BRAF wild-type melanoma in situ arising in a BRAF V600E mutant dysplastic nevus

IMPORTANCE The BRAF V600E mutation accounts for the majority of BRAF mutations found in cutaneous melanoma and is also commonly found in nevi. We used dermoscopy-targeted sampling and a microbiopsy device coupled with DNA sequence analysis to highlight BRAF V600E heterogeneity within a multicomponent melanocytic proliferation. This sampling technique demonstrates the prospect of in vivo application in a clinical setting

BRAFV600E Mutation Status of Involuting and Stable Nevi in Dabrafenib Therapy with or without Trametinib

IMPORTANCE Recent advances in targeting BRAF(V600E) mutations, which occur in roughly 50% of melanomas and 70% of benign nevi, have improved response rates and survival in patients with melanoma. With increased survival, the importance of other comorbidities increases and requires consideration in long-term management. This case report discusses dynamic dermoscopic nevus changes that occur during dabrafenib therapy and offers some conclusions regarding BRAF mutations and the changes

Genomics: Think Global, Act Local

Long a slogan for environmentalists, “think global, act local” could be a new rallying cry for biologists. As genome-wide techniques advance and their costs drop, scientists are expanding into larger and larger territories—metagenomics, global proteomic approaches, and analyses of thousands of genomes. These massive data sets are opening up new possibilities for understanding some of the smallest details of the genome. Here, we look at four such cases—investigating the evolutionary role of insertions and deletions in the genome, connecting an orphan enzyme with its gene, mapping the fine details of chromatin structure, and characterizing global interactions between proteins and RNA—all of which depend on a combination of global thinking and local action

Environmental Emission of Pharmaceuticals from Wastewater Treatment Plants in the USA

The residual drugs, drug bioconjugates, and their metabolites, mostly from human and veterinary usage, are routinely flushed down the drain, and enter wastewater treatment plants (WWTP). Increasing population, excessive use of allopathic medicine, continual introduction of novel drugs, and existing inefficient wastewater treatment processes result in the discharge of large volumes of pharmaceuticals and their metabolites from the WWTPs into the environment. The effluent from the WWTPs globally contaminate ~25% of rivers and the lakes. Pharmaceuticals in the environment, as contaminants of emerging concerns, behave as pseudo-persistent despite their relatively short environmental half-lives in the environment. Therefore, residual levels of pharmaceuticals in the environment not only pose a threat to the wildlife but also affect human health through contaminated food and drinking water. This chapter highlights WWTPs as point-sources of their environmental emissions and various effects on the aquatic and terrestrial ecosystem

Maternal health interventions in resource limited countries: a systematic review of packages, impacts and factors for change

The burden of maternal mortality in resource limited countries is still huge despite being at the top of the global public health agenda for over the last 20 years. We systematically reviewed the impacts of interventions on maternal health and factors for change in these countries. A systematic review was carried out using the guidelines for Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles published in the English language reporting on implementation of interventions, their impacts and underlying factors for maternal health in resource limited countries in the past 23 years were searched from PubMed, Popline, African Index Medicus, internet sources including reproductive health gateway and Google, hand-searching, reference lists and grey literature. Out of a total of 5084 articles resulting from the search only 58 qualified for systematic review. Programs integrating multiple interventions were more likely to have significant positive impacts on maternal outcomes. Training in emergency obstetric care (EmOC), placement of care providers, refurbishment of existing health facility infrastructure and improved supply of drugs, consumables and equipment for obstetric care were the most frequent interventions integrated in 52%-65% of all 54 reviewed programs. Statistically significant reduction of maternal mortality ratio and case fatality rate were reported in 55% and 40% of the programs respectively. Births in EmOC facilities and caesarean section rates increased significantly in 71%-75% of programs using these indicators. Insufficient implementation of evidence-based interventions in resources limited countries was closely linked to a lack of national resources, leadership skills and end-users factors. This article presents a list of evidenced-based packages of interventions for maternal health, their impacts and factors for change in resource limited countries. It indicates that no single magic bullet intervention exists for reduction of maternal mortality and that all interventional programs should be integrated in order to bring significant changes. State leaders and key actors in the health sectors in these countries and the international community are proposed to translate the lessons learnt into actions and intensify efforts in order to achieve the goals set for maternal health

Elevated neutrophil and monocyte counts in peripheral blood are associated with poor survival in patients with metastatic melanoma: a prognostic model

We aimed to create a prognostic model in metastatic melanoma based on independent prognostic factors in 321 patients receiving interleukin-2 (IL-2)-based immunotherapy with a median follow-up time for patients currently alive of 52 months (range 15–189 months). The patients were treated as part of several phase II protocols and the majority received treatment with intermediate dose subcutaneous IL-2 and interferon-α. Neutrophil and monocyte counts, lactate dehydrogenase (LDH), number of metastatic sites, location of metastases and performance status were all statistically significant prognostic factors in univariate analyses. Subsequently, a multivariate Cox's regression analysis identified elevated LDH (P<0.001, hazard ratio 2.8), elevated neutrophil counts (P=0.02, hazard ratio 1.4) and a performance status of 2 (P=0.008, hazard ratio 1.6) as independent prognostic factors for poor survival. An elevated monocyte count could replace an elevated neutrophil count. Patients were assigned to one of three risk groups according to the cumulative risk defined as the sum of simplified risk scores of the three independent prognostic factors. Low-, intermediate- and high-risk patients achieved a median survival of 12.6 months (95% confidence interval (CI), 11.4–13.8), 6.0 months (95% CI, 4.8–7.2) and 3.4 months (95% CI, 1.2–5.6), respectively. The low-risk group encompassed the majority of long-term survivors, whereas the patients in the high-risk group with a very poor prognosis should probably not be offered IL-2-based immunotherapy

Senescent cells as a source of inflammatory factors for tumor progression

Cellular senescence, which is associated with aging, is a process by which cells enter a state of permanent cell cycle arrest, therefore constituting a potent tumor suppressive mechanism. Recent studies show that, despite the beneficial effects of cellular senescence, senescent cells can also exert harmful effects on the tissue microenvironment. The most significant of these effects is the acquisition of a senescent-associated secretory phenotype (SASP), which entails a striking increase in the secretion of pro-inflammatory cytokines. Here, we summarize our knowledge of the SASP and the impact it has on tissue microenvironments and ability to stimulate tumor progression

Trace metal distribution in the bed, bank and suspended sediment of the Ravensbourne River and its implication for sediment monitoring in an urban river

Purpose This study aims to identify a suitable sediment compartment for sediment quality monitoring by: (a) studying the concentration of trace metals (Cd, Cu, Ni, Pb and Zn) in the bed, bank and suspended sediment compartments of the Ravensbourne River to establish any differences in trace metal concentrations with compartment; (b) determining the influence of sediment particle size fractions ( 0.05) in the concentrations of metals between the suspended sediment and the < 63 μm bed sediment fraction, but there was a significant difference (p < 0.05) between the suspended sediment and the < 63 μm bank sediment fraction. There were also significant differences between the concentrations of metals in the < 63 μm and the 63 μm–2 mm fractions. Generally, the Ravensbourne River did not comply with the draft UK sediment quality guidelines for the metals analysed. Conclusions This study shows the importance of identifying a suitable sediment compartment to sample for compliance with sediment quality standards. The bed and suspended sediments are the most widely used sediment compartments for sediment monitoring, but collecting sufficient mass of the < 63 μm sediment fraction for monitoring presents a challenge for urban gravel bed rivers like the Ravensbourne River. It seems appropriate to establish individual monitoring regimes for different rivers