*Editorial* **Special Issue "New Therapies of Liver Diseases"**

**Pierluigi Toniutto**

Hepatology and Liver Transplantation Unit, Academic Hospital, University of Udine, 33100 Udine, Italy<EMAIL_ADDRESS>
Medical and surgical treatments aimed at curing severe liver diseases and prolonging the survival of patients have improved dramatically in recent years. These advances have mainly been achieved by obtaining a better understanding of the pathophysiology of liver diseases [1]. New and old pharmacological therapies have been applied in a better way based on the new insights obtained in the pathophysiological studies. Moreover, the increased application of technology innovations, both in diagnostic imaging [2] and in surgery [3], enable the cure rate to be increased in patients with advanced liver diseases.

A Special Issue in the *Journal of Clinical Medicine (JCM)* has been dedicated to collecting high-quality scientific contributions from leading experts by focusing on updating the horizon of new pharmacological therapies and new surgical approaches that can be applied to cure several types of liver diseases as a method to address this challenging topic in greater detail.

Two studies investigated the current and future management of cholestatic liver diseases [4,5]. The first study retrospectively evaluated the real-world clinical management of patients with primary biliary cholangitis (PBC), according to the indications of the recent updated clinical guidelines. A study conducted in a large cohort of European patients revealed that biochemical response rates adopting the standard first-line treatment with ursodeoxycholic acid (UDCA) were achieved in a large proportion of patients, depending on the response criteria adopted. In UDCA nonresponders, second-line treatment regimens in which obeticholic acid or bezafibrate were added were promptly applied, leading to significantly increased response rates. These results confirm in real clinical practice that UDCA first-line standard treatment is largely effective in patients with PBC, but highlight the need to detect high-risk patients with an insufficient response to UDCA early in life, since early treatment modification significantly increases subsequent response rates. In addition to obeticholic acid and fibrates, several other molecules are currently under evaluation as potential new therapies both for patients with PBC and with primary sclerosing cholangitis (PSC). This issue has been extensively discussed in a subsequent study [5]. Given the complex nature of PBC and PSC, future treatments for these diseases will probably be based on a combination of drugs, aimed at influencing specific pathophysiological mechanisms in different stages of disease severity.

The current therapeutic strategies for the management of patients with cirrhosis are focused on the prevention or treatment of specific clinical complications such as ascites, gastrointestinal bleeding and hepatic encephalopathy [6]. "Etiologic therapy", which is designed to remove the causative agents of the disease (i.e., viruses or alcohol), prevents clinical decompensation in most patients with cirrhosis. In contrast, a significant proportion of patients with decompensated cirrhosis remain at risk of further disease progression despite the application of etiologic treatments. Thus, the identification of new therapies targeting specific key points in the complex pathophysiological cascade of decompensated cirrhosis is urgently needed. These therapies are presented in updated detail in this Special Issue of *JCM* [7]. Poorly absorbable oral antibiotics, statins, and albumin have been proposed as potential disease-modifying agents for cirrhosis (DMAC), since clinical studies have shown their capacity to prolong survival. The ideal DMACs candidate should be

**Citation:** Toniutto, P. Special Issue "New Therapies of Liver Diseases". *J. Clin. Med.* **2022**, *11*, 1798. https:// doi.org/10.3390/jcm11071798

Received: 17 March 2022 Accepted: 19 March 2022 Published: 24 March 2022

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

**Copyright:** © 2022 by the author. 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/).

directed to modify the key mechanisms in the pathogenetic network of the gut-liver axis, such systemic inflammation, and immune dysfunction.

The development of ascites is one of the typical complications of advanced cirrhosis. Treatment of non-tense ascites comprises the assumption of a combination of furosemide and anti-aldosterone diuretics, accompanied by a restrictive sodium and water diet [6]. Tolvaptan, a selective vasopressin type 2 receptor antagonist, was approved in some countries for treating ascites in patients who responded insufficiently to conventional diuretics. Several still unresolved questions persist regarding both the long-term efficacy of tolvaptan and its effect on the survival of patients with cirrhotic ascites. A recent Japanese retrospective study presented in this issue of *JCM* seems to show that the addition of tolvaptan prolongs the survival of patients with cirrhotic ascites compared to standard diuretic drug combination alone, especially when tolvaptan is started before high-dose furosemide administration [8]. Although these results are encouraging, further prospective studies in different countries must be performed to standardize the use of aquaretic drugs in treating cirrhotic ascites.

More challenging is the treatment of ascites when it reaches the stage of refractoriness. An updated and exhaustive analysis of this topic has been reported in this issue of *JCM*, including the more recent data regarding the placement of a transjugular intrahepatic portosystemic shunt (TIPS) and chronic albumin administration [9]. TIPS reduces portal hypertension, allows greater control of ascites, and in some cases improves the clinical course of the disease. Some concerns persist regarding both the correct selection of patients with ascites who may truly benefit from TIPS and the prevention of cardiac and neurologic complications after TIPS placement in the long term. The effect of long-term human albumin administration in treating grade 2–3 ascites has been studied in the ANSWER [10] and MATCH [11] randomized clinical trials, producing contradictory results. The different results might be at least partially explained by differences in disease severity of the patients enrolled (slightly less severe in the ANSWER trial) and dosage and duration of albumin treatment (higher and longer, respectively, in the ANSWER trial). Regardless, the longterm albumin administration in patients with persistent ascites remains not systematically used in various parts of the world, despite proved effectiveness both in ascites control and long-term survival. The placement of implantable ascites drainage devices has been experimented with contradictory results. To date, there is no clear indication to use these devices except as part of controlled clinical trials.

In addition to ascites, gastrointestinal bleeding and the development of hepatic encephalopathy (HE) represent the other key determinants of the transition from clinically compensated to decompensated liver cirrhosis. Two contributions to the present issue of *JCM* are devoted to exploring these clinical complications of cirrhosis. The most recent advances in the management of esophageal variceal hemorrhage in cirrhotic patients have been updated [12]. These guidelines were derived from the applications of specific treatment algorithms involving the use of indirect measurement of portal pressure (HVPG) and the rescue placement of TIPS, in addition to vasoconstrictors, endoscopic band ligation of esophageal varices and antibiotic prophylaxis. Patients who may benefit more from early rescue TIPS placement are active bleeders with poor predictors of the response to standard medical treatment (Child C class, portal vein thrombosis, HVPG > 20 mmHg, and systolic blood pressure < 100 mmHg at admission). Although the use of preemptive TIPS in these patients has been recommended since the Baveno V consensus [13], only a minority of potential candidates finally undergo a preemptive TIPS. This finding indicates that preemptive TIPS is largely underutilized in real-life practice. This is a topic where it is probably necessary to implement scientific information in the community of hepatologists, in order not to lose the clinical and survival advantages that the correct indication of the positioning of the preemptive TIPS can bring to patients.

HE in cirrhosis has profound implications in terms of the patients' ability to fulfil their family and social roles, to drive and to provide for themselves. The past few years have been characterized by significantly more attention to HE and its implications. Its definition has been refined, and a small number of new drugs or alternative management strategies have become available, while others are underway [14]. Currently, overt HE is generally managed by the correction of any identified precipitating factors and institution of ammonia-lowering treatment with nonabsorbable disaccharides and nonabsorbable antibiotics [15]. Many therapies other than nonabsorbable disaccharides and nonabsorbable antibiotics have been studied. Among them, L-Ornithine L-Aspartate (LOLA), which is a substrate for the urea cycle and increases urea production in peri-portal hepatocytes, has been extensively studied. Despite promising results, a recent review and meta-analysis suggests that the effect of LOLA is comparable to other ammonia-lowering agents in treating HE regardless of clinical severity. The use of nonurea nitrogen scavengers (sodium benzoate, sodium, glycerol phenylbutyrate, and ornithine phenylacetate) has not been shown to be superior to placebo or to standard treatment in clinically improving HE. Muscle loss impacts nitrogen and ammonia metabolism and is associated with an increased risk of HE. Thus, the maintenance of adequate daily energy (35–40 kcal/kg ideal body weight) and protein intake (1.2–1.5 g/kg ideal body weight) has been associated with the improvement of psychometric performance and quality of life and with the reduction in the risk of overt HE development. In addition to small meals consumed throughout the day, a late evening snack comprising complex carbohydrates should be strongly recommended, as they reduce protein catabolism and interrupt the long fast between dinner and breakfast. The postulated efficacy of branched chain amino acids (BCAAs) administration in treating HE is probably a surrogate for an increase in the intake of proteins containing BCAAs, particularly in patients consuming vegetable diets.

If the development of ascites, gastrointestinal bleeding, HE or any combination of these conditions are the distinct features of acute decompensation of liver cirrhosis, acuteon-chronic liver failure (ACLF) is a distinct syndrome that develops in patients with acutely decompensated chronic liver disease and is characterized by a high 28-day mortality rate. Thus, a special article dedicated to ACLF has been presented in this issue of *JCM* [16]. The key elements identifying the appearance of ACLF are the strong association with precipitating factor(s), the development of single- or multiple organ failures (OFs) and an intense systemic inflammation. Excessive inflammation is responsible for tissue damage and for necrotic cell death, leading to the release of damage-associated molecular patterns (DAMPs) that maintain inflammation by binding to pattern-recognition receptors (PRRs). Although many of the pathophysiological mechanisms responsible for the development of ACLF have been elucidated, additional knowledge is needed to develop treatments besides supportive measures for OFs. To date, early liver transplantation (LT) produces good outcomes in a subset of patients presenting grade 3 ACLF, thus these patients must be early referred to a liver transplant center to verify the feasibility of liver transplant.

Due to the availability of direct antiviral agents (DAAs) for curing hepatitis C virus infection [17], the only two major hepatitis viruses are still awaiting a definitive cure are hepatitis B (HBV) and hepatitis D (HDV). More recent advances in treating these viruses have been highlighted in another article presented in this issue of *JCM* [18]. The main endpoint of all current treatment strategies for these chronic infections is the suppression of HBV DNA and HDV RNA for those patients coinfected with HDV. Unfortunately, the profound suppression of viral replication does not translate to an effective and complete cure of HBV or HBV/HDV coinfection. Among the known barriers to achieve a "functional cure", the most worrisome is HBV covalently closed circular DNA (cccDNA), which allows the virus to permanently persist in hepatocytes and against which nucleot(s)ide analogs have little effect. Regarding HDV infection, the ideal goal of treatment is to obtain simultaneously the clearance of HBsAg and a sustained HDV virological suppression, at least 6 months after stopping the treatment. Unfortunately, both aims are still not reachable. Improving knowledge of the structure and replication cycle of both HBV and HDV has facilitated the development of novel antivirals directly targeting multiple steps in virus replication and preventing the synthesis of new cccDNA. Furthermore, immunomodulators may also be needed to reverse the state of tolerance typical of the chronic phase of viral

infection and subsequently promote the immune-induced death of infected hepatocytes, which is crucial for the neutralization of circulating virions. New nucleotide analogs in advanced phase of development are besifovir, metacavir and two prodrugs of tenofovir (tenofovir exalidex and tenofovir disoproxil orotate). Other drugs in development are the attachment/entry inhibitors, such as bulevirtide, which acts upon the sodium taurocholate co-transporting polypeptide (NTCP), a receptor of both HBV and HDV. Therefore, this new drug blocks both HBV and HDV entry in the hepatocytes. Bulevirtide was approved in the European Union in July 2020 as the first effective drug for the treatment of chronic HDV in patients with compensated liver disease. In addition to bulevirtide, a further new drug is lonafarnib (LNF), a farnesyl transferase inhibitor that blocks the assembly and secretion of virions in the cell through HDV antigen prenylation. Preliminary data seem to support the combined use of LNF with ritonavir (RTV). Nucleic acid polymers (NAPs), such REP 2139, are under clinical evaluation and produced promising results, as among 12 enrolled patients 7 have become HDV RNA- and 5 hepatitis B surface antigen (HBsAg)-negative, respectively, after a follow-up of 1 year.

Three contributions presented in this issue of *JCM* have been devoted to providing the main updated knowledge regarding the approach to treat patients with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). One article focused on CCA [19], and two focused on HCC [20,21]. CCA is anatomically classified in intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) CCA. Surgical resection, obtaining negative margins, represents the best curative therapy for CCA. Systemic treatment with cisplatin plus gemcitabine (GEMCIS) is the first-line approach for patients with advanced-stage CCA, but the results are unsatisfactory, with a 5-year survival rate of approximately 5–15%. Targeted therapies, specific molecular profiling and biomarkers are needed to select new effective therapies for each patient with CCA. For example, approximately 15–20% of iCCAs have been observed to contain FGRF2 translocations, which are implicated in promoting cell proliferation and angiogenesis. Thus, several FGFR 1–3 inhibitors (i.e., pemigatinib and infigratinib) are being evaluated in phase III trials involving patients with advanced CCA, and the preliminary results seem to be encouraging. Mutations in epidermal growth factor receptor (EGFR) have a great importance in guiding treatments in different cancers, nevertheless, no evidence of their efficacy against CCA has been demonstrated. Immune checkpoint inhibitors (ICIs), peptide- and dendritic cell-based vaccines, and adoptive cell therapy, are under investigation to treat patients with CCA. Although the use of immunotherapy in patients with CCA is still limited, several clinical trials are currently evaluating the therapeutic properties of anti-CTLA-4 monoclonal antibodies, the targeting of PD-L1 or its receptor, PD-1, as well as chimeric antigen receptor T (CAR-T) cell immunotherapy. Unfortunately, ICI monotherapy has shown insufficient efficacy in patients with CCA. However, a better understanding of immunologically based therapeutic strategies should be reached, before to design a real precision medicine strategy allowing to reduce clinical aggressiveness of the tumor and to improve the prognosis of patients with CCA.

Compared to patients with CCA, very different treatment scenarios are on the horizon for patients with HCC. In addition to the well-known therapeutic options referring to surgical resection or to locoregional treatments of the tumor, a very large quantity of data is expected from new systemic treatments based on the use of ICIs in combination with other agents, among which vascular endothelial growth factor (VEGFR)-targeted therapies generated very encouraging results. Therefore, atezolizumab (a monoclonal antibody against PD-L1) plus bevacizumab (a monoclonal antibody against VEGF) has been approved as the first-line treatment option for advanced HCC, becoming the standard of care for these patients. Immunotherapy-based treatments will increase the landscape of HCC therapy soon. A very attractive first-line treatment modality in patients with intermediate-stage HCC is to combine locoregional treatments with ICIs, since ablative and intraarterial techniques indirectly induce a peripheral immune response that may enhance the effect of ICIs. Both radiofrequency ablation and transarterial chemoembolization induce necrosis of tumor cells, promoting the release of tumor antigens and the activation of immune-mediated

death of tumor cells, which in turn stimulates a peripheral systemic immune response that is potentially amplified by the administration of ICIs. In contrast, the survival benefit for patients' candidates for second-line treatment options (regorafenib/cabozantinib or ramucirumab), although significant, is still modest. Thus, nivolumab with or without ipilimumab and pembrolizumab received FDA approval as second-line treatments.

In addition to locoregional and systemic treatments, liver transplantation (LT) remains the better treatment option for a subset of patients with HCC, since the surgical procedure removes both the tumor and the liver at the same time, which remains the potential source of new neoplastic clones. The Milan criteria (MC) were developed more than 25 years ago and are still considered the benchmark for LT in patients with HCC. However, the strict application of MC might exclude some patients who may receive a clinical benefit from LT. Several expanded criteria have been proposed. Some consider pretransplant morphological and biological variables of the tumor, others consider post-LT variables such as the histology of the tumor, and others combine pre- and post-LT variables. More recently, the HCC response to locoregional treatments before transplantation emerged as a surrogate marker of the biological aggressiveness of the tumor to be used as a better selection criterion for LT in patients beyond the MC at presentation. These issues have been comprehensively updated in this *JCM* Special Issue [21] to present new policies that may be applied to better select patients with HCC for LT. The main innovative approach to select patients for LT presenting at baseline beyond the MC is to evaluate the characteristics and the duration of tumor response after locoregional (or systemic) therapies (downstaging treatment) and consider it a surrogate marker of biological HCC aggressiveness and of the risk of recurrence. It is mandatory to assess the success of downstaging treatments, to confirm the absence of tumor progression during an observation period of at least 3 months after treatment. Patients experiencing a successful downstaging are those eligible for LT as they present a less aggressive tumor biology and a better post-LT survival. Thus, the American and European associations for the study of the liver guidelines are concordant in recommending the adoption of locoregional (systemic) treatment procedures in patients with HCC beyond MC at baseline and the consideration of those who achieved successful downstaging for at least 3–6 months as suitable candidates for LT [22,23].

HCC represents approximately 50% of the indications for LT in Europe and the US. Constant indications for LT are decompensated liver cirrhosis due to cholestatic and autoimmune liver diseases, as well as chronic HBV infection. Decompensated cirrhosis due to chronic HCV infection is declining as an indication for LT, while alcohol- and non-alcoholic steato-hepatitis (NASH)-related liver diseases have increased progressively as indications for LT in recent years. In addition to the established indications for LT, clinical conditions historically considered exclusion criteria for LT, such as severe alcoholic hepatitis (AH), acute-on-chronic liver failure (ACLF), colorectal cancer metastases and cholangiocarcinoma, have been considered new indications for LT in recent years, producing promising survival advantages for patients. This topic has been highlighted in a very updated review [24] presented in this issue of *JCM*, where pros and cons for every new potential indication for LT have been critically discussed. Importantly, all newer indications for LT increase the pressure in an already difficult context of organ shortage. Strategies are therefore needed to increase the pool of transplantable organs, aiming to ensure a better balance between new candidate patients and available resources (organs). Moreover, a very challenging issue will be to optimize the patient selection criteria to ensure a clear gain in life expectancy for those who undergo LT, avoiding the increase in waiting list mortality for those patients who continue to await LT. A multidisciplinary transplant team is needed soon to face and solve this very delicate problem. Furthermore, the new scenario of transplants makes it essential to review and standardize ethical considerations across countries to ensure the same treatment options for all patients.

The COVID-19 pandemic has completely disrupted the global landscape of health systems. The repercussions have been highlighted in all sectors and in that of liver diseases. Data regarding the effect of COVID-19 on LT recipients are still scarce and often

contradictory. A recent systematic review [25] presented in this issue of *JCM* showed that the COVID-19 clinical outcome of the LT population was not per se worse than that of the general population, although careful management of immunosuppressive therapy may be needed. In this regard, complete therapy discontinuation is not encouraged, but caution is needed in the use of mycophenolate mofetil (MMF), favoring tacrolimus (TAC) use. Anti-SARS-CoV-2 mRNA vaccine immunogenicity appeared to be low in LT patients, despite a booster dose being strongly recommended by the main scientific societies. The newest SARS-CoV-2 variants, such as Omicron, may further reduce vaccine-induced immunogenicity, suggesting that the level of surveillance should remain very high in this population.

A large body of new insights are derived from the collective work presented in this Special Issue of *JCM* entitled "New therapies for liver diseases". All of them should be considered the beginning of a new era in exploring the pathophysiology of liver diseases and the mechanisms inducing cancer transformation of the liver with the help of technology, artificial intelligence and human perspectives. These new insights will promote the development of new and more effective treatments for several liver diseases that will improve quality of life and patient survival. As the Guest Editor of this Special Issue of *JCM*, I would like to express special thanks to the authors for their remarkable contributions and the reviewers for their professional comments. Furthermore, I would like to thank the *JCM* team for their professional and exceptional support that enabled the project to be achieved.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The author declares no conflict of interest.

#### **References**


*Article* **Marian Devotion on the Camino de Santiago during the Middle Ages**

**Piotr Roszak 1,\* and Jesus Tanco Lerga 2**

**Abstract:** This article presents the theological basis of Marian devotion on the medieval Camino de Santiago and its manifestation in the form of Marian advocacies (Virgen Peregrina, Virgen del Camino). The presence of the cult of the Virgin Mary on the pilgrimage route to Compostela, closely linked to the Jacobean tradition from the very beginning, grows out of the main Mariological trend in the Middle Ages, expressed in the synthesis of Thomas Aquinas. However, a special relationship must be sought in the Mariology of the Hispanic–Mozarabic rite, which created the spiritual climate for the Compostela pilgrimages in the first centuries of their existence.

**Keywords:** Thomism; Mariology; Camino de Santiago; medieval pilgrimage; cult of saints; Mozarabic rite

### **1. Introduction**

The notable presence of Marian devotion in the twelve centuries of pilgrimage to Santiago de Compostela to venerate the remains of St. James the Great in the *Finis Terrae* of Western Europe is palpable and significant (Rucquoi 2018; Greenia 2018; Mróz and Mróz 2013; Mróz et al. 2022). It has given rise to abundant bibliographies throughout these centuries, to which pilgrims, scholars and also theologians of great prestige have contributed. Some of them, such as Robert Plötz, refer to a curious "competition" between the Mother of Christ and the apostle (Plötz 1997, p. 174). For this German expert, there are two key questions on this subject, summarized as follows: What happened in the Hispanic lands and, above all, along the Way of St. James that caused the competition between the Virgin Mary and the Apostle? How and in what way did they leave traces in the historical testimony?

#### **2. The Presence of the Marian Cult in Medieval Camino**

On the Way of St. James, there are numerous temples dedicated to the mother of Jesus, just as—to a lesser extent—others are dedicated to saints and can be visited in that kind of devotional altarpiece that is contemplated by those who walk this spiritual and human journey. It is of vital importance to give value to the intermediate sanctuaries on the Camino; many of them are, in turn, the objects of regional or national veneration, especially when we observe the increase in the number of pilgrimages divided into sections (Tanco Lerga 2010, p. 61; Gonzalez and de la Calle 2020). Some saints—such as Saint Millán, with his life related to Bishop Braulio of Zaragoza and his *Glosas Emilianenses*, completed around 994—are a good example of this (Tanco Lerga 2011, pp. 31–53). It is no coincidence that the first written testimony we have of a pilgrim on the French Way, Bishop Godescalco, left a copy of a book in the monastery of San Martín de Albelda in 950 (La Rioja, then part of the kingdom of Pamplona and near Nájera). It was logically handwritten, and was a Marian treatise written by Saint Ildefonso of Toledo, which he would collect on his return from the cathedral of Compostela the following year on his return to his seeing of Le Puy in France. It also shows that, in the land of Mary, as Spain is known, devotion

**Citation:** Roszak, Piotr, and Jesus Tanco Lerga. 2022. Marian Devotion on the Camino de Santiago during the Middle Ages. *Religions* 13: 1213. https://doi.org/10.3390/ rel13121213

Academic Editor: José María Salvador-González

Received: 2 December 2022 Accepted: 12 December 2022 Published: 14 December 2022

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

**Copyright:** © 2022 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/).

to the Mother of Jesus, who, according to the tradition, visited St. James around year 40 in Saragossa, had an influence in the first millennium of Christianity in fostering Marian devotion. The study of the role of the Virgin in the Reconquest—first in Andalusia and then in the Christian kingdoms as the Reconquest progressed—is very interesting, first in Covadonga from 918 onwards and then in so many invocations of victories and spiritual struggle, such as the knightly Santiago, protector of faith, popularly known as Santiago Matamoros after the battle of Clavijo. The Virgin and Saint James the Apostle, although not exclusively—there are San Millán and the Victoria crosses and other signs of protection in the struggle to restore faith—represent the symbols to which the fighters for the Christian faith in reconquering Spain took refuge.

In the second millennium, following the Marian spread promoted by the monasteries, mainly Benedictine and Cistercian—St. Bernard is very emblematic—devotion to Mary is widespread throughout the pilgrimage to Santiago. Pilgrimage centers such as Le Puy, Rocamador, and Monserrat, and hospitals named after the Mother of God, such as Roncesvalles, are very present along the Camino on the different routes that pilgrims choose from their homes to reach Compostela. In the burials of pilgrims who died with their "boots on", in addition to the motifs attributed to their *santiaguera* condition, we see insignia of Marian devotion sewn or attached to the tunics and attire proper for their purpose (Pugliese et al. 2013). Those who go on pilgrimages to Galicia have many allusions in medieval Hispanic literature and, to a lesser extent, in the Romance languages that were also incipient in other nations, which justify their popular roots. *Loores de Nuestra Señora*, Gonzalo de Berceo in the background; and the *Cantigas del rey Sabio*, with the *Virgen Blanca* from Villalcázar de Sirga, serve as examples in this respect. It is worthy to underline that the *Cantigas* are a reflection of the oral tradition of the people, so they are of great interest as a source of miracles and legends of the Camino.

To take a starting reference to this mutual relationship between the Marian and the Jacobean, we can turn to the Liber Sancti Jacobi, a masterpiece relating to the pilgrimage with its five books, not all by the same author, but which do highlight the overall movement of the Jacobean pilgrimage at a time of splendor, such as the first third of the 12th century (Moralejo et al. 1993, p. 634). As is well known, between 1120 and 1124, the first archbishop of Santiago, Diego Gelmirez, asked a group of theologians and intellectuals of his time for a compilation of texts, completed by contributions from different pens until their definitive writing, which we have to place around 1160. The aim of the group of authors was to show that it was the Cluniac pope Calixtus II (1119–1124) who wrote the text in his own hand and has given the five books of the work the name *Codex Calixtinus*.

Already in Book I, the author emphasizes the preponderant role of Mary in the history of Salvation: "The clouds rained down on the Just One when the apostles preached him to the world. He opened the earth when the Virgin Mary received Him. The earth bore the fruit of the Saviour when the Virgin Mother of God gave birth to Christ who saved the world from the ruin of sin" (Moralejo et al. 1993, p. 33). In the Miracles attributed to St. James, the Book refers on several occasions to Mary's salvific role, as in the case of the man who committed suicide at the instigation of the devil and was resurrected with the help of Mary. Book II of the Codex describes twenty-two miracles, including the one mentioned above and the one worked by the Apostle who punished—in an exemplary manner—an innkeeper from Pamplona who swindled a French pilgrim from Poitou who was making the pilgrimage to Compostela with his wife who had died in the capital of Navarre and their two children. The author calls some of the miracles as examples, because their aim is to exemplify or teach good behavior on the pilgrimage.

In the great miracle of St. James—number XVII of Book II of the *Codex Calixtinus*, which is attributed to the pen of St. Anselm of Canterbury—the pilgrim narrator, who has been made to change his journey from the Way to Santiago to that of Rome, has a vision of the Virgin narrated in these words: "Thus", says the narrator, "compelled by him we came to Rome, where by the church of St. Peter the Apostle there was a green and spacious place in the plain of the air, to which innumerable multitudes of saints had come for an assembly.

The Venerable Lady Mother of God and ever-virgin Mary presided over it, and many great men were seated to the right and left of them.  She was not tall, but of medium height, with a beautiful face and a delightful appearance. The holy Apostle, my most pious advocate, immediately appeared before her, and before all, he cried out how the fallacy of Satan had defeated me. And she immediately turned to the demons and said: Ah, you wretches, what were you looking for in a pilgrim of my Lord and Son, and of James his loyal one?" (Moralejo et al. 1993, own translation).

Book V of *Codex Calixtinus* describes the routes and stages of the pilgrims in the era of splendor, the 11th and 12th centuries of the Romanesque and Cluny, the Gregorian reform that replaced the Hispanic rites in many aspects, and in which Sancho III the Great of Navarre (1004–1035) played a preponderant role in orchestrating the Reconquest and uniting of the Christian peninsular kingdoms. The author of Book V declares in the first person: "I have limited myself to enumerating these towns and the aforementioned journeys so that pilgrims on their way to Santiago may foresee, with this information, the necessary expenses for their journey" (Moralejo et al. 1993, p. 507). Further on, after describing the rivers, he says: "I have described these rivers so that pilgrims on their way to Santiago may avoid drinking in unhealthy ones and may choose the good ones for themselves and their horses". The author of the book—according to many authors, the French cleric and priest of Parthenay, Aymeric Picaud—when speaking of the Navarrese, especially in the northern pilgrimage area, quotes a list of Basque words used by the natives of that mountainous area near Roncesvalles, which brought back such bad memories of Charlemagne's defeat in 778, including the name of the Virgin: "God is called Urcia; the Mother of God, Andrea Maria; the bread, orgui; the wine, ardum; the meat, aragui; the house, echea; the owner of the house, iaona; the lady, andrea; the church, elicera; the presbyter, belaterra; the wheat, gari; the water, uric; the king, ereguía; Santiago, Iaona domne Iacue".

#### *2.1. Marian Shrines on the Way of St. James*

Book V of the *Codex Calixtinus* lists places of religious tradition and devotion to the saints exposed along the way, with the relics that are essential for Eucharistic celebrations and the object of great popular veneration as well as social and cultural references. Many of these milestones along the route had temples, sanctuaries and hermitages related to Mary.

One example is the dedication of large cathedrals on pilgrimage routes. To stick to the French Route in Spain, we can observe the dedication of the cathedrals of Pamplona (*Santa María la Real*); Logroño (*Santa María de la Redonda*); Burgos (with the same Marian title); *Santa María la Blanca in* León—another of the great Spanish cathedrals—and many other Marian shrines. A specialist and promoter of pilgrimage initiatives, Jesús Arraiza, wrote an enlightening book on the Marian presence on the Way of St. James, entitled *Por la ruta jacobea con Santa María* (Arraiza Frauca 1993).

The author lists nearly two hundred temples, sanctuaries and hermitages on the French Route in Spain and on the route from Oviedo to Santiago via Lugo that have the Virgin Mary as their main patron saint (Roszak 2018). In the pages of this book, we find, among many others: *Santa María de Roncesvalles, Santa María del Perdón* in Astráin, *Santa María de Eunate*, *Santa María la Real* (Rocamador) in Sangüesa, *Santa María de Los Arcos*, and in the short space of four kilometers—Estella and Ayegui—three images of great importance: El Puy, Rocamador and Irache of medieval origin and with a clear Jacobean connotation. In La Rioja, *Santa María la Real* de Nájera stands out. The lands of Burgos, such as *Santa María de la Calle* in Redecilla; *Santa María* de Oca; and *Santa María del Manzano* in Castrojeriz; are very rich in these dedications to the Virgin. In the Palencia area, there are *La Blanca* de Villalcaázar de Sirga; Santa María del Castillo in Frómista; the *Virgen del Camino* in Carrión de los Condes. Jesús Arraiza continues with other devotions, such as in León—in addition to the cathedral dedicated to the aforementioned *Virgen Blanca*, the *Virgen Peregrina* in Sahagún; *Nuestra Señora del Camino* in the village of La Virgen del Camino; *Nuestra Señora* *de la Majestad*, which presides over the cathedral of Astorga; the *Virgen de la Encina*—a Jacobean enclave in Ponferrada if ever there was one; and the great chapel of the *Quinta Angustia* in Molinaseca; Galicia welcomes the pilgrim with the Marian temple of *Santa María la Real* in Cebreiro and continues with *La Merced* in Sarria, *Virgen de las Victorias* in Portomarín; and many others to culminate in Santiago with several venerated images, such as *La Peregrina, Virgen del Portal, la Corticela* and Virgen del Camino.

On the way to Oviedo and Lugo, we can see *Santa María de Arbas*, *Virgen de las Nieves* in the Pajares pass; *Virgen del Carmen* in Mieres del Camino; *la Balesquida*, Virgen del Rey Casto and *Virgen del Socorro* in Oviedo; *Nuestra Señora del Fresno* in Grado, *Virgen del Viso* in Salas and *Santa María la Real* in Obona. In Cangas de Narcea there is *Virgen del Acebo*; in Pola de Allande, *Virgen del Avellano*; in Fonsagrada, *Virgen de la Fuente* and in Lugo, *Virgen de los Ojos Grandes*. Jesús Arraiza, with photographs and descriptions included, describes two hundred sanctuaries, churches and hermitages on the Camino Frances. Many of these milestones, as on other routes, have devotional brotherhoods attached to them that provide help and collaboration to the ecclesiastical leaders of these enclaves. Many of them offer a Christian welcome and generous hospitality to pilgrims.

#### *2.2. Studies on Marian Devotion on the Camino de Santiago*

The Marian bibliography on the Pilgrim's Way is very varied and extensive. I would like to highlight the work of the couple María Cuende and Darío Izquierdo, who have several titles on the subject under the title *La Virgen María en las rutas jacobeas* (The Virgin Mary on the Jacobean Routes). One of them, which I know was very well received, was on the presence of the Virgin Mary in Portugal during the pilgrimage (Izquierdo and Cuende 2005). The series began with a study of the French Way (Cuende and Izquierdo 1997) and has served, as in the case of Jesús Arraiza's book, to awaken scientific and informative interest in the subject. Juan José Cebrián collected a repertoire in Galicia. The pairing of Mary and the Pilgrim's Way to Santiago has given rise to initiatives of great significance in recent years of the revival of the pilgrimage. By way of example, the Castilian–Leonese exhibitions of the "Ages of Man" have always offered samples of Marian images along the way. On other occasions, specific exhibitions have been held with great success, which have served to publicize and enhance the value of images, both in Spain and abroad. Various national studies, the treatment of which goes beyond the scope of this article, serve as a reference for those who wish to look into this extraordinary world of Marian devotion on pilgrimages and especially on the Pilgrim's Way to the apostolic tomb in Compostela.

Special mention should be made of the Marian invocation of the *Virgen Peregrina*, who is venerated in different places. The Galician city of Pontevedra has her as its patron saint with a basilica that is much frequented by her devotees, but also by the pilgrims who pass through this part of the Portuguese Way. In Sahagún, there has been a special cult of the Pilgrim Virgin who have occupied a place of honor in the Benedictine monastery, which is now in a sacred museum. La Rioja, in the town of Leiva, also has an image with the attire of a pilgrim, a large hat, a staff and a sash. In Zúñiga (Navarre), the Pilgrim Virgin is also prayed to in a similar way.

The holy Dominican founder, Domingo de Guzmán (13th century) and pilgrim to Santiago, a Spaniard from Burgos and a great promoter of the Holy Rosary, would be very happy if the litany of the Rosary included the protection of pilgrims to the Virgin, that is, Holy Mary, Queen of pilgrims, pray for us.

#### **3. Theological Background of Camino Piety: Medieval Mariology in Its Two Characteristics**

The manifestations of devotion and veneration in a particular epoch of history find their justification in the Mariology prevalent at the time. The way in which the mystery of Mary's life was presented and the attention paid to certain themes became the motif for many manifestations of art, imagery and prayers, which were also created on the Way of St. James and formed the identity of the pilgrim (Huzarek 2014, 2021; Roszak and Seryczy ´nska 2020). The medieval pilgrim and his imagination and his way of experiencing the pilgrimage route to Compostela may have been influenced by two main theological currents associated with the Way of St. James. On the one hand, it was the synthesis of Thomas Aquinas, which, over time, became a classic study and reached many of the faithful through sermons. On the other hand, due to the peculiarities of the Spanish context, one can try to discern theological influences going back to the Hispanic–Mozarabic rite in pilgrims walking to Santiago.

#### *3.1. Thomistic Mariology in the Christocentric Perspective*

St. Thomas presents his reflection on the Blessed Virgin Mary not in isolation from Christology, but as a kind of preparation for it, contemplating Her as via *Christi*—as a path to Christ. Therefore, all theological justifications concerning Mary have a Christological background in Aquinas (Mróz and Roszak 2011, p. 202).

The main Mariological theme in the Thomistic view is the motherhood of the Blessed Virgin Mary, which Thomas presents in the spirit of the teaching of the Council of Chalcedon, which emphasizes the belief in the singularity of the person of Christ: the human and divine natures exist in the one hypostasis of the Word. This means that there is only one divine act of Christ's being, and thus Mary's motherhood is *vere et naturalis*, not merely symbolic (Dabrowski 2002; Thomas Aquinas, *Compendium Theologiae*, cap. 222). Aquinas advocates a way of doing Mariology in which the person of Mary and her true divine parentage become the center of gravity of all the other mysteries of her life, and thus in their relation to Christ as the Savior (Thomas Aquinas, *Summa Theologiae*, III, q.29. a2c). He therefore considers her motherhood in the context of a proper grasp of the mystery of the Incarnation (Stancati 2009, p. 26), hence recalling his birth from the Father before the ages and his birth in time.

Aquinas therefore sees in Mary's motherhood the key to understanding her role also in relation to the Mystical Body of Christ, which is the Church. For she is not limited to a single event, but becomes a model for Christians (and the Church) of how Christ is born in the life of faith. Certainly, this theme is present in the multiple manifestations of art on the Way of St. James, where reverence towards Mary is linked to her divine motherhood: it reminds us that the pilgrim life is also the formation of Christ in each of the faithful. She gives birth to the Son who is the Light of the World, but by extension Mary is also *lux* in her attitude towards God—as resounds in the sermon of Thomas' *Lux orta*, full of Old Testament allusions and delivered on the occasion of the birth of the Blessed Virgin Mary.

A second strand of Thomistic Mariology is the emphasis placed on Mary as a 'dialogical woman', which Thomas Aquinas considers in the context of the scene of the Annunciation (Thomas Aquinas, *Summa Theologiae*, III, q.30, a.4c). For Mary, dialogue with God is the foundation of her witness: she carries it out in order to become a more confident witness to this mystery. Mary's dialogue does not stop at an exchange with the divine messenger; it is a commitment made in a spirit of obedience (Thomas Aquinas, *Summa Theologiae*, III, q.30, a.1c). The Mother of God's spoken fiat is an indication of the importance of the cooperation of a free creature in the work of redemption, and comes from a rational consideration of the word received. Mary as a free person, as Aquinas depicts her, points to the path that God proposes to man. The mystery of the Annunciation shows that Mary first becomes a disciple of the Lord and a person of faith, and only then, as a consequence, the physical Mother of Christ: He must be "conceived" by faith first in her heart rather than in her body.

What draws attention—also in the context of other scholastic mariologies—is the Trinitarian context. It is expressed, among other things, by Aquinas' commentary on Psalm 17, in which he calls the Virgin Mary 'the way to Jesus Christ' (*via Christi est Virgo Beata*) because her Son himself is the way to God (*via Dei est ipse Christus*). It is through Mary that Christ 'came' to humanity, and this is where her special ministry (ministerium) lies. For the Christian, it is an indication to take the path like Mary, for she is the *dux itinerantium*—the guide towards Christ. It is thus a journey of grace, during which man can count not only

on natural light, but on all the colors of the light of grace, as indicated by the Marian title *mater gratuita colorum*. It involves her accepting the will of the Father, which she fulfills in the spirit of her own mediation in the work of salvation, which is obviously incomparable to the mediation of Christ.

This spiritual mediation is analyzed by Thomas in the light of the miracle at the wedding at Cana, which, in his view, reveals two characteristics of Mary: piety (*pietas*) and mercy (*misericordia*). It is her ability to see those in need and to identify with them, and this is due to her identification with Christ (Thomas Aquinas, *In Ioannem*, cap. II, lect.1). Mary helps to find a solution for those people who do not see where to look. Mary presents their requests in a simple, simpliciter way, without unnecessary complexity. She begins to act, not at the last minute, but by being close to other people, she initiates action at the right moment. She shows herself to be caring and preventive when it comes to the welfare of other people by helping especially those who often try to hide their shortcomings and do not acknowledge them. Such mediation of Mary's mercy is possible because she is 'as close to Christ' as possible—which is what piety is supposed to lead towards. All these qualities are undoubtedly revealed in the worship of Mary on the pilgrimage routes: she teaches a mercy and piety that manifests itself not in spiritual closure, but in openness to fellow pilgrims and to the key issue of closeness to Christ through the sacraments.

It is still worth highlighting the theme of 'Mary's holiness', which Thomas discusses in detail, especially in a negative way—that is, by pointing out what Mary was free from. Undoubtedly, Thomas adopts the perspective of St. Paul, who speaks of the sin that has cast a shadow over all humanity. Nevertheless, in the case of Mary, he wishes to emphasize that her motherhood does not mean giving up her daily life—her vocation as a woman, wife and mother—in order to become God's chosen instrument. All the gifts of the Holy Spirit are in her—through which the greatness of the human being who follows the will of God and accepts his grace is shown. It is freedom from sin and the ability to act deservedly, freely responding to the good that is set before man.

By that means, the term 'full of grace' has a twofold sense for Aquinas—being linked to her participation in the grace of Christ as the Head. First, it is 'immunity from sin' and perfection of the virtues; second—redundancy of grace and being a *mediatrix* of grace for other people (Thomas Aquinas, *Summa Theologiae* III, q.27, a.5, ad 1), but always in relation to the source of grace, which is Christ.

#### *3.2. Virgin Mary in Medieval Mozarabic Tradition*

For a study of the Mariology evident on the Camino de Santiago in the form of works of art and euchology, it is worth noting the Marian devotion witnessed in the Hispanic– Mozarabic rite (Ibañez and Mendoza 1990; Roszak 2015; Ihnat 2019). It is about celebrating the liturgy according to the original custom that developed in the Iberian Peninsula from the first days of the evangelization of that country (Ihnat 2016). Despite the Arabization that began in 711, with the crossing of Gibraltar by Arab troops, the rite developed during the Visigothic period remained present and was a source of identity for Christians living in a culture increasingly distant from their faith (Pinell 1998). Many Christians from the south, particularly from Andalusia, migrated towards the northern kingdoms of Spain, bringing their piety, growing out of the Hispanic rite and the theology of the Visigothic period, especially St. Isidore, St. Leander or St. Ildefonso of Toledo (Ferrer Grenesche 2008; Porosło 2021), by maintaining the cult of St. James, who in time became the patron saint of the Reconquista. Nevertheless, it is important to note the very presence of a number of Marian feasts, which only later found their way into the Roman liturgy.

Mozarabic Mariology developed three fundamental themes related to Mary's role in the work of salvation, which became the main lines of Mariological systematization in the Middle Ages. On the one hand is the theme of Mary's virgin motherhood.

In the Hispanic liturgy, the designation of Mary as 'always Virgin', as well as her Immaculate Conception, appear in many Mass forms (Aldazabal 1990). At the same time, the need to place Marian reflection in the context of Christ's mission is emphasized (Garrido

1962). This, in turn, translates into reading Mary through the lens of her mission in the work of redemption. She is the advocate of inclusion in the church; she becomes the mediatrix leading to Christ, and so it is per Mariam that the Christian vocation is realized. It is noteworthy that the Mariology of the Hispanic Rite focuses on the notion of 'mission' and 'vocation', introducing a significant dynamic reflected in the forms of following Mary in the lives of Christians.

A distinctive feature of Hispanic prayers is the conviction that Mary's faith is a 'resting place' for Christ, who wishes to meet humanity in this way. This means that Visigothic or Mozarabic Mariology seeks to combine two traditions: both the Western one, with its emphasis on the physicality of motherhood (focus on the 'body'); and the Greek one, preferring to speak of Mary's spiritual quality (focus on the 'soul') (Girones 1970, p. 464). The idea was to emphasize that *mente et ventre concepit*, *virgo spiritualiter et corporaliter*.

What is noteworthy is that it was important for the Hispanic theologians creating the euchology of the Mozarabic rite to see in Mary the way in which God accomplishes his saving intentions (Janini 1987). This is done not 'in spite of' human choices, but through the free decisions of creatures. The key remains her consent and commitment (Ibáñez 1975).

#### **4. Conclusions**

The two-pronged analysis undertaken—of the presence of forms of Marian devotion in the contemporary Camino de Santiago, but also of the theological origins of these foundations—has shown the influence of many theological themes debated in the Middle Ages on the concrete manifestations of Marian devotion among pilgrims to Compostela. The influence of both Western and Eastern Mariology can be seen, which is not surprising given that the Camino became a route for the exchange of many theological ideas, manifesting forms of piety brought from their own countries. In the future, it would be worthwhile to reach out for research that could show how local traditions from many European countries formed Marian devotion on the Camino de Santiago.

In the representations of the Virgen del Camino or Virgen Peregrina, it is not so much the divine motherhood of Mary that is revealed, as her role in the history of salvation. It is to point to Mary as the way to Christ, and as a model of responding to God's call in the midst of life's journey. Marian statues on the Way of St. James make not only the condition of *homo viator* or *homo peregrinus* visible, but Mary's mediation of mercy towards the Church to bring about an encounter with Christ—the meaning of every pilgrimage in Christian theology (Roszak 2022). Apart from that, what is emphasized in the mystery of the Virgin is the gifts of grace (*gratia plena*) with which God has adorned her (Ferrer Grenesche 2019). In this way, her obedience of faith that brings Christ to the people seems to be the central Mariological truth on the Way of St. James (Ferrer Grenesche 2012).

Marian devotion on the Way of St. James is therefore not a 'foreign body' but a logical consequence, not only of the history of the apostolic mission of St. James—as evidenced by the cult of the Virgen del Pilar—but of the sense of pilgrimage (Mróz et al. 2019). Seeing Mary on the road, the pilgrim becomes aware of his or her vocation and call (Seryczy ´nska 2019), and at the same time that he or she is not going alone but is accompanied by the intercession of the Mother of God. Being on the road ceases to be a mere description of a physical condition and begins the perspective of a soteriological interpretation of the pilgrimage experience (Roszak 2019; Doburzy ´nski 2021; Oviedo 2022).

**Author Contributions:** Conceptualization, P.R. and J.T.L.; methodology, P.R.; writing—original draft preparation, P.R.; writing—review and editing, J.T.L. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Conflicts of Interest:** The authors declare no conflict of interest.

#### **References**

Aldazabal, Jose. 1990. La misa en el rito hispano-mozárabe renovado. *Phase* 175: 57–77.

Arraiza Frauca, Jesús. 1993. *Por la Ruta Jacobea con Santa María*. Santiago de Compostela: Xunta de Galicia.

Seryczy´nska, Berenika. 2019. Creative escapism and the Camino de Santiago. *International Journal of Religious Tourism and Pilgrimage* 7: 48–55.

Stancati, Tommaso. 2009. *Tre mariologie: Alberto Magno, Tommaso d'Aquino, Tommaso da Kempis*. Napoli: Editrice Domenicana Italiana.

Tanco Lerga, Jesus. 2010. Peregrinos y devociones en santuarios situados en el Camino. In *Oviedo y el Tesoro de su Catedral en los orígenes del Camino de Santiago*. Oviedo: Fundación María Cristina Masaveu Peterson.

Tanco Lerga, Jesus. 2011. San Millán de la Cogolla. In *Santuarios de Peregrinación en Torno al Camino de Santiago*. Oviedo: Fundación María Cristina Masaveu Peterson, pp. 31–53.


**Acknowledgements**

I would like to express my special thanks to Sistema FIEP, the institution that made problem-solving methodology possible for adolescents and believes in the power of transformation in education. I would also like to thank my leader, José Antonio Fares, who has always supported and guided me in my process as a manager. Finally, I would like to thank Professor Fernando Pianaro, who supported me in doing this research.

#### **Thanks**

*Metacognition in Learning*

conclude basic education? Organizing it into learning aims and skills students need to achieve by the end of the school year is the first step to create a more meaningful curriculum. Most documents point out only isolated contents which do not explain why it would be useful to learn them. By having learning aims and skills as its main pillars, the pedagogical team can then organize clusters according to areas of interest (environment, citizenship, technology, etc.), and not fragmented subjects. These clusters will be the background for

proposing themes that will raise students' interest toward learning.

enhance adolescents' self-regulation skills.

effective for adolescents.

2.Methodology: the school is an extension of the adolescent's life. Therefore, it should promote different experiences to help them learn how to think of alternatives, solve situations, collaborate, know how to deal with frustration, learn how to search for answers, become proactive, exercise creativity, develop socioemotional skills, and use risk taking to contribute to a more productive environment. A problem-solving methodology is an appropriate approach as it influences students to act in order to learn. It touches their willingness to "survive." For this reason, (a) the curriculum organized by aims and clusters will help teachers to set big questions as challenges. Students will achieve the learning aims by seeking solutions for the challenge. (b) Protagonism: they should be able to choose what challenge to work on. This will give them power to work on what interests them and have more responsibility toward what they choose and what they need to learn is not imposed. (c) Infrastructure: spaces in the school should be tools to influence experiences. Furniture in the classroom should be planned in a way to make students work in teams, collaborate, use materials to help them work on the challenge, debate, search, etc. (d) Regulation of learning: students need to be assessed using the learning aims from the curriculum and in different perspectives. They should also be challenged to self-evaluate themselves in order to perceive progress and gaps they should work on. Technology can be a great ally to teachers in order to personalize what each student needs to focus more on. Simple questions at the end of the lesson, or making the learning aims available at the beginning of the term, or teaching study techniques can help students perceive their own learning and become more effective in focusing on overcoming their difficulties or improving their strengths. More research on possible methods regarding the student-centered field could be run in order to find more alternatives to

3.Teacher's role: for a student-centered methodology, teachers need to work as facilitators. They need to learn strategies to activate students' willingness to "survive" and, therefore, learn more and better. This will develop their autonomy to seek for answers, to collaborate more and to learn from their mistakes. Teachers are no longer information owners (which can be found anywhere with the spread of the Internet): their job is much more complex than that. Their job is to teach strategies to help students become more self-regulated. Therefore, it is of great importance to work on research that tests different strategies by the teachers in the classroom and identify which ones can be

4.School's role: the school's environment is also a focus when self-regulated learning is the goal. It should engage adolescents in activities in which they can either suggest or show contributions of their own. Social work, sports, students' council, students' school band, and book club are some examples of engaging activities that could help students practice their responsibility and

**60**

My special thanks to my family and my husband.

#### **Author details**

Giovana Chimentão Punhagui Sistema FIEP, Curitiba, Brazil

\*Address all correspondence to<EMAIL_ADDRESS>
© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**2. European corn borer**

European corn borer (*Ostrinia nubilalis* Hübner) (Crambidae, Lepidoptera) (**Figure 1**) is a destructive pest on maize, but it also occurs on many other plant species such as peppers and tomatoes. In eastern Croatia, ECBs have been studied for many years [10, 11], population dynamics and intensity of attack of ECB have been monitored since 1965 (Ivezić, personal commun.). In Croatia, ECB usually develops two generations per year; however, the third generation may occur in years with favorable agro-climatic conditions [12]. Larvae feed on aboveground parts of a plant and pass through five larval stages before attaining the pupal stage. The first larval stage tends to move toward higher moisture conditions in

**79**

**Figure 2.**

proposed [17].

**2.2 Potential of ECB natural enemies**

*Leaf damage from ECB larvae (Photo: Sarajlić, 2010).*

*The Role of Irrigation and Nitrogen Fertilization on the Feeding Behavior of European Corn Borer*

plants, and for this reason, they feed within the whorls of leaves. When all leaves are developed, typical symptoms of larval feeding can be observed as small holes on leaves, lined in one row (**Figure 2**). Third stage larvae bore into the plant stalk or fruits and disrupt physiological processes inside the plant. Larvae pupate into the stalk holes (**Figure 3**). Larvae are the most abundant in the tasseling and silking stage of maize. During these stages, maize plants are the most attractive for

High-temperature stress has a negative impact on plant growth, productivity, and metabolism, and plants are the most vulnerable in the reproductive phase [14]. Climatic stress has a significant impact on ECB oviposition and larvae mortality. The first and second larval stages are the most sensitive to stress, and mortality rates can reach up to 62% [15, 16]. Quantity of available water can be regulated by the irrigation system, but other climatic factors, such as air temperatures, cannot be manipulated in field crops. Excessive rainfalls and lower temperatures can delay ECB appearance from 10 and more days, and the intensity of attack is lower; consequently, the damage is also lowered [2]. We are already facing often deviations from average multiyear precipitation and air temperature; therefore, models to predict the occurrence of a new generation of ECB have been

During the vegetation, ECB has been exposed to different species of natural enemies, such as wasps and flies that feed on eggs or larval stages of this pest. The most investigated natural enemies of ECB are *Trichogramma* spp*.* Contradicting results on their effectiveness have been reported [18]. *Trichogramma* wasps are insect egg parasitoids. We have detected the natural parasitism of ECB eggs by these wasps in Croatia on the second generation of ECB. We reported low populations of natural enemies in the field crop, insufficient to significantly reduce the population of ECB and keep it under the economic threshold. Only artificial release of

*DOI: http://dx.doi.org/10.5772/intechopen.92598*

insects to feed on due to the low content of flavonoids [13].

**2.1 Influence of agroclimatic conditions on European corn borer**

**Figure 1.** *Female and male of European corn borer (Photo: Sarajlić, 2010).*

*The Role of Irrigation and Nitrogen Fertilization on the Feeding Behavior of European Corn Borer DOI: http://dx.doi.org/10.5772/intechopen.92598*

plants, and for this reason, they feed within the whorls of leaves. When all leaves are developed, typical symptoms of larval feeding can be observed as small holes on leaves, lined in one row (**Figure 2**). Third stage larvae bore into the plant stalk or fruits and disrupt physiological processes inside the plant. Larvae pupate into the stalk holes (**Figure 3**). Larvae are the most abundant in the tasseling and silking stage of maize. During these stages, maize plants are the most attractive for insects to feed on due to the low content of flavonoids [13].


3.1.3. Satisfaction with Life

Apart from experiencing positive emotions and the lack of negative emotions, satisfaction with life is an element of good mood. The results of the SWLS are presented in Table 4.

**Table 4.** The characteristics of the study participants regarding the level of satisfaction with life.

No difference was observed in the number of people with low, medium, and high levels of satisfaction with life.

### 3.1.4. Optimism

Dispositional optimism is a generalized tendency to expect good outcomes in future. Research shows that such optimism is an important predictor of a person's wellbeing and that it facilitates success and resistance to stressful life situations, e.g., the pandemic [27]. The results of the LOT-R are presented in Table 5.

**Table 5.** The characteristics of the study participants regarding life orientation.

The optimistic orientation was most common among the respondents, while the pessimistic one was the second most common and the neutral one was the least frequent.

#### 3.1.5. Styles of Coping with Stressful Situations

In psychological literature, different definitions of "stress" and "coping with stress" can be found. In this research, the authors assumed that stress results from the lack of balance between demands and abilities to cope with them. Coping with stress, in turn, includes "constantly changing cognitive and behavioural efforts to manage specific external and/or internal demands that are appraised as taxing or exceeding the resources of the

person" [33] (p. 141). The results obtained by the research participants in terms of their coping with stress styles are presented in Table 6.

**Table 6.** The characteristics of the study participants regarding styles of coping with stress.

1 TOC—task-oriented coping, 2 EOC—emotion-oriented coping, 3 AOC—avoidance-oriented coping, 4 D—distraction, 5 SD—social diversion.

The avoidance-oriented style was slightly dominant among the participants. Avoidanceoriented coping may take the form of distraction and social diversion. Both forms are aimed at avoiding a stressful situation [29]. Of the two forms, distraction is more often chosen. The second most frequently indicated is an emotion-oriented coping style, which includes focusing on one's emotions and taking up actions aimed at lowering emotional tension. The least frequently chosen style is task-oriented coping (which includes taking actions aimed at solving a problem (e.g., through planning or taking up particular activities).

### *3.2. Predictors of Positive and Negative Emotions*

Another issue that was analyzed was the influence of demographical variables, health situation related to COVID-19, mood, optimism, satisfaction with life, as well as styles of coping with stress, on experiencing positive and negative emotions. The results of the analyses are presented in the Table 7.

**Table 7.** Predictors of positive and negative emotions—linear regression results.

**Table 7.** *Cont.*

\* *p* —values below 0.05; 1 PA—Positive Affect, 2 NA—Negative Affect, 3 HT—Hedonic Tone, 4 TA—Tense Arousal, 5 EA—Energetic Arousal, 6 TOC—task-oriented coping, 7 EOC—emotion-oriented coping, 8 AOC—avoidance-oriented coping, 9 D—distraction, 10 SD—social diversion.

#### 3.2.1. Predictors of Positive Emotions (PA)

The multivariate model of linear regression confirmed that significant (*p* < 0.05) independent predictors of PA included: an emotion-oriented style of coping with stress (beta = −0.104; *p* = 0.001) and task-oriented coping (beta = 0.18; *p* < 0.001), level of satisfaction with life (beta = 0.235; *p* < 0.001), and level of energetic arousal in the description of mood (beta = −0.8; *p* < 0.001). A weaker predictor of experiencing positive emotions was being a man (beta = 1.935; *p* = 0.002), hedonic tone in the description of mood (beta = 0.357; *p* = 0.008), and being an employed student (beta = 2.198; *p* = 0.016). The R2 coefficient for this model (PE) was 54.57%, which means that 54.57% of PA variability was explained by the variables used in the model. The remaining 45.43% depends on the variables that were not taken into account in the model and accidental factors.

#### 3.2.2. Predictors of Positive of Negative Emotions (NA)

The multivariate model of linear regression confirmed that the significant (*p* < 0.05) independent predictors of NA were: tense arousal in the description of mood (beta = 1.545; *p* < 0.001) and an emotion-oriented coping with stress (beta = 0.103; *p* < 0.001). Other significant predictors included being over 60 years old (beta = 3.282; *p* = 0.047), living in a medium-sized city (beta = −1.606; 0.022), living in a village (beta = −1.37; *p* = 0.013), as well as decreased (beta = 1.452; *p* = 0.007) and increased (beta = 2.314; *p* = 0.007) level of life in the recent time. The R2 coefficient for this model was 63.42%, which means that 63.42% of NA variability was explained by the variables used in the model. The remaining 36.58% depends on the variables that were not taken into account in the model and accidental factors.

#### **4. Discussion**

Experiencing negative emotions during the pandemic is a fully understandable phenomenon. In the case of 60% of respondents, the intensification of negative emotions reached a high level. Such emotions may result from a variety of factors, the importance of which may be different in various cultural contexts. In the case of the Polish respondents,

this may include the following factors: the threat to one's health and to the health of family members; isolation and, at the same time, the inability to distance oneself from people with whom we live; and economic uncertainty, together with a simultaneous crisis of trust in public institutions [8]. The objective of this research was to search for predictors of the experience of positive and negative emotions of Polish respondents during the second wave of the COVID-19 pandemic in the hope that the diagnosis of their mental condition will help design actions that might prevent negative consequences for their mental health.

Referring to the research that was conducted earlier, it is worth analyzing the key social and demographical variables. Whereas sex was not an important predictor of experiencing negative emotions, being a man was a predictor of experiencing positive emotions. In the majority of Polish analyses that were conducted earlier and that considered the sex variable, women's results were worse as far as mental wellbeing was concerned (e.g., anxiety, stress, or depression) [6,7,9,10,17,18]. Only in one study was the difference between the sexes statistically insignificant in some measurements [13]. Women stand on the frontline in the fight against the coronavirus. In a UN report published in April 2020, a strong thesis was formulated: "The COVID-19 global crisis has made starkly visible the fact that the world's formal economies and the maintenance of our daily lives are built on the invisible and unpaid labor of women and girls" [34]. In this situation, in which responsibility for caring for children, for the ill, and for the elderly was largely moved from the state to individuals and families, in most cases, women became the ones who had to take responsibility for it. This also limited women's ability to work the well-paid jobs they had before the pandemic, and from a long-term perspective, it may constitute a serious obstacle on their career path [35]. Moreover, jobs performed by women are often jobs with a high risk of becoming infected with the virus (medical staff, teachers, office workers) [34]. Finally, in December, apart from the above-mentioned factors, women were burdened with preparations for Christmas which, in traditional Polish families, are mainly the responsibility of women. Thus, on the one hand, negative emotions experienced by women at that time could be based on culturally determined tasks related to unpaid and unappreciated work that involves caring for others' needs. On the other hand, women's negative feelings could be based on stronger social approval of experiencing such emotions by women rather than by men. However, such a trend was not confirmed by our research. Emotional costs take the form of a ricochet: a higher probability of a higher level of positive emotions among the men than among the women participating in our research.

Many analyses performed in different parts of the world have shown that the emotional distress experienced during the pandemic mainly influenced people from younger age groups. A meta-analysis of the research on emotional well-being of young people during the pandemic [36] showed that they are much more threatened with the risk of experiencing anxiety, stress, and depression than older people. In addition, young people experienced problems with sleeping [37], somatization disorders, and obsessive-compulsive disorders [38]. Stronger symptoms of emotional disorders among young people may be explained by lower psychological resilience resulting from, e.g., shorter life experience or a more drastic change in the lifestyle they led [13]. Nevertheless, in our research, the only age-related predictor of emotions was being over 60 years old, which was a predictor of negative emotions. The pandemic negatively influenced the way in which older people function because they lost the opportunity to move around, they became lonelier, and they experienced more conflicts within their families [39]. Another source of negative emotions in this age group might be older people's increased susceptibility to contracting the virus and being more seriously affected than younger people [40]. Moreover, considering the fact that the greatest source of stress for Poles is the state of the health service [16,20], which older people use most frequently, a higher risk of experiencing negative emotions among them is perfectly understandable. Finally, for older people, isolation bears different connotations than for younger people. Older people have lower technological competences, and they often fear using new forms of media communication, which makes them feel much more isolated than young people [41].

In contrast, one of the predictors of positive emotions was combining work with studies. On the one hand, the simultaneous fulfillment of two tasks is a great challenge, especially due to the risk of losing a job to which young people working in services are often exposed, and due to dynamic changes in the system of education (the necessity to deal with the requirements of online education) [36]. On the other hand, the necessity to fulfil tasks in two social contexts at the same time increases the probability of maintaining social relationships and weakens the sense of isolation, which is one of the sources of anxiety and other disorders [42,43].

From the research, the authors have concluded that research participants living in villages and medium-sized cities experience negative emotions to a lesser degree. Living in a big city increases the risk of contracting the virus, makes it more difficult to maintain social distance, and limits the opportunity to engage in outdoor activities [19]. Furthermore, the pandemic limited people's access to the biggest attractions connected with living in a city (access to cultural institutions and to a variety of attractive services). Other factors that increase the possibility of experiencing negative emotions may include limited and closed spaces, the necessity to maintain contact with strangers, and the sense of greater anonymity.

The strongest predictors of emotions included the styles of coping with stress. A predictor of positive emotions was a task-oriented style, while in the case of negative emotions, an emotion-oriented way of coping was a predictor. The latter style also lowered the opportunity to experience positive emotions. Task-oriented coping relates to an important element of constructive coping with pandemic stress: control over one's surrounding reality [44]. This style involves reformulating the evaluation of the situation from a threat to a challenge or a task to be fulfilled. In the context of the pandemic, the style may be reflected in behaviors that reduce the risk of becoming infected with the virus, as well as actions such as planning everyday routines, looking for reliable information about the virus, etc.

In our research, emotion-oriented coping was a predictor of negative emotions and the original affect dimension related to lower mood (tense arousal). The adaptive way of dealing with negative emotions involves recognizing, naming, and accepting emotions that accompany difficult situations. The emotion-oriented style of coping with stress, the essence of which is focusing on one's own emotions and taking up actions aimed at reducing emotional tension, seems to be a non-adaptive solution, especially because, in the case of uncertain and uncontrollable conditions, these actions are doomed to failure. Continuous tense arousal and energetic arousal related to our body's preparation to respond to threats results in exhaustion. However, an important predictor of positive emotions was hedonic tone.

Similar to other analyses [45,46], our research has confirmed the relationship between mental wellbeing and satisfaction with life. Comparing this conclusion with the statement that an increased or decreased standard of living within the last 10 months is an important predictor of negative emotions, it could be noticed that one of the protective factors is the opportunity to use the resources gathered during the pandemic and to maintain a sense of stability/unchangeability in a changing world.

#### **5. Conclusions**

Surveys that diagnose the mental state of people in different countries are very useful in preventing negative consequences for their inhabitants' mental health. Such a diagnosis should take into account the high dynamic of changes people face during a pandemic, as well as different ways of experiencing and interpreting pandemic stress by people from a variety of cultural contexts. In the Polish reality, people are not worried about their own illness or death to a high degree, but they are concerned about their family members' health and about the crisis of trust in governmental institutions during the pandemic.

In the presented research, which was conducted during the second wave of the pandemic (December 2020), 60% of the participants revealed a high level of negative emotions. Due to the possible connection between the high intensity of negative emotions and negative consequences for one's mental health, it is important for researchers to look for factors that increase the risk of experiencing negative feelings. Significant predictors of negative emotions include mood-related tense arousal in the description of mood and an emotion-oriented style of coping with stress. On the other hand, important predictors of positive emotions are a task-oriented style of coping with stress, level of satisfaction with life, and hedonic tone in the description of mood. These aspects may become the basic indicators for specialists who will work on preventive actions and psychological care.

In addition, it is worth focusing on supporting particular at-risk groups, i.e., people over 60 years old (e.g., through increasing their online activities) or women (through increasing their chances to experience good emotions by appreciating the value of their unpaid work).

It should be emphasized that these results must be considered in the light of numerous limitations. Adults of different ages (i.e., over 18 years old) were recruited for the research. However, because of our recruitment method (i.e., snowball sampling), both men, people with primary/middle school and vocational education, and older people were underrepresented in the research sample. Another limitation is related to the type of the research. A better solution would be longitudinal research, which would allow to make reliable conclusions about the change and its dynamics in the psychological wellbeing of the sample. Finally, the research was conducted mainly by means of the Internet to provide comfort and safety to the participants. As a result, the sample consisted primarily of people who have access to the Internet. The abovementioned limitations make it impossible to generalize the research results as representative of the population as a whole.

Despite the limitations, the research results obtained shed some light on the emotional wellbeing of adult Poles during the second wave of the COVID-19 pandemic. These findings are important because the intensification of negative emotions can contribute to problems not only in mental health, but also in everyday activities, such as study, work, social relations, or sexual contacts. The authors are aware that further research should be conducted to increase the number of participants in each age group, from children to seniors.

In the context of an unpredictable future, researchers face the task of monitoring the emotional condition of the general population and of particular at-risk groups in order to inspire practical preventive and therapeutic actions, as well as social initiatives that reinforce solidarity, mutual care, and responsibility.

**Author Contributions:** Conceptualization, E.T.-S.; methodology, E.T.-S.; validation, I.R., K.B. and A.S.; formal analysis, E.T.-S. and I.R.; investigation, E.T.-S.; resources, E.T.-S. and I.R.; data curation, E.T.-S.; writing—original draft preparation, E.T.-S. and I.R.; writing—review and editing, A.S. and K.B.; visualization, E.T.-S. and I.R. All authors have read and agreed to the published version of the manuscript.

**Funding:** This research received no external funding.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of Jesuit University Ignatianum in Krakow (15 June 2021).

**Informed Consent Statement:** Informed consent was obtained from all subjects involved in the study.

**Data Availability Statement:** The data presented in this study are available on request from the corresponding author.

**Conflicts of Interest:** The authors declare no conflict of interest.


**4. Conclusions**

Stroke related to TAVR represents one of the most common and scary complications and is an independent risk factor that predicts morbidity and mortality; therefore, new strategies have been implemented to reduce its appearance. CPDs represent a novel strategy in stroke protection in patients undergoing TAVR. This evidence suggests that the use of CPD reduces the number and size of ischemic lesions identified on magnetic resonance; however, they are not yet established as a protective measure in the appearance of embolic phenomena and the reduction of ischemic lesions in TAVR patients. None of the devices we mainly studied managed to reduce the appearance of stroke; however, there was a reduction in the number of disabling strokes, which has an impact ultimately in a possible better quality of life.

*Cerebral Protection Devices in Transcatheter Aortic-Valve Replacement DOI: http://dx.doi.org/10.5772/intechopen.112661*