Journal Description
Diseases
Diseases
is an international, peer-reviewed, open access, multidisciplinary journal which focuses on the latest and outstanding research on diseases and conditions published monthly online by MDPI. The first issue is released in 2013.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, ESCI (Web of Science), PubMed, PMC, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Medicine, Research and Experimental)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 21.4 days after submission; acceptance to publication is undertaken in 2.7 days (median values for papers published in this journal in the second half of 2024).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 7 topical sections.
Impact Factor:
2.9 (2023)
Latest Articles
Real-World Efficacy and Safety of Dupilumab Use in Japanese Adult Patients with Atopic Dermatitis: A Single-Center, Retrospective, 104-Week, Observational Study
Diseases 2025, 13(2), 44; https://doi.org/10.3390/diseases13020044 (registering DOI) - 3 Feb 2025
Abstract
►
Show Figures
Background/Objectives: Dupilumab is an interlekin-4 receptor antibody that exerts its efficacy by inhibiting the signaling pathway of interleukin-4/interleukin-13, and it is currently used clinically as a highly potent therapeutic for atopic dermatitis. However, there have been few reports on the therapeutic effect of
[...] Read more.
Background/Objectives: Dupilumab is an interlekin-4 receptor antibody that exerts its efficacy by inhibiting the signaling pathway of interleukin-4/interleukin-13, and it is currently used clinically as a highly potent therapeutic for atopic dermatitis. However, there have been few reports on the therapeutic effect of dupilumab using long-term real-world data. To accumulate further real-world data through long-term use of dupilumab, we performed a retrospective study on the courses of patients with atopic dermatitis who were treated with dupilumab for at least 104 weeks in our university hospital. Methods: We examined the treatment courses of 30 adult patients. Results: Subjective (e.g., itch visual analog scale and Dermatology Life Quality Index) and objective (e.g., Eczema Area and Severity Index) indices and some biomarkers showed improvements over time with dupilumab treatment, even in cases with poor early response to dupilumab treatment. As for the therapeutic effect on anatomical regions, although the therapeutic effect on the head and neck region was weak in the early stages, it improved over time, and at 104 weeks, it showed a therapeutic effect that was comparable to other regions. Conclusions: Therefore, our study demonstrated the advantages of prolonged administration of dupilumab in atopic dermatitis.
Full article
Open AccessCommunication
Impact of HPV Types and Dendritic Cells on Recurrent Respiratory Papillomatosis’ Aggressiveness
by
Ellen Eduarda Fernandes, Maria Leticia de Almeida Lança, Yan Aparecido de Souza, Vivian Narana El-Achkar, Victor Costa, Román Carlos, Alfredo Ribeiro-Silva, Laura Sichero, Luisa Lina Villa, Jorge Esquiche León and Estela Kaminagakura
Diseases 2025, 13(2), 43; https://doi.org/10.3390/diseases13020043 (registering DOI) - 3 Feb 2025
Abstract
►▼
Show Figures
Objective: This study assesses the associations between dendritic cells, HPV 6 and 11, and Recurrent Respiratory Papillomatosis (RRP) aggressiveness. Methods: The Derkay score was calculated using information obtained from the medical records. Biopsies from 36 patients with juvenile RRP (JRRP) and 43 adult
[...] Read more.
Objective: This study assesses the associations between dendritic cells, HPV 6 and 11, and Recurrent Respiratory Papillomatosis (RRP) aggressiveness. Methods: The Derkay score was calculated using information obtained from the medical records. Biopsies from 36 patients with juvenile RRP (JRRP) and 43 adult RRP (ARRP) patients were analyzed under light microscopy, and their clinical data were collected. Immunohistochemical analysis using antibodies against CD83, CD1a, Factor XIIIa, and S100 was performed, and inflammatory cells were quantified. Data obtained were analyzed using the chi-squared test, in addition to the Mann–Whitney and Z tests for two proportions, considering a confidence interval of 95% and p < 0.05 as statistically significant. Results: A higher quantity of S100 was identified in the epithelium (p < 0.001) and in the conjunctive tissue (p = 0.027) among the ARRP cases, while CD83 (p = 0.025) and Factor XIIIa (p = 0.018), both in the epithelium, were identified among the JRRP cases. We observed significant association between a higher quantity of CD83 in the epithelium in the juvenile group with a low Derkay index (p = 0.034) and with HPV 6 (p = 0.039). Conclusions: An increased quantity of dendritic cells is present in individuals diagnosed with RRP, regardless of age, and this may be related to the lower Derkay index, regardless of the HPV type detected.
Full article
Figure 1
Open AccessReview
The Role of Cortisol and Dehydroepiandrosterone in Obesity, Pain, and Aging
by
Nikolina Erceg, Miodrag Micic, Eli Forouzan and Nebojsa Nick Knezevic
Diseases 2025, 13(2), 42; https://doi.org/10.3390/diseases13020042 (registering DOI) - 1 Feb 2025
Abstract
Obesity, chronic pain, and aging are prevalent global challenges with profound implications for health and well-being. Central to these processes are adrenal hormones, particularly cortisol and dehydroepiandrosterone (DHEA), along with its sulfated form (DHEAS). Cortisol, essential for stress adaptation, can have adverse effects
[...] Read more.
Obesity, chronic pain, and aging are prevalent global challenges with profound implications for health and well-being. Central to these processes are adrenal hormones, particularly cortisol and dehydroepiandrosterone (DHEA), along with its sulfated form (DHEAS). Cortisol, essential for stress adaptation, can have adverse effects on pain perception and aging when dysregulated, while DHEA/S possess properties that may mitigate these effects. This review explores the roles of cortisol and DHEA/S in the contexts of obesity, acute and chronic pain, aging, and age-related diseases. We examine the hormonal balance, specifically the cortisol-to-DHEA ratio (CDR), as a key marker of stress system functionality and its impact on pain sensitivity, neurodegeneration, and physical decline. Elevated CDR and decreased DHEA/S levels are associated with worsened outcomes, including increased frailty, immune dysfunction, and the progression of age-related conditions such as osteoporosis and Alzheimer’s disease. This review synthesizes the current literature to highlight the complex interplay between these hormones and their broader implications for health. It aims to provide insights into potential future therapies to improve pain management and promote healthy weight and aging. By investigating these mechanisms, this work contributes to a deeper understanding of the physiological intersections between pain, aging, and the endocrine system.
Full article
Open AccessReview
The Critical Role of Penicillin in Syphilis Treatment and Emerging Resistance Challenges
by
Arun Kumar Jaiswal, Lucas Gabriel Rodrigues Gomes, Aline Ferreira Maciel de Oliveira, Siomar de Castro Soares and Vasco Azevedo
Diseases 2025, 13(2), 41; https://doi.org/10.3390/diseases13020041 (registering DOI) - 31 Jan 2025
Abstract
Syphilis, a global healthcare burden, is a sexually transmitted infection caused by the spirochete Treponema pallidum, a spiral-shaped, Gram-negative obligate human pathogen. Despite its easy identification and treatability, the disease affects over 50 million people worldwide, with 8 million new cases in
[...] Read more.
Syphilis, a global healthcare burden, is a sexually transmitted infection caused by the spirochete Treponema pallidum, a spiral-shaped, Gram-negative obligate human pathogen. Despite its easy identification and treatability, the disease affects over 50 million people worldwide, with 8 million new cases in the 15–49 age group annually, as per the WHO 2024 report. If left untreated, syphilis progresses through its primary, secondary, latent, and tertiary stages, causing severe complications like neurosyphilis, congenital syphilis, and organ damage. The first-line treatment, penicillin, faces challenges, including logistical issues, shortages, allergic reactions, and patient non-compliance. Secondary treatment options are sparse, and there are reported cases of T. pallidum strains resistant to those antibiotics. The absence of an effective vaccine for syphilis has led to efforts to control its spread through sexual education, condom usage, and post-exposure prophylaxis with doxycycline, which raises concerns about antimicrobial resistance (AMR). The continued reliance on penicillin and the increasing rates of doxycycline post-exposure prophylaxis (DoxyPEP) use have both contributed to concerns about AMR development. Recent works pointing to emerging antibiotic resistance and treatment failures highlight the urgent need for new antibiotics to manage syphilis effectively and reduce dependency on penicillin. This review has focused on the shortcomings and limitations of penicillin treatment, recently identified antimicrobial-resistant strains of T. pallidum, and case studies where its application failed to treat the disease adequately.
Full article
Open AccessArticle
A Retrospective Review of 28 Cases of Pediatric Malignant Renal Tumors at a Single Institution
by
Takafumi Kawano, Koshiro Sugita, Ryuta Masuya, Nanako Nishida, Ayaka Nagano, Masakazu Murakami, Keisuke Yano, Shun Onishi, Toshio Harumatsu, Tatsuro Nakamura, Koji Yamada, Waka Yamada, Mitsuru Muto, Yuichi Kodama, Takuro Nishikawa, Tatsuru Kaji, Yasuhiro Okamoto and Satoshi Ieiri
Diseases 2025, 13(2), 40; https://doi.org/10.3390/diseases13020040 - 31 Jan 2025
Abstract
Advances in treatment have dramatically improved the outcomes of pediatric renal malignancies. We reviewed cases of renal malignant tumors that were managed in our institution. The patients’ background factors, pathological diagnoses, stages, outcomes and late complications were retrospectively reviewed using medical records of
[...] Read more.
Advances in treatment have dramatically improved the outcomes of pediatric renal malignancies. We reviewed cases of renal malignant tumors that were managed in our institution. The patients’ background factors, pathological diagnoses, stages, outcomes and late complications were retrospectively reviewed using medical records of 28 patients with renal tumors who were treated at our institution from 1984 to 2022. Wilms’ tumors were recognized in 24 patients (85.7%), all of whom had favorable histology. Wilms’ tumors were Stage I in six patients (6/24; 25.0%), Stage II in nine patients (9/24; 37.5%), Stage III in five patients (5/24; 20.8%), Stage IV in two patients (2/24; 8.3%), and Stage V in two patients (2/24; 8.3%). Two patients (7.1%) with clear cell sarcoma of the kidney both had Stage I disease. One patient had Stage IV rhabdoid sarcoma of the kidney (3.5%), and one had Stage IV renal cell carcinoma (3.5%). The overall 5-year survival rate was 85.2% for all renal malignancies. Late complications included chronic renal failure in four patients (14.2%). The outcomes are comparable to those reported previously. However, the prognosis of MRTK and renal cell carcinoma remained poor in advanced cases; thus, another therapeutic protocol should be established.
Full article
Open AccessReview
The Spectrum of Cognitive Impairment in Atypical Parkinsonism Syndromes: A Comprehensive Review of Current Understanding and Research
by
Kurt A. Jellinger
Diseases 2025, 13(2), 39; https://doi.org/10.3390/diseases13020039 - 31 Jan 2025
Abstract
Multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) are the most common atypical parkinsonism (AP) syndromes. They are clinically characterized by varying combinations of levodopa-poorly responsive parkinsonism, motor, cerebellar, and other signs. They are associated with a wide spectrum
[...] Read more.
Multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD) are the most common atypical parkinsonism (AP) syndromes. They are clinically characterized by varying combinations of levodopa-poorly responsive parkinsonism, motor, cerebellar, and other signs. They are associated with a wide spectrum of non-motor symptoms, including prominent cognitive impairment such as global cognitive deficits, memory, executive, attentional, visuospatial, language, and non-verbal reasoning dysfunctions. Within the APs, their cognitive functioning is distributed along a continuum from MSA with the least impaired cognitive profile (similar to Parkinson’s disease) to PSP and CBD with the greatest decline in global cognitive and executive domains. Although their pathological hallmarks are different—MSA α-synucleinopathy, CBD, and PSP 4-repeat tauopathies—cognitive dysfunctions in APs show both overlaps and dissimilarities. They are often preceding and anticipate motor dysfunctions, finally contributing to reduced quality of life of patients and caregivers. The present paper will review the current evidence of the prevalence and type of cognitive impairment in these AP syndromes, their neuroimaging, pathogenic backgrounds, and current management options based on extensive literature research. Cognitive dysfunctions in APs are due to disruption of prefronto-subcortical and striato-thalamo-cortical circuitries and multiple essential brain networks. This supports the concept that they are brain network disorders due to complex pathogenic mechanisms related to the basic proteinopathies that are still poorly understood. Therefore, the pathophysiology and pathogenesis of cognitive impairment in APs deserve further elucidation as a basis for early diagnosis and adequate treatment of these debilitating comorbidities.
Full article
(This article belongs to the Section Neuro-psychiatric Disorders)
Open AccessCase Report
Herpes Simplex Keratitis and Vitamin D Receptor Agonist: Two Case Reports
by
Atsushi Kawahara
Diseases 2025, 13(2), 38; https://doi.org/10.3390/diseases13020038 - 30 Jan 2025
Abstract
►▼
Show Figures
Background: Herpes simplex keratitis (HSK) is a disease characterized by the recurrent infection of the cornea, mainly due to infection caused by herpes simplex virus type 1. The suppression of recurrence can suppress progressive corneal scarring, ulcers, and perforation. Cornea contains vitamin D
[...] Read more.
Background: Herpes simplex keratitis (HSK) is a disease characterized by the recurrent infection of the cornea, mainly due to infection caused by herpes simplex virus type 1. The suppression of recurrence can suppress progressive corneal scarring, ulcers, and perforation. Cornea contains vitamin D receptors (VDRs). VDR agonists show antimicrobial activity. Case presentation: In this case report, I describe two female patients aged 76 and 85 years old in whom the administration of a VDR agonist led to the suppression of the recurrence of HSK. The former patient had repeated HSK recurrence for over 10 years after the initial infection. The latter patient developed HSK immediately after vitrectomy, and her cornea remained susceptible to infection, resulting in recurrence. Both patients were trying to suppress recurrence by applying acyclovir ophthalmic ointment, but their medication adherence was declining. So, they switched to oral treatment with 0.5 μg of the VDR agonist per day, and since then, there has been no recurrence of HSK. Oral treatment with the VDR agonist is still ongoing. Conclusions: This report highlights the cases where ways were examined to improve medication adherence in elderly patients who had a risk of HSK recurrence. Both patients responded to VDR agonist treatment and were able to suppress recurrence.
Full article
Figure 1
Open AccessArticle
Is There Bias in the Assessment of Contraindications for Resection? Disparities in the Surgical Management of Early-Stage Esophageal Cancer
by
Christina S. Boutros, Lauren M. Drapalik, Christine E. Alvarado, Aria Bassiri, Jillian Sinopoli, Leonidas Tapias Vargas, Philip A. Linden and Christopher W. Towe
Diseases 2025, 13(2), 37; https://doi.org/10.3390/diseases13020037 - 30 Jan 2025
Abstract
►▼
Show Figures
Background: Resection is considered the standard of care for patients with localized esophageal cancer who are “physiologically fit”. Patients who do not meet this standard are considered contraindicated to receive surgery. We hypothesized that among patients with non-metastatic esophageal cancer, the consideration of
[...] Read more.
Background: Resection is considered the standard of care for patients with localized esophageal cancer who are “physiologically fit”. Patients who do not meet this standard are considered contraindicated to receive surgery. We hypothesized that among patients with non-metastatic esophageal cancer, the consideration of contraindication status would vary based on clinical and demographic factors and would vary between institutions. Methods: We identified patients with non-metastatic gastric and esophageal cancer in the National Cancer Database (NCDB) from 2004 to 2018. Patients were categorized into three groups based on surgical treatment: surgical resection (including endoscopic mucosal resection), resection contraindicated, and refusal of resection based on the coding of the “reason for no surgery” data element. Demographic, clinical, and institutional characteristics were compared between the groups using bivariate and multivariate techniques to identify factors associated with contraindicated status. A subgroup analysis of cT1N0M0 patients was also used to assess every institution in the NCDB’s observed–expected ratio for contraindication status. Results: In total, 144,591 patients with non-metastatic disease met inclusion criteria: 124,972 (86%) underwent resection, 13,793 (10%) were contraindicated for resection, and 5826 (4%) refused resection. Contraindication was associated with age, non-Hispanic Black race, socioeconomic status, Charlson–Deyo score, insurance type, institution characteristics, clinical T-stage, and clinical N-stage. There were 9459 patients who were cT1N0M0 and had no co-morbidities. In this cohort, there were more than 1000-fold differences between individual programs regarding observed–expected ratio of contraindication status when adjusting for clinical and demographic characteristics. Conclusions: Variation in the assessment of contraindication status varies dramatically between institutions. Underserved minorities, including age, race, and insurance type, are risk factors for being considered contraindicated. These findings highlight the disparities that exist regarding surgical care of non-metastatic esophageal cancer in the United States.
Full article
Figure 1
Open AccessArticle
Ultradiluted Eupatorium perfoliatum Prevents and Alleviates SARS-CoV-2 Spike Protein-Induced Lung Pathogenesis by Regulating Inflammatory Response and Apoptosis
by
Anirban Roy, Avipsha Sarkar, Asit Kumar Roy, Tanusree Ghorai, Debadatta Nayak, Subhash Kaushik and Satadal Das
Diseases 2025, 13(2), 36; https://doi.org/10.3390/diseases13020036 - 30 Jan 2025
Abstract
►▼
Show Figures
Background/Objectives: SARS-CoV-2 provokes acute oxidative stress in the lungs via cytokines, inflammatory mediators, and apoptotic factors, which might cause alveolar injury followed by severe respiratory syndrome during COVID-19 infection. The lack of particular antivirals for SARS-CoV-2 has opened novel avenues of complementary and
[...] Read more.
Background/Objectives: SARS-CoV-2 provokes acute oxidative stress in the lungs via cytokines, inflammatory mediators, and apoptotic factors, which might cause alveolar injury followed by severe respiratory syndrome during COVID-19 infection. The lack of particular antivirals for SARS-CoV-2 has opened novel avenues of complementary and alternative medicine as a potential remedy. The current study explored the mechanistic role of the ultradiluted formulation of Eupatorium (UDE) against SARS-CoV-2 recombinant S protein-mediated oxidative stress and mitochondriopathy. Methods: Cell line and BALB/c mice were used to report that SARS-CoV-2 S protein caused an inflammatory response and subsequent cytokine storm via the NF-κB pathway in the lung along with oxidative damage. Morphological examination was performed using DAPI staining and histology for treated cells and lung tissues of animals, respectively. The molecular mechanism of action of UDE was investigated through qRT-PCR for the genetic expressions of various cytokines, inflammatory, and apoptotic mediators; ELISA, immunofluorescence, immunohistochemistry, and Western blot for the translational expression of the same molecules assayed for genetic expressions; and biochemical assays for various enzymes and ROS. Results: UDE treatment suppressed the inflammatory cell infiltration and tissue-level oxidative stress and safeguarded mitochondrial integrity from free radical-mediated oxidative damage. Additionally, UDE played a direct role in restoring cellular redox homeostasis and reducing the inflammatory response by suppressing NF-κB, IL-1β, IL-18, caspase-1 expression, and ROS formation. Further, a plausible mechanism of action of UDE against S protein-induced damage was proposed. Conclusions: This study described a novel therapeutic approach against S protein-mediated hyperinflammation, apoptosis, and oxidative damage. Hence, UDE may be considered as a prospective alternative to combat life-threatening consequences of SARS-CoV-2 infection.
Full article
Figure 1
Open AccessArticle
Burden and Economic Impact of Respiratory Viral Infections in Adults Aged 60 and Older: A Focus on RSV
by
Adrián Peláez, Sara Jimeno, Mercedes Villarreal, Manuel Gil, Inés Gutiérrez, Marta Sanz and Silvina Natalini Martínez
Diseases 2025, 13(2), 35; https://doi.org/10.3390/diseases13020035 - 28 Jan 2025
Abstract
Background/Objectives: Respiratory syncytial virus (RSV) represents a significant cause of acute respiratory infections (ARIs) in adults aged 60 years and older, often leading to severe clinical outcomes and high healthcare costs. This study aimed to evaluate the clinical and economic burden of RSV
[...] Read more.
Background/Objectives: Respiratory syncytial virus (RSV) represents a significant cause of acute respiratory infections (ARIs) in adults aged 60 years and older, often leading to severe clinical outcomes and high healthcare costs. This study aimed to evaluate the clinical and economic burden of RSV compared to other ARIs, focusing on specific age groups, comorbidities, and demographic factors. Methods: A retrospective observational study was conducted using the electronic medical records of adults aged ≥60 years hospitalized for ARIs, including RSV, in Spain. Direct costs related to hospitalizations, intensive care unit (ICU) admissions, and treatments were analyzed. The study also assessed demographic, clinical, and comorbidity-related factors influencing the economic burden. Results: RSV infections resulted in significantly higher direct costs compared to other ARIs, particularly in patients aged 70–80 years. Comorbidities such as asthma and smoking history were associated with increased costs in RSV cases. Although ICU costs were comparable between groups, hospitalizations for RSV required longer stays and more intensive treatments, amplifying the overall economic burden. Differences in costs by age and sex highlighted the need for tailored clinical management strategies. Conclusions: RSV poses a substantial economic and clinical burden on adults aged 60 years and older, particularly in those with comorbidities. Preventive measures, such as vaccination, could reduce healthcare costs and improve outcomes in this vulnerable population. These findings support the inclusion of RSV vaccines in immunization programs, especially in aging populations like Spain, to alleviate healthcare pressures during peak respiratory disease seasons.
Full article
Open AccessArticle
Understanding General Practitioner and Patient Perceptions Regarding Integration of Non-Pharmacological Interventions in Chronic Non-Cancer Pain Management—A Cross-Sectional Mixed-Methods Study in the RELIEF Project
by
Regina Poß-Doering, Sarina Carter, Sabrina Brinkmöller, Melanie Möhler, Dominik Dupont, Cinara Paul, Marco R. Zugaj, Viktoria Wurmbach, Alexandra Balzer, Michel Wensing and Cornelia Straßner
Diseases 2025, 13(2), 34; https://doi.org/10.3390/diseases13020034 - 28 Jan 2025
Abstract
►▼
Show Figures
Background: Chronic non-cancer-related pain is an independent condition with a multicausal genesis. Guidelines highlight the need for holistic treatment based on the bio-psycho-social model. While prescribing medication is common, it remains unclear how and to what extent non-pharmacological interventions are considered and recommended
[...] Read more.
Background: Chronic non-cancer-related pain is an independent condition with a multicausal genesis. Guidelines highlight the need for holistic treatment based on the bio-psycho-social model. While prescribing medication is common, it remains unclear how and to what extent non-pharmacological interventions are considered and recommended in general practice pain management. The project RELIEF explored the integration of non-pharmacological interventions in general practices in Germany from both physician and patient perspectives. Methods: A mixed-methods study collected data with patients and general practitioners via semi-structured telephone interviews and self-developed questionnaires. Qualitative data were analyzed in a reflexive thematic analysis. Survey data were analyzed descriptively. Results: N = 383 questionnaires (n = 131 general practitioners, n = 252 patients) and n = 61 interviews (n = 21 general practitioners, n = 40 patients) were analyzed. Patient and physician perceptions regarding the integration of non-pharmacological interventions differed. Patients felt pharmacological therapy was recommended primarily, applied non-pharmacological interventions based on their own initiative, and were aware of bio-psycho-social interrelations. Physicians perceived that they often recommended physiotherapy and psychotherapy alongside analgesics, and asked about non-pharmacological interventions (79.4%), explained the bio-psycho-social chronic pain genesis (55.7%), and provided information on physical (48.9%) and social (35.9%) activity, relaxation techniques (42%), topical applications (31.9%), and support groups (25.2%). Conclusions: The integration of holistic pain management and communication between patients and general practitioners appear to need strengthening.
Full article
Figure 1
Open AccessArticle
Risk of Insulin Resistance in 44,939 Spanish Healthcare Workers: Association with Sociodemographic Variables and Healthy Habits
by
Pedro Javier Tárraga Marcos, Ángel Arturo López-González, Emilio Martínez-Almoyna Rifá, Hernán Paublini Oliveira, Cristina Martorell Sánchez, Pedro Juan Tárraga López and José Ignacio Ramírez-Manent
Diseases 2025, 13(2), 33; https://doi.org/10.3390/diseases13020033 - 27 Jan 2025
Abstract
►▼
Show Figures
Introduction: Insulin resistance (IR) is a highly prevalent pathophysiological entity implicated in the development of a wide variety of metabolic, cardiovascular, and endocrine disorders. The aim of this study is to assess the association between sociodemographic variables and healthy habits with IR risk
[...] Read more.
Introduction: Insulin resistance (IR) is a highly prevalent pathophysiological entity implicated in the development of a wide variety of metabolic, cardiovascular, and endocrine disorders. The aim of this study is to assess the association between sociodemographic variables and healthy habits with IR risk scales. Methodology: This dual study, incorporating both longitudinal-retrospective and cross-sectional designs, analyzed healthcare workers across four professional categories (physicians, nurses, healthcare technicians, and auxiliary personnel). It examined the association of age, sex, professional category, smoking status, physical activity, and adherence to the Mediterranean diet with elevated scores on insulin resistance risk scales. Results: All the variables analyzed were associated with the presence of elevated values of the IR scales, with age, sex, and physical activity showing the strongest association (reflected in the odds ratio values). Conclusions: The profile of an individual with a higher risk of presenting elevated values of the IR risk scales would be an elderly male auxiliary health worker who is a smoker and is physically inactive, with a low adherence to the Mediterranean diet.
Full article
Figure 1
Open AccessArticle
Novel Pathways of Oxidative and Nitrosative Inactivation of the Human MGMT Protein in Colon Cancer and Glioblastoma Cells: Increased Efficacy of Alkylating Agents In Vitro and In Vivo
by
Debasish Basak, Agm Mostofa, Hanumantha Rao Madala and Kalkunte S. Srivenugopal
Diseases 2025, 13(2), 32; https://doi.org/10.3390/diseases13020032 - 25 Jan 2025
Abstract
Background: O6-Methylguanine-DNA methyltransferase (MGMT) is a unique antimutagenic DNA repair protein that plays a crucial role in conferring resistance to various alkylating agents in brain tumor therapy. In this study, we exploited the susceptibility of the active site Cys145 of MGMT
[...] Read more.
Background: O6-Methylguanine-DNA methyltransferase (MGMT) is a unique antimutagenic DNA repair protein that plays a crucial role in conferring resistance to various alkylating agents in brain tumor therapy. In this study, we exploited the susceptibility of the active site Cys145 of MGMT for thiolation and nitrosylation, both of which inactivate the enzyme. Methods: We designed a redox perturbing glutathione mimetic, a platinated homoglutathione disulfide (hGTX) by adding small amounts of cisplatin (1000:10) and used a nitric oxide-donor spermine NONOate. N6022, a potent inhibitor of S-nitrosoglutathione reductase was used to extend the retention of nitrosylated MGMT in tumor cell culture and subcutaneous xenografts. Results: Both hGTX and spermine NONOate inhibited MGMT activity in HT29, SF188, T98G, and other brain tumor cells. There was a robust increase in the alkylation-induced DNA interstrand cross-linking, G2/M cell cycle arrest, cytotoxicity, and the levels of apoptotic markers when either of the agents was used with alkylating agents. In the nude mice bearing T98G and HT29-luc2 xenografts, combinations of hGTX and spermine NONOate with alkylating agents produced a marked reduction in MGMT protein and tumor growth delay and regressions. N6022 treatment increased the presence of nitrosylated MGMT for a longer time, thereby extending the DNA-repair deficient state both in cell culture and preclinical settings. Conclusions: Our findings highlight the options for redox-driven therapeutic strategies for MGMT and suggest that oxidative and/or nitrosative inactivation of DNA repair in combination with alkylating agents could be exploited.
Full article
(This article belongs to the Section Oncology)
Open AccessArticle
Age and Tumor Stage Interplay in Intrahepatic Cholangiocarcinoma: Prognostic Factors, Mortality Trends, and Therapeutic Implications from a SEER-Based Analysis
by
Ayrton Bangolo, Vignesh K. Nagesh, Hadrian Hoang-Vu Tran, Brooke Sens, Daniel Elias, Behzad Amoozgar, Chase Tomasino, Izage Kianifar Aguilar, Charlene Mansour, Elizabeth Gagen, Lili Zhang, Sarvarinder Gill, Nisrene Jebara, Emma Madigan, Christin Candela, Dohaa Amin, Peter Giunta, Shubhangi Singh, Aman Siddiqui, Auda Auda, Paul Peej, Timophyll Y. H. Fong, Simcha Weissman, Printhia Matshi Lihau and John Bukasa-Kakambaadd
Show full author list
remove
Hide full author list
Diseases 2025, 13(2), 31; https://doi.org/10.3390/diseases13020031 - 25 Jan 2025
Abstract
Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent
[...] Read more.
Background: Intrahepatic cholangiocarcinoma (ICC), a malignancy originating from the epithelial cells of bile ducts, has shown a notable rise in its incidence over the years. It ranks as the second most frequent primary liver cancer after hepatocellular carcinoma. This study investigates how independent prognostic factors, specifically, age and tumor stage, interact to impact mortality in ICC patients. Furthermore, it examines the clinical features, survival rates, and prognostic indicators of ICC cases diagnosed between 2010 and 2017. Methods: Using data from 5083 patients obtained from the Surveillance, Epidemiology, and End Results (SEER) database, this study evaluated demographic and clinical factors alongside overall mortality (OM) and cancer-specific mortality (CSM). Variables achieving a p-value below 0.1 in univariate Cox regression analysis were incorporated into multivariate Cox regression models to identify independent prognostic factors. Hazard ratios (HRs) exceeding 1 were interpreted as markers of poor prognosis. Additionally, this study explored the interaction between age and tumor stage in shaping survival outcomes. Results: The multivariate Cox proportional hazards analysis indicated higher OM in males (HR = 1.19, 95% CI: 1.12–1.26, p < 0.01) and residents of metropolitan counties with populations exceeding 250,000 (HR = 1.15, 95% CI: 1.01–1.31, p < 0.05). Conversely, lower OM was observed in individuals aged 40–59 years (HR = 0.58, 95% CI: 0.38–0.89, p < 0.05), those aged 60–79 years (HR = 0.65, 95% CI: 0.43–0.98, p < 0.05), and patients who received radiation therapy (HR = 0.78, 95% CI: 0.72–0.85, p < 0.01), chemotherapy (HR = 0.54, 95% CI: 0.51–0.58, p < 0.01), or surgery (HR = 0.29, 95% CI: 0.26–0.31, p < 0.01). For CSM, males exhibited higher risks (HR = 1.17, 95% CI: 1.10–1.25, p < 0.01), as did individuals in metropolitan counties with populations over 250,000 (HR = 1.18, 95% CI: 1.03–1.35, p < 0.05). Reduced CSM was observed in patients aged 40–59 years (HR = 0.52, 95% CI: 0.34–0.79, p < 0.01), those aged 60–79 years (HR = 0.57, 95% CI: 0.38–0.86, p < 0.01), and those undergoing radiation therapy (HR = 0.76, 95% CI: 0.70–0.83, p < 0.01), chemotherapy (HR = 0.55, 95% CI: 0.51–0.59, p < 0.01), or surgery (HR = 0.27, 95% CI: 0.25–0.30, p < 0.01). When examining the interaction between age and tumor stage, higher OM was observed in patients aged 40–59 with tumors involving lymph nodes (HR = 1.26, 95% CI: 1.14–2.67, p < 0.05). Similarly, CSM was elevated in patients aged 40–59 with lymph node involvement alone (HR = 2.60, 95% CI: 1.26–5.36, p < 0.05) or with direct spread (HR = 2.81, 95% CI: 1.04–7.61, p < 0.05). Among those aged 60–79, higher CSM was noted in cases with lymph node involvement only (HR = 2.24, 95% CI: 1.11–4.50, p < 0.05) or lymph node involvement accompanied by direct extension (HR = 2.93, 95% CI: 1.10–7.82, p < 0.05). Conclusions: This retrospective analysis, utilizing data from the SEER database, provides new insights into mortality patterns in intrahepatic cholangiocarcinoma (ICC). This study identifies a significant interplay between two key prognostic factors, emphasizing their collective role in influencing mortality outcomes. Despite the predominance of advanced-stage diagnoses, our analysis underscores the substantial survival benefits associated with treatment interventions, with surgical procedures demonstrating the most pronounced impact. These findings highlight the importance of recognizing patients who may benefit from timely and intensive therapeutic strategies. Furthermore, the results underscore the need for future prospective randomized studies to deepen our understanding of these interactions in ICC, particularly as advancements in precision oncology continue to refine patient care.
Full article
(This article belongs to the Section Gastroenterology)
Open AccessArticle
Comparative Analysis of Blood MMP-9 Concentration in Alcohol- and Opioid-Addicted Patients
by
Tamar Kartvelishvili, Nelly Sapojnikova, Nino Asatiani, Lali Asanishvili, Victor Sokhadze, Nestan Sichinava and Zaza Chikovani
Diseases 2025, 13(2), 30; https://doi.org/10.3390/diseases13020030 - 24 Jan 2025
Abstract
►▼
Show Figures
Background/Objectives: In brain physiology and disease, MMP-9 is a significant and apparently peculiar factor. Numerous studies have implicated neuroinflammatory processes involving MMP-9 in the pathophysiology of addiction. This study aims to evaluate plasma MMP-9 level as a biomarker for the stages of alcohol
[...] Read more.
Background/Objectives: In brain physiology and disease, MMP-9 is a significant and apparently peculiar factor. Numerous studies have implicated neuroinflammatory processes involving MMP-9 in the pathophysiology of addiction. This study aims to evaluate plasma MMP-9 level as a biomarker for the stages of alcohol and opioid addiction. Methods: The case subjects were patients with opioid and alcohol addiction. The quantitative assessment of MMP-9 plasma concentration was performed using monoclonal antibodies against human MMP-9. Results: MMP-9 levels in the plasma of patients with alcohol and opioid dependence differ from MMP-9 concentrations in apparently healthy donors. During the intoxication stage, MMP-9 concentrations in individuals with alcohol and opioid dependence are similar and higher than in the control group. While the MMP-9 level is close to the control level after alcohol withdrawal, it stays increased during opioid withdrawal. When MMP-9 levels in plasma were measured in three distinct intoxicated states (light, moderate, and heavy) in cases of alcohol addiction, the results were all similar. Two distinct opioid intoxicated states (methadone and buprenorphine) and three withdrawals—following methadone, buprenorphine, and heroin abuse—were associated with high MMP-9 levels.
Full article
Figure 1
Open AccessCase Report
Pseudohypertriglyceridemia in a Patient with Pancreatitis Without Evidence for Glycerol Kinase Deficiency: A Rare Case Report and Review of the Literature
by
Jianping Zhu, Chunjuan Zhang and Rui Zhao
Diseases 2025, 13(2), 29; https://doi.org/10.3390/diseases13020029 - 23 Jan 2025
Abstract
►▼
Show Figures
Background: Pseudohypertriglyceridemia (pseudo-HTG) is a condition in patients with glycerol kinase deficiency or other disorders of glycerol metabolism, as well as in individuals with alcoholism, severe liver disease, or metabolic disturbances, and those receiving heparin therapy. Exogenous glycerol intake can also trigger this
[...] Read more.
Background: Pseudohypertriglyceridemia (pseudo-HTG) is a condition in patients with glycerol kinase deficiency or other disorders of glycerol metabolism, as well as in individuals with alcoholism, severe liver disease, or metabolic disturbances, and those receiving heparin therapy. Exogenous glycerol intake can also trigger this condition. However, the causes of pseudo-HTG are poorly understood, and a clinical algorithm for its diagnosing remains to be developed. Case presentation: We present the case of a 46-year-old man admitted to hospital with hypertriglyceridemia-induced severe acute pancreatitis (HTG-SAP) and type 2 diabetes mellitus. Upon admission, his plasma triglyceride (TG) level was critically high at 43.78 mmol/L (3877 mg/dL). During hospitalization, he developed acute renal insufficiency and diabetic ketoacidosis (DKA). Despite conventional lipid-lowering treatments, including extracorporeal lipoprotein apheresis, his TG levels remained elevated. The unusually clear serum led to suspicion of pseudo-HTG. A glycerol-corrected TG assay confirmed normal TG values, thereby diagnosing pseudo-HTG. Conclusions: This report presents the first confirmed case of pseudo-HTG verified through definitive glycerol kinase (GK) gene testing in a patient without glycerol kinase deficiency. We also include a review of the relevant literature and propose a clinical algorithm. The case report highlights the importance of considering pseudo-HTG in hypertriglyceridemia patients who do not respond well to the standard TG-lowering treatment. Our proposed clinical algorithm for diagnosing pseudo-HTG is potentially invaluable in clinical practice, and helps to prevent unnecessary lipid-lowering treatments for patients with pseudo-HTG.
Full article
Figure 1
Open AccessArticle
The Association Between Childhood Experience of Living with a Heavy Drinker and Self-Rated Mental Health in the Adult General Population
by
Danica Romac, Varja Gaić Đogaš, Ljiljana Muslić, Sandro Krašić, Marija Kušan Jukić and Sanja Musić Milanović
Diseases 2025, 13(2), 28; https://doi.org/10.3390/diseases13020028 - 23 Jan 2025
Abstract
Background and Objectives: Considering the link between childhood experiences with adult health and well-being, this study examined how living with a heavy drinker (HD) during childhood affected self-rated mental health (SRMH) in adulthood, while identifying risk and protective factors and assessing the prevalence
[...] Read more.
Background and Objectives: Considering the link between childhood experiences with adult health and well-being, this study examined how living with a heavy drinker (HD) during childhood affected self-rated mental health (SRMH) in adulthood, while identifying risk and protective factors and assessing the prevalence within a regional context. Materials and Methods: Data (N = 11,113) were obtained from a cross-sectional DEEP SEAS survey (2021) of the general population, aged 18–64 years, in six countries (Croatia, Bosnia and Herzegovina, Slovenia, Austria, Hungary, and Italy). Results: A statistically significant difference in SRMH was found, related to the childhood experience of living with an HD (MD = −0.221, 95% CI −0.250–0.172, N = 10,886) and being negatively affected (MD = −0.216, 95% CI −0.311–0.122, N = 2978). The correlation analysis revealed that individuals who lived with an HD during childhood perceived poorer SRMH in adulthood, consistently across all observed countries. Subsequent logistic regression identified different predictors for SRMH between those who were negatively affected and those who were not. The relationship satisfaction (RAS) was the strongest predictor, significantly contributing to better SRMH, especially in the subgroup that was not negatively affected (OR 28.724, 95% CI 3.450–239.173). A high prevalence of individuals negatively affected was found, especially in Hungary (34.4%) and Croatia (26.5%). Conclusions: Growing up with someone who was a heavy drinker may have lasting negative consequences on SRMH, with a negative subjective evaluation of mental health in adulthood. Targeted public health and preventive measures are needed to protect those living with heavy drinkers.
Full article
(This article belongs to the Special Issue Mental Health Across the Lifespan: Integrating Multidisciplinary Perspectives)
Open AccessArticle
Outcomes of Outpatient Elective Esophageal Varices Band Ligation in Cirrhosis Patients with Significant Thrombocytopenia
by
Nisar Amin, Mark Ayoub, Julton Tomanguillo, Harleen Chela, Veysel Tahan and Ebubekir Daglilar
Diseases 2025, 13(2), 27; https://doi.org/10.3390/diseases13020027 - 23 Jan 2025
Abstract
Background: Current guidelines advise against platelet transfusion prior to emergent esophageal variceal band ligation (EVL) in cirrhotic patients with platelet counts below 50 × 103/μL. However, recommendations for elective EVL remain unclear. This study evaluates the outcomes of cirrhotic patients undergoing
[...] Read more.
Background: Current guidelines advise against platelet transfusion prior to emergent esophageal variceal band ligation (EVL) in cirrhotic patients with platelet counts below 50 × 103/μL. However, recommendations for elective EVL remain unclear. This study evaluates the outcomes of cirrhotic patients undergoing outpatient EVL. Methods: Adult patients aged 18 years and older diagnosed with cirrhosis, with or without significant thrombocytopenia (<50 × 103/μL), were identified using the TriNetX database. Patients who received platelet transfusions within one week prior to or on the day of EVL were excluded. Cirrhotic patients with significant thrombocytopenia undergoing outpatient elective EVL were categorized into two cohorts: (1) those with platelet counts between 30 and 49 × 103/μL and (2) those with platelet counts ≥50 × 103/μL. Propensity score matching (PSM) was employed to compare rates of post-EVL esophageal variceal bleeding and 14-day mortality between the two cohorts. Results: A total of 16,718 cirrhotic patients undergoing outpatient EVL were included in the analysis. Of these, 17.2% (n = 2874) had significant thrombocytopenia, while 82.8% (n = 13,844) had platelet counts ≥50 × 103/μL. Two well-matched cohorts (2864 patients each) were created using 1:1 PSM. No statistically significant differences were observed between the groups regarding 14-day post-EVL esophageal variceal bleeding (13.7% vs. 15.2%; p = 0.12), 14-day mortality (5.7% vs. 5.0%; p = 0.28), and 28-day mortality (8.4% vs. 7.5%; p = 0.20). Conclusions: Elective EVL appears to be safe in cirrhotic patients with platelet counts as low as 30 × 103/μL, challenging the current threshold of 50 × 103/μL for platelet transfusion.
Full article
(This article belongs to the Section Gastroenterology)
►▼
Show Figures
Figure 1
Open AccessArticle
Change in Estimated Glomerular Filtration Rate After Direct-Acting Antiviral Treatment in Chronic Hepatitis C Patients
by
Gantogtokh Dashjamts, Amin-Erdene Ganzorig, Yumchinsuren Tsedendorj, Dolgion Daramjav, Enkhmend Khayankhyarvaa, Bolor Ulziitsogt, Otgongerel Nergui, Ganchimeg Dondov, Tegshjargal Badamjav, Tulgaa Lonjid, Chung-Feng Huang, Po-Cheng Liang, Batbold Batsaikhan and Chia-Yen Dai
Diseases 2025, 13(2), 26; https://doi.org/10.3390/diseases13020026 - 21 Jan 2025
Abstract
►▼
Show Figures
Background: Hepatitis C virus (HCV) infection accelerates the progression of chronic kidney disease (CKD), increasing the risk of kidney failure and end-stage renal disease. Direct-acting antiviral (DAA) therapies for HCV infection inhibit viral replication by 95–97%, leading to a sustained virologic response. Our
[...] Read more.
Background: Hepatitis C virus (HCV) infection accelerates the progression of chronic kidney disease (CKD), increasing the risk of kidney failure and end-stage renal disease. Direct-acting antiviral (DAA) therapies for HCV infection inhibit viral replication by 95–97%, leading to a sustained virologic response. Our objective was to assess renal function in patients with chronic HCV infection in Taiwan after receiving DAA therapy. Goal: Our study included 4823 patients with HCV infection who were undergoing DAA therapy. Renal function was evaluated by calculating the glomerular filtration rate (eGFR). eGFR assessed at the initiation of the treatment, during treatment, and at 3 months, 6 months, 1 year, and 3 years after completion of treatment. The baseline demographic and laboratory parameters of the study participants were evaluated, and the results were analyzed using statistical methods. Results: The average age of the study participants was 61.35 ± 12.50 years, and 54.5% of were male. The mean of eGFR in baseline and after treatment showed a decrease. Liver fibrosis scores (FIB4, APRI, Fibroscan) and liver function tests were significantly improved after DAA treatment (p = 0.001). However, white blood count (5.41 ± 1.7 vs. 5.73 ± 1.9), platelet count (168.04 ± 74.0 vs. 182.11 ± 69.4), and creatinine levels (1.05 ± 1.3 vs. 1.12 ± 1.3) increased after treatment (p = 0.001). The number of patients with an eGFR of 60 mL/min/1.73 m2 decreased both during and after treatment (p < 0.001). Among patients with CKD, eGFR improved after DAA treatment (n = 690, 35.93 ± 19.7 vs. 38.71 ± 23.8; 95% CI −3.56–1.98; p = 0.001). Logistic regression analysis revealed that renal function improved in patients with CKD who had an eGFR of less than 60 mL/min/1.73 m2 before DAA treatment (OR 1.62, 95% CI 1.37–1.91, p = 0.001). Conclusions: In individuals with CKD and a baseline eGFR < 60 mL/min per 1.73 m2, eGFR level was increased during DAA treatment. This suggests that initiating DAA therapy in HCV-infected patients, even those without clinical manifestations, could be a crucial strategy to prevent further decline in renal function.
Full article
Figure 1
Open AccessSystematic Review
CD34+ Hematopoietic Stem Cell Counts in Alzheimer’s Disease: A Meta-Analysis
by
Vinay Suresh, Malavika Rudrakumar, Anmol Kaur, Victor Ghosh, Poorvikha Satish, Amogh Verma, Priyanka Roy and Mainak Bardhan
Diseases 2025, 13(2), 25; https://doi.org/10.3390/diseases13020025 - 21 Jan 2025
Abstract
►▼
Show Figures
Purpose: To assess the presence and quantity of CD34+ hematopoietic stem cells in patients with Alzheimer’s disease (AD) through a meta-analysis. Methods: A systematic search of the databases identified the observational and interventional studies reporting baseline CD34+ cell counts in AD patients. The
[...] Read more.
Purpose: To assess the presence and quantity of CD34+ hematopoietic stem cells in patients with Alzheimer’s disease (AD) through a meta-analysis. Methods: A systematic search of the databases identified the observational and interventional studies reporting baseline CD34+ cell counts in AD patients. The data on mean counts and the measures of variation were extracted. Standardized mean differences (SMDs) were calculated using common and random effects models to compare the CD34+ cell counts between the AD patients and controls. Heterogeneity among the studies was evaluated using tau2, tau, and I2 statistics. The risk of bias was assessed using the Newcastle–Ottawa Scale and the ROBINS-I tool. Patients: Five studies were included, comprising four observational studies and one open-label trial, with a total of 271 participants (139 AD patients and 132 controls). Results: The meta-analysis indicated an increase in CD34+ cell counts of the AD patients when compared to the controls. The common effects model showed a moderate SMD of 0.2964 (95% CI:0.0490–0.5437). However, the random effects model yielded a non-significant SMD of 0.2326 (95% CI: −0.4832–0.9484). Significant heterogeneity was observed among the studies (I2 = 87.1%, p < 0.0001). Conclusion: AD patients may exhibit higher circulating CD34+ cell counts than the controls, but substantial heterogeneity and potential biases limit definitive conclusions.
Full article
Figure 1
Highly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Cancers, Current Oncology, Diagnostics, Diseases, Onco
Artificial Intelligence in Cancer Pathology and Prognosis
Topic Editors: Hamid Khayyam, Ali Hekmatnia, Rahele Kafieh, Ali JamaliDeadline: 1 May 2025
Topic in
Biomolecules, Cancers, Diseases, Neurology International, Biomedicines
Brain Cancer Stem Cells and Their Microenvironment
Topic Editors: Maria Patrizia Stoppelli, Luca Colucci-D'Amato, Francesca BianchiniDeadline: 31 December 2025
Topic in
Biomedicines, Diseases, JCM, JPM, Uro, Reports
Clinical, Translational, and Basic Research and Novel Therapy on Functional Bladder Diseases and Lower Urinary Tract Dysfunctions
Topic Editors: Hann-Chorng Kuo, Yao-Chi Chuang, Chun-Hou LiaoDeadline: 31 December 2026
Topic in
Cancers, Current Oncology, Diseases
Cellular and Molecular Mechanisms of Obesity-Associated Cancer Development and Treatments
Topic Editors: Ming Yang, Chunye ZhangDeadline: 31 August 2027
Conferences
Special Issues
Special Issue in
Diseases
Infectious Disease Epidemiology 2024
Guest Editors: Amal Mitra, Fernando MonroyDeadline: 1 March 2025
Special Issue in
Diseases
Advanced Research and Practice in Acute and Chronic Pancreatitis
Guest Editors: Veysel Tahan, Ebubekir DaglilarDeadline: 31 March 2025
Special Issue in
Diseases
Epidemiological Trends and Risk Factors in Geriatric and Infectious Diseases
Guest Editor: Nicola VeroneseDeadline: 31 March 2025
Special Issue in
Diseases
Treatment Strategies and Immune Responses in Rheumatic Diseases
Guest Editor: Rita Aguiar MouraDeadline: 30 April 2025
Topical Collections
Topical Collection in
Diseases
Effects of Food Antioxidants on Cardiovascular Diseases and Human Cancers
Collection Editors: Esra Capanoglu, Maurizio Battino
Topical Collection in
Diseases
Lysosomal Storage Diseases
Collection Editors: José A. Sánchez-Alcázar, Luis Jiménez Jiménez