFS and OS beyond microsatellite instability (MSI)/TMB alone. In a 189 patient (10 tumor types) PD-L1 IHC comparison cohort, IRS, but not PD-L1 IHC nor TMB, was significantly associated with anti-PD-L1 rwPFS. In a 1,103-patient cohort (from five relevant tumor types), rwPFS did not significantly differ in IRS-UL patients treated with chemotherapy versus chemotherapy plus anti-PD-(L)1, nor in IRS-H patients treated with anti-PD-(L)1 versus anti-PD-(L)1 + chemotherapy. IRS associations were consistent across subgroups, including both Europeans and non-Europeans. These results confirm the utility of IRS utility for predicting pan-solid tumor PD-(L)1 monotherapy benefit beyond available biomarkers and demonstrate utility for informing on anti-PD-(L)1 and/or chemotherapy treatment. Significance: This study confirms the utility of the integrative IRS biomarker for predicting anti-PD-L1/PD-1 benefit. IRS significantly improved upon currently available biomarkers, including PD-L1 IHC, TMB, and MSI status. Additional utility for informing on chemotherapy, anti-PD-L1/PD-1, and anti-PD-L1/PD-1 plus chemotherapy treatments decisions is shown.

An exploratory qualitative study of the meaning and value of a running/walking program for women after a diagnosis of breast cancer.

PURPOSE: To generate insights into the personal meaning and value of a running/walking program for women after a diagnosis of breast cancer. METHODS: After completing a 12-week running/walking program with a 5-km training goal, eight women were interviewed and seven participated in a focus group. The interviews and focus group were audio-recorded and transcribed verbatim. Data were thematically analyzed. RESULTS: Data portrayed the personal benefits and value of the clinic. Four themes were identified: (1) receiving practical information and addressing targeted concerns, (2) pushing personal limits, (3) enabling a committed mindset, and (4) seeing benefits and challenges of running/walking with a group. CONCLUSIONS: Findings provide initial understanding of how women experience a running/walking program after a diagnosis of breast cancer and what they find to be important about their experiences. The range of positive benefits experienced by women suggests a running/walking program can help fill a gap in care for women diagnosed with breast cancer, and thus be part of cancer rehabilitation. However, because some women felt isolated at times, future research should seek to examine how running/walking programs can be modified and tailored so that all women find it socially beneficial. Implications for Rehabilitation The diagnosis and treatment of breast cancer can result in side effects and increase the risk of long-term disability. Physical activity can help women manage the side effects and lessen the risk of long-term disability. In a relatively small sample, this study shows that participation in a running/walking program can be an important part of breast cancer recovery.

Colder environments are associated with a greater cancer incidence in the female population of the United States.

Cancer incidence and/or mortality among individuals varies with diet, socio-culture, ethnicity, race, gender, and age. Similarly, environmental temperature modulates many biological functions. To study the effect of environment temperature on cancer incidence, the US population was selected. Because, county-wise cancer incidence rate data of various anatomical site-specific cancers and different races/ethnicities for both males and females are available. Moreover, the differences amongst the aforementioned factors among individuals are much less, as compared to the world population. Statistical analysis showed a negative correlation between the average annual temperature and cancer incidence rate at all anatomical sites and individually for 13 types (out of 16 types) of anatomical site-specific cancer incidence rates (e.g. uterine, bladder, thyroid, breast, esophagus, ovary, melanoma, non-Hodgkin lymphoma, leukemia, brain, pancreas, etc.) for females. Further analysis found a similar inverse trend in all races/ethnicities of the female population but not in all male races/ethnicities or anatomical site-specific cancers. Moreover, the majority of the counties having the top-most cancer incidence rate in females are located above the latitude 36.5°N. These findings indicate that living in a cold county in the United States might have a higher risk of cancer irrespective of cancer type (except cervical and liver) and races/ethnicities for females but not in all such cases for the male population.

Cycles of silence: First Nations women overcoming social and historical barriers in supportive cancer care.

BACKGROUND: First Nations people with cancer in Canada confront several critical inequities in physical and psychosocial domains. First Nations women are at a particular disadvantage as they are disproportionately affected by social determinants of health, but how they navigate these challenges within their communities is poorly understood. OBJECTIVE: Our study explores survivorship experiences of First Nations women with cancer and their caregivers. Drawing from a larger data set on survivorship, we identify several major barriers to cancer communication and support in First Nations communities. METHODS: Our team conducted a participatory, arts-based study using several data collection methods (interviews, sharing sessions, photovoice, and other creative activities) with 43 participants (24 cancer survivors and 19 caregivers) from four First Nations communities in Canada. RESULTS: Two major themes have emerged out of our data analyses: (1) suffering without support leads to cycles of silence and (2) community-based supports can disrupt these cycles. We identified several social, historical, and institutional barriers to speaking about cancer and finding/providing support; however, communities met the challenge of silence through voluntary and unsolicited provision of support. CONCLUSIONS: Widespread silence around cancer reflects both the limited access First Nations people have to formal, supportive programs and services, as well as the creative ways they provide emotional, social, and financial support within their informal networks. Beyond the support of their communities, they also required institutional provision of care that is culturally safe, addressing the colonial impacts on cancer communication and the disproportionate burdens of disease in First Nations communities.

Critical care of obese patients during and after spine surgery.

Obesity is one of the most prevalent health problems facing the United States today, with a recent JAMA article published in 2014 estimating the prevalence of one third of all adults in the United States being obese. Also, due to technological advancements, the incidence of spine surgeries is growing. Considering these overall increases in both obesity and the performance of spinal surgeries, it can be inferred that more spinal surgery candidates will be obese. Due to this, certain factors must be taken into consideration when dealing with spine surgeries in the obese. Obesity is closely correlated with additional medical comorbidities, including hypertension, coronary artery disease, congestive heart failure, and diabetes mellitus. The pre-operative evaluation may be more difficult, as a more extensive medical evaluation may be needed. Also, adequate radiographic images can be difficult to obtain due to patient size and equipment limitations. Administering anesthesia becomes more difficult, as does proper patient positioning. Post-operatively, the obese patient is at greater risk for reintubation, difficulty with pain control, wound infection and deep vein thrombosis. However, despite these concerns, appropriate clinical outcomes can still be achieved in the obese spine surgical candidate. Obesity, therefore, is not a contraindication to spine surgery, and appropriate patient selection remains the key to obtaining favorable clinical outcomes.

Composing hope through collage: A community-based intervention for cancer survivors living with lymphedema.

Secondary lymphedema after cancer may result in distress, yet few interventions exist to support coping skills in this population. As part of a community-based intervention, we piloted the use of creative practices to promote active orientations to hope. A total of 19 participants completed the workshops; 11 collaged. The main themes address the collage processes as well as their content. The former addresses sub-themes such as selecting/composing. The latter includes sub-themes related to movement depicted in the collages. Collages and their associated discussions concretized hoping as an active and accessible process for participants living with two chronic illnesses.

The mammalian target of rapamycin modulates the immunoproteasome system in the heart.

The mammalian target of rapamycin (mTOR) plays an important role in cardiac development and function. Inhibition of mTOR by rapamycin has been shown to attenuate pathological cardiac hypertrophy and improve the function of aging heart, accompanied by an inhibition of the cardiac proteasome activity. The current study aimed to determine the potential mechanism(s) by which mTOR inhibition modulates cardiac proteasome. Inhibition of mTOR by rapamycin was found to reduce primarily the immunoproteasome in both H9c2 cells in vitro and mouse heart in vivo, without significant effect on the constitutive proteasome and protein ubiquitination. Concurrent with the reduction of the immunoproteasome, rapamycin reduced two important inflammatory response pathways, the NF-κB and Stat3 signaling. In addition, rapamycin attenuated the induction of the immunoproteasome in H9c2 cells by inflammatory cytokines, including INFγ and TNFα, by suppressing NF-κB signaling. These data indicate that rapamycin indirectly modulated immunoproteasome through the suppression of inflammatory response pathways. Lastly, the role of the immunoproteasome during the development of cardiac hypertrophy was investigated. Administration of a specific inhibitor of the immunoproteasome ONX 0914 attenuated isoproterenol-induced cardiac hypertrophy, suggesting that the immunoproteasome may be involved in the development of cardiac hypertrophy and therefore could be a therapeutic target. In conclusion, rapamycin inhibits the immunoproteasome through its effect on the inflammatory signaling pathways and the immunoproteasome could be a potential therapeutic target for pathological cardiac hypertrophy.

Can certified health professionals treat obesity in a community-based programme? A quasi-experimental study.

OBJECTIVE: To test the effectiveness of a non-pharmaceutical programme for obese participants in a rural Eastern Canadian Province using certified health professionals. DESIGN: A prospective quasi-experimental design with repeated premeasure and postmeasure. PARTICIPANTS: 146 participants with obesity (body mass index >30 kg/m(2)) from rural and urban communities in an Eastern Canadian Province were divided into four groups. INTERVENTION: A 6-month intensive active community-based lifestyle intervention (InI) delivered by Certified Exercise Physiologists, Certified Personal Trainers and Registered Dietitians, followed by 6 months of self-management. A second intervention (InII) was nested in InI and consisted of group-mediated cognitive-behavioral intervention (GMCBI) delivered by an exercise psychologist to two of the four InI groups. OUTCOMES: (1) Improving health outcomes among the participants' preactive and postactive 6-month intervention and self-management period, (2) Documenting the impact of InII (GMCBI) and location of the intervention (urban vs rural). RESULTS: The 6-month active InI significantly improved cardiovascular health for participants who completed the intervention. InII (GMCBI) significantly lowered the attrition rate among the participants. The self-management period was challenging for the participants and they did not make further gains; however, most were able to maintain the gains achieved during the active intervention. The location of the intervention, urban or rural, had little impact on outcomes. CONCLUSIONS: A community-based programme utilising healthcare professionals other than physicians to treat obese patients was effective based on premeasure and postmeasure. During the self-management phase, the participants were able to maintain the gains. Psychological support is essential to participant retention.

miR-214: a potential biomarker and therapeutic for different cancers.

miRNAs (miRs), or small approximately 22-nucleotide-long single-stranded noncoding RNA molecules, interact with 3' untranslated regions of target mRNAs, leading to inhibition of protein production. miR-214 is often dysregulated in various cancers, which governs both tumorigenic and tumor suppressive functions. This review focuses on the current knowledge of miR-214 switching in diverse forms of cancer either by its upregulation or downregulation and sheds light on the mechanism of its tumorigenic and suppressive roles. This article describes known targets and signaling pathways that impact tumorigenesis and tumor suppression and summarizes all information available on circulating levels of miR-214 to address whether miR-214 may function as a potential biomarker and therapy for cancer patients in the future.

Illustrating the (in)visible: understanding the impact of loss in adults living with secondary lymphedema after cancer.

Life with a disability is often riddled with paradoxes, one of which is being visibly marked, while personal experiences, losses, and challenges remain hidden. Our article draws attention to this paradox among people who live with secondary lymphedema after cancer (SLC). SLC is a relatively unfamiliar chronic condition within medical and lay discourses of cancer, which proves challenging for the many cancer survivors who are in search of information and understanding. Thirteen men and women with SLC were recruited from two research sites (Fredericton, NB, and Ottawa, ON, Canada) to participate in semi-structured interviews about the physical and psychosocial aspects of SLC. Using a methodology of interpretive description, our analysis of participant interviews reveals the complex ways in which men and women felt both visible and invisible within various contexts. We discuss three majors themes: (in)visibility and appearance related to material losses; (in)visibility and action connected to visible losses in function, as well as invisible struggles to care for oneself; and the loss of present and future well-being, as SLC renders some limitations visible while potentially obscuring a hopeful future indefinitely. Our research indicates that timely diagnosis of SLC would be an immediate first step in recognizing the physical and emotional dimensions of the condition. To accomplish this, increased awareness is needed. To enhance quality of life for those living with SLC, the development of new resources and psychosocial supports is also required.

Ovarian hormone loss induces bioenergetic deficits and mitochondrial ß-amyloid.

Previously, we demonstrated that reproductive senescence was associated with mitochondrial deficits comparable to those of female triple-transgenic Alzheimer's mice (3xTgAD). Herein, we investigated the impact of chronic ovarian hormone deprivation and 17ß-estradiol (E2) replacement on mitochondrial function in nontransgenic (nonTg) and 3xTgAD female mouse brain. Depletion of ovarian hormones by ovariectomy (OVX) in nontransgenic mice significantly decreased brain bioenergetics, and induced mitochondrial dysfunction and oxidative stress. In 3xTgAD mice, OVX significantly exacerbated mitochondrial dysfunction and induced mitochondrial ß-amyloid and ß-amyloid (Aß)-binding-alcohol-dehydrogenase (ABAD) expression. Treatment with E2 at OVX prevented OVX-induced mitochondrial deficits, sustained mitochondrial bioenergetic function, decreased oxidative stress, and prevented mitochondrial ß-amyloid and ABAD accumulation. In vitro, E2 increased maximal mitochondrial respiration in neurons and basal and maximal respiration in glia. Collectively, these data demonstrate that ovarian hormone loss induced a mitochondrial phenotype comparable to a transgenic female model of Alzheimer's disease (AD), which was prevented by E2. These findings provide a plausible mechanism for increased risk of Alzheimer's disease in premenopausally oophorectomized women while also suggesting a therapeutic strategy for prevention.

Do breast cancer survivors' post-surgery difficulties with recreational activities persist over time?

INTRODUCTION: Most longitudinal breast cancer studies have found that treatment-related sequelae such as arm morbidity [lymphedema, pain, and range of motion (ROM) restrictions] can have a significant impact on quality of life. In a previous study, we found that at 6-12 months after breast cancer surgery, 49% of participants had difficulties engaging in recreational activities and that arm morbidity significantly predicted difficulties with participation in recreation. METHODS: A longitudinal national study employing clinical assessments and survey methods followed 178 women over 43 months (3.6 years) to assess issues related to arm morbidity post-breast cancer surgery. Hierarchical multiple regression analyses were conducted to identify which variables were predictive of recreational difficulties experienced by women 8 and 43 months post-surgery. RESULTS: Between 8 months (T1) and 43 months (T2) post-breast cancer surgery, women demonstrated slight increases in lymphedema. Conversely, a significant decrease was observed in the number of ROM restrictions and pain when using the arm. Despite the overall improvements in arm morbidity, some women continued to report moderate pain and ROM restrictions. The two arm morbidity factors were found to be statistically significant (p < 0.001) predictors of recreational difficulties at both 8 and 43 months post-surgery, with pain accounting for the greatest proportion of variance. DISCUSSION/CONCLUSION: Pain and ROM restrictions were the only significant predictors of recreational difficulties during the first 3.6 years after breast cancer surgery. Specifically, women who still experience pain years after breast cancer surgery report difficulties in their recreational pursuits. IMPLICATIONS FOR CANCER SURVIVORS: Pain and ROM restrictions may prohibit participation in recreational activity and targeted intervention should be sought.

Hippocampal responsiveness to 17ß-estradiol and equol after long-term ovariectomy: implication for a therapeutic window of opportunity.

A 'critical window of opportunity' has been proposed for the efficacy of ovarian hormone intervention in peri- and post-menopausal women. We sought to address this hypothesis using a long-term ovariectomized non-human primate (NHP) model, the cynomolgus macaque (Macaca fascicularis). In these studies, we assessed the ability of 17ß-estradiol and equol to regulate markers of hippocampal bioenergetic capacity. Results indicated that 17ß-estradiol treatment significantly increased expression of mitochondrial respiratory chain proteins complex-I and -III in the hippocampus when compared to non-hormone-treated animals. Expression of the TCA cycle protein succinate dehydrogenase α was decreased in animals treated with equol compared to those treated with 17ß-estradiol. There were no significant effects of either 17ß-estradiol or equol treatment on glycolytic protein expression in the hippocampus, nor were there significant effects of treatment on expression levels of antioxidant enzymes. Similarly, 17ß-estradiol and equol treatment had no effect on mitochondrial fission and fusion protein expression. In summary, findings indicate that while 17ß-estradiol induced a significant increase in several proteins, the overall profile of bioenergetic system proteins was neutral to slightly positively responsive. The profile of responses with the ERß-preferring molecule equol was consistent with overall nonresponsiveness. Collectively, the data indicate that long-term ovariectomy is associated with a decline in response to estrogens and estrogen-like compounds. By extension, the data are consistent with a primary tenet of the critical window hypothesis, i.e., that the brains of post-menopausal women ultimately lose their ability to respond positively to estrogenic stimulation.

The effect of dietary soy isoflavones before and after ovariectomy on hippocampal protein markers of mitochondrial bioenergetics and antioxidant activity in female monkeys.

Estrogen therapy can promote cognitive function if initiated within a 'critical window' during the menopausal transition. However, in the absence of a progestogen, estrogens increase endometrial cancer risk which has spurred research into developing estrogenic alternatives that have the beneficial effects of estrogen but which are clinically safer. Soy protein is rich in isoflavones, which are a class of potential estrogenic alternatives. We sought to determine the effects of two diets, one with casein-lactalbumin as the main protein source and the other with soy protein containing isoflavones, on protein markers of hippocampal bioenergetic capacity in adult female cynomolgus macaques (Macaca fascicularis). Further, we assessed the effects of dietary soy isoflavones before or after ovariectomy. Animals receiving soy diet premenopausally then casein/lactalbumin post-ovariectomy had higher relative hippocampal content of glycolytic enzymes glyceraldehyde 3-phosphate dehydrogenase and pyruvate dehydrogenase subunit e1α. Post-ovariectomy consumption of soy was associated with higher succinate dehydrogenase α levels and lower levels of isocitrate dehydrogenase, both proteins involved in the tricarboxylic acid cycle, significantly decreased expression of the antioxidant enzyme peroxiredoxin-V, and a non-significant trend towards decreased manganese superoxide dismutase expression. None of the diet paradigms significantly affected expression levels of oxidative phosphorylation enzyme complexes, or of mitochondrial fission and fusion proteins. Together, these data suggest that long-term soy diet produces minimal effects on hippocampal expression of proteins involved in bioenergetics, but that switching between a diet containing primarily animal protein and one containing soy isoflavones before and after menopause may result in complex effects on brain chemistry.

Oscillatory shear stress induces mitochondrial superoxide production: implication of NADPH oxidase and c-Jun NH2-terminal kinase signaling.

Fluid shear stress is intimately linked with vascular oxidative stress and atherosclerosis. We posited that atherogenic oscillatory shear stress (OSS) induced mitochondrial superoxide (mtO2•-) production via NADPH oxidase and c-Jun NH(2)-terminal kinase (JNK-1 and JNK-2) signaling. In bovine aortic endothelial cells, OSS (±3 dyn/cm2) induced JNK activation, which peaked at 1 h, accompanied by an increase in fluorescein isothiocyanate-conjugated JNK fluorescent and MitoSOX Red (specific for mtO2•- production) intensities. Pretreatment with apocynin (NADPH oxidase inhibitor) or N-acetyl cysteine (antioxidant) significantly attenuated OSS-induced JNK activation. Apocynin further reduced OSS-mediated dihydroethidium and MitoSOX Red intensities specific for cytosolic O2•- and mtO2•- production, respectively. As a corollary, transfecting bovine aortic endothelial cells with JNK siRNA (siJNK) and pretreating with SP600125 (JNK inhibitor) significantly attenuated OSS-mediated mtO2•- production. Immunohistochemistry on explants of human coronary arteries further revealed prominent phosphorylated JNK staining in OSS-exposed regions. These findings indicate that OSS induces mtO2•- production via NADPH oxidase and JNK activation relevant for vascular oxidative stress.

Medroxyprogesterone acetate antagonizes estrogen up-regulation of brain mitochondrial function.

The impact of clinical progestins used in contraception and hormone therapies on the metabolic capacity of the brain has long-term implications for neurological health in pre- and postmenopausal women. Previous analyses indicated that progesterone and 17ß-estradiol (E2) sustain and enhance brain mitochondrial energy-transducing capacity. Herein we determined the impact of the clinical progestin, medroxyprogesterone acetate (MPA), on glycolysis, oxidative stress, and mitochondrial function in brain. Ovariectomized female rats were treated with MPA, E2, E2+MPA, or vehicle with ovary-intact rats serving as a positive control. MPA alone and MPA plus E2 resulted in diminished mitochondrial protein levels for pyruvate dehydrogenase, cytochrome oxidase, ATP synthase, manganese-superoxide dismutase, and peroxiredoxin V. MPA alone did not rescue the ovariectomy-induced decrease in mitochondrial bioenergetic function, whereas the coadministration of E2 and MPA exhibited moderate efficacy. However, the coadministration of MPA was detrimental to antioxidant defense, including manganese-superoxide dismutase activity/expression and peroxiredoxin V expression. Accumulated lipid peroxides were cleared by E2 treatment alone but not in combination with MPA. Furthermore, MPA abolished E2-induced enhancement of mitochondrial respiration in primary cultures of the hippocampal neurons and glia. Collectively these findings indicate that the effects of MPA differ significantly from the bioenergetic profile induced by progesterone and that, overall, MPA induced a decline in glycolytic and oxidative phosphorylation protein and activity. These preclinical findings on the basis of acute exposure to MPA raise concerns regarding neurological health after chronic use of MPA in contraceptive and hormone therapy.

"You can only take so much, and it took everything out of me": coping strategies used by parents of children with cancer.

OBJECTIVE: This study qualitatively assesses the coping strategies of parents who care for a child with cancer. METHOD: Semi-structured interviews were conducted with 28 French and English families who had had a child diagnosed with cancer in the last ten years in two Eastern Canadian provinces. Interviews were transcribed verbatim and coded with a focus on parental coping strategies. RESULTS: Using coping behaviors as described and categorized in the Family Adjustment and Adaptation Response (FAAR) model as a foundation, we found that families used a variety of appraisal-, emotion-, and problem-focused coping. Appraisal-focused coping strategies involved trying to stay "positive" and "making positive comparisons." Problem-focused coping involved behaviors such as being an advocate for the child and seeking information. The majority of parents, however, described using emotion-focused coping behaviors such as trying to avoid "feeling too much" by hiding difficult emotions and "escaping" from problems. Others used more positive emotion-focused coping behaviors such as humor, seeking support (informal or formal), or writing diaries. A small group of parents used ineffective coping strategies (alcohol abuse, misdirected anger) that added to family stress. These ineffective strategies have led to a modification of the FAAR model indicating that not all coping behaviors are beneficial to family adjustment in crisis. Overall, many parents felt that their coping strategies were effective; however, a few described having a complete "coping breakdown". SIGNIFICANCE OF RESULTS: Parents used a range of coping strategies of which emotion-focused coping was the most prominent. We have enhanced the FAAR model by including additional coping behaviors as well as a description of how some coping behaviors add to the daily stressors for parents dealing with a child's illness. Professional health care providers need to understand the variability of the coping behaviors in order to appropriately assist parents to avoid coping breakdowns.

Predicting recreational difficulties and decreased leisure activities in women 6-12 months post breast cancer surgery.

INTRODUCTION: A Canadian research team is conducting a multi-centered, non-interventional national study with the objective of charting the course of arm morbidity after breast cancer surgery. This paper examined the relationship between arm morbidity and leisure and recreational activities of affected women. METHODS: Five hundred and forty seven women with stage I-III breast cancer were recruited in four centers across Canada: Surrey (BC); Winnipeg (MB), Montreal (QB) and Fredericton (NB). Participants were enrolled in the study 6-12 months post surgery. Physical examination was used to assess arm and shoulder functioning and questionnaires were used to assess disability, pain, and participation in recreational and leisure activities. RESULTS: At the first clinical assessment (T1), the mean number of months post breast cancer surgery was 8.4. At T1 49% of women reported difficulty with recreational activities that involved "some force or impact" and 29% experienced negative changes to their involvement in leisure activities. A hierarchical multiple regression analysis found that several arm morbidity variables were significant predictors of difficulty with participation in recreational activities. A second hierarchical regression found also that arm morbidity factors were significant predictors of negative changes in leisure activities. Follow-up analyses found that arm morbidity, was most closely related to difficulty with recreational activities requiring free movement of the arm and using force. CONCLUSION: Many women treated for breast cancer experience arm morbidity. Arm morbidity is related to difficulties with recreational activities and negative changes in leisure activity participation. IMPLICATIONS: Breast cancer survivors should engage in recreational and leisure activities that are compatible with reduced range of motion and pain, and avoid those that exacerbate their arm morbidity.