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The rise of soft robotics in recent years has motivated significant developments in smart materials (and vice versa), as these materials allow for more compact robotic designs thanks to the embodied intelligence that they provide. Hydrogels have long been postulated as one of the potential candidates to be used in soft robotics due to their softness, elasticity, and smart properties that can be tuned with nanomaterials. However, nowadays they represent only a small percentage of the materials used in the field. In this perspective, the drawbacks that have hindered their utilization so far are analyzed as well as the current state of hydrogel-based soft actuators, sensors, and manufacturing possibilities. The future improvements that need to be made to achieve a real application of hydrogels in soft robotics are also discussed.
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Examining sub-threshold autistic traits in non-autistic first-degree relatives of individuals on the autism spectrum, known as the Broad Autism Phenotype (BAP), could provide new insights into the associations and familial aggregation of autistic traits. This study was a retrospective cross-sectional study of parents (n = 1008), probands with autism (n = 613), and unaffected siblings (n = 221) of probands with autism. BAP traits were examined by the BAP Questionnaire and Communication Checklist-Adult in parents, Autism Developmental Observation Scale-Second edition in probands, and Social Responsiveness Scale in siblings. Multivariable linear regression analyses were used to investigate the associations of parental BAP traits on autistic traits in probands and unaffected sibling BAP traits. Fathers showed significantly increased aloofness, pragmatic language difficulties, and social engagement problems compared to mothers. Female siblings showed increased difficulties with social cognition compared to male siblings. Adjusted models of the regression analyses showed that all BAP traits in fathers were significantly associated with BAP trait expression in probands with autism. Additionally, all of mother's BAP traits were significantly associated with unaffected siblings' BAP trait expression while only fathers' aloofness and rigidity traits were inversely associated with siblings' BAP trait expression. Finally, there were significant inverse interactions noted between parent's BAP traits and their children's BAP trait expression. This study demonstrated differences in how males and females express BAP traits and also identified differences in parent-child associations by sex, with fathers having a greater effect on their proband children's expression of BAP traits than mothers.
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Increased inflammation is associated with the pathogenesis of heart failure (HF). Increased circulating levels of cytokines have been previously reported and generally associated with worse clinical outcomes. In this context, the modulation of inflammation-related parameters seems to be a reasonable therapeutic option for improving the clinical course of the disease. Based on this, we aimed to compare changes in circulating cytokines when Mediterranean diet alone or in combination with hypercaloric, hyperproteic oral nutritional supplements (ONS), enriched with omega-3 (n-3) polyunsaturated fatty acids were administered to patients with HF. Briefly, patients were randomly assigned to receive Mediterranean Diet (control group) vs. Mediterranean Diet plus ONS (intervention group). We observed increased circulating levels of IL-6, IL-8, MCP-1 and IP-10. MCP-1 and IL-6 were associated with overweight and obesity (p = 0.01-0.01-0.04, respectively); IL-6 and IL-8 were positively correlated with fat mass and CRP serum levels (p = 0.02-0.04, respectively). Circulating levels of IL-8 significantly decreased in all patients treated with the Mediterranean diet, while IL-6 and IP-10 only significantly decreased in patients that received plus ONS. In the univariate analysis, MCP-1 and its combination with IL-6 were associated with increased mortality (p = 0.02), while the multivariate analysis confirmed that MCP-1 was an independent factor for mortality (OR 1.01, 95%ci 1.01-1.02). In conclusion, nutritional support using hypercaloric, hyperproteic, n-3 enriched ONS in combination with Mediterranean Diet was associated with decreased circulating levels of some cytokines and could represent an interesting step for improving heart functionality of patients with HF.
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Citocinas , Dieta Mediterránea , Suplementos Dietéticos , Ácidos Grasos Omega-3 , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/dietoterapia , Insuficiencia Cardíaca/terapia , Masculino , Femenino , Citocinas/sangre , Anciano , Persona de Mediana Edad , Ácidos Grasos Omega-3/administración & dosificación , Quimiocina CCL2/sangre , Apoyo Nutricional/métodos , Interleucina-6/sangre , Interleucina-8/sangre , Inflamación/sangreRESUMEN
Chaperone-mediated autophagy (CMA) is part of the mammalian cellular proteostasis network that ensures protein quality control, maintenance of proteome homeostasis, and proteome changes required for the adaptation to stress. Loss of proteostasis is one of the hallmarks of aging. CMA decreases with age in multiple rodent tissues and human cell types. A decrease in lysosomal levels of the lysosome-associated membrane protein type 2A (LAMP2A), the CMA receptor, has been identified as a main reason for declined CMA in aging. Here, we report constitutive activation of CMA with calorie restriction (CR), an intervention that extends healthspan, in old rodent livers and in an in vitro model of CR with cultured fibroblasts. We found that CR-mediated upregulation of CMA is due to improved stability of LAMP2A at the lysosome membrane. We also explore the translational value of our observations using calorie-restriction mimetics (CRMs), pharmacologically active substances that reproduce the biochemical and functional effects of CR. We show that acute treatment of old mice with CRMs also robustly activates CMA in several tissues and that this activation is required for the higher resistance to lipid dietary challenges conferred by treatment with CRMs. We conclude that part of the beneficial effects associated with CR/CRMs could be a consequence of the constitutive activation of CMA mediated by these interventions.
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Restricción Calórica , Autofagia Mediada por Chaperones , Proteína 2 de la Membrana Asociada a los Lisosomas , Lisosomas , Animales , Ratones , Proteína 2 de la Membrana Asociada a los Lisosomas/metabolismo , Proteína 2 de la Membrana Asociada a los Lisosomas/genética , Lisosomas/metabolismo , Humanos , Envejecimiento/metabolismo , Fibroblastos/metabolismo , Proteostasis , Hígado/metabolismo , Ratones Endogámicos C57BL , Masculino , AutofagiaRESUMEN
There is increasing evidence about the role of inflammation in sarcopenia and tumor progression; thus, its modulation would represent a valuable strategy for improving clinical outcomes in patients with cancer. Several studies have reported that whey protein has significant anti-inflammatory and antioxidant characteristics in humans. We aimed to evaluate the effects of whey protein-based oral nutritional support on circulating cytokines in patients with solid tumors undergoing systemic treatment. Forty-six patients with solid tumors of different origin and undergoing systemic treatment were evaluated. Nutritional support with two daily whey protein-based oral supplements was administered. Circulating levels of IL-6, IL-8, IL-10, MCP-1 and IP-10 were determined. Nutritional evaluation included anthropometric, instrumental and biochemical parameters. Over 63% of the evaluated patients underwent surgery, 56.5% required chemotherapy and almost 50% received combined treatment. Patients with resected primary tumor presented with lower baseline IL-6 (p < 0.05) and IP-10 (p < 0.001); after three months of nutritional support, they presented with lower IL-8 (p < 0.05) and tended to present lower IL-6 and IP-10 (p = 0.053 and 0.067, respectively). Significant positive correlations between circulating cytokines, C-reactive protein and ferritin were observed; similarly, negative correlations with anthropometric and biochemical nutritional parameters were noticed (p < 0.05). We did not observe significant changes in circulating cytokine levels (IL-6, IL-8, IL-10, MCP-1 and IP-10) in patients with cancer undergoing systemic treatment after three months of nutritional support with whey protein-based oral supplements. According to a univariate analysis in our cohort, circulating IL-8 was associated with mortality in these patients, additionally, MCP-1 and IP-10 tended to correlate; but an age- and sex-adjusted multivariate analysis revealed that only baseline MCP-1 was significantly associated with mortality (OR 1.03 (95% CI: 1.00-1.05)). In conclusion, surgery of the primary solid tumor and combination treatment allow significant reduction in circulating cytokine levels, which remained stable while patients received nutritional support with whey protein-based oral supplements over three months. The role of MCP-1 as an independent factor for mortality in these patients should be further evaluated.
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Citocinas , Inflamación , Neoplasias , Apoyo Nutricional , Proteína de Suero de Leche , Humanos , Femenino , Masculino , Persona de Mediana Edad , Anciano , Inflamación/sangre , Apoyo Nutricional/métodos , Citocinas/sangre , Adulto , Suplementos Dietéticos , Quimiocina CCL2/sangreRESUMEN
INTRODUCTION AND OBJECTIVES: The association between HDL cholesterol (HDL-C) levels and death from cardiovascular disease follows a U-shaped pattern, increasing at the extremes. The objective of the study was to characterize a sample of subjects with extreme hyperalphalipoproteinemia (HAE). MATERIAL AND METHODS: 53 cases with HAE were recruited, 24 women (HDL-C>135mg/ dL) and 29 men (HDL-C>116mg/ dL). A detailed medical history was taken and questionnaires on adherence to the Mediterranean diet and physical activity were collected. Carotid ultrasounds were performed to detect the presence of suclinical atherosclerosis. RESULTS: The most prevalent cardiovascular risk factor (CVRF) was dyslipidemia (64%) with no significant differences between men and women, unlike hypertension (21% in women, versus 55% in men, p=0.01) and others CVRF, for example, diabetes. 7% of the series had previous cardiovascular disease, women had higher LDL cholesterol (p=0.002) and HDL-C than men (without significant differences). Plaque was detected in 53% of cases, being more prevalent in men. Patients with plaque were older, drank more alcohol and smoked more (p<0.05). CONCLUSIONS: Men had a higher prevalence of CVRF than women, except for dyslipidemia. Subclinical atherosclerosis occurred in more than half of the series. Age, alcohol consumption and smoking were independently associated with the presence of plaque, however, our data do not show a significant influence of HDL-C levels.
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The current evolutionary trends in soft robotics try to exploit the capacities of smart materials to achieve compact robotics designs with embodied intelligence. In this way, the number of elements that compose the soft robot can be reduced, as the smart material can cover different aspects (e.g., structure and sensorization) all in one. This work follows this tendency and presents a custom-designed hydrogel that exhibits two smart features, self-healing and ionic conductivity, used to build a pneumatic actuator. The self-healing capability provides the actuator's structure with the ability to self-repair from damages (e.g., punctures or cuts), an important quality to prolong the life cycle of the actuator. The ionic conductivity enables the actuator's proprioception: the structure itself serves as a curvature sensor. The behavior of this proprioceptive curvature sensor is analyzed in this work, studying its linearity, stability, and performance after a self-healing process. This sensor is also proposed as feedback in a closed-loop scheme to automatically control the actuator's curvature. A proportional-integral-derivative controller is designed based on an empirical model of the actuator's dynamics, and then validated in experimental tests, proving the proprioceptive sensor as proper feedback. These control tests are performed over undamaged and self-healed actuators, thus demonstrating all the capabilities of our soft material.
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Pesticides are considered one of the main sources of contamination of surface waters, especially in rural areas highly influenced by traditional agricultural practices. The objective of this work was to evaluate the impact caused by pesticides and their transformation products (TPs) related to olive groves in surface waters with strong agricultural pressure. 11 streams were monitored during four sampling campaigns over 2 years. A solid-phase extraction, followed by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) analysis was used in the quantitative target approach, with more than 70 validated compounds. Target method was combined with a suspect screening strategy involving more than 500 pesticides and TPs, using ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) to identify additional pesticides and TPs out of the scope of analysis. A total of 43 different compounds were detected with the target method. The herbicide MCPA was present in all samples and at the highest concentration (1260 ng L-1), followed by the fungicide carbendazim (1110 ng L-1), and the herbicide chlorotoluron (706 ng L-1). The suspect screening strategy revealed the presence of 7 compounds out of the target analysis (1 pesticide and 6 TPs). 6 analytes were confirmed with the analytical standards. Semi-quantification results revealed that TPs exhibited higher concentrations than their corresponding parent compounds, indicating higher persistency. Some small streams showed a comparable number of pesticides and concentrations to the most polluted large river. The determined pesticide and TPs concentrations represented an estimated environmental hazard in almost all sampling sites under study. This work underscores the importance of including pesticide TPs and small streams impacted by extensive agricultural activities in water quality monitoring programs.
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Agricultura , Monitoreo del Ambiente , Olea , Plaguicidas , Ríos , Espectrometría de Masas en Tándem , Contaminantes Químicos del Agua , Ríos/química , Contaminantes Químicos del Agua/análisis , Plaguicidas/análisis , Medición de Riesgo , Olea/química , Extracción en Fase Sólida , Carbamatos/análisis , Cromatografía Líquida de Alta Presión , Herbicidas/análisis , Bencimidazoles/análisis , Compuestos de FenilureaRESUMEN
Cells exposed to proteotoxic stress invoke adaptive responses aimed at restoring proteostasis. Our previous studies have established a firm role for the transcription factor Nuclear factor-erythroid derived-2-related factor-1 (Nrf1) in responding to proteotoxic stress elicited by inhibition of cellular proteasome. Following proteasome inhibition, Nrf1 mediates new proteasome synthesis, thus enabling the cells to mitigate the proteotoxic stress. Here, we report that under similar circumstances, multiple components of the autophagy-lysosomal pathway (ALP) were transcriptionally upregulated in an Nrf1-dependent fashion, thus providing the cells with an additional route to cope with proteasome insufficiency. In response to proteasome inhibitors, Nrf1-deficient cells displayed profound defects in invoking autophagy and clearance of aggresomes. This phenomenon was also recapitulated in NGLY1 knockout cells, where Nrf1 is known to be non-functional. Conversely, overexpression of Nrf1 induced ALP genes and endowed the cells with an increased capacity to clear aggresomes. Overall, our results significantly expand the role of Nrf1 in shaping the cellular response to proteotoxic stress.
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Autofagia , Factor 1 Relacionado con NF-E2 , Estrés Proteotóxico , Animales , Humanos , Ratones , Autofagia/genética , Lisosomas/metabolismo , Factor 1 Relacionado con NF-E2/metabolismo , Factor 1 Relacionado con NF-E2/genética , Complejo de la Endopetidasa Proteasomal/metabolismo , Complejo de la Endopetidasa Proteasomal/genética , Inhibidores de Proteasoma/farmacología , Proteostasis , Estrés FisiológicoRESUMEN
In this article, we have studied the potential of flexible microtube plasma (FµTP) as ionization source for the liquid chromatography high-resolution mass spectrometry detection of non-easily ionizable pesticides (viz. nonpolar and non-ionizable by acid/basic moieties). Phthalimide-related compounds such as dicofol, dinocap, o-phenylphenol, captan, captafol, folpet and their metabolites were studied. Dielectric barrier discharge ionization (DBDI) was examined using two electrode configurations, including the miniaturized one based on a single high-voltage (HV) electrode and a virtual ground electrode configuration (FµTP), and also the two-ring electrode DBDI configuration. Different ionization pathways were observed to ionize these challenging, non-easily ionizable nonpolar compounds, involving nucleophilic substitutions and proton abstraction, with subtle differences in the spectra obtained compared with APCI. An average sensitivity increase of 5-fold was attained compared with the standard APCI source. In addition, more tolerance with matrix effects was observed in both DBDI sources. The importance of the data reported is not just limited to the sensitivity enhancement compared to APCI, but, more notably, to the ability to effectively ionize nonpolar, late-eluting (in reverse-phase chromatography) non-ionizable compounds. Besides o-phenylphenol ([M - H]-), all the parent species were efficiently ionized through different mechanisms involving bond cleavages through the effect of plasma reagent species or its combination with thermal degradation and subsequent ionization. This tool can be used to figure out overlooked nonpolar compounds in different environmental samples of societal interest through non-target screening (NTS) strategies.
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Espectrometría de Masas , Plaguicidas , Plaguicidas/análisis , Plaguicidas/química , Plaguicidas/sangre , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , Ftalimidas/química , Ftalimidas/análisis , Contaminación de Alimentos/análisis , Miniaturización , Captano/análisis , Captano/sangre , Captano/química , Análisis de los Alimentos/métodosRESUMEN
Hamstring injuries in soccer continue to be a challenge for professionals who work with soccer players daily. Although its origin is multifactorial, the proper management of neuromuscular fatigue during the training microcycle is a very important factor to consider. There are no clear guidelines regarding the weekly distribution of certain exercises that demand the hamstrings. The main objective of this study was to describe the usual training practices of professional European soccer teams. An international observational survey design was applied to some of the strength and conditioning coaches of professional soccer teams. The survey included different neuromuscular demanding exercises for the hamstrings. For each exercise, the strength and conditioning coaches had to respond in relation to their frequency of use and timepoint depending on the day of the weekly microcycle. Although there is no strong consensus in this regard, there does seem to be a trend when applying certain exercises, especially on the days matchday-4 and matchday-3.
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As individuals diagnosed with Parkinson's disease enter older age, the myriad challenges and complications associated with this condition tend to escalate. Hence, there is a critical necessity to comprehensively discern the perceived needs of these individuals, along with their proposed remedies and essential support requisites. Additionally, understanding the perspectives of their families becomes imperative to formulate tailored interventions aimed at enhancing their overall development, progression, and quality of life. The study's main objective is to assess the perceived needs of individuals with PD and their family members, propose necessary solutions, and suggest future perspectives. The study encompassed a cohort of 268 participants, comprising 179 individuals diagnosed with Parkinson's disease and 89 of their relatives. A meticulously designed structured interview instrument consisting of 93 items was employed to assess various domains encompassing perceived needs, institutional support mechanisms, essential solutions, and future anticipations. Results: Statistically significant differences were found in health resources, social services resources, obstacles, solutions, and future outlook, with higher mean values from the relatives. Conclusions: The results highlight the most concerning needs in this context. Specifically, those needs related to health resources, social services resources, and future outlook present the greatest differences between the two subsamples, with the family members perceiving more needs. This alignment extended to both the categorization of unmet needs and the requisite solutions envisioned to address them. Suggested improvements include a sociosanitary strategy, stakeholder involvement, and prioritizing flexible home assistance to support older individuals with PD and their families.
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Renal transplantation is an effective treatment for severe chronic kidney diseases. However, young patients often face a scarcity of kidneys from donors of similar age, resulting in the transplantation of older organs, which increase the risk of graft rejection and several complications compared with older individuals who receive kidneys from donors of similar age or younger. This article focuses on studying different senescence biomarkers in donors and patients who received kidneys from various age ranges complying with the STROBE requirements. We studied 61 patients subjected to renal transplant isolating blood samples 24 h before, and 24 h, 3 days, 7 days, 3 months, and 6 months after transplant. The patients were divided into three groups: older donor than the patient (Old Donor), younger donor than the patient (Young Donor), and similar age (Matched). We studied different senescence markers such as p16, p21, interleukin 6 (IL-6), and senescence-associated secretory phenotype (SASP) release. Young patients who receive older organs showed increased mRNA and protein expression of the senescence makers. Hence, increased SASP release was also observed in patients from older donor. In contrast, older patients who receive younger organs showed a slow but consistent improvement in their initial senescent phenotype. In addition, macrophage cell model treated with blood-derived serum from patients 6 months after the transplant showed a pro-senescence environment in macrophages proposed by the SASP from the patients. These results lead the hypothesis that senolytics could reduce the presence of senescent cells and mitigate the complications associated with the transplantation of older organs in young patients.
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Biomarcadores , Senescencia Celular , Trasplante de Riñón , Donantes de Tejidos , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Factores de Edad , Anciano , Fenotipo Secretor Asociado a la Senescencia , Interleucina-6/metabolismo , Interleucina-6/sangreRESUMEN
Young people in OOHC have complex mental health concerns, therefore the South Western Sydney Local Health District (SWSLHD) has trialled a tiered model of mental health care. Under this model the OOHC mental health team (OOHC-MHT) provides specialist tier four service delivery for those with the most severe, intense mental health needs. OOHC consumers with a reduced level of severity access services at a tier three centre-based iCAMHS. This study aims to understand the characteristics of young people in OOHC accessing different service provision options in Sydney, Australia. Sixty-six OOHC consumers 8-17 years accessing mental health services across SWSLHD from January 2020-December 2021 participated in the study. Group differences in OOHC-MHT and iCAMHS outcome measures were compared. HoNOSCA scores were significantly worse for OOHC-MHT than iCAMHS, indicating more severe psychopathology for OOHC-MHT at baseline. In OOHC-MHT, HoNOSCA decreased significantly from admission to discharge and scores on the CGAS increased significantly, indicating significant improvements in psychopathology and functioning. In the iCAMHS group scores on the HoNOSCA significantly decreased indicating improved psychopathology over this period. These findings support a tiered model of service delivery for OOHC consumers, with this tailored level of care resulting in significantly improved outcomes across a range of complexity.
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Servicios de Atención de Salud a Domicilio , Servicios de Salud Mental , Humanos , Adolescente , Australia , Salud Mental , Evaluación de Resultado en la Atención de SaludRESUMEN
Listeria monocytogenes is a foodborne pathogen which, in 2021, was considered the fifth most commonly reported zoonosis in humans in the European Union (EU). Ready-to-eat (RTE) fishery products, deli meats or soft cheeses have been mostly involved in food safety alerts and outbreaks in the last years. Hurdle technology by food industries has been widely used to enhance the safety of foods. Among the barriers, the application of acid and osmotic stress during processing is extensively used worldwide. This study aims to gain knowledge about the inter-strain variability of twenty-six clinical and food L. monocytogenes isolates with the estimation of their cardinal parameters using turbidimetric measurements. To analyse the data and to obtain the estimated cardinal values, a common statistical procedure was set up. The estimation of cardinal parameters showed a high inter-strain variability of L. monocytogenes, and no correlation was observed between Aw min and pHmin values for the studied strains. By grouping the strains in clinical, meat and fish origin, it was observed that strains from the meat group presented the lowest average pHmin values (4.57), thus showing potential acid adaptation. This work contributes to gain knowledge of the inter-strain variability of L. monocytogenes in relation with pH and Aw cardinal values, as well as provide a starting point for future validation studies in fish and meat food matrices.
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Listeria monocytogenes , Productos de la Carne , Animales , Humanos , Microbiología de Alimentos , Carne , Concentración de Iones de Hidrógeno , Contaminación de Alimentos/análisisRESUMEN
Salmonellosis is globally recognized as one of the leading causes of acute human bacterial gastroenteritis resulting from the consumption of animal-derived products, particularly those derived from the poultry and pig industry. Salmonella spp. is generally associated with self-limiting gastrointestinal symptoms, lasting between 2 and 7 days, which can vary from mild to severe. The bacteria can also spread in the bloodstream, causing sepsis and requiring effective antimicrobial therapy; however, sepsis rarely occurs. Salmonellosis control strategies are based on two fundamental aspects: (a) the reduction of prevalence levels in animals by means of health, biosecurity, or food strategies and (b) protection against infection in humans. At the food chain level, the prevention of salmonellosis requires a comprehensive approach at farm, manufacturing, distribution, and consumer levels. Proper handling of food, avoiding cross-contamination, and thorough cooking can reduce the risk and ensure the safety of food. Efforts to reduce transmission of Salmonella by food and other routes must be implemented using a One Health approach. Therefore, in this review we provide an update on Salmonella, one of the main zoonotic pathogens, emphasizing its relationship with animal and public health. We carry out a review on different topics about Salmonella and salmonellosis, with a special emphasis on epidemiology and public health, microbial behavior along the food chain, predictive microbiology principles, antimicrobial resistance, and control strategies.
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Chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI) are pathways for selective degradation of cytosolic proteins in lysosomes and late endosomes, respectively. These autophagic processes share as a first step the recognition of the same five-amino-acid motif in substrate proteins by the Hsc70 chaperone, raising the possibility of coordinated activity of both pathways. In this work, we show the existence of a compensatory relationship between CMA and eMI and identify a role for the chaperone protein Bag6 in triage and internalization of eMI substrates into late endosomes. Association and dynamics of Bag6 at the late endosome membrane change during starvation, a stressor that, contrary to other autophagic pathways, causes a decline in eMI activity. Collectively, these results show a coordinated function of eMI with CMA, identify the interchangeable subproteome degraded by these pathways, and start to elucidate the molecular mechanisms that facilitate the switch between them.
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Autofagia Mediada por Chaperones , Microautofagia , Autofagia , Endosomas/metabolismo , Lisosomas/metabolismo , Chaperonas Moleculares/metabolismoRESUMEN
Chronic wounds, especially those that are hard-to-heal, constitute a serious public-health problem. Although progress has been made in the development of wound dressings for healing, there is little high-quality evidence of their efficacy, with no evidence of superiority in the use of one hydrogel over another. To evaluate the superiority of a hydrogel (EHO-85), containing Olea europaea leaf extract (OELE), over a standard hydrogel (SH), the promotion and/or improvement of healing of difficult-to-heal wounds was compared in a prospective, parallel-group multicenter, randomized, observer-blinded, controlled trial ("MACAON"). Non-hospitalized patients with pressure, venous or diabetic foot-ulcers difficult-to-heal were recruited and treated with standard care, and EHO-85 (n = 35) or VariHesive (n = 34) as SH. Wound-area reduction (WAR; percentage) and healing rate (HR; mm2/day) were measured. EHO-85 showed a statistically significant superior effect over VariHesive. At the end of the follow-up period, the relative WAR decreased by 51.6% vs. 18.9% (p < 0.001), with a HR mean of 10.5 ± 5.7 vs. 1.0 ± 7.5 mm2/day (p = 0.036). EHO-85 superiority is probably based on its optimal ability to balance the ulcer bed, by modulating pH and oxidative stress. That complements the wetting and barrier functions, characteristics of conventional hydrogels. These results support the use of EHO-85 dressing, for treatment of hard-to-heal ulcers. Trial Registration AEMPS:PS/CR623/17/CE.