The initial experience of electronic brachytherapy for the treatment of non-melanoma skin cancer

<p>Abstract</p> <p>Background</p> <p>Millions of people are diagnosed with non-melanoma skin cancers (NMSC) worldwide each year. While surgical approaches are the standard treatment, some patients are appropriate candidates for radiation therapy for NMSC. High dose rate (HDR) brachytherapy using surface applicators has shown efficacy in the treatment of NMSC and shortens the radiation treatment schedule by using a condensed hypofractionated approach. An electronic brachytherapy (EBT) system permits treatment of NMSC without the use of a radioactive isotope.</p> <p>Methods</p> <p>Data were collected retrospectively from patients treated from July 2009 through March 2010. Pre-treatment biopsy was performed to confirm a malignant cutaneous diagnosis. A CT scan was performed to assess lesion depth for treatment planning, and an appropriate size of surface applicator was selected to provide an acceptable margin. An HDR EBT system delivered a dose of 40.0 Gy in eight fractions twice weekly with 48 hours between fractions, prescribed to a depth of 3-7 mm. Treatment feasibility, acute safety, efficacy outcomes, and cosmetic results were assessed.</p> <p>Results</p> <p>Thirty-seven patients (mean age 72.5 years) with 44 cutaneous malignancies were treated. Of 44 lesions treated, 39 (89%) were T1, 1 (2%) Tis, 1 (2%) T2, and 3 (7%) lesions were recurrent. Lesion locations included the nose for 16 lesions (36.4%), ear 5 (11%), scalp 5 (11%), face 14 (32%), and an extremity for 4 (9%). Median follow-up was 4.1 months. No severe toxicities occurred. Cosmesis ratings were good to excellent for 100% of the lesions at follow-up.</p> <p>Conclusions</p> <p>The early outcomes of EBT for the treatment of NMSC appear to show acceptable acute safety and favorable cosmetic outcomes. Using a hypofractionated approach, EBT provides a convenient treatment schedule.</p

Benign Ancient Schwannoma of the abdominal wall: An unwanted birthday present

<p>Abstract</p> <p>Background</p> <p>There has been a recent growth in the use of whole body Computerised Tomography (CT) scans in the private sector as a screening test for asymptomatic disease. This is despite scant evidence to show any positive effect on morbidity or mortality. There has been concern raised over the possible harms of the test in terms of radiation exposure as well as the risk and anxiety of further investigation and treatment for the large numbers of benign lesions identified.</p> <p>Case Presentation</p> <p>A healthy 64 year old lady received a privately funded whole body CT scan for her birthday which revealed an incidental mass in the right iliac fossa. This was investigated with further imaging and colonoscopy and as confident diagnosis could not be made, eventually excised. Histology demonstrated this to be a benign ancient schwannoma and we believe this to be the first reported case of an abdominal wall schwannoma in the English literature</p> <p>Conclusions</p> <p>Ancient schwannomas are rare tumours of the peripheral nerve sheaths more usually found in the head, neck and flexor surfaces of extremities. They are a subtype of classical schwannomas with a predominance of degenerative changes. Our case highlights the pitfalls of such screening tests in demonstrating benign disease and subjecting patients to what turns out to be unnecessary invasive investigation and treatment. It provides evidence as to the consequences of the large number of false positive results that are created by blind CT scanning of asymptomatic patients i.e. its tendency to detect pseudodiesease rather than affect survival rates. Should the number of scans increase there may be an unnecessary burden on NHS resources due to the large numbers of benign lesions picked up, that are then referred for further investigation.</p

The burden of respiratory infections among older adults in long-term care:a systematic review

BACKGROUND: Respiratory infections among older adults in long-term care facilities (LTCFs) are a major global concern, yet a rigorous systematic synthesis of the literature on the burden of respiratory infections in the LTCF setting is lacking. To address the critical need for evidence regarding the global burden of respiratory infections in LTCFs, we assessed the burden of respiratory infections in LTCFs through a systematic review of the published literature. METHODS: We identified articles published between April 1964 and March 2019 through searches of PubMed (MEDLINE), EMBASE, and the Cochrane Library. Experimental and observational studies published in English that included adults aged ≥60 residing in LTCFs who were unvaccinated (to identify the natural infection burden), and that reported measures of occurrence for influenza, respiratory syncytial virus (RSV), or pneumonia were included. Disagreements about article inclusion were discussed and articles were included based on consensus. Data on study design, population, and findings were extracted from each article. Findings were synthesized qualitatively. RESULTS: A total of 1451 articles were screened for eligibility, 345 were selected for full-text review, and 26 were included. Study population mean ages ranged from 70.8 to 90.1 years. Three (12%) studies reported influenza estimates, 7 (27%) RSV, and 16 (62%) pneumonia. Eighteen (69%) studies reported incidence estimates, 7 (27%) prevalence estimates, and 1 (4%) both. Seven (27%) studies reported outbreaks. Respiratory infection incidence estimates ranged from 1.1 to 85.2% and prevalence estimates ranging from 1.4 to 55.8%. Influenza incidences ranged from 5.9 to 85.2%. RSV incidence proportions ranged from 1.1 to 13.5%. Pneumonia prevalence proportions ranged from 1.4 to 55.8% while incidence proportions ranged from 4.8 to 41.2%. CONCLUSIONS: The reported incidence and prevalence estimates of respiratory infections among older LTCF residents varied widely between published studies. The wide range of estimates offers little useful guidance for decision-making to decrease respiratory infection burden. Large, well-designed epidemiologic studies are therefore still necessary to credibly quantify the burden of respiratory infections among older adults in LTCFs, which will ultimately help inform future surveillance and intervention efforts

Experimental Microbial Evolution of Extremophiles

Experimental microbial evolutions (EME) involves studying closely a microbial population after it has been through a large number of generations under controlled conditions (Kussell 2013). Adaptive laboratory evolution (ALE) selects for fitness under experimentally imposed conditions (Bennett and Hughes 2009; Dragosits and Mattanovich 2013). However, experimental evolution studies focusing on the contributions of genetic drift and natural mutation rates to evolution are conducted under non-selective conditions to avoid changes imposed by selection (Hindré et al. 2012). To understand the application of experimental evolutionary methods to extremophiles it is essential to consider the recent growth in this field over the last decade using model non-extremophilic microorganisms. This growth reflects both a greater appreciation of the power of experimental evolution for testing evolutionary hypotheses and, especially recently, the new power of genomic methods for analyzing changes in experimentally evolved lineages. Since many crucial processes are driven by microorganisms in nature, it is essential to understand and appreciate how microbial communities function, particularly with relevance to selection. However, many theories developed to understand microbial ecological patterns focus on the distribution and the structure of diversity within a microbial population comprised of single species (Prosser et al. 2007). Therefore an understanding of the concept of species is needed. A common definition of species using a genetic concept is a group of interbreeding individuals that is isolated from other such groups by barriers of recombination (Prosser et al. 2007). An alternative ecological species concept defines a species as set of individuals that can be considered identical in all relevant ecological traits (Cohan 2001). This is particularly important because of the abundance and deep phylogenetic complexity of microbial communities. Cohan postulated that “bacteria occupy discrete niches and that periodic selection will purge genetic variation within each niche without preventing divergence between the inhabitants of different niches”. The importance of gene exchange mechanisms likely in bacteria and archaea and therefore extremophiles, arises from the fact that their genomes are divided into two distinct parts, the core genome and the accessory genome (Cohan 2001). The core genome consists of genes that are crucial for the functioning of an organism and the accessory genome consists of genes that are capable of adapting to the changing ecosystem through gain and loss of function. Strains that belong to the same species can differ in the composition of accessory genes and therefore their capability to adapt to changing ecosystems (Cohan 2001; Tettelin et al. 2005; Gill et al. 2005). Additional ecological diversity exists in plasmids, transposons and pathogenicity islands as they can be easily shared in a favorable environment but still be absent in the same species found elsewhere (Wertz et al. 2003). This poses a major challenge for studying ALE and community microbial ecology indicating a continued need to develop a fitting theory that connects the fluid nature of microbial communities to their ecology (Wertz et al. 2003; Coleman et al. 2006). Understanding the nature and contribution of different processes that determine the frequencies of genes in any population is the biggest concern in population and evolutionary genetics (Prosser et al. 2007) and it is critical for an understanding of experimental evolution

Trade-offs between vegetative growth and acorn production in Quercus lobata during a mast year: the relevance of crop size and hierarchical level within the canopy

The concept of trade-offs between reproduction and other fitness traits is a fundamental principle of life history theory. For many plant species, the cost of sexual reproduction affects vegetative growth in years of high seed production through the allocation of resources to reproduction at different hierarchical levels of canopy organization. We have examined these tradeoffs at the shoot and branch level in an endemic California oak, Quercus lobata, during a mast year. To determine whether acorn production caused a reduction in vegetative growth, we studied trees that were high and low acorn producers, respectively. We observed that in both low and high acorn producers, shoots without acorns located adjacent to reproductive shoots showed reduced vegetative growth but that reduced branch-level growth on acorn-bearing branches occurred only in low acorn producers. The availability of local resources, measured as previous year growth, was the main factor determining acorn biomass. These findings show that the costs of reproduction varied among hierarchical levels, suggesting some degree of physiological autonomy of shoots in terms of acorn production. Costs also differed among trees with different acorn crops, suggesting that trees with large acorn crops had more available resources to allocate for growth and acorn production and to compensate for immediate local costs of seed production. These findings provide new insight into the proximate mechanisms for mast-seeding as a reproductive strategy

Investigation of the Genes Involved in Antigenic Switching at the vlsE Locus in Borrelia burgdorferi: An Essential Role for the RuvAB Branch Migrase

Persistent infection by pathogenic organisms requires effective strategies for the defense of these organisms against the host immune response. A common strategy employed by many pathogens to escape immune recognition and clearance is to continually vary surface epitopes through recombinational shuffling of genetic information. Borrelia burgdorferi, a causative agent of Lyme borreliosis, encodes a surface-bound lipoprotein, VlsE. This protein is encoded by the vlsE locus carried at the right end of the linear plasmid lp28-1. Adjacent to the expression locus are 15 silent cassettes carrying information that is moved into the vlsE locus through segmental gene conversion events. The protein players and molecular mechanism of recombinational switching at vlsE have not been characterized. In this study, we analyzed the effect of the independent disruption of 17 genes that encode factors involved in DNA recombination, repair or replication on recombinational switching at the vlsE locus during murine infection. In Neisseria gonorrhoeae, 10 such genes have been implicated in recombinational switching at the pilE locus. Eight of these genes, including recA, are either absent from B. burgdorferi, or do not show an obvious requirement for switching at vlsE. The only genes that are required in both organisms are ruvA and ruvB, which encode subunits of a Holliday junction branch migrase. Disruption of these genes results in a dramatic decrease in vlsE recombination with a phenotype similar to that observed for lp28-1 or vls-minus spirochetes: productive infection at week 1 with clearance by day 21. In SCID mice, the persistence defect observed with ruvA and ruvB mutants was fully rescued as previously observed for vlsE-deficient B. burgdorferi. We report the requirement of the RuvAB branch migrase in recombinational switching at vlsE, the first essential factor to be identified in this process. These findings are supported by the independent work of Lin et al. in the accompanying article, who also found a requirement for the RuvAB branch migrase. Our results also indicate that the mechanism of switching at vlsE in B. burgdorferi is distinct from switching at pilE in N. gonorrhoeae, which is the only other organism analyzed genetically in detail. Finally, our findings suggest a unique mechanism for switching at vlsE and a role for currently unidentified B. burgdorferi proteins in this process

Endophytes vs tree pathogens and pests: can they be used as biological control agents to improve tree health?

Like all other plants, trees are vulnerable to attack by a multitude of pests and pathogens. Current control measures for many of these diseases are limited and relatively ineffective. Several methods, including the use of conventional synthetic agro-chemicals, are employed to reduce the impact of pests and diseases. However, because of mounting concerns about adverse effects on the environment and a variety of economic reasons, this limited management of tree diseases by chemical methods is losing ground. The use of biological control, as a more environmentally friendly alternative, is becoming increasingly popular in plant protection. This can include the deployment of soil inoculants and foliar sprays, but the increased knowledge of microbial ecology in the phytosphere, in particular phylloplane microbes and endophytes, has stimulated new thinking for biocontrol approaches. Endophytes are microbes that live within plant tissues. As such, they hold potential as biocontrol agents against plant diseases because they are able to colonize the same ecological niche favoured by many invading pathogens. However, the development and exploitation of endophytes as biocontrol agents will have to overcome numerous challenges. The optimization and improvement of strategies employed in endophyte research can contribute towards discovering effective and competent biocontrol agents. The impact of environment and plant genotype on selecting potentially beneficial and exploitable endophytes for biocontrol is poorly understood. How endophytes synergise or antagonise one another is also an important factor. This review focusses on recent research addressing the biocontrol of plant diseases and pests using endophytic fungi and bacteria, alongside the challenges and limitations encountered and how these can be overcome. We frame this review in the context of tree pests and diseases, since trees are arguably the most difficult plant species to study, work on and manage, yet they represent one of the most important organisms on Earth

Endophytes vs tree pathogens and pests: can they be used as biological control agents to improve tree health?

Like all other plants, trees are vulnerable to attack by a multitude of pests and pathogens. Current control measures for many of these diseases are limited and relatively ineffective. Several methods, including the use of conventional synthetic agro-chemicals, are employed to reduce the impact of pests and diseases. However, because of mounting concerns about adverse effects on the environment and a variety of economic reasons, this limited management of tree diseases by chemical methods is losing ground. The use of biological control, as a more environmentally friendly alternative, is becoming increasingly popular in plant protection. This can include the deployment of soil inoculants and foliar sprays, but the increased knowledge of microbial ecology in the phytosphere, in particular phylloplane microbes and endophytes, has stimulated new thinking for biocontrol approaches. Endophytes are microbes that live within plant tissues. As such, they hold potential as biocontrol agents against plant diseases because they are able to colonize the same ecological niche favoured by many invading pathogens. However, the development and exploitation of endophytes as biocontrol agents will have to overcome numerous challenges. The optimization and improvement of strategies employed in endophyte research can contribute towards discovering effective and competent biocontrol agents. The impact of environment and plant genotype on selecting potentially beneficial and exploitable endophytes for biocontrol is poorly understood. How endophytes synergise or antagonise one another is also an important factor. This review focusses on recent research addressing the biocontrol of plant diseases and pests using endophytic fungi and bacteria, alongside the challenges and limitations encountered and how these can be overcome. We frame this review in the context of tree pests and diseases, since trees are arguably the most difficult plant species to study, work on and manage, yet they represent one of the most important organisms on Earth