Safety of Food throughout the Supply Chain

*Fraidoon Karimi*

### **Abstract**

Today, in addition to food security, food safety is very important, because one of the prominent causes of increasing diseases is changing people's eating habits and lack of food safety along the food chain. Vegetables and fruits, in all stages of the food supply chain, are contaminated with a variety of bacteria, viruses, protozoa, and parasites. The prevalence of many diseases has been recorded in the past as a result of eating fruits and vegetables. The results of extensive research conducted in this field around the world were used in this chapter, and melon is discussed in detail as an example. Research findings show that pathogens that lodge in the skin of melon can enter the melon flesh when cut and infect it. Similarly, in hot climates, the bacteria Salmonella, Listeria, and *E*. *coli* multiply easily in melon flesh at low pH and soon reach pathogenic doses. Therefore, appropriate hygiene measures should be considered along the food chain. These hygiene measures are considered very important from the perspective that very small contamination by campylobacter, *Escherichia coli*, and norovirus, for example, can cause a major health problem. Highly vulnerable people include pregnant women, young children, the elderly, and the sick.

**Keywords:** safety, supply chain, human health, microbial hazards, chemical hazards

### **1. Introduction**

Food security and food safety are two basic concepts of human nutrition and, especially recently, have played an important role in the food industry and trade worldwide. According to the Codex's definition [1] "Food safety is the absence or presence of small amounts of hazardous substances in food that do not threaten the health of the consumer; these include microbial, chemical, and physical factors that are often not seen, such as bacteria, viruses, or chemical residues [1].

Melons (*Cucumis melo* L.) and watermelons (*Citrullus lanatus* L.) are important members of the Cucurbitaceae family. The term musk melons include various cultivars of melon. Commercial melons are evaluated based on their various characteristics, such as shape (spherical or oblong), skin color, and shape of the flesh [2]. More than 100 million tons of melons and watermelons are produced worldwide, 80% of which are from Asia. The main producer, from 2009 to 2011, is China with 60% of world production. However, the exports of this country account for only 0.13% of the total exports of the world [3]. Major exporters of melons have been reported from Mexico,

Spain, the United States, and Brazil [3]. In Europe, melons are grown mainly in southern regions, such as Spain, Portugal, Italy, and Greece. In Europe, 3 million tons of watermelon and 2 million tons of different melon cultivars are produced every year [3]. Melons and watermelons are not produced in Germany [2]. Afghanistan is one of the main centers of melon production, which is currently producing 15 different varieties of melons, mainly in the northern and southern parts of the country. These varieties include Jane Tour, Zermati, Bori Kaleh, Asqalani, Sabz-Maghaz, Alishabi, Sefal-Sar, Marpost, Ghazikhani, Andalak, Qandak, Alla-Poqaq, Arkani, Arkani-Garmah, and Sard-e-Lelmi [4].

Fresh vegetables and fruits are contaminated with a variety of pathogens along the production-to-consumption chain, resulting in dangerous diseases in humans [4]. For example, melon is one of the fruits that is known among people as a fever and disease stimulator that some doctors even include this fruit in the list of patients to avoid (personal interview, August 20, 2018).

Pathogens identified in melon include Salmonella, Listeria monocytogenes, and Enterohemorrhagic Escherichia coli (E. coli) [5]. Campylobacter, E. coli, and Norovirus can cause serious diseases [5].

A report prepared for the Codex Committee in 2011 states that between 1950 and 2011, 85 cases of the melon disease were recorded [1]. Some cases of the melon disease have also been reported in Germany [2]. Melons, on the other hand, do not appear to contain substances that are harmful to health. Therefore, in this study, it was assumed that external factors cause diseases in consumers, these factors are transmitted from the skin to the inner parts of the fruit when the fruit is peeled and gets contaminated. To test this hypothesis, various relevant sources, including research reports and articles, have been studied and their key concepts have been included in this chapter. Due to production and supply conditions, melon skin is in contact with germs and parasites, especially in melons that have large and rough skin. On the other hand, disinfection of melon fruit does not include the stages of production, supply, and consumption, and therefore the fruit remains contaminated and causes health problems.

## **2. Methodology**

This study has been done using various first-hand sources that include reports and research articles. The study materials were collected in the first step, and in terms of logical relationship with the hypothesis, were divided into three categories: (1) very relevant, (2) relevant, and (3) less relevant.


**2.2. Brincyclovir (BCV; hexadecyloxypropyl-cidofovir; CMX001)**

This compound is a lipidic conjugate of cidofovir. It prevents AdV induced mortality in a permissive, immunosuppressed animal model [23].


**1. Introduction**

Hollow zein particles have been fabricated by wrapping sodium carbonate (Na2CO3) nanoprecipitate as sacrificial templet with zein in ethanol–water binary mixture followed by antisolvent precipitation [1]. Hollow particles in the loading and controlled release of bioactive components were preferred over their solid counterpart for more surface area and low density [2], but proteinaceous nature limits their utility as an efficient delivery system due to destabilization around pI (5–6.5), presence of counterion and high temperatureinduced denaturation [3,4]. Numerous strategies have been adopted to overcome instability issues of zein particles, for instance, coating with proteins [5,6], polysaccharides [7] and lipids [8]. Pectin is an anionic biodegradable polymer found in the plant cell wall and mainly made up of methyl esterified 1-4 linked α-D-galacturonic acid and 1-2-linked α-Lrhamnopyranose. Composite hollow zein particles with casein and pectin were developed by heating at 80 ◦C and 6.2 pH for 1 h to attain outstanding stability under simulated gastrointestinal conditions. Still, these composite particles were limited only to encapsulate and deliver heat-sensitive bioactives [9].

Chitosan-coated solid zein particles were fabricated through hydrophobic, hydrogen and van der Waals interactions at pH 4, improving the entrapment, photo/thermal

**Citation:** Khan, M.A.; Zhou, C.; Zheng, P.; Zhao, M.; Liang, L. Improving Physicochemical Stability of Quercetin-Loaded Hollow Zein Particles with Chitosan/Pectin Complex Coating. *Antioxidants* **2021**, *10*, 1476. https://doi.org/10.3390/ antiox10091476

Academic Editor: Elisabetta Esposito

Received: 26 August 2021 Accepted: 13 September 2021 Published: 16 September 2021

**Publisher's Note:** MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

**Copyright:** © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

protection and controlled release of bioactive components [10–12]. Chitosan, a N-acetyl-Dglucosamine and D-glucosamine β1-4 linked cationic polymer, is obtained by deacetylation of chitin and considerably used for the stabilization of delivery systems [13]. However, the deprotonation of the amine groups of chitosan above pka (~pH 6.5) reduces charge density, and chitosan competes with counterions with the increase in ionic strength, heading towards destabilization [12,14]. It has been reported that pectin imparted good pH and heating stability to zein core–shell nanoparticles, but the endurance for increasing ionic strength was extremely weak [15,16]. Chitosan and pectin could form polyelectrolyte complexes via electrostatic interaction [17], which was used to improve the physiochemical stability of nanoliposome [18]. Therefore, a combination of chitosan and pectin may synergistically and resourcefully bear variation in pH, temperature and counterions.

Quercetin is a flavonoid with antioxidant, anticarcinogenic, antiviral and anti-inflamm atory properties. Its low solubility in water and chemical instability have been addressed through biopolymer-based nano/micro-delivery systems for the application in functional foods [19,20]. In the current work, composite hollow zein particles were fabricated with chitosan-pectin complex coating for the encapsulation and protection of quercetin. The particles were characterized for size, ζ-potential and loading efficiency of quercetin. The lyophilized samples of quercetin-loaded composite particles were analyzed with infrared and X-ray diffraction techniques. Moreover, the particle dispersions were subject to varying pH, ionic strength and temperature conditions to assess physical stability. Finally, the antioxidant activity, photochemical and storage stability of quercetin encapsulated in composite hollow zein particles were examined to judge the protective effects of the particles. This study focused on the fabrication of composite hollow zein particles with improved physical stability and better protective effect on flavonoids through tailoring a complex polysaccharide interfacial layer.


**Abstract**

Nowadays, there is more and more interest in the microbiological resources from different ecosystems, not only because this would allow knowing more about the microbial biodiversity related with these substrata but also because it provides an opportunity to study their characteristics and technological properties which may be of potential interest. This knowledge may allow finding future biotechnological applications for these microorganisms on bio-conservation and reuse of agricultural by-products and may also lead to studies on the improvement of raw material processing. Some raw materials and processing plants in wine and related industries constitute a suitable place for yeast growth; for example, musts, wines in cellars, piquettes, bagasse, pomace, grape skins and yeast lees in the ethanol industry all provide an inexhaustible supply of yeasts. Few microbiological studies have been published so far about the biodiversity of the yeast population in distillery plants. For that reason, the aim of this research was to determine yeast biodiversity and their distribution in different distillery plants in the La Mancha region which are at least 100 years old.

**Keywords:** distilleries, non-*Saccharomyces*, *Saccharomyces* spp., wine by-products, cell vitality, biocontrol


However, we highlight that our estimates should be taken with some caution since they were based on FAO statistical data (apart from Italy) and are referred to 2011. These data could differ to some extent from national statistics or DCF data, which are usually not fully accessible at the GSA level. For instance, Spain reported covering about 70–90% of national landings per assessment area referring to average values 2008– 2010. Such estimate includes species assessed by ICCAT (which were excluded in our analysis). These values are quite different from our estimations referred to 2011 landings (53% in total), even though we considered the same set of species. Moreover, Spain reported that out of the 29 and 27 stocks they selected in relation to GSAs 1–2 and 5–6, only in 22 and 23 stocks indicators were applicable, due to lack of data.

It is worth mentioning that after the initial steps of the MSFD were implemented (early 2013), member states defined monitoring programs to fill the gaps of knowledge that emerged, defined the programmes of measures, and in some cases had already refined the species list to be considered in their assessments. However, different approaches can be identified. For instance, in 2015, Malta increased the number of species to be considered, including taxa not previously considered (e.g., cephalopods). In contrast, in the process of carrying out the monitoring programs, Italy amended some previous definition of GES. In this context, Italy identified commercial species to be considered as "those under Reg. 1967/2006, provided that they belong to G1 and G2 MEDITS species or they are MEDIAS species" (free translation from Decree of the Ministry of Environment of 17 October 2014; Decree 2014; MEDITS: International bottom trawl survey in the Mediterranean; MEDIAS: Mediterranean Acoustic Survey on Small Pelagics). These new selection criteria would sharply reduce the number of stocks considered per assessment area in the forthcoming assessment to 11 stocks, in contrast to the average of 36 stocks that were included in the previous assessment (**Table 3**).

# GES and Environmental Target Setting

Further inconsistencies emerge when considering the definition of GES and ETs by member states. Overall, the definition of GES differed among member states and within subregions in relation to: (i) different interpretations or limited description of which stocks should be considered for GES assessment; (ii) whether to consider MSY-related reference points as targets or limits; and (iii) which shares of stocks should be within safe biological limits to achieve GES. Each of these items would produce different outcomes in terms of GES assessment and requirements to achieve GES. Indeed, applying different criteria for selecting stocks prevents member states from conducting assessments on similar stocks or similar shares of landings. At the same time, using MSY-related reference points as a target allows for the possibility of being above or below the reference point, which is less restrictive than setting the reference point as a limit. In addition, using different criteria to achieve GES in terms of the percentage or number of stocks that must be within safe biological limits would also have implications in the measures to be adopted to achieve GES. In this context, following a strict application of the MSFD criteria and methodological standards would have implied the inclusion of all stocks for which data are collected under the DCF in the assessment, the use of MSYrelated reference points as limits, and the need to have 100% of stocks in safe biological limits to reach GES.

These discrepancies across member states clearly prevented a coherent definition of GES criteria. Moreover, only some countries adopted and defined GES in relation to secondary indicators, particularly for indicators of Criteria 3.3 (population age and size distribution). The latter case could possibly be linked to the lack of agreement on procedures to define reference limits to assess indicators of Criteria 3.3. Indeed, the recent advice proposed by ICES in relation to length-based indicators suggests that related indicators are not fully operational and that additional research will be needed to reach a consensus on defined reference levels (ICES, 2017).

Some member states applied GES estimation considering only assessed stocks, or in some cases applying secondary indicators associated with FMSY and SSBMSY as primary indicators. However, restricting the analysis to only stocks formally assessed under a quantitative stock assessment procedure would clearly restrict the share of landings subjected to GES assessment, especially in the case of the Mediterranean Sea. Indeed, although the number and range of stock assessments have increased in the last decade, the share of landings for which such assessments were available at the time of MSFD implementation ranged between 10 and 30% in three subregions (ISCM, WM, ALS), and up to 60% in the case of the AS.

The application of the Data Collection Regional Framework (DCRF) from GFCM might substantially improve such figure, reaching coverage between 40 and 60% for all subregions in relation to stocks for which assessment will be routinely carried out (GFCM, 2016; A1 list species). If such an approach will be extended to stocks not regularly assessed, such figures will increase to a range of 50–80% depending on the subregion (GFCM, 2016 A2 list species). Levels that are similar (yet different in relation to subregions) should be achieved in the future according to the application of the revised DCF (EU-COM, 2016).

The ETs set by member states might not be considered fully compliant with the MSFD expectations, as in the case of GES definitions. Again, the major reasons for such discrepancies are a lack of clarity on some definitions, a set of targets that are less ambitious than the MSFD objectives, or the reference to policies that were not already established when the targets were defined. Some member states justified the choice of not defining the percentage of stocks for which GES should be achieved by mentioning the intrinsic difficulties derived from ecosystem interactions and environmental fluctuations of having all commercial stocks simultaneously at MSY levels. Indeed, as pointed out by Link (2002), the sum of single species MSY is greater than MSY for the ecosystem, and it is energetically impossible to simultaneously maximize yield for multiple species. This issue was also acknowledged by Borja et al. (2013), who suggested revising the 100% threshold (i.e., all stocks should be in safe biological limits) and applying a lower operational threshold. The definition of such threshold would in turn affect the process of stocks selection moving from single stocks consideration to a proper ecosystem based approach implementation.

# Moving Forward toward the 2018 Assessment and GES Goals for 2020

From our analysis, major inconsistencies among member states in the implementation of the IA and the definition of GES and ETs emerged at Mediterranean level. In contrast, at the national level, coherent approaches were applied in the case of several assessment areas, whether or not being displaced in one or more subregions. This in turn shows that the approaches were not appropriately coordinated at a subregional level as well.

In particular, the use of reference points based on MSY values as targets rather than limits is inconsistent with not only the MSFD criteria and methodological standards (EU-COM, 2010) but also with CFP objectives. However, it is worth mentioning that the latter were defined in 2013 after the MSFD was issued (EU, 2013). This lack of coherence reflected in ETs that are less ambitious than the MSFD policy objectives is likely to have hampered the potential synergies between MSFD and CFP.

As mentioned, member states sharing a marine region or subregion should have cooperated to ensure that the measures required to achieve the objectives of MSFD would have been coherent and coordinated across marine regions or subregions. In particular, existing regional institutional cooperation structures, including those under Regional Sea Conventions, were identified by MSFD as the tool for coordination between member states and other countries whose national waters are comprised within the same region or subregion and then for the enforcement of a regional approach to fishery management between EU member states and non-EU countries.

For this purpose, at the Mediterranean level and in the context of the Barcelona Convention, the UNEP/MAP established the Ecosystem Approach (EcAp) process, as agreed by the Conference of the Parties in 2008 (Decision IG17/6; UNEP, 2008) aiming to achieve GES in the Mediterranean by 2020. This process entails engaging all contracting parties (both EU and non-EU Mediterranean countries) in the definition of GES, related indicators, ecological objectives, and monitoring process. However, as pointed out by Cinnirella et al. (2014), differences between MSFD and EcAp are also evident because the latter has no financial support and applies to all Mediterranean countries. There is thus a high imbalance in terms of the economic development of countries involved compared to EU Mediterranean countries.

The lack of coherence in the MSFD implementation among Mediterranean EU member states (a problem that has emerged also in the context of other EU regions; van Leeuwen et al., 2014) also possibly derives from the difficulties in achieving a consensus among Mediterranean countries on indicators and methodologies to be applied for GES assessment within EcAp. Moreover, as shown by Freire-Gibb et al. (2014), there is uncertainty in the respective roles of different authorities responsible for executing the MSFD (i.e., the European Union, member states and Regional Sea Conventions), particularly in relation to their levels of authority, which might have been a key issue in preventing coordination among member states.

In the context of the Barcelona Convention, there has been a long revision process (that was also triggered by involving GFCM for technical support) of fishery-related ecological objective (i.e., Populations of commercially exploited fish and shellfish are within biologically safe limits; EO3). The definition of indicators as well as technical and data requirements has recently been subjected to strong improvements. Indeed, the 19th Meeting of Contracting Parties (Decision IG.22/7; UNEP, 2016) held in February 2016, adopted the EcAp-based Integrated Monitoring and Assessment Programme (IMAP) of the Mediterranean Sea and Coast and Related Assessment Criteria, for which EO3 (corresponding to MSFD Descriptor 3) is still to be consolidated. However, candidate indicators have been defined and include: SSB, total landings, F, fishing effort, catch per unit of effort or landing per unit of effort as a proxy, and bycatch of vulnerable and non-target species (UNEP, 2016). The involvement of GFCM in the definition of target species, fishing-related GES, common indicators, and ecological objectives has strengthened the coherence between EcAp-IMAP and MSFD objectives for Descriptor 3, even if there are still some differences in the defined process. In particular, no secondary indicators have been defined in relation to fishing pressure and SSB. However, the EO3 definition is now benefiting from the enforcement of the GFCM Data Collection Regional Framework (GFCM, 2016), which should boost data availability in the future in parallel to the new DCF (EU-COM, 2016).

The definition of stocks and data availability is only a part of the process to achieve regional and subregional coherence in GES assessment for Descriptor 3. Indeed, in our analyses, we did not consider methodological approaches adopted to assess indicators based on time-series and to aggregate information from multiple indicators and criteria from assessment areas to the national and subregional level. For the first item, many approaches could be applied (e.g., Spearman rank correlation, linear regressions, etc.; ICES, 2014b), and a regional coherence in the approach would be needed to ensure consistency. Coherence is also needed in regard to aggregation methods. As shown by Borja et al. (2014), the vast range of methods could result in inconsistent outcomes.

## The New Scenario Arising from the Recent Revision of Criteria and Methodological Standards for GES

On May 17, 2017, the Commission Decision (EU) 2017/848 (EU-COM, 2017) was issued as an update of the former decision on criteria and methodological standards on GES of marine waters. This decision is aimed at improving the consistency of methodological approaches in relation to GES assessment. In relation to Descriptor 3 and when considering the Mediterranean subregion (Annex, Part I, EU-COM, 2017), several elements emerge in relation to the main issues we identified, i.e., the spatial scale, selection of stocks, interpretation of reference points, use of trend-based indicators, and criteria for the aggregation of information from several stocks.

In regard to the spatial scale, the Commission Decision states that "populations of each species are assessed at ecologically relevant scales within each region or sub-region, as established by appropriate scientific bodies referred to in Article 26 of Regulation (EU) No. 1380/2013 based on specified aggregations of GFCM geo-graphical sub-areas" (EU-COM, 2017). This statement clarifies that GSA aggregations could be considered and also assigns a role to the STECF in the definition of the appropriate spatial scale to be considered.

In relation to the selection of stocks to be included in GES assessment, "Member States shall establish through regional or subregional cooperation a list of commercially exploited fish and shellfish," (. . . ) taking into account Council Regulation (EC) No. 199/2008, "all stocks that are managed under Regulation (EU) No. 1380/2013; the species for which minimum conservation reference sizes are set under Regulation (EC) No. 1967/2006; the species under multiannual plans according to Article 9 of Regulation (EU) No. 1380/2013; the species under national management plans according to Article 19 of Regulation (EC) No. 1967/2006; any important species on a regional or national scale for small-scale/local coastal fisheries," among others (EU-COM, 2017). This requirement should foster an increase in the consistency of stock selection for GES assessment within the Mediterranean Region and subregions. In this context, the role of the Barcelona Convention and GFCM will be essential to ensure that consistency will be achieved. However, the lack of clear specifications of a minimum requirement (e.g., % of landings, the number of common stocks) does not allow for current inference of how many stocks will be considered.

All three criteria (F, SSB, and age-size distribution) shall be considered, although it is recognized that data for age-size distribution might be not available for the 2018 assessment. Given the lack of consolidated reference points for related indicators, this condition will most likely result in an unbalanced application of this criterion among member states. Reference levels of F and SSB are mentioned as limits. Moreover, "In relation to stocks managed under a multiannual plan according to Article 9 of Regulation (EU) No. 1380/2013, in situations of mixed fisheries, the target F and the biomass levels capable of producing MSY shall be in accordance with the relevant multiannual plan" (EU-COM, 2017). This definition will increase consistency in the GES assessment for stocks for which analytical assessment is available, since the use of reference points as targets should not be an option. Moreover, it will increase the alignment with management plans established under the CFP. However, regarding stocks for which secondary indicators (i.e., catch/biomass ratio, and biomass related indexes) will be considered, "An appropriate method for trend analysis shall be adopted (e.g., the current value can be compared to the long-term historical average)." We highlight that without an agreed common analytical approach at the regional level for the application of trend analyses, high inconsistency is expected in the outcomes of the assessment of stock status evaluation.

Finally, the Commission Decision states that "the extent to which GES has been achieved shall be expressed for each area assessed as follows: (a) the populations assessed, the values achieved for each criterion and whether the levels for D3C1 and D3C2 and the threshold values for D3C3 have been achieved, and the overall status of the population on the basis of criteria integration rules agreed at Union level" (EU-COM, 2017). The criteria integration rules defined at the Union level are not yet specified, including in relation to methods of integration from assessment areas to subregional and regional levels (Zampoukas et al., 2014). Again, if no common agreement on the approach is achieved, it will prevent a consistent GES assessment at the Mediterranean level.

# CONCLUSIONS

We analyzed and compared the approaches applied by EU Mediterranean member states in the early phases of the implementation of the MSFD in relation to commercial fisheries. What emerged is a lack of consistency in the selection of stocks, application of reference points, and definition of GES and ETs. MSFD criteria and methodological standards were applied with different interpretations across member states, showing that subregional and regional coordination was not effectively enforced. Moreover, only a partial use of potentially available data for GES assessment was identified, while new frameworks in relation to data collection (both at the EU and GFCM levels) suggest an increase in data availability for GES assessment for the future.

The recently reformed Commission Decision on criteria and methodological standards for GES (EU-COM) supports a more coherent approach to be applied in the forthcoming assessment of GES, which would also foster better coherence with the reformed CFP. However, several elements that could determine the uneven application of MSFD are still not completely clarified, particularly stock selection and criteria for the integration of GES assessment from stocks to assessment areas and subregions, as well as the methodological approach to the use of secondary indicators. The definition of a common, regional, and subregional approach is given to relevant regional and subregional cooperation bodies. Thus, their capability of defining and agreeing on a common, structured approach will be essential to ensure an even application of the MSFD in relation to commercial fisheries. However, since the next GES assessment will need to be carried out by 2018, there is an urgent need to implement such a process in the short term, and we hope this research will add to this framework.

Achieving consistency in MSFD implementation should also foster an improvement of stocks status in the Mediterranean region, which is lagging behind in comparison to the Northern-Atlantic countries in terms of tangible results (Cardinale and Scarcella, 2017). Ensuring that MSFD and CFP policies will be applied with the needed consistency at the pan-European level requires increased cooperation among scientists and member states from Mediterranean countries within GFCM and the Barcelona Convention, and collaboration between these institutions, ICES, other Regional Sea Conventions, and STECF/SGMED (Freire-Gibb et al., 2014; van Leeuwen et al., 2014).

Current data of F (Cardinale and Scarcella, 2017) suggest a low probability of reaching GES in the short term in the

### REFERENCES

Mediterranean. Beyond the technical issues associated with GES definition and assessment, reaching this goal will also need better coordination among member states and other countries in relation to the definition of the programmers of measures, since the Mediterranean Sea is typically characterized by shared stocks (e.g., in the Adriatic Sea and Strait of Sicily). This is another complexity that adds to the multispecificity of fishing activities, the relevance of small-scale fisheries, and the political diversity of the area.

# AUTHOR CONTRIBUTIONS

SR conceived the work. SR, PB, and TF collected data. TF and SR performed the analysis. All the authors wrote and revised the paper.

### ACKNOWLEDGMENTS

This research benefited from the experience of the authors obtained in the framework of ISPRA activities in relation to MSFD implementation. This research activity was partially supported by POR project in relation to fishery co-management. The definition of its goals benefited from the participation to several ICES WGs which was supported to SR as invited expert by ICES, which is gratefully acknowledged. We thank the reviewers for their insightful comments on the paper, which allowed us to improve the manuscript.

### SUPPLEMENTARY MATERIAL

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fmars. 2017.00316/full#supplementary-material

and Repealing Council Regulations (EC) No 2371/2002 and (EC) No 639/2004 and Council Decision 2004/585/EC Official Journal of the European Union (Brussels).

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2017 Raicevich, Battaglia, Fortibuoni, Romeo, Giovanardi and Andaloro. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

# Corrigendum: Mediterranean Sea: A Failure of the European Fisheries Management System

### Frontiers Editorial Office\*

Frontiers Media S.A., Lausanne, Switzerland

Keywords: Mediterranean, common fishery policy, management, effort, failure

### **A commentary on**

### Edited and reviewed by:

Frontiers in Marine Science Editorial Office, Frontiers, Switzerland

> \*Correspondence: Frontiers Editorial Office<EMAIL_ADDRESS>
### Specialty section:

This article was submitted to Marine Affairs and Policy, a section of the journal Frontiers in Marine Science

Received: 25 April 2018 Accepted: 26 April 2018 Published: 04 June 2018

### Citation:

Frontiers Editorial Office (2018) Corrigendum: Mediterranean Sea: A Failure of the European Fisheries Management System. Front. Mar. Sci. 5:169. doi: 10.3389/fmars.2018.00169 **Mediterranean Sea: A Failure of the European Fisheries Management System** by Cardinale, M., and Scarcella, G. (2017). Front. Mar. Sci. 4:72. doi: 10.3389/fmars.2017.00072

Following an investigation by the European Commission's Joint Research Center, it was found that Dr. Giacomo Chato Osio meets the criteria to be listed as an author on this manuscript. The authorship list is therefore updated to be:

Massimiliano Cardinale1<sup>∗</sup> , Giacomo Chato Osio<sup>2</sup> and Giuseppe Scarcella<sup>3</sup>

<sup>1</sup>Department of Aquatic Resources, Marine Research Institute, Swedish University of Agricultural Sciences, Lysekil, Sweden

<sup>2</sup>Directorate D - Sustainable Resources, Unit D.02 Water and Marine Resources, European Commission Joint Research Centre (JRC), Ispra, Italy

3 Institute of Marine Sciences of the Italian National Research Council, Ancona, Italy<EMAIL_ADDRESS>
The original article has been updated.

**Conflict of Interest Statement:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2018 Frontiers Editorial Office. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.


**1. Introduction**

Somma-Vesuvius volcano has shaded many volcanological avenues since the two letters of Pliny the Younger to Tacitus [1]. He described the dynamism of the Pompeii Plinian eruption. Since then, Somma-Vesuvius has utterly been studied by many earth scientists worldwide who have increased the knowledge of the volcano. Today, Somma-Vesuvius is the best studied and monitored volcano in the world. The volcano is very much known about its volcano stratigraphy and by the chemistry of the volcanic products as well as by the physical architecture of the volcano. Anyhow, it is little known how the population feel about the impact of the hazardous volcanic eruptions [2–6]. To envisage different volcanic scenarios is a must in order to help the population around Vesuvius to better understand the type of next eruption that will impact on the region nearby Somma-Vesuvius. A simplified scheme of AD 79 eruption related to all the volcanic activity of a such destructive volcano can shed

light and ease the Neapolitan population that live around Somma-Vesuvius in case of future Plinian eruption. This simplified review on an open access international journal can also be available for students and general population and help high school students to understand the hazard of Somma-Vesuvius and to discuss this issue with their family.


*2.1. General Measures*

In combination with initial systemic stabilization (i.e., protection of circulatory and respiratory status) and start of intravenous proton pump inhibitors (PPIs), as in any patient hospitalized with upper GI bleeding, specific nuances in the management of patients with cirrhosis include a *restrictive* transfusion strategy and the use of prophylactic antibiotic therapy [5–8]. Additional measures include management of both coagulopathy and therapy with PPIs. For patients with alcohol-related liver disease, immediate and sustained cessation of alcohol consumption is particularly important to improve liver function and reduce risks of further bleeding, decompensation and mortality by reducing liver damage and portal pressure [9].

#### 2.1.1. Blood Transfusion Strategy

The main driver for development of esophageal VH is clinically significant portal hypertension [10]. In a way, the acute loss of intravascular volume due to bleeding reduces splanchnic pressure and may lead to self-limitation or self-interruption of active hemorrhage. By contrast, a sudden restitution of intravascular volume is associated with a rebound increase in portal pressure, which in turn may lead to failure to control bleeding and/or early rebleeding [11]. In a seminal randomized control trial (RCT), a "restrictive" transfusion strategy (hemoglobin threshold for transfusion of 7 g/dL with target range of 7–9 g/dL) was associated with a significantly higher probability of survival compared with a "liberal" strategy (hemoglobin threshold for transfusion of 9 g/dL with target range of 9–11 g/dL) [12]. Therefore, current guidelines recommend initiating transfusions in cirrhosis when hemoglobin levels decrease to <7 g/dL, with a target level of 7–9 g/dL [5–8].

Restitution of intravascular volume should be managed with large peripheral lines (16–18 gauges), and blood loss has to be replaced by red blood packed cells [8]. Replacement of fluids and electrolytes is important to prevent pre-renal acute kidney injury, which is common in cirrhosis with GI bleeding and is associated with increased mortality [13]. Nephrotoxic drugs such as nonsteroidal anti-inflammatory drugs, non-selective betablockers (NSBBs), and other hypotensive drugs may be suspended during the acute course of VH [6]. As occurrence of acute decompensation may be associated with instability in the feeble hemostatic balance of decompensated cirrhosis, the need for invasive procedures should be evaluated carefully on an individual basis. As discussed below, clotting factors may be replaced only to correct an eventual dilutional coagulopathy, whereas there is no indication to prophylactically correct a prolonged prothrombin time or a low platelet count [5–8].

#### 2.1.2. Antibiotic Prophylaxis

Bacterial infections are observed in up to 50% patients with cirrhosis hospitalized for GI bleeding, and are associated with strong risks of failure to control bleeding, early re-bleeding and mortality [14–16]. A recent meta-analysis including 12 studies comparing antibiotic prophylaxis vs. either placebo or no intervention demonstrated that the administration of prophylactic antibiotics was associated with reduced all-cause mortality (relative risk (RR): 0.79, 95% CI: 0.63–0.98), infection-driven mortality (RR: 0.43, 95% CI: 0.19–0.97), risk of bacterial infection (RR: 0.35, 95% CI: 0.26–0.47), rebleeding (RR: 0.53, 95% CI: 0.38–0.74), and length of stay (mean difference −1.9 days, 95% CI: −3.8–0.02) [17]. Therefore, a timely, short-term course of prophylactic antibiotics is an important step in the management of patients with cirrhosis and VH, and shall be instituted as early as possible upon admission, before upper endoscopy [5–8].

Whether severity of cirrhosis affects the importance of prophylaxis is unclear. In fact, while the role of prophylaxis is incontrovertible in patients with most advanced liver dysfunction (Child B and C), in those with less advanced liver disease conflicting data have been reported. In one retrospective analysis, Child A patients had lower risks of infection in the absence of prophylaxis (2%), and no difference in mortality was observed in treated vs. non treated patients [18]. The same study showed that the use of antibiotics was associated with a substantial reduction in mortality in Child C class [18]. However, prospective data are required to evaluate whether antibiotic prophylaxis can be avoided in Child A and current recommendation is to administer prophylaxis in all patients with cirrhosis presenting with VH, independent of child [5–8].

Intravenous ceftriaxone (1 g/24 h) for 7 days is the first choice in patients belonging to Child B and C classes, in those who were on quinolone prophylaxis, and in hospitals in which there is a high frequency of quinolone-resistant bacteria. Norfloxacin 400 mg twice daily may be used in the other patients. However, due to widespread quinolone resistance, ceftriaxone (a third-generation cephalosporin) has become the antibiotic of choice [5–7]. As approximately 30% of infection are from multidrug resistance antibiotics bacteria [19], evaluation of local resistance, if doable, may further improve definition of antibiotic regimen and should be considered [8]. Prophylactic antibiotics should be administered for a maximum of seven days, and their use should not be extended after discharge from the hospital [5–7]. In patients discharged before Day 7, transition to an oral antibiotic with the goal of completing seven days of treatment may be considered [8].

In a recent, nationwide study from Spain including 1656 patients with cirrhosis hospitalized for VH between 2013 and 2015, Martinez et al. investigated current epidemiology and trends of bacterial infections in these patients [20]. Interestingly, despite prophylaxis as currently recommended by international guidelines [5–7], 20% of patients developed bacterial infections, particularly respiratory tract infection. Development of infection was observed early (median time from admission 3 days) and was independently associated with Child C class (odds ratio (OR): 3.1; 95% CI: 1.4–6.7), Grade III–IV encephalopathy at admission (OR: 2.8; 95% CI: 1.8–4.4), orotracheal intubation for endoscopy (OR: 2.6; 95% CI: 1.8–3.8), and placement of nasogastric tube/balloon tamponade (OR: 1.7; 95% CI: 1.2–2.4 and 2.4; 95% CI: 1.2–4.9, respectively) [20]. Such procedures should, therefore, be minimized whenever possible, particularly in patients with additional risk factors, and active screening for respiratory infections shall be performed in case of early clinical deterioration. Whether patients at risk for respiratory infection would benefit from tailored regiments of antibiotic prophylaxis, particularly in settings with high risk of resistant strains bacteria, it remains to be evaluated in further studies.


**7. Final considerations**

PDT is a noninvasive technique, with few potential adverse reactions, that presents good curative rates and excellent cosmetic outcome. It may be chosen as a first option for patients with small lesions of nonmelanoma skin cancer, especially the ones in complex sites for surgical ressection or in high risk patients.

PDT protocols and customized dosimetry for each target skin lesion still need to be defined. The development of new PDT drugs and delivery systems has the potential of increasing the curative rates of the present protocols. Instrumentation of light sources designed to adapt the emission geometry to the anatomical site characteristics is also important to improve PDT performance in cancer treatment.

The local treatment of infected lesions and cosmetics are PDT indications that have been fastly increasing. New protocols and drugs have been investigated, as well as new light devices developed, making PDT in Dermatology an exciting and growing field.


**About the Editor**

## **Yasemin D. Aktas**

A structural/conservation engineer by training, Yasemin is currently a lecturer at the Engineering and Architectural Design course jointly developed between Civil, Environmental and Geomatic Engineering (CEGE), Bartlett School of Architecture and Bartlett Institute of Environmental Design and Engineering, teaching sustainable building design and adaptive reuse. She is also the deputy academic director of the UK Centre for Moisture in Buildings (UKCMB). Her research interests include climate induced hazards and their mitigation, urban climate modelling, the impact of built environment on the urban microclimate, interrelations between climatic and geophysical hazards, and physical vulnerability to climatic impact with specific emphasis on heritage materials and building envelopes.


**4. Changing landscape in the treatment of CAD**

discussion of a hybrid approach with MIDCAB for the LAD and PCI of the other vessels. However, the evidence supporting this approach is still limited; the most recent European Society of Cardiology (ESC) Guidelines give a *Class IIb recommendation* to this approach *(Level of Evidence B) for those "patients with conditions likely to prevent healing after sternotomy"* [26]. This approach does have significant promise and further research is required before it is adopted

**3.5. Evidence of survival benefit for revascularization in stable ischemic heart disease**

The current framework for patient selection in treatment strategy for MVD is largely shaped by early studies comparing medical therapy and CABG. This body of evidence has been best synthesized by a meta-analysis performed by Yusuf et al in the Lancet in 1994 [27]. This metaanalysis was an individual patient data analysis of 2549 patients derived from three large randomized controlled trials, the Coronary Artery Surgery Study (CASS), Veterans Adminis‐ tration (VA) study and the European Coronary Surgery Study (ECSS) as well as four other smaller randomized studies [27]. The population studied consisted of patients with stable symptomatic coronary artery disease of a wide spectrum of severity [27]. However, only 10 percent were single vessel disease (1VD); the remainder consisted of MVD with 59.4% affecting

**Figure 1.** Survival curve for medical therapy versus coronary artery bypass grafting (CABG). Reproduced with permis‐

on a population level.

the proximal LAD [27].

sion from Yusuf S. et al. Lancet 1994. 344;8922:563-568

**(SIHD)**

320 Artery Bypass

Many of the earlier studies comparing surgical revascularization with medical therapy was during a period in cardiology where the BB and nitrates were the mainstay of medical therapy. Although antiplatelets were available, these were only taken by approximately 20% of the patients at the time [27]. It may hence be important to interpret these results in the context of current medical practice, which include contemporary treatments (standard secondary prevention with antiplatelets, statin therapy, BB and ACEi) that have all made further advancements in the survival and prognosis of patients with CAD [7].

ASA for secondary prevention has an estimated RRR of 18 percent in total serious vascular events (including stroke and major coronary event) with an **annual ARR of 1.5 percent**; the decrease in major coronary event (non-fatal myocardial infarction (MI) and cardiovascular death) is estimated at **annual ARR of 1.0 percent** [29]. As an adjunctive antiplatelet clopidogrel has further reduced death from cardiovascular causes, non-fatal MI and stroke in patients with Non ST elevation acute coronary syndromes (NSTEACS) with an **ARR of 2.1 percent**[30]. Most recently, newer agents such as prasugrel and ticagralor have both shown benefit compared to clopidogrel in patients with acute coronary syndromes (ACS). Prasugrel compared with clopidogrel in PCI treated ACS has demonstrated an **ARR of 2.2 percent** with regards to death from cardiovascular causes, nonfatal MI or non-fatal stroke over the 6-15 month follow up period [31]. Ticagralor has shown similar reduction in the same composite endpoint in patients with ACS over clopidogrel with an **ARR of 1.9 percent** [32]. In addition, ticagralor also showed an overall **reduction in all cause mortality with an ARR of 1.4 percent** [32].

BB's have a longstanding history in the management of CAD [7]. Although BB's can be used in patients post-MI with a normal ejection fraction (EF), the evidence for this is not as strong as that for those with significant Left Ventricular (LV) dysfunction [8]. It was previously shown that Carvedilol compared with placebo in patients with chronic heart failure (HF) and severe LV dysfunction (average EF 22-23 percent**) reduces all cause mortality with an ARR of 4.6 percent** [33].

The introduction of 3-hydroxyl-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors otherwise known as the "statins," has significantly improved the care of patients with coronary artery disease [34, 35]. Simvastatin 40mg orally daily compared to placebo in patients with known vascular disease was shown in the Heart Protection Study (HPS) to *reduce all cause mortality with an ARR of 1.8 percent* over a five year period [34]. This was paralleled with a **reduction of coronary death with an ARR 1.2%** [34].

[**0.23 95% CI 0.13-0.41) and [0.35, 95% CI 0.17-0.69]** respectively [24]. Finally, compared to even the zotarolimus second generation DES, the CoCr EES still demonstrated a robust reduction

Multivessel Disease in the Modern Era of Percutaneous Coronary Intervention

http://dx.doi.org/10.5772/55103

323

There have been numerous randomized studies comparing PCI with surgical revasculariza‐ tion in MVD. A recent systematic review including 10 major trials over and the individual data from over 7800 patients found similar mortality in patients treated with CABG (15%) compared to patients treated with angioplasty (16%) over median survival of 5.9 years (p=0.12) [45]. There was, however a significantly lower rate of death or repeat revascularization in those treated with CABG (9.9%) compared with those treated with PCI (24.5%) [45]. This suggests that in fact the major benefit seen in CABG over PCI in this comparison is a lower need for repeat revascularization and is paralleled by a lower incidence of angina in the CABG group (14%) compared to the PCI group (26%) at one year (p<0.0001) [45]. The major caveat to this data is that stenting (which is known to reduce restenosis rates) only represented 37 percent of the

Subgroup analysis revealed that patients with diabetes have overall *better survival* when treated with surgical revascularization than when treated with angioplasty **with an ARR of 7.7% over 5 years** [45]. More definitive data supporting the use of CABG in patients with diabetes will be presented in *Section 6.2.* Interestingly, there was also a graded age interaction that was significant (p=0.002) [45]. For patients younger than 55 years of age, mortality was lower with PCI (8%) than CABG (10%). In patients between ages 55-64, PCI and CABG had similar mortality rates at 15 and 14 percent respectively [45]. And for patients older than 65 years of age, CABG had a lower overall mortality (20%) compared with PCI (24%) [45]. Prior to this study, this interaction had not been previously reported and we can only speculate whether

Other subgroups did not prove to contribute any significant interaction to the overall treatment effect [45]. Six of the trials included had POBA as the main mode of PCI whereas four trials used BMS; neither of these groups had significantly different survival rates when compared with surgery [45]. There was no overall interaction contributed by the presence/absence of proximal LAD disease, 3VD, abnormal LV function, previous MI or unstable symptoms [45].

LV function has never been shown to have a significant interaction with mode of revasculari‐ zation (PCI versus CABG) with regard to survival. In fact, the majority of studies comparing PCI with CABG enrolled a low percentage of patients with abnormal LV function *(20 percent or less)* [45]. However, it has been considered an important variable that favors revasculariza‐ tion with surgery due to historical data showing that patients with significant LV dysfunction

**6. Factors favoring surgery as the mode of revascularization**

in stent thrombosis with an OR **[0.21, 95% CI 0.17-0.69]** at one year [24].

**5. PCI versus CABG in SIHD**

total angioplasty group [45].

the effect is a true function of age.

**6.1. LV dysfunction**

ACEi's have also been established to have a significant benefit towards long-term cardiovas‐ cular outcomes. It was shown in the Heart Outcomes Prevention Evaluation Study that in highrisk patients (vascular disease or diabetes plus one other risk factor) Ramipril compared with Placebo provides a *relative risk reduction* in myocardial infarction, stroke and death from cardiovascular causes of *21 percent* and *ARR of 3.8 percent* [36] over the mean follow up period of 5 years. There was also a *reduction in all cause death with an ARR of 1.8 percent* [36].

Concurrently, there was the advent and evolution of percutaneous approaches to revascula‐ rization. The first generation of angioplasty that truly adopted popular practice involved serial balloon inflations at the site of stenoses restore normal flow dynamics down the conducting epicardial vessels [6]. This approach, although promising was limited by a high rate of restenoses as a result of localized vascular recoil and epithelial hyperplasia [20, 37]. The bare metal stents (BMS) were created as a scaffolding technique that limited the degree of recoil but still faced significant re-stenosis rates due to mediated by injury to the medial layer, increased inflammation resulting from stent strut penetration into the lipid core and ultimately neoin‐ timal growth [38].

Pacitaxel and Sirolimus DES were developed in the next phase to overcome the challenge of restenosis requiring repeat intervention [20]. Although there was no difference in mortality or rates of myocardial infarction seen with DES compared with BMS, there were considerable reductions in restenosis rates with an estimated RRR of 0.44 [21, 22, 39-41].

Early enthusiasm for the use of drug eluting stents was curbed by a significantly higher rate of stent thrombosis, particularly in the face of an initially shorter duration (6 months) of dual antiplatelet therapy (DAPT) [22, 42, 43]. Currently the American College of Cardiology/ American Heart Association (ACC/AHA) recommends at least *12 months of DAPT* in patients receiving DES for non-ACS indication and *12 months of DAPT* for ACS indication regardless of the stent type (BMS or DES) *(Class I recommendation, Level B evidence)* [14].

The most recent development in stent technology has been the introduction of secondgeneration (everolimus and zotarolimus) drug eluting stents. A large Swedish registry observational study containing 94, 384 patients demonstrated the advantage of the secondgeneration stents over its predecessors (first generation DES and BMS) both in terms of *restenosis* and *definite stent thrombosis* [44]. The second generation DES in this study was shown to have lower risk of restenosis compared with both BMS and the first generation DES with **Hazard Ratios (HR**) of **[0.29, 95% confidence interval (CI) 0.25-0.33]** and **[0.62, CI: 0.53 -0.72]** respectively [44]. The Cobalt Chromium Everolimus eluting stents (CoCr EES) have shown the most promise in reducing stent thrombosis. In a recent network meta-analysis of 50844 patients, the CoCr EES was shown to have a lower rate of 1 year definite stent thrombosis compared to both paclitaxel DES and sirolimus DES with odds ratio (OR) of **[0.41 95% CI 0.24-0.70]** and **[0.28 95% CI 0.16-0.48]** respectively [24]. The CoCr EES also had a lower rate of definite stent thrombosis compared with BMS at 1 year and 2 years with an odds ratio [OR] of [**0.23 95% CI 0.13-0.41) and [0.35, 95% CI 0.17-0.69]** respectively [24]. Finally, compared to even the zotarolimus second generation DES, the CoCr EES still demonstrated a robust reduction in stent thrombosis with an OR **[0.21, 95% CI 0.17-0.69]** at one year [24].