The Gracilis Myocutaneous Free Flap: A Quantitative Analysis of the Fasciocutaneous Blood Supply and Implications for Autologous Breast Reconstruction

BACKGROUND: Mastectomies are one of the most common surgical procedures in women of the developed world. The gracilis myocutaneous flap is favoured by many reconstructive surgeons due to the donor site profile and speed of dissection. The distal component of the longitudinal skin paddle of the gracilis myocutaneous flap is unreliable. This study quantifies the fasciocutaneous vascular territories of the gracilis flap and offers the potential to reconstruct breasts of all sizes. METHODS: Twenty-seven human cadaver dissections were performed and injected using lead oxide into the gracilis vascular pedicles, followed by radiographic studies to identify the muscular and fasciocutaneous perforator patterns. The vascular territories and choke zones were characterized quantitatively using the 'Lymphatic Vessel Analysis Protocol' (LVAP) plug-in for Image J® software. RESULTS: We found a step-wise decrease in the average vessel density from the upper to middle and lower thirds of both the gracilis muscle and the overlying skin paddle with a significantly higher average vessel density in the skin compared to the muscle. The average vessel width was greater in the muscle. Distal to the main pedicle, there were either one (7/27 cases), two (14/27 cases) or three (6/27 cases) minor pedicles. The gracilis angiosome was T-shaped and the maximum cutaneous vascular territory for the main and first minor pedicle was 35 × 19 cm and 34 × 10 cm, respectively. CONCLUSION: Our findings support the concept that small volume breast reconstructions can be performed on suitable patients, based on septocutaneous perforators from the minor pedicle without the need to harvest any muscle, further reducing donor site morbidity. For large reconstructions, if a 'T' or tri-lobed flap with an extended vertical component is needed, it is important to establish if three territories are present. Flap reliability and size may be optimized following computed tomographic angiography and surgical delay

Using habitat models to identify marine Important Bird and Biodiversity Areas for Chinstrap penguins in the South Orkney Islands

Tracking individual marine predators can provide vital information to aid the identification of important activity (foraging, commuting, rafting, resting, etc.) hotspots and therefore also to delineate priority sites for conservation. However, in certain locations (e.g. Antarctica) many marine mammal or seabird colonies remain untracked due to logistical constraints, and the colonies that are studied may not be the most important in terms of conservation priorities. Using data for one of the most abundant seabirds in the Antarctic as a case study (the Chinstrap penguin Pygoscelis antarcticus), we tested the use of correlative habitat models (used to predict distribution around untracked colonies) to overcome this limitation, and to enable the identification of important areas at-sea for colonies where tracking data are not available. First, Important Bird and Biodiversity Areas (IBA) were identified using a standardised, published approach using empirical data from birds tracked from colonies located in the South Orkney Islands. Subsequently, novel approaches using predicted distributions of Chinstrap penguins derived from habitatcorrelative habitat models were applied to identify important marine areas, and the results compared with the IBAs. Data were collected from 4 colonies over 4 years and during different stages of the breeding season. Results showed a high degree of overlap between the areas identified as important by observed data (IBAs) and by predicted distributions, revealing that habitat preference models can be used with a high degree of confidence to identify marine IBAs for these penguins. We provide a new method for designating a network of marine IBAs for penguins in Antarctic waters, based on outputs from habitatcorrelative habitat models when tracking data are not available. This can contribute to an evidence-based and precautionary approach to aid the management framework for Antarctic fisheries and for the protection of birds

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

A review of a decade of lessons from one of the world’s largest MPAs: conservation gains and key challenges

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordtribute to global conservation targets, we review outcomes of the last decade of marine conservation research in the British Indian Ocean Territory (BIOT), one of the largest MPAs in the world. The BIOT MPA consists of the atolls of the Chagos Archipelago, interspersed with and surrounded by deep oceanic waters. Islands around the atoll rims serve as nesting grounds for sea birds. Extensive and diverse shallow and mesophotic reef habitats provide essential habitat and feeding grounds for all marine life, and the absence of local human impacts may improve recovery after coral bleaching events. Census data have shown recent increases in the abundance of sea turtles, high numbers of nesting seabirds and high fsh abundance, at least some of which is linked to the lack of recent harvesting. For example, across the archipelago the annual number of green turtle clutches (Chelonia mydas) is~20,500 and increasing and the number of seabirds is ~1 million. Animal tracking studies have shown that some taxa breed and/or forage consistently within the MPA (e.g. some reef fshes, elasmobranchs and seabirds), suggesting the MPA has the potential to provide long-term protection. In contrast, post-nesting green turtles travel up to 4000 km to distant foraging sites, so the protected beaches in the Chagos Archipelago provide a nesting sanctuary for individuals that forage across an ocean basin and several geopolitical borders. Surveys using divers and underwater video systems show high habitat diversity and abundant marine life on all trophic levels. For example, coral cover can be as high as 40–50%. Ecological studies are shedding light on how remote ecosystems function, connect to each other and respond to climate-driven stressors compared to other locations that are more locally impacted. However, important threats to this MPA have been identifed, particularly global heating events, and Illegal, Unreported and Unregulated (IUU) fshing activity, which considerably impact both reef and pelagic fshes.Bertarelli Foundatio

Mutant p53 Mediates Sensitivity to Cancer Treatment Agents in Oesophageal Adenocarcinoma Associated with MicroRNA and SLC7A11 Expression

TP53 gene mutations occur in 70% of oesophageal adenocarcinomas (OACs). Given the central role of p53 in controlling cellular response to therapy we investigated the role of mutant (mut-) p53 and SLC7A11 in a CRISPR-mediated JH-EsoAd1 TP53 knockout model. Response to 2 Gy irradiation, cisplatin, 5-FU, 4-hydroxytamoxifen, and endoxifen was assessed, followed by a TaqMan OpenArray qPCR screening for differences in miRNA expression. Knockout of mut-p53 resulted in increased chemo- and radioresistance (2 Gy survival fraction: 38% vs. 56%, p < 0.0001) and in altered miRNA expression levels. Target mRNA pathways analyses indicated several potential mechanisms of treatment resistance. SLC7A11 knockdown restored radiosensitivity (2 Gy SF: 46% vs. 73%; p = 0.0239), possibly via enhanced sensitivity to oxidative stress. Pathway analysis of the mRNA targets of differentially expressed miRNAs indicated potential involvement in several pathways associated with apoptosis, ribosomes, and p53 signaling pathways. The data suggest that mut-p53 in JH-EsoAd1, despite being classified as non-functional, has some function related to radio- and chemoresistance. The results also highlight the important role of SLC7A11 in cancer metabolism and redox balance and the influence of p53 on these processes. Inhibition of the SLC7A11-glutathione axis may represent a promising approach to overcome resistance associated with mut-p53