Confronting chemobrain: an in-depth look at survivors’ reports of impact on work, social networks, and health care response

Mild cognitive impairment following chemotherapy is one of the most commonly reported post treatment symptoms by breast cancer survivors. This deterioration in cognitive function, commonly referred to as “chemobrain” or “chemofog,” was largely unacknowledged by the medical community until recent years. Although chemobrain has now become the subject of more vigorous exploration, little is known about this specific phenomenon’s psychosocial impact on breast cancer survivors. This research documents in-depth the effects that cognitive impairment has on women’s personal and professional lives, and our data suggest that greater attention needs to be focused on this arena of survivorship. The results are based on an in-depth qualitative study of 74 white and African American breast cancer survivors in California who experience post-treatment side effects. The data reported herein were obtained through the use of focus groups and in-depth interviews. Our data indicate that cognitive impairment can be problematic for survivors, with many asserting that it is their most troublesome post treatment symptom. Survivors report diminished quality of life and daily functioning as a result of chemobrain. Respondents detail a range of coping strategies that they are forced to employ in order to manage their social and professional lives. Chemobrain significantly impairs a proportion of cancer survivors, at great cost to them economically, emotionally, and interpersonally. This suggests that more research needs to be conducted on the psychosocial ramifications of post treatment symptoms in order to inform the efforts of the medical and mental health communities as well as the support networks of survivors. A better and broader understanding of the effects of cognitive impairment both in the medical community and among lay people could pave the way for improved social and psychological services for this population

Fluoxetine reverses the memory impairment and reduction in proliferation and survival of hippocampal cells caused by methotrexate chemotherapy

RATIONALE: Adjuvant cancer chemotherapy can cause long-lasting, cognitive deficits. It is postulated that these impairments are due to these drugs targeting neural precursors within the adult hippocampus, the loss of which has been associated with memory impairment. OBJECTIVES: The present study investigates the effects of the chemotherapy, methotrexate (MTX) on spatial working memory and the proliferation and survival of the neural precursors involved in hippocampal neurogenesis, and the possible neuroprotective properties of the antidepressant fluoxetine. METHODS: Male Lister hooded rats were administered MTX (75 mg/kg, two i.v. doses a week apart) followed by leucovorin rescue (i.p. 18 h after MTX at 6 mg/kg and at 26, 42 and 50 h at 3 mg/kg) and/or fluoxetine (10 mg/kg/day in drinking water for 40 days). Memory was tested using the novel location recognition (NLR) test. Using markers, cell proliferation (Ki67) and survival (bromodeoxyuridine/BrdU), in the dentate gyrus were quantified. RESULTS: MTX-treated rats showed a cognitive deficit in the NLR task compared with the vehicle and fluoxetine-treated groups. Cognitive ability was restored in the group receiving both MTX and fluoxetine. MTX reduced both the number of proliferating cells in the SGZ and their survival. This was prevented by the co-administration of fluoxetine, which alone increased cell numbers. CONCLUSIONS: These results demonstrate that MTX induces an impairment in spatial working memory and has a negative long-term effect on hippocampal neurogenesis, which is counteracted by the co-administration of fluoxetine. If translatable to patients, this finding has the potential to prevent the chemotherapy-induced cognitive deficits experienced by many cancer survivors

Can physical activity help to maintain cognitive functioning and psychosocial well-being among breast cancer patients treated with chemotherapy? A randomised controlled trial: study protocol

Background: Evidence suggests chemotherapy treatment for breast cancer is associated with side effects such as cognitive impairment in domains of memory, attention, concentration and executive function. Cognitive impairments reported by patients have been associated with higher levels of emotional distress. To date, intervention studies to alleviate cognitive impairment associated with chemotherapy have focused on psycho-educational techniques or cognitive training. Studies have not yet considered physical activity as a potential for alleviating cognitive problems. Physical activity interventions are reported to be effective in alleviating emotional distress and fatigue in those with breast cancer. They have also been reported to improve cognitive functioning in the elderly, in those suffering with dementia and in children. We propose that physical activity could also help to alleviate cognitive impairments in women diagnosed with breast cancer. The study has been designed using a recently developed taxonomy of behaviour change techniques to reliably report the content of the intervention to allow future replication. Method: This study will deliver a home-based moderate intensity walking intervention to women diagnosed with breast cancer mid-way through their chemotherapy treatment and will compare them to patients receiving usual care alone. The primary outcome measure for this intervention is changes in an objective measure of memory assessed using the Digit Span. Secondary outcome measures include: objective measures of executive function; attention; visual spatial skills; self report cognitive function; self-report fatigue; anxiety; depression; mood and self-esteem. As emotional distress has been associated with self-reporting of cognitive problems, this intervention will further test whether emotional distress mediates between the amount of walking undertaken during the intervention period and levels of self-reported cognitive functioning. Discussion: The development of an effective intervention for preventing difficulties in emotional and cognitive functioning of cancer patients’ post-treatment will help to guide health care professionals to improve patients’ overall quality of life. It will also provide direction for future research, ultimately to improve the day to day functioning of breast cancer survivors. Trial Registration: Current Controlled Trials ISRCTN50709297. Keywords: Intervention, Breast cancer, Chemotherapy, Physical activity, Exercise, Walking, Cognitive function, Emotional distress, Psychosocial well-bein

Semantic and syntactic features of the paremias about the moral qualities of a person in Ukrainian language.

Praca magisterska składa się ze wstępu, czterech rozdziałów, wniosków i aneksu. W rozdziale teoretycznym pracy magisterskiej rozpatrzono genezę paremiologii i paremiografii; wyjaśniono pojęcia mentalność, mentalitet i moralność; przeanalizowano mentalitet ukraiński z perspektywy przysłów i porzekadeł. W rozdziałach praktycznych pracy magisterskiej dokonano analizy ugrupowań semantycznych słów oraz możliwości ekspresyjnych paremii ukraińskich o cechach moralnych człowieka; przeanalizowano osobliwości składniowe paremii.The Master Degree Thesis consists of an introduction, four chapters, a conclusion and annexes.The genesis of paremiology and paremiography has been considered in the theoretical section of the Master Degree Thesis; the concepts of mentality, mindset, morality have been covered; the Ukrainian mindset has been analyzed through the prism of proverbs and sayings. The analysis of semantic groupings of words and expressing possibilities of the Ukrainian paremias about the moral qualities of a person has been carried out in the practical sections of the Master Degree Thesis. The syntactic features of paremias have been analyzed.Магістерська робота складається зі вступу, чотирьох розділів, висновків та додатків.У теоретичному розділі магістерської роботи розглянуто генезу пареміології та пареміографії; висвітлено поняття ментальність, менталітет та мораль; проаналізовано український менталітет крізь призму прислів’їв та приказок. У практичних розділах магістерської роботи здійснено аналіз семантичних угруповань слів та виражальних можливостей українських паремій про моральні якості людини; проаналізовано синтаксичні особливості паремій

The Design, Synthesis, and Investigation of Functional Cationic Amphiphilic Polyproline Helices (CAPHs)

Antimicrobial peptides are a class of antibiotics that generally act by targeting the microbial cell membrane, resulting in cell lysis. We have designed and synthesized unnatural proline-rich peptides that have been evaluated for antibacterial activity. P14LRRFl is a non-membrane lytic, broad spectrum antimicrobial with efficient mammalian cell penetration. Herein, we report on the elucidation of the mechanism of bacterial action of this peptide. By using the biotin labeled analogue BP14LRRFl, we have isolated protein targets from Staphylococcus aureus and Escherichia coli. Proteomics analysis has identified enolase, a 47 kDa protein, as the intracellular target of P14LRRFl for S. aureus and glycerol dehydrogenase, a 42 kDa protein, for E. coli. Validity of enolase as an intracellular target for the P14LRRAc was confirmed using inhibition kinetics. It was also demonstrated that P14LRRAc binds uncompetitively to enolase. Finally, enolase was also pulled-down from other gram positive strains of bacteria incubated with BP14LRRFl. The therapeutic value of aminoglycoside antibiotics against intracellular bacteria is limited due to their inability to traverse the eukaryotic membrane. While P14LRRFl displays a good reduction in intracellular bacteria, more potent agents are needed to effectively eradicate pathogenic bacteria from mammalian cells. To address this problem, a cleavable conjugate of the antibiotic kanamycin and P14LRR, was prepared. This approach would allow kanamycin to enter mammalian cells as an antimicrobial peptide conjugate, P14KanS, linked via cleavable tether. Potent antimicrobial activity of the P14KanS conjugate was demonstrated with Gram positive and negative bacteria in vitro. Successful clearance of Mycobacterium tuberculosis and smegmatis within macrophages was observed with the antibiotic conjugate, with 93 and 95% reduction, respectively. Additionally, Salmonella enteritidis and Acinetobacter baumannii levels were also significantly reduced in an in vivo Caenorhabditis elegans model as compared to the individual antibiotics, with 70 and 100% reduction, respectively

Comparison of drug reimbursement principles in healthcare systems in Poland and Ukraine

System opieki zdrowotnej w Polsce i na Ukrainie opiera się na modelu ubezpieczeniowym. Ministerstwo Zdrowia odpowiada za politykę i regulacje dotyczące systemu ochrony zdrowia, a NFZ/NSZU za finansowanie i kontrakty z publicznymi i niepublicznymi świadczeniodawcami. Pośrednie albo bezpośrednie mechanizmy kontroli cen leków po stronie podaży lub popytu pozwalają racjonalizować wydatki oraz kontrolować koszty w ochronie zdrowia. Refundacja zapewnia pacjentom łatwiejszy dostęp do bezpiecznych i skutecznych produktów leczniczych. Celem niniejszej pracy jest analiza i porównanie zasad refundacji leków w systemach opieki zdrowotnej w Polsce i na Ukrainie, a także szczegółowe porównanie refundacji leków przeciwnadciśnieniowych. Ustalono, że w Polsce i na Ukrainie obowiązuje wykaz leków refundowanych, który w Polsce istnieje dłużej, jest bardziej obszerny i częściej aktualizowany. Na Ukrainie wyróżnia się mniej poziomów odpłatności, lecz więcej dodatkowych uprawnień dla pacjentów. Uprawnienia do przepisywania recept refundowanych w Polsce ma aż 7 przedstawicieli zawodów medycznych, natomiast na Ukrainie tylko 3. Praktyka wystawiania refundowanych recept elektronicznych rozwija się w obu krajach, z tym że w Polsce działa sprawniej oraz jest szerzej stosowana, tymczasem na Ukrainie jest możliwa jedynie w ramach jednego programu rządowego. W najbliższych miesiącach jednak ukraińska lista refundacyjna ma zostać poszerzona o nowe leki, na które również będzie obowiązywała e-recepta. Wnioskując, w Polsce pacjenci mają większy dostęp do produktów refundowanych. Odpowiedni dostęp do leków hipotensyjnych dla pacjentów jest szczególnie istotny ze względu na olbrzymi wpływ chorób sercowo-naczyniowych, w tym nadciśnienia tętniczego na śmiertelność społeczeństwa. Wykazano, że ceny leków przeciwnadciśnieniowych oraz opłaty pacjentów za leki na Ukrainie są w większości niższe niż w Polsce.The healthcare system in Poland and Ukraine is based on the social health insurance model. The Ministry of Health is responsible for healthcare policy and regulations, and the NFZ / NSZU for financing and contracts with public and non-public service providers. Direct or indirect drug price control mechanisms on the supply or demand side allow to rationalize expenses and control costs in healthcare. Reimbursement provides patients with easier access to safe and effective drugs. The aim of this study is to analyze and compare the principles of drugs reimbursement in healthcare systems in Poland and Ukraine, as well as a detailed comparison of reimbursement of antihypertensive drugs. It was established that in Poland and Ukraine there is a list of reimbursable drugs, which in Poland is earlier introduced, more extensive and more frequently updated. In Ukraine, there are fewer payment levels but more additional entitlements for patients. In Poland, the authorization to prescribe reimbursable prescriptions have 7 representatives of medical professions, while in Ukraine only 3. The practice of prescribing reimbursable e-prescriptions is developing in both countries, but in Poland it works more efficiently and is more widely used, while in Ukraine it works only in 1 government program. Adequate access to antihypertensive drugs for patients is particularly important due to the enormous impact of cardiovascular diseases, including hypertension, on mortality in society. It has been shown that the prices of antihypertensive drugs and patients' fees for medicines in Ukraine are mostly lower than in Poland

Overcoming Endocrine Resistance in Hormone Receptor–Positive Breast Cancer

Endocrine therapy, a major modality in the treatment of hormone receptor (HR)–positive breast cancer (BCA), has improved outcomes in metastatic and nonmetastatic disease. However, a limiting factor to the use of endocrine therapy in BCA is resistance resulting from the development of escape pathways that promote the survival of cancer cells despite estrogen receptor (er)–targeted therapy. The resistance pathways involve extensive cross-talk between ER and receptor tyrosine kinase growth factors [epidermal growth factor receptor, human epidermal growth factor receptor 2 (HER2), and insulin-like growth factor 1 receptor] and their downstream signalling pathways—most notably pi3k/akt/mtor and mapk. In some cases, resistance develops as a result of genetic or epigenetic alterations in various components of the signalling pathways, such as overexpression of HER2 and ERα co-activators, aberrant expression of cell-cycle regulators, and PIK3CA mutations. By combining endocrine therapy with various molecularly targeted agents and signal transduction inhibitors, some success has been achieved in overcoming and modulating endocrine resistance in HR-positive BCA. Established strategies include selective ER downregulators, anti-HER2 agents, mtor (mechanistic target of rapamycin) inhibitors, and inhibitors of cyclin-dependent kinases 4 and 6. Inhibitors of pi3ka are not currently a treatment option for women with HR-positive BCA outside the context of clinical trial. Ongoing clinical trials are exploring more agents that could be combined with endocrine therapy, and biomarkers that would help to guide decision-making and maximize clinical efficacy. In this review article, we address current treatment strategies for endocrine resistance, and we highlight future therapeutic targets in the endocrine pathway of BCA