Activation of Shh/Smo is sufficient to maintain oligodendrocyte precursor cells in an undifferentiated state and is not necessary for myelin formation and (re)myelination.

Myelination is the terminal step in a complex and precisely timed program that orchestrates the proliferation, migration and differentiation of oligodendroglial cells. It is thought that Sonic Hedgehog (Shh) acting on Smoothened (Smo) participates in regulating this process, but that these effects are highly context dependent. Here, we investigate oligodendroglial development and remyelination from three specific transgenic lines: NG2-CreERT2 (control), Smofl/fl/NG2-CreERT2 (loss of function), and SmoM2/NG2-CreERT2 (gain of function), as well as pharmacological manipulation that enhance or inhibit the Smo pathway (Smoothened Agonist (SAG) or cyclopamine treatment, respectively). To explore the effects of Shh/Smo on differentiation and myelination in vivo, we developed a highly quantifiable model by transplanting oligodendrocyte precursor cells (OPCs) in the retina. We find that myelination is greatly enhanced upon cyclopamine treatment and hypothesize that Shh/Smo could promote OPC proliferation to subsequently inhibit differentiation. Consistent with this hypothesis, we find that the genetic activation of Smo significantly increased numbers of OPCs and decreased oligodendrocyte differentiation when we examined the corpus callosum during development and after cuprizone demyelination and remyelination. However, upon loss of function with the conditional ablation of Smo, myelination in the same scenarios are unchanged. Taken together, our present findings suggest that the Shh pathway is sufficient to maintain OPCs in an undifferentiated state, but is not necessary for myelination and remyelination.

Internet of Things and citizen science as alternative water quality monitoring approaches and the importance of effective water quality communication.

The increasing demand for water and worsening climate change place significant pressure on this vital resource, making its preservation a global priority. Water quality monitoring programs are essential for effectively managing this resource. Current programs rely on traditional monitoring approaches, leading to limitations such as low spatiotemporal resolution and high operational costs. Despite the adoption of novel monitoring approaches that enable better data resolution, the public's comprehension of water quality matters remains low, primarily due to communication process deficiencies. This study explores the advantages and challenges of using Internet of Things (IoT) and citizen science as alternative monitoring approaches, emphasizing the need for enhancing public communication of water quality data. Through a systematic review of studies implemented on-field, we identify and propose strategies to address five key challenges that IoT and citizen science monitoring approaches must overcome to mature into robust sources of water quality information. Additionally, we highlight three fundamental problems affecting the water quality communication process and outline strategies to convey this topic effectively to the public.

Response to botulinum toxin may predict response to peroral pyloromyotomy in patients with gastroparesis.

BACKGROUND : Patients with gastroparesis who have undergone prior intrapyloric botulinum toxin injection (BTI) may seek an opinion regarding peroral pyloromyotomy (POP). There are only two small reports assessing the role of BTI as a predictor for successful treatment with POP. METHODS: We performed a retrospective cohort study to assess whether symptomatic improvement after BTI predicts a response to POP. We included 119 patients who had undergone both BTI and POP at Cleveland Clinic Ohio or Cleveland Clinic Florida from January 2016 to September 2019. RESULTS: 65.5 % of patients had symptomatic improvement after BTI. Gastroparesis Cardinal Symptom Index (GCSI) scores were available for 74 patients, with 64 % achieving a response to POP, defined as a decrease in mean GCSI ≥ 1. In multivariable analysis, response to BTI (odds ratio [OR] 7.7 [95 %CI 2.2-26.1]) and higher pre-POP GCSI score (OR 2.3 [95 %CI 1.2-4.6]) were independent predictors of response to POP. CONCLUSIONS: Clinical improvement after BTI is a predictor of response to POP in patients with gastroparesis. This information may aid in improving patient selection for POP.

Overcoming Nanoscale Inhomogeneities in Thin-Film Perovskites via Exceptional Post-annealing Grain Growth for Enhanced Photodetection.

Antisolvent-assisted spin coating has been widely used for fabricating metal halide perovskite films with smooth and compact morphology. However, localized nanoscale inhomogeneities exist in these films owing to rapid crystallization, undermining their overall optoelectronic performance. Here, we show that by relaxing the requirement for film smoothness, outstanding film quality can be obtained simply through a post-annealing grain growth process without passivation agents. The morphological changes, driven by a vaporized methylammonium chloride (MACl)-dimethylformamide (DMF) solution, lead to comprehensive defect elimination. Our nanoscale characterization visualizes the local defective clusters in the as-deposited film and their elimination following treatment, which couples with the observation of emissive grain boundaries and excellent inter- and intragrain optoelectronic uniformity in the polycrystalline film. Overcoming these performance-limiting inhomogeneities results in the enhancement of the photoresponse to low-light (<0.1 mW cm-2) illumination by up to 40-fold, yielding high-performance photodiodes with superior low-light detection.

A continuous process in mixers-settlers for the removal/recovery of chromium in effluents from the tanning industry.

One of the main environmental issues caused by the tanning industry is given by the high concentration of chromium contained on its effluents. The removal of this pollutant has become a technological challenge. To solve this issue, this work proposes a continuous process based on mixers-settlers for the removal of the chromium present in effluents from the tanning industry. The process involves the use of liquid-liquid extraction systems. The study includes the development of isotherms for the removal and stripping, which are further represented through a mathematical model to determine the number of theoretical extraction stages and other operational variables. The results show that a better extraction is achieved in a system with two theoretical stages using Cyanex 272 as extractant, reaching more than 94% of removal of chromium with an extractant concentration of 0.32 mol/L. For stripping, sulfuric acid is used, obtaining a maximum recovery of 94%.

Cross-sectoral impacts of the 2018-2019 Central European drought and climate resilience in the German part of the Elbe River basin.

The 2018-2019 Central European drought was probably the most extreme in Germany since the early sixteenth century. We assess the multiple consequences of the drought for natural systems, the economy and human health in the German part of the Elbe River basin, an area of 97,175 km2 including the cities of Berlin and Hamburg and contributing about 18% to the German GDP. We employ meteorological, hydrological and socio-economic data to build a comprehensive picture of the drought severity, its multiple effects and cross-sectoral consequences in the basin. Time series of different drought indices illustrate the severity of the 2018-2019 drought and how it progressed from meteorological water deficits via soil water depletion towards low groundwater levels and river runoff, and losses in vegetation productivity. The event resulted in severe production losses in agriculture (minus 20-40% for staple crops) and forestry (especially through forced logging of damaged wood: 25.1 million tons in 2018-2020 compared to only 3.4 million tons in 2015-2017), while other economic sectors remained largely unaffected. However, there is no guarantee that this socio-economic stability will be sustained in future drought events; this is discussed in the light of 2022, another dry year holding the potential for a compound crisis. Given the increased probability for more intense and long-lasting droughts in most parts of Europe, this example of actual cross-sectoral drought impacts will be relevant for drought awareness and preparation planning in other regions. Supplementary Information: The online version contains supplementary material available at 10.1007/s10113-023-02032-3.

Emerging Bioelectronic Strategies for Cardiovascular Tissue Engineering and Implantation.

Heart diseases are currently the leading cause of death worldwide. The ability to create cardiovascular tissue has numerous applications in understanding tissue development, disease progression, pharmacological testing, bio-actuators, and transplantation; yet current cardiovascular tissue engineering (CTE) methods are limited. However, there have been emerging developments in the bioelectronics field, with the creation of biomimetic devices that can intimately interact with cardiac cells, provide monitoring capabilities, and regulate tissue formation. Combining bioelectronics with cardiac tissue engineering can overcome current limitations and produce physiologically relevant tissue that can be used in various areas of cardiovascular research and medicine. This review highlights the recent advances in cardiovascular-based bioelectronics. First, cardiac tissue engineering and the potential of bioelectronic therapies for cardiovascular diseases are discussed. Second, advantageous bioelectronic materials for CTE and implantation and their properties are reviewed. Third, several representative cardiovascular tissue-bioelectronic interface models and the beneficial functions that bioelectronics can demonstrate in in vitro and in vivo applications are explored. Finally, the prospects and remaining challenges for clinical application are discussed.

Clinical indications for image-guided interventional procedures in the musculoskeletal system: a Delphi-based consensus paper from the European Society of Musculoskeletal Radiology (ESSR)-part VII, nerves of the lower limb.

OBJECTIVES: To perform a Delphi-based consensus on published evidence on image-guided interventional procedures for peripheral nerves of the lower limb (excluding Morton's neuroma) and provide clinical indications. METHODS: We report the results of a Delphi-based consensus of 53 experts from the European Society of Musculoskeletal Radiology who reviewed the published literature for evidence on image-guided interventional procedures offered around peripheral nerves in the lower limb (excluding Morton's neuroma) to derive their clinical indications. Experts drafted a list of statements and graded them according to the Oxford Centre for evidence-based medicine levels of evidence. Consensus was considered strong when > 95% of experts agreed with the statement or broad when > 80% but < 95% agreed. The results of the Delphi-based consensus were used to write the paper. RESULTS: Nine statements on image-guided interventional procedures for peripheral nerves of the lower limb have been drafted. All of them received strong consensus. Image-guided pudendal nerve block is safe, effective, and well tolerated with few complications. US-guided perisciatic injection of anesthetic provides good symptom relief in patients with piriformis syndrome; however, the addition of corticosteroids to local anesthetics still has an unclear role. US-guided lateral femoral cutaneous nerve block can be used to provide effective post-operative regional analgesia. CONCLUSION: Despite the promising results reported by published papers on image-guided interventional procedures for peripheral nerves of the lower limb, there is still a lack of evidence on the efficacy of most procedures. KEY POINTS: • Image-guided pudendal nerve block is safe, effective, and well tolerated with few complications. • US-guided perisciatic injection of anesthetic provides good symptom relief in patients with piriformis syndrome; however, the addition of corticosteroids to local anesthetics still has an unclear role. • US-guided lateral femoral cutaneous nerve block can be used to provide effective post-operative regional analgesia. The volume of local anesthetic affects the size of the blocked sensory area.

Clinical indications for image-guided interventional procedures in the musculoskeletal system: a Delphi-based consensus paper from the European Society of Musculoskeletal Radiology (ESSR)-part VI, foot and ankle.

OBJECTIVES: Clarity regarding accuracy and effectiveness for interventional procedures around the foot and ankle is lacking. Consequently, a board of 53 members of the Ultrasound and Interventional Subcommittees of the European Society of Musculoskeletal Radiology (ESSR) reviewed the published literature to evaluate the evidence on image-guided musculoskeletal interventional procedures around this anatomical region. METHODS: We report the results of a Delphi-based consensus of 53 experts from the European Society of Musculoskeletal Radiology who reviewed the published literature for evidence on image-guided interventional procedures offered around foot and ankle in order to derive their clinical indications. Experts drafted a list of statements and graded them according to the Oxford Centre for evidence-based medicine levels of evidence. Consensus was considered strong when > 95% of experts agreed with the statement or broad when > 80% but < 95% agreed. The results of the Delphi-based consensus were used to write the paper that was shared with all panel members for final approval. RESULTS: A list of 16 evidence-based statements on clinical indications for image-guided musculoskeletal interventional procedures in the foot and ankle were drafted after a literature review. The highest level of evidence was reported for four statements, all receiving 100% agreement. CONCLUSION: According to this consensus, image-guided interventions should not be considered a first-level approach for treating Achilles tendinopathy, while ultrasonography guidance is strongly recommended to improve the efficacy of interventional procedures for plantar fasciitis and Morton's neuroma, particularly using platelet-rich plasma and corticosteroids, respectively. KEY POINTS: • The expert panel of the ESSR listed 16 evidence-based statements on clinical indications of image-guided musculoskeletal interventional procedures in the foot and ankle. • Strong consensus was obtained for all statements. • The highest level of evidence was reached by four statements concerning the effectiveness of US-guided injections of corticosteroid for Morton's neuroma and PRP for plantar fasciitis.

Clinical indications for image-guided interventional procedures in the musculoskeletal system: a Delphi-based consensus paper from the European Society of Musculoskeletal Radiology (ESSR)-part V, knee.

OBJECTIVES: Interventional procedures around the knee are widely adopted for treating different musculoskeletal conditions. A panel of experts from the Ultrasound and Interventional Subcommittees of the European Society of Musculoskeletal Radiology (ESSR) reviewed the existing literature to assess the evidence on image-guided musculoskeletal interventional procedures around the knee, with the goal of highlighting some controversies associated with these procedures, specifically the role of imaging guidance, as well as the efficacy of the medications routinely injected. METHODS: We report the results of a Delphi-based consensus of 53 experts in musculoskeletal radiology, who reviewed the published literature for evidence on image-guided interventional procedures around the knee to derive a list of pertinent clinical indications. RESULTS: A list of 10 statements about clinical indications of image-guided procedures around the knee was created by a Delphi-based consensus. Only two of them had the highest level of evidence; all of them received 100% consensus. CONCLUSIONS: Ultrasonography guidance is strongly recommended for intra-articular and patellar tendinopathy procedures to ensure the precision and efficacy of these treatments. Prospective randomized studies remain warranted to better understand the role of imaging guidance and assess some of the medications used for interventional procedures around the knee. KEY POINTS: • A list of 10 evidence-based statements on clinical indications of image-guided interventional procedures around the knee was produced by an expert panel of the ESSR. • Strong consensus with 100% agreement was obtained for all statements. • Two statements reached the highest level of evidence, allowing us to strongly recommend the use of ultrasonography to guide intra-articular and patellar tendon procedures to ensure higher accuracy and efficacy of these treatments.

Clinical indications for image-guided interventional procedures in the musculoskeletal system: a Delphi-based consensus paper from the European Society of Musculoskeletal Radiology (ESSR)-part IV, hip.

OBJECTIVES: Image-guided musculoskeletal interventional procedures around the hip are widely used in daily clinical practice. The need for clarity concerning the actual added value of imaging guidance and types of medications to be offered led the Ultrasound and the Interventional Subcommittees of the European Society of Musculoskeletal Radiology (ESSR) to promote, with the support of its Research Committee, a collaborative project to review the published literature on image-guided musculoskeletal interventional procedures in the lower limb in order to derive a list of clinical indications. METHODS: In this article, we report the results of a Delphi-based consensus of 53 experts who reviewed the published literature for evidence on image-guided interventional procedures offered in the joint and soft tissues around the hip in order of their clinical indications. RESULTS: Ten statements concerning image-guided treatment procedures around the hip have been collected by the panel of ESSR experts. CONCLUSIONS: This work highlighted that there is still low evidence in the existing literature on some of these interventional procedures. Further large prospective randomized trials are essential to better confirm the benefits and objectively clarify the role of imaging to guide musculoskeletal interventional procedures around the hip. KEY POINTS: • Expert consensus produced a list of 10 evidence-based statements on clinical indications of image-guided interventional procedures around the hip. • The highest level of evidence was only reached for one statement. • Strong consensus was obtained for all statements.

Ustekinumab does not increase risk of new or recurrent cancer in inflammatory bowel disease patients with prior malignancy.

BACKGROUND AND AIM: There is limited data on the rate of new or recurrent cancer in patients with inflammatory bowel disease (IBD) and a history of prior or current malignancy who are initiated on biologic therapies. Furthermore, there is no data on this topic in patients using ustekinumab. METHODS: The retrospective study included 341 patients with IBD and a history of cancer who were subsequently treated with vedolizumab (VDZ; n = 34), ustekinumab (USK; n = 27), tumor necrosis factor α antagonists (anti-TNF; n = 99), or had no immunosuppressive therapy (control; n = 181). Cox proportional hazard models were developed to determine the independent effect of post-cancer immunosuppressive treatment on the occurrence of incident cancer. RESULTS: Over a median of 5.2 person-years of follow up, cancer recurrence occurred in only one patient on anti-TNF, while new cancers developed in one patient on VDZ, three patients on USK, and six patients on anti-TNF, corresponding to cancer rates of 0.4, 1.8, and 0.7 per 100 person-years, respectively. The rate of incident cancer in control patients was 2.4 per 100 person-years and included 18 new and 9 recurrent cancers. Compared with controls, a stepwise Cox proportional hazards model adjusting for significant covariates found no increased risk of incident cancer in patients receiving post-malignancy treatment with USK (hazard ratio [HR] 0.88; 95% confidence interval [CI] 0.25-3.03), VDZ (HR 0.18; 95% CI 0.03-1.35), or anti-TNF (HR 0.47; 95% CI 0.20-1.12). CONCLUSION: Use of biologic therapy in IBD patients with a previous history of malignancy was not associated with an increased risk of new or recurrent cancer.

Global drought trends and future projections.

Drought is one of the most difficult natural hazards to quantify and is divided into categories (meteorological, agricultural, ecological and hydrological), which makes assessing recent changes and future scenarios extremely difficult. This opinion piece includes a review of the recent scientific literature on the topic and analyses trends in meteorological droughts by using long-term precipitation records and different drought metrics to evaluate the role of global warming processes in trends of agricultural, hydrological and ecological drought severity over the last four decades, during which a sharp increase in atmospheric evaporative demand (AED) has been recorded. Meteorological droughts do not show any substantial changes at the global scale in at least the last 120 years, but an increase in the severity of agricultural and ecological droughts seems to emerge as a consequence of the increase in the severity of AED. Lastly, this study evaluates drought projections from earth system models and focuses on the most important aspects that need to be considered when evaluating drought processes in a changing climate, such as the use of different metrics and the uncertainty of modelling approaches. This article is part of the Royal Society Science+ meeting issue 'Drought risk in the Anthropocene'.

Kimura-Takemoto Classification: A Tool to Predict Gastric Intestinal Metaplasia Progression to Advanced Gastric Neoplasia.

BACKGROUND AND AIMS: Gastric cancer is a leading cause of morbidity and mortality worldwide. Gastric intestinal metaplasia (GIM) has been described as a key histologic step in the development of gastric adenocarcinoma. However, not all people with GIM develop malignancy. We studied the factors associated with progression to dysplasia and advanced gastric neoplasia (aGN) in patients with baseline GIM. METHODS: Retrospective cohort analysis of patients with baseline GIM and subsequent endoscopic evaluation at Cleveland Clinic Florida and Ohio Main Campus between 2005 and 2017. Demographic and exposure risk factors, as well as Kimura-Takemoto classification (KTc), were used as variables for hazards ratio (HR) and Kaplan-Meier survival-free analysis for aGN and any form of dysplasia progression. RESULTS: There were 708 patients identified with GIM; 29 patients (4.1%) progressed to any degree of dysplasia. From these, LGD was present in 12 cases (1.7%), HGD in 4 cases (0.6%), and gastric cancer in 13 cases (1.8%), for a total of 17 aGN cases. KTc was associated with dysplasia and aGN progression (p < 0.001), and no cases progressed if KTc findings were absent. Open-type KTc was associated with aGN (HR 6.36, p < 0.001) and any dysplasia progression (HR 13.34, p < 0.001) compared to closed-type or absent KTc features. No other factors were associated with aGN or dysplasia progression. Open-type KTc was also associated with shorter cancer survival-free progression. CONCLUSION: Patients with baseline GIM present a higher progression risk to aGN, dysplasia, or cancer if concomitant KTc findings are present, particularly an open-type KTc pattern.

Myeloid-derived suppressor cells support remyelination in a murine model of multiple sclerosis by promoting oligodendrocyte precursor cell survival, proliferation, and differentiation.

The most frequent variant of multiple sclerosis (MS) is the relapsing-remitting form, characterized by symptomatic phases followed by periods of total/partial recovery. Hence, it is possible that these patients can benefit from endogenous agents that control the inflammatory process and favor spontaneous remyelination. In this context, there is increasing interest in the role of myeloid-derived suppressor cells (MDSCs) during the clinical course of experimental autoimmune encephalomyelitis (EAE). MDSCs speed up infiltrated T-cell anergy and apoptosis. In different animal models of MS, a milder disease course is related to higher presence/density of MDSCs in the periphery, and smaller demyelinated lesions in the central nervous system (CNS). These observations lead us to wonder whether MDSCs might not only exert an anti-inflammatory effect but might also have direct influence on oligodendrocyte precursor cells (OPCs) and remyelination. In the present work, we reveal for the first time the relationship between OPCs and MDSCs in EAE, relationship that is guided by the distance from the inflammatory core. We describe the effects of MDSCs on survival, proliferation, as well as potent promoters of OPC differentiation toward mature phenotypes. We show for the first time that osteopontin is remarkably present in the analyzed secretome of MDSCs. The ablation of this cue from MDSCs-secretome demonstrates that osteopontin is the main MDSC effector on these oligodendroglial cells. These data highlight a crucial pathogenic interaction between innate immunity and the CNS, opening ways to develop MDSC- and/or osteopontin-based therapies to promote effective myelin preservation and repair in MS patients.

Risk Factors Associated With Postendoscopic Mucosal Resection Bleeding in Patients With Cirrhosis: A Retrospective Multicenter Cohort Study.

BACKGROUND AND AIM: There is limited data regarding the safety of endoscopic mucosal resection (EMR) in the cirrhotic population. Our study aimed to evaluate the safety of colonoscopic EMR in cirrhosis. MATERIALS AND METHODS: This was a retrospective review of cirrhotics who underwent colonic EMR at 8 Cleveland Clinic Centers between January 1, 2006, and December 31, 2018. Patient data including polyp details and complications occurring within 30 days of the procedure were noted. Univariable and multivariable logistic regression analyses were conducted to find risk factors for post-EMR bleeding. RESULTS: A total of 238 patients who underwent EMR were included. There were 145 males (60.9%) and the mean age was 61.9±8.6 years. Immediate and delayed bleeding, and postpolypectomy syndrome rates were 9.2%, 5.8%, and 1.3%, respectively. Significant risk factors for postpolypectomy bleeding were: increased age (P=0.001), procedure duration >37 minutes (P=0.001), antiplatelet use within 5 days (P=0.023), and lesion diameter >15 mm (P=0.004). Multivariable analysis revealed independent predictors of procedure-related bleeding: age above 65 years [odds ratio (OR) 2.14, P=0.044], antiplatelet use within 5 days (OR 2.42, P=0.047), right colon polyp (OR 3.51, P=0.001), and lesion diameter >15 mm (OR 3.22, P=0.003). CONCLUSIONS: EMR in cirrhotics has an acceptable bleeding risk. Age above 65 years, right colon polyp, polyp size >15 mm, and use of antiplatelets within 5 days are independent risk factors for bleeding.

Complex-Valued Phase Transmittance RBF Neural Networks for Massive MIMO-OFDM Receivers.

Multi-input multi-output (MIMO) transmission schemes have become the techniques of choice for increasing spectral efficiency in bandwidth-congested areas. However, the design of cost-effective receivers for MIMO channels remains a challenging task. The maximum likelihood detector can achieve excellent performance-usually, the best performance-but its computational complexity is a limiting factor in practical implementation. In the present work, a novel MIMO scheme using a practically feasible decoding algorithm based on the phase transmittance radial basis function (PTRBF) neural network is proposed. For some practical scenarios, the proposed scheme achieves improved receiver performance with lower computational complexity relative to the maximum likelihood decoding, thus substantially increasing the applicability of the algorithm. Simulation results are presented for MIMO-OFDM under 5G wireless Rayleigh channels so that a fair performance comparison with other reference techniques can be established.

Dynamics of Central Remyelination and Treatment Evolution in a Model of Multiple Sclerosis with Optic Coherence Tomography.

The need for remyelinating drugs is essential for healing disabling diseases such as multiple sclerosis (MS). One of the reasons for the lack of this class of therapies is the impossibility to monitor remyelination in vivo, which is of utmost importance to perform effective clinical trials. Here, we show how optical coherence tomography (OCT), a cheap and non-invasive technique commonly used in ophthalmology, may be used to assess remyelination in vivo in MS patients. Our pioneer approach validates OCT as a technique to study remyelination of the optic nerve and reflects what is occurring in non-accessible central nervous system (CNS) structures, like the spinal cord. In this study we used the orally bioavailable small molecule VP3.15, confirming its therapeutical potential as a neuroprotective, anti-inflammatory, and probably remyelinating drug for MS. Altogether, our results confirm the usefulness of OCT to monitor the efficacy of remyelinating therapies in vivo and underscore the relevance of VP3.15 as a potential disease modifying drug for MS therapy.

Valorization of pelagic sargassum biomass into sustainable applications: Current trends and challenges.

Since long ago, pelagic Sargassum mats have been known to be abundant in the Sargasso Sea, where they provide habitat to diverse organisms. However, over the last few years, massive amounts of pelagic Sargassum have reached the coast of several countries in the Caribbean and West Africa, causing economic and environmental problems. Aiming for lessening the impacts of the blooms, governments and private companies remove the seaweeds from the shore, but this process results expensive. The valorization of this abundant biomass can render Sargassum tides into an economic opportunity and concurrently solve their associated environmental problems. Despite the diverse fields where algae have found applications and the relevance of this recurrent situation, Sargassum biomass remains without large scale applications. Therefore, this review aims to present the potential uses of these algae, identifying the limitations that must be assessed to effectively valorize this bioresource. Due to the constraints identified for each of the presented applications, it is concluded that a biorefinery approach should be developed to effectively valorize this abundant biomass. However, there is an urgent need for investigations focusing on holopelagic Sargassum to be able to truly valorize this seaweed.

The proportion of myeloid-derived suppressor cells in the spleen is related to the severity of the clinical course and tissue damage extent in a murine model of multiple sclerosis.

Multiple Sclerosis (MS) is the second cause of paraplegia among young adults, after all types of CNS traumatic lesions. In its most frequent relapsing-remitting form, the severity of the disease course is very heterogeneous, and its reliable evaluation remains a key issue for clinicians. Myeloid-Derived sSuppressor Cells (MDSCs) are immature myeloid cells that suppress the inflammatory response, a phenomenon related to the resolution or recovery of the clinical symptoms associated with experimental autoimmune encephalomyelitis (EAE), the most common model for MS. Here, we establish the severity index as a new parameter for the clinical assessment in EAE. It is derived from the relationship between the maximal clinical score and the time elapsed since disease onset. Moreover, we relate this new index with several histopathological hallmarks in EAE and with the peripheral content of MDSCs. Based on this new parameter, we show that the splenic MDSC content is related to the evolution of the clinical course of EAE, ranging from mild to severe. Indeed, when the severity index indicates a severe disease course, EAE mice display more intense lymphocyte infiltration, demyelination and axonal damage. A direct correlation was drawn between the MDSC population in the peripheral immune system, and the preservation of myelin and axons, which was also correlated with T cell apoptosis within the CNS (being these cells the main target for MDSC suppression). The data presented clearly indicated that the severity index is a suitable tool to analyze disease severity in EAE. Moreover, our data suggest a clear relationship between circulating MDSC enrichment and disease outcome, opening new perspectives for the future targeting of this population as an indicator of MS severity.