Abstract Merkel cell carcinoma (MCC) is a rare skin cancer that is associated with Merkel cell polyomavirus infection in most cases. Incidence rates of MCC have increased in past decades. Risk ...factors for MCC include ultraviolet light exposure, immunosuppression and advanced age. MCC is an aggressive malignancy with frequent recurrences and a high mortality rate, although patient outcomes are generally more favourable if the patient is referred for treatment at an early stage. Although advances have been made recently in the MCC field, large gaps remain with regard to definitive biomarkers and prognostic indicators. Although MCC is chemosensitive, responses in advanced stages are mostly of short duration, and the associated clinical benefit on overall survival is unclear. Recent nonrandomised phase 2 clinical trials with anti–PD-L1/PD-1 antibodies have demonstrated safety and efficacy; however, there are still no approved treatments for patients with metastatic MCC. Patients with advanced disease are encouraged to participate in clinical trials for treatment, indicating the largely unmet need for durable, safe treatment within this population.
Summary The purpose of this study was to review the evidence of the economic burden of falls in old age. This review showed that falls are a relevant economic burden. Efforts should be directed to ...fall-prevention programmes. Introduction Falls are a common mechanism of injury and a leading cause of costs of injury in the elderly. The purpose of this study was to review for the first time the evidence of the economic burden caused by falls in old age. Methods A systematic review was conducted in the databases of PubMed, of the Centre for Reviews and Dissemination and in the Cochrane Database of Systematic Reviews until June 2009. Studies were assessed for inclusion, classified and synthesised. Costs per inhabitant, the share of fall-related costs in total health care expenditures and in gross domestic products (GDP) were calculated. If appropriate, cost data were inflated to the year 2006 and converted to US Dollar (USD PPP). Results A total of 32 studies were included. National fall-related costs of prevalence-based studies were between 0.85% and 1.5% of the total health care expenditures, 0.07% to 0.20% of the GDP and ranged from 113 to 547 USD PPP per inhabitant. Direct costs occurred especially in higher age groups, in females, in hospitals and long-term care facilities and for fractures. Mean costs per fall victim, per fall and per fall-related hospitalisation ranged from 2,044 to 25,955; 1,059 to 10,913 and 5,654 to 42,840 USD PPP and depended on fall severity. A more detailed comparison is restricted by the limited number of studies. Conclusion Falls are a relevant economic burden to society. Efforts should be directed to economic evaluations of fall-prevention programmes aiming at reducing fall-related fractures, which contribute substantially to fall-related costs.
Habitat loss and disease are main drivers of global amphibian declines, yet the interaction between them remains largely unexplored. Here we show that paradoxically, habitat loss is negatively ...associated with occurrence, prevalence, and infection intensity of the chytrid fungus Batrachochytrium dendrobatidis (Bd) in amphibian populations in the tropics. At a large spatial scale, increased habitat loss predicted lower disease risk in amphibian populations across Costa Rica and eastern Australia, even after jointly considering the effect of potential biotic and abiotic correlates. Lower host-species richness and suboptimal microclimates for Bd in disturbed habitats are potential mechanisms underlying this pattern. Furthermore, we found that anthropogenic deforestation practices biased to lowlands and natural vegetation remaining in inaccessible highlands explain increased Bd occurrence at higher elevations. At a smaller spatial scale, holding constant elevation, latitude, and macroclimate, we also found a negative relationship between habitat loss, and both Bd prevalence and infection intensity in frog populations in two landscapes of the Brazilian Atlantic Forest. Our results indicate that amphibians will be disproportionately affected by emerging diseases in pristine environments, and that, paradoxically, disturbed habitats may act as shelters from disease, but only for the very few species that can tolerate deforestation. Thus, tropical amphibian faunas are threatened both by destruction of natural habitats as well as increased disease in pristine forests. To curb further extinctions and develop effective mitigation and restoration programs we must look to interactions between habitat loss and disease, the two main factors at the root of global amphibian declines.
Solid tumors are more than an accumulation of cancer cells. Indeed, cancerous cells create a permissive microenvironment by exploiting non-transformed host cells. Thus, solid tumors rather resemble ...abnormal organs composed of the cancerous cells itself and the stroma providing the supportive framework. The stroma can be divided into the extracellular matrix consisting of proteoglycans, hyaluronic acid, and fibrous proteins, as well as stromal cells including mesenchymal and immune cells; moreover, it contains various peptide factors and metabolites. Here, we will focus on immune-modulating capacities of the tumor microenvironment.
Treatment with trametinib, a MEK inhibitor, resulted in significantly improved progression-free and overall survival, as compared with chemotherapy, in patients with advanced melanoma and activating ...BRAF mutations.
About 160,000 new cases of melanoma are diagnosed and 48,000 melanoma-related deaths occur worldwide each year.
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Among cancers in patients under 40 years of age, the incidence of melanoma is second only to that of breast cancer for women and leukemia for men.
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Before 2010, no systemic therapy had been shown to improve overall survival among patients with metastatic melanoma, and only modest improvements were observed with interferon as an adjuvant drug.
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Ipilimumab, a monoclonal antibody targeting cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), and vemurafenib, a selective BRAF inhibitor, have both been shown to improve survival among patients with metastatic melanoma . . .
Merkel cell carcinoma Becker, Jürgen C; Stang, Andreas; DeCaprio, James A ...
Nature reviews. Disease primers,
10/2017, Letnik:
3
Journal Article
Recenzirano
Odprti dostop
Merkel cell carcinoma (MCC) is a rare but highly aggressive skin cancer with neuroendocrine features. MCC pathogenesis is associated with either the presence of Merkel cell polyomavirus or chronic ...exposure to ultraviolet light (UV), which can cause a characteristic pattern of multiple DNA mutations. Notably, in the Northern hemisphere, the majority of MCC cases are of viral aetiology; by contrast, in areas with high UV exposure, UV-mediated carcinogenesis is predominant. The two aetiologies share similar clinical, histopathological and prognostic characteristics. MCC presents with a solitary cutaneous or subcutaneous nodule, most frequently in sun-exposed areas. In fact, UV exposure is probably involved in both viral-mediated and non-viral-mediated carcinogenesis, by contributing to immunosuppression or DNA damage, respectively. Confirmation of diagnosis relies on analyses of histological features and immunological marker expression profiles of the lesion. At primary diagnosis, loco-regional metastases are already present in ∼30% of patients. Excision of the tumour is the first-line therapy; if not feasible, radiotherapy can often effectively control the disease. Chemotherapy was the only alternative in advanced-stage or refractory MCC until several clinical trials demonstrated the efficacy of immune-checkpoint inhibitors.
Neoliberalism has become the dominant ideology in many parts of the world. Yet there is little empirical research on its psychological impact. On the basis of a social identity approach to health, we ...hypothesize that, by increasing competition and by reducing people’s sense of connection to others, neoliberalism can increase loneliness and compromise our well‐being. Study 1 (N = 246) shows that the more neoliberal people perceive society to be, the worse their well‐being, and that this relationship is mediated via loneliness. In two experiments, we showed that exposure to neoliberal ideology increases loneliness (Study 2, N = 204) and, through this, decreases well‐being (Study 3, N = 173). In Study 4 (N = 303), we found that exposure to neoliberal ideology increased loneliness and decreased well‐being by reducing people’s sense of connection to others and by increasing perceptions of being in competition with others. In Study 4, the effect of neoliberalism on well‐being was evident for liberals only. We discuss the potential impact of neoliberalism on different social groups in society.
The southeastern United States experiences an extended hot season with a high environmental temperature and relative humidity. With increasing global temperatures, managing dairy cattle in regions ...with tropical, subtropical, and Mediterranean climates is becoming an increasing challenge. Heat-stressed cows will decrease feed intake, decrease productivity, and increase respiration rate in an attempt to maintain internal body temperature. Temperature-humidity index (THI) is a unitless value that has been used to measure the magnitude of heat stress on dairy cows. Many researchers have studied the THI threshold at which dairy cattle begin to experience heat stress. When housing cows in a confinement setting, a pasture-based setting, or a combination of the two, the appropriate heat abatement should be implemented to allow cows to perform to their potential and to improve overall animal welfare. This review summarizes heat abatement strategies that have been studied to reduce the negative effects of heat stress.
Biologists and social scientists have long tried to understand why some societies have more fluid and open interpersonal relationships and how those differences influence culture. This study measures ...relational mobility, a socioecological variable quantifying voluntary (high relational mobility) vs. fixed (low relational mobility) interpersonal relationships. We measure relational mobility in 39 societies and test whether it predicts social behavior. People in societies with higher relational mobility report more proactive interpersonal behaviors (e.g., self-disclosure and social support) and psychological tendencies that help them build and retain relationships (e.g., general trust, intimacy, self-esteem). Finally, we explore ecological factors that could explain relational mobility differences across societies. Relational mobility was lower in societies that practiced settled, interdependent subsistence styles, such as rice farming, and in societies that had stronger ecological and historical threats.
Merkel Cell Polyomavirus (MCPyV) is the etiological agent of the majority of Merkel Cell Carcinomas (MCC). MCPyV positive MCCs harbor integrated, defective viral genomes that constitutively express ...viral oncogenes. Which molecular mechanisms promote viral integration, if distinct integration patterns exist, and if integration occurs preferentially at loci with specific chromatin states is unknown. We here combined short and long-read (nanopore) next-generation sequencing and present the first high-resolution analysis of integration site structure in MCC cell lines as well as primary tumor material. We find two main types of integration site structure: Linear patterns with chromosomal breakpoints that map closely together, and complex integration loci that exhibit local amplification of genomic sequences flanking the viral DNA. Sequence analysis suggests that linear patterns are produced during viral replication by integration of defective/linear genomes into host DNA double strand breaks via non-homologous end joining, NHEJ. In contrast, our data strongly suggest that complex integration patterns are mediated by microhomology-mediated break-induced replication, MMBIR. Furthermore, we show by ChIP-Seq and RNA-Seq analysis that MCPyV preferably integrates in open chromatin and provide evidence that viral oncogene expression is driven by the viral promoter region, rather than transcription from juxtaposed host promoters. Taken together, our data explain the characteristics of MCPyV integration and may also provide a model for integration of other oncogenic DNA viruses such as papillomaviruses.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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