Specific Delivery of Therapeutics to Cancer Cells Using pHLIP

Localized delivery is vital for the successful development of novel and effective therapeutics for the treatment of cancer. Currently, most targeting methods are based on cancer markers, such as cell surface receptors. However, this approach suffers from two major drawbacks: biomarkers are not specific to cancer cells, which can result in off-target toxicity, and cancer cells have a tendency to evolve quickly, which can lead to a loss of biomarkers, thus therapy resistance. However, nearly all solid tumors have a low extracellular pH, regardless of their tissue or cellular origin. Moreover, tumors\u27 aggressiveness and metastatic potential are fostered at low extracellular pH. For these reasons, acidosis is a hallmark of tumor progression and may provide an opportunity for tumor-targeted therapy.The targeting and delivery described herein is based on the pH(Low) Insertion Peptide (pHLIP), a unique delivery peptide that can selectively target tumors in mice based solely on their acidity rather than a specific marker. pHLIP is a soluble peptide in aqueous solutions at normal pH, but inserts unidirectionally (C-terminus across) into cell membrane as a transmembrane helix under acidic conditions. My thesis research focused on developing new strategies to inhibit cancer cell growth by delivering therapeutics to cells using pHLIP. We hypothesize that the localized targeting achievable with pHLIP when combined with potent therapeutics will synergize to create an advantageous treatment for cancer. I will present my results in (1) inhibiting cancer cell proliferation and tumor through the delivery of monomethyl auristatin derivatives, (2) modulating the activity of G-Protein coupled receptors by interfering with their cytoplasmic domains, and (3) promoting cancer cells toxicity by inducing mitochondrial membrane disruption through the delivery of antimicrobial peptide analogs

Effects of multidisciplinary team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 722 women

Objectives To describe the effect of multidisciplinary care on survival in women treated for breast cancer

The Resilience in Illness Model Part 2: Confirmatory Evaluation in Adolescents and Young Adults With Cancer

BACKGROUND: Empirically derived and tested models are necessary to develop effective, holistic interventions to improve positive health outcomes in adolescents and young adults (AYA) with cancer, yet few exist. This article is the second of 2 articles reporting on evaluation of the Resilience in Illness Model (RIM) as a predictive model to guide positive health research and practice. OBJECTIVE: The aim of this study was to report the confirmatory model evaluation of the RIM. METHODS: A confirmatory evaluation of RIM was done using baseline data from a sample of 113 AYA aged 11 to 24 years who were undergoing hematopoietic stem cell transplant and enrolled in a randomized controlled trial of a behavioral intervention to enhance resilience. Data were analyzed using latent variable structural equation modeling. RESULTS: Goodness-of-fit indices supported RIM as a confirmed model that accounted for large amounts of variance in the outcomes of self-transcendence (62%) and resilience (72%), and in 3 of 5 mediators, specifically social integration (74%), courageous coping (80%), and hope-derived meaning (87%), as well as small to moderate amounts of variance in the remaining mediators of defensive coping (1%) and family environment (35%). CONCLUSIONS: Findings establish the RIM as a plausible predictive framework for explaining ways AYA with cancer transcend their illness and achieve resilience resolution and for guiding intervention studies in this population. Additional research is needed to explore RIM's transferability based on stage of illness, other chronic diseases, and cultural diversity. IMPLICATIONS FOR PRACTICE: Results support the RIM as an appropriate guide for developing and evaluating interventions to foster positive adjustment in AYA with cancer

The relation between athletic sports and prevalence of amenorrhea and oligomenorrhea in Iranian female athletes

<p>Abstract</p> <p>Background</p> <p>In 1992, the concept of female athlete triad was introduced to describe the interrelated problems of amenorrhea, eating disorders and osteoporosis seen in female athletes. To gain a clearer picture of amenorrhea/oligomenorrhea in Iran, one of the main components of the female athlete triad, we therefore established this study on the prevalence of amenorrhea/oligomenorrhea in elite Iranian female athletes, also evaluating the risk factors of these disorders in the same population.</p> <p>Methods</p> <p>This study performed as a cross-sectional study. All elite Iranian female athletes of 34 sports federation, including female athletes in national teams and medalists of Tehran were invited to participate. A total of 788 (95% response rate) returned the questionnaires and were examined. Younger athletes under the age of menarche were excluded. Each athlete completed a self-administered questionnaire, which covered the following questions about participant's demographic information, athletic history, history of injuries and menstrual pattern. In order to diagnose the causes of amenorrhea/Oligomenorrhea including polycystic ovary syndrome(PCOS), participants with amenorrhea/Oligomenorrhea underwent further investigation. They were evaluated by following Para clinic investigation, and an ultrasonographic study of ovary.</p> <p>Results</p> <p>The age ranged from 13–37 (mean = 21.1, SD = 4.5). Seventy one (9.0%) individuals had amenorrhea/oligomenorrhea, among those, 11 (15.5%) had PCOS.</p> <p>There was also a positive association between amenorrhea/oligomenorrhea and the following: age under 20 OR; 2.67, 95%CI(1.47 – 4.85), weight class sports OR; 2.09, 95%CI(1.15 – 3.82), endurance sports OR; 2.89, 95%CI(1.22 – 6.84), late onset of menarche OR; 3.32 95%CI(1.04–10.51), and use of oral contraceptive pills OR; 6.17, 95%CI(3.00 – 12.69). Intensity of training sport or BMI were not risk factors.</p> <p>Conclusion</p> <p>These findings support the previous findings in the literature that the prevalence of amenorrhea/oligomenorrhea is high in athletes. Furthermore, we provided the first report on the prevalence of PCOS in female athletes with amenorrhea/oligomenorrhea. Athletes would be greatly benefited by greater general awareness about the complications of amenorrhea/oligomenorrhea.</p> <p>To increase awareness of exercise-associated menstrual cycle irregularities, it is necessary to design complete and comprehensive education programs for female athletes, their parents, their coaches, and the relevant authorities.</p

How financial cutbacks affect job quality and care of the elderly

Based on case studies in 12 nursing homes in the United Kingdom, the authors illustrate how financial cutbacks affect job quality and the quality of care. The dimensions of job quality that suffered most were those directly related to the ability of workers to provide care: reductions in staffing, longer working hours, and work intensification. Cuts to labor costs eroded the quality of workers’ jobs in all 12 homes but with two differential outcomes: in seven homes, care quality was maintained, and in five homes, it deteriorated. Care quality was maintained in homes where a patient-centered care approach and remaining job quality allowed workers to develop work-arounds to protect residents from spillover effects. Care quality declined in homes where custodial approaches to care and low job quality did not provide workers the time or resources to protect residents or to maintain prior levels of care. A tipping point was reached, leading to a spillover into impoverished care

Seasonal Habitat Preference and Foraging Behaviour of Post-Moult Weddell Seals in the Western Ross Sea

Weddell seals (Leptonychotes weddellii) are important predators in the Southern Ocean and are among the best-studied pinnipeds on Earth, yet much still needs to be learned about their year-round movements and foraging behaviour. Using biologgers, we tagged 62 post-moult Weddell seals in McMurdo Sound and vicinity between 2010 and 2012. Generalized additive mixed models were used to (i) explain and predict the probability of seal presence and foraging behaviour from eight environmental variables, and (ii) examine foraging behaviour in relation to dive metrics. Foraging probability was highest in winter and lowest in summer, and foraging occurred mostly in the water column or just above the bottom; across all seasons, seals preferentially exploited the shallow banks and deeper troughs of the Ross Sea, the latter providing a pathway for Circumpolar Deep Water to flow onto the shelf. In addition, the probability of Weddell seal occurrence and foraging increased with increasing bathymetric slope and where water depth was typically less than 600 m. Although the probability of occurrence was higher closer to the shelf break, foraging was higher in areas closer to shore and over banks. This study highlights the importance of overwinter foraging for recouping body mass lost during the previous summer

Impact of animal breeding on GHG emissions and farm economics

This report reviews the existing evidence regarding the current and potential use of animal breeding to reduce GHG emissions. It also comments on the likely impact of breeding on farm economics, identifies barriers to achieving GHG reductions via breeding and highlights some future research needs. The report focuses on the following livestock commodities within the EU-28: cattle meat, cattle milk, pigmeat, chicken meat and hen’s eggs. Together these account for approximately 95% of the emissions from European livestock (measured from cradle to farm gate, i.e. including on-farm emissions plus emissions arising pre-farm from the production of inputs such as feed, fertiliser and fuel).JRC.D.4-Economics of Agricultur

Randomized clinical trial of therapeutic music video intervention for resilience outcomes in adolescents/young adults undergoing hematopoietic stem cell transplant: a report from the Children's Oncology Group

BACKGROUND: To reduce the risk of adjustment problems associated with hematopoietic stem cell transplant (HSCT) for adolescents/young adults (AYAs), we examined efficacy of a therapeutic music video (TMV) intervention delivered during the acute phase of HSCT to: 1) increase protective factors of spiritual perspective, social integration, family environment, courageous coping, and hope-derived meaning; 2) decrease risk factors of illness-related distress and defensive coping; and 3) increase outcomes of self-transcendence and resilience. METHODS: This was a multisite randomized, controlled trial (COG-ANUR0631) conducted at 8 Children's Oncology Group sites involving 113 AYAs aged 11-24 years undergoing myeloablative HSCT. Participants, randomized to the TMV or low-dose control (audiobooks) group, completed 6 sessions over 3 weeks with a board-certified music therapist. Variables were based on Haase's Resilience in Illness Model (RIM). Participants completed measures related to latent variables of illness-related distress, social integration, spiritual perspective, family environment, coping, hope-derived meaning, and resilience at baseline (T1), postintervention (T2), and 100 days posttransplant (T3). RESULTS: At T2, the TMV group reported significantly better courageous coping (Effect Size [ES], 0.505; P = .030). At T3, the TMV group reported significantly better social integration (ES, 0.543; P = .028) and family environment (ES, 0.663; P = .008), as well as moderate nonsignificant effect sizes for spiritual perspective (ES, 0.450; P = .071) and self-transcendence (ES, 0.424; P = .088). CONCLUSIONS: The TMV intervention improves positive health outcomes of courageous coping, social integration, and family environment during a high-risk cancer treatment. We recommend the TMV be examined in a broader population of AYAs with high-risk cancers

New horizons in geriatric medicine education and training: the need for pan-European education and training standards

The ageing population ought to be celebrated as evidence for the efficacy of modern medicine, but the challenge that this demographic shift presents for 21st century healthcare systems, with increasing numbers of people living with multi-morbidity and frailty, cannot be ignored. There is therefore a need to ensure that all healthcare professionals grasp the basic principles of care of older people. In this paper, we make a case for the development of pan-European education and training standards for the field of geriatric medicine. Firstly, the challenges which face the implementation and delivery of geriatric medicine in a systematic way across Europe are described – these include, but are not limited to; variance in geriatric medicine practice across Europe, insecurity of the specialty in some countries and significant heterogeneity in geriatric medicine training programs across Europe. The opportunities for geriatric medicine are then presented and we consider how engendering core geriatric medicine competencies amongst nongeriatricians has potential to bridge existing gaps in service provision across Europe. Finally, we consider how work can proceed to teach sufficient numbers of doctors and health professionals in the core knowledge, skills and attitudes required to do this. To safeguard the future of the specialty across Europe, we contend that there is a need to strive towards harmonisation of post-graduate geriatric medicine training across Europe, through the establishment of pan-European education and training standards in the specialty