Antibiotic Nanoparticles-Loaded Wound Dressings Against Pseudomonas aeruginosa's Skin Infection: A Systematic Review.

Pseudomonas aeruginosa (P. aeruginosa) is a common nosocomial pathogen that can cause severe infections in critically ill patients. Due to its resistance to multiple drugs, it is challenging to treat, which can result in serious illness and death. Conventional treatments for infected wounds often involve the topical or systemic application of antibiotics, which can lead to systemic toxicity and the development of drug resistance. The combination of wound dressings that promote wound healing with nanoparticles (NPs) represents a revolutionary strategy for optimizing the safety and efficacy of antibiotics. This review assesses a systematic search to identify the latest approaches where the evaluation of wound dressings loaded with antibiotic NPs is conducted. The properties of NPs, the features of wound dressings, the antimicrobial activity and biocompatibility of the different strategies are analyzed. The results indicate that most research in this field is focused on dressings loaded with silver NPs (57.1%) or other inorganic materials (22.4%). Wound dressings loaded with polymeric NPs and carbon-based NPs represent 14.3% and 6.1% of the evaluated studies, respectively. Nevertheless, there are no clinical trials that have evaluated the efficacy of NPs-loaded wound dressings in patients. Further research is required to ensure the safety of these treatments and to translate the findings from the bench to the bedside.

Towards more sustainable cooking practices to increase the bioaccessibility of colourless and provitamin A carotenoids in cooked carrots.

The effect of different cooking methods (boiling, baking, steaming and microwaving) on the colour and texture of carrots, as well as on the bioaccessibility of carotenoids, was investigated in order to identify the more "sustainable cooking" methods. Cooking resulted in statistically significant increases in total carotenoid bioaccessibility, both with intensity and duration of treatments. In particular, significant increases in carotenoid bioaccessible content (CBC) were observed, ranging from 6.03-fold (microwave) to 8.90-fold (baking) for the most intense cooking conditions tested. Although the relative concentration of the colourless carotenoids (phytoene and phytofluene) in raw carrots is lower than that of provitamins A α- and ß-carotene, the bioaccessible content of the colourless ones is much higher. From an energy consumption standpoint and considering samples with the same tenderness, the highest CBC values per kWh decreased in the order microwaving > baking > water cooking > steaming. Our findings are important to help combat vitamin A deficiency since increases of up to ∼40-fold and ∼70-fold in the CBCs of the vitamin A precursors α- and ß-carotene, respectively, were observed. These results provide a basis for defining "sustainable cooking" as "cooking practices that optimize intensity, duration and other parameters leading to a more efficient use of energy to maximize the bioavailability of nutrients and other beneficial food components (such as bioactives) while ensuring food appeal and safety".

Graphene-enhanced PCL electrospun nanofiber scaffolds for cardiac tissue engineering.

Cardiovascular diseases, particularly myocardial infarction, have significant healthcare challenges due to the limited regenerative capacity of injured heart tissue. Cardiac tissue engineering (CTE) offers a promising approach to repairing myocardial damage using biomaterials that mimic the heart's extracellular matrix. This study investigates the potential of graphene nanopowder (Gnp)-enhanced polycaprolactone (PCL) scaffolds fabricated via electrospinning to improve the properties necessary for effective cardiac repair. This work aimed to analyze scaffolds with varying graphene concentrations (0.5%, 1%, 1.5%, and 2% by weight) to determine their morphological, chemical, mechanical, and biocompatibility characteristics. The results presented that incorporating graphene improves PCL scaffolds' mechanical properties and cellular interactions. The optimal concentration of 1% graphene significantly enhanced mechanical properties and biocompatibility, promoting cell adhesion and proliferation. These findings suggest that Gnp-enhanced PCL scaffolds at this concentration can serve as a potent substrate for CTE providing insights into designing more effective biomaterials for myocardial restoration.

Uncommon Etiologies of Acute Abdominal Pain: A Case Report on Omental Infarction.

Omental infarction is an uncommon cause of abdominal pain. The condition is often misdiagnosed due to its clinical similarity to more common abdominal pathologies like appendicitis and cholecystitis. This report presents the case of a 57-year-old female with a one-week history of left-sided abdominal pain, initially aggravated by eating and defecation. The patient, a long-term smoker with a complex medical history that includes deep vein thrombosis and pulmonary embolism, was hemodynamically stable on presentation. A CT scan revealed a nodular infiltration consistent with an omental infarct. Conservative management was pursued, resulting in symptom resolution by the third day of hospitalization. This case underscores the diagnostic challenges associated with omental infarction, particularly its differentiation from other causes of acute abdominal pain. It highlights the importance of considering rare etiologies in patients with atypical presentations and emphasizes the role of imaging, particularly CT scans, in accurate diagnosis. The patient's successful conservative management aligns with current recommendations, which advocate for non-surgical treatment in most cases. This approach avoids unnecessary surgical interventions and ensures a favorable prognosis with low complication rates in patients with prompt and appropriate management.

Potential protein biomarkers in saliva for detection of frailty syndrome by targeted proteomics.

Frailty is a physiological geriatric syndrome, caused by immunosenescence, inflammation and alterations at the protein level leading to metabolic and microbiota changes. Currently, this syndrome is evaluated clinically with the Frailty-VIG index. The aim of the study was therefore to investigate the potential suitability of saliva as a non-invasive proximal biological fluid for the characterisation and identification of possible protein-level biomarkers in frailty syndrome. This cross-sectional study was conducted in a rural population of older Spanish adults using the SMR proteomics technique. A differential protein profile of eight potential and surrogate proteins (CYTC, CYTD, CYTS, CYTB, MIF, ALBU, CD44 and B2MG) was detected in saliva, all of which correlated with factors characterising frailty syndrome, such as vascular ageing (arterial stiffness and cardiovascular disease), obesity, mood problems, global cognitive impairment, changes in gait and hand pressure strength. The proteins CYTD (r = 0.415, p = 0.013) and CYTC (r = 0.280, p = 0.026), which were detected differentially in the protein profile, were associated with the Frailty-VIG index. All analysed proteins are associated not only with the clinical symptoms of frailty syndrome, but also with an acute inflammatory response, endothelial cell proliferation and the complement system, among others.

Use of a Capsaicin Cough Challenge Test to Compare Four Different Techniques for Nebulization Delivery in Cats.

Successful aerosol therapy might rely more heavily on proper drug delivery than on the effectiveness of the medication. This study compared four techniques for nebulization delivery in cats. Tolerance rate (TR) was subjectively evaluated (1-3). Increasing capsaicin concentrations were nebulized for objective evaluation of efficiency. The positive response (PR) was considered when more than five coughs were induced. The following delivery methods were tested: flow-by (FB); face mask (FM); plastic-covered Elizabethan collar (EC); and plexiglass chamber (PC). The number of PRs (NPR) and the concentration of capsaicin that induced a PR (CCP) were statistically compared (p < 0.05). The PC method was the best tolerated (TR = 3.0 ± 0.0), followed by the FB (2.7 ± 0.5) and FM (2.6 ± 0.5). The EC was very stressful, and the test had to be suspended in four out of nine cats. The lowest CCP was found with the FM (91.8 ± 157.2 µM), followed by the FB (166.7 ± 190.9 µM), PC (242.6 ± 244.8 µM), and EC (350.0 ± 225.7 µM), with significant differences only between the FM and EC (p = 0.02). The highest NPR (8) corresponded to the FM, followed by the FB (7), the PC (5), and the EC (3), with significant differences between the FM and EC (p = 0.016). In conclusion, the capsaicin cough test induces reproducible and quantifiable cat responses. The FM is the most efficient for nebulization delivery, offering good compliance and the best quantitative results. FB nebulization is less efficient but may be practical if the FM is not tolerated. PC offers minor efficiency but may be useful for very stressed or aggressive cats. The EC presents low efficiency and compliance.

Infantile Hemangioma in Infancy: A Case Study on the Natural Course and Therapeutic Management.

Infantile hemangiomas (IHs) are common benign vascular tumors that affect infants. In this case report, we detail the natural course of an IH in an infant monitored over four months without medical intervention, illustrating the benign progression and potential for spontaneous stabilization of such lesions. The aim was to observe changes in the size and morphology of the hemangioma, alongside the infant's overall health and developmental milestones, through regular clinical assessments. This case presented a challenge as the patient's parents lacked English fluency, lacked healthcare access, and had low socioeconomic status. It highlights the importance of individualized patient care, advocating for careful observation and restraint in the application of pharmacological treatments when clinically unnecessary. The report contributes to existing pediatric dermatology knowledge by emphasizing the natural benign behavior of IH and the need for a balanced approach to treatment decisions, ensuring safe and favorable long-term outcomes for patients.

External validation and comparison of six cardiovascular risk prediction models in the Prospective Urban Rural Epidemiology (PURE)-Colombia study.

AIMS: To external validate the SCORE2, AHA/ACC Pooled Cohort Equation (PCE), Framingham Risk Score (FRS), Non-Laboratory INTERHEART Risk Score (NL-IHRS), Globorisk-LAC, and WHO prediction models and compare their discrimination and calibration capacity. METHODS: Validation in individuals aged 40-69 years with at least 10 years follow-up and without baseline use of statins or cardiovascular diseases from the Prospective Urban Rural Epidemiology prospective cohort study (PURE)-Colombia. For discrimination, the C-statistic, and Receiver Operating Characteristic curves with the integrated area under the curve (AUCi) were used and compared. For calibration, the smoothed time-to-event method was used, choosing a recalibration factor based on the integrated calibration index (ICI). In the NL-IHRS, linear regressions were used. RESULTS: In 3,802 participants (59.1% women), baseline risk ranged from 4.8% (SCORE2 women) to 55.7% (NL-IHRS). After a mean follow-up of 13.2 years, 234 events were reported (4.8 cases per 1000 person-years). The C-statistic ranged between 0.637 (0.601-0.672) in NL-IHRS and 0.767 (0.657-0.877) in AHA/ACC PCE. Discrimination was similar between AUCi. In women, higher overprediction was observed in the Globorisk-LAC (61%) and WHO (59%). In men, higher overprediction was observed in FRS (72%) and AHA/ACC PCE (71%). Overestimations were corrected after multiplying by a factor derived from the ICI. CONCLUSIONS: Six prediction models had a similar discrimination capacity, supporting their use after multiplying by a correction factor. If blood tests are unavailable, NL-IHRS is a reasonable option. Our results suggest that these models could be used in other countries of Latin America after correcting the overestimations with a multiplying factor.

Detecting people at high risk of cardiovascular disease and implementing preventive interventions in this population is a key strategy in primary prevention. Recently, new risk calculation tools have been developed, but before their application and routine use in populations different from those where it was developed, it's necessary to validate them. The recommendations for predicting cardiovascular risk in Colombia's guidelines are based on studies with noteworthy limitations. This study involving 3,802 healthy individuals in Colombia supports the recommendation of using these prediction models. The estimation result should be multiplied by a correction factor, because most of the prediction models overestimate cardiovascular risk. For example, the correction factors suggested in women for AHA/ACC PCE and SCORE2 are 0.54 and 0.75, respectively. In men, the correction factors suggested in AHA/ACC PCE and SCORE2 are 0.28 and 0.61, respectively. Therefore, the present study with a contemporary population provides additional evidence to update these recommendations in Colombia and perhaps in Latin America.

Solitary Bone Cyst in the Lumbar Spine: Case Report and Literature Review.

Introduction: To describe a rare case of solitary bone cyst in the vertebral body of the lumbar vertebra in an adult patient. The solitary bone cyst is defined as a cystic lesion with liquid content. Few cases have been described in the vertebral location without preference for the posterior arch or vertebral body. Most have been treated with resection, curettage, and/or grafting. No case described to date has been treated with polymethylmetacrylate (PMMA) injection in the vertebral location. Case Presentation. A 50-year-old male patient was consulted for lumbar pain with no traumatic history and no neurologic deficit. The radiological study showed lumbar arthrodesis with L2-L4 instrumentation due to an L3 fracture twenty years earlier. Computed tomography (CT) scan showed a lytic lesion occupying practically the entire vertebral body of L5, with incomplete septum and sclerotic edge, without cortical rupture. The previous steel instrumentation was removed, to avoid the presence of artifacts when performing the magnetic resonance (MR), and a biopsy of L5 vertebra was performed via transpedicular in the same act. The MR study findings and biopsy were compatible with the simple bone cyst. Finally, a new intervention was performed by filling the lesion with PMMA. Follow-up at 5 years was satisfactory without lumbar pain as well as the radiological study and with a return to previous activity. Conclusions: The spinal location of the simple bone cyst is extremely infrequent. Its diagnosis excludes other lesions and is made by imaging studies and biopsy. Treatment can be performed by excision, curettage, or filling with graft or as in this case, with PMMA.

The "Hypointense Focal Brain" on susceptibility-weighted imaging as a sign of venous congestion in cranial dural arteriovenous fistulas.

BACKGROUND: Cranial dural arteriovenous fistulas (dAVFs) are complex neurovascular malformations accounting for approximately 10%-15% of all intracranial arteriovenous malformations. The objective is to investigate the utility of susceptibility-weighted imaging (SWI) in identifying "hypointense focal brain" as an additional helpful sign of venous congestion in cranial dAVFs. MATERIALS AND METHODS: A retrospective review of patients diagnosed with cranial dAVFs between January 2015 and June 2023 was conducted, and SWI was used to identify the "hypointense focal brain" sign within the venous drainage region of the dAVF. The "hypointense focal brain" on SWI was identified as a low-intensity signal within the venous drainage region, indicative of venous congestion. The presence of this imaging sign was assessed by two neuroradiologists and signal intensity measurements were performed to support the presence of the sign. RESULTS: The study included six patients with cranial dAVFs exhibiting cortical venous retrograde drainage and the "hypointense focal brain" on SWI. Follow-up imaging post-treatment revealed resolution or improvement of the hypointense signal, confirming its association with venous congestion. Signal intensity measurements further supported the presence of this imaging sign in pre-treatment scans. CONCLUSION: The study's findings demonstrate the presence of a reversible "hypointense focal brain" sign on SWI in patients with cranial dAVFs and CVR, which can be useful as an additional imaging sign for venous congestion.

Prevalence and characterization of pain in radiation oncology: the PREDORT multicenter cross-sectional study.

BACKGROUND: Pain in cancer patients has enormous impact on their quality-of-life. Radiation therapy (RT) is a cornerstone in cancer treatment. The objective of the PREDORT study is to estimate the prevalence of pain in patients attending at Radiation Oncology (RO) Services. METHODS: A prospective, multicenter study was designed for patients treated at the RO Services of reference hospitals. Patients were seen in their initial Nursing consultation, during which key data was collected, including demographic and comorbidities data, medical history, and oncological and pain characteristics. The study has received approval from the Ethics Committee of Navarra, and all patients signed the Informed Consent. RESULTS: Of the 860 participating patients, 306 reported some type of pain, which implies a prevalence of 35.6%. Of them, 213 identified a cause of oncological origin. The proportion of pain was similar among sexes, but the proportion of non-cancer pain was higher among women (p < 0.05). Regarding pain intensity, the magnitude of breakthrough pain in patients with oncological pain is nearly 1 point greater than in patients with non-oncological pain (7.53 vs 6.81; p = 0.064). Cancer pain is more likely to be limiting of normal life than non-cancer pain (59% versus 38%, p < 0.001). Regarding analgesic treatment, only 60/306 patients (19.6%) were receiving strong opioids. There were 68 patients with pain without any treatment (22.2%). CONCLUSIONS: The prevalence of pain in cancer patients referred to RO services is 35.6%, with the prevalence of exclusively oncological pain being 24.8%. Understanding and addressing oncological pain is essential to provide comprehensive care to patients.

Attention Analysis in Robotic-Assistive Therapy for Children With Autism.

Children with Autism Spectrum Disorder (ASD) show severe attention deficits, hindering their capacity to acquire new skills. The automatic assessment of their attention response would provide the therapists with an important biomarker to better quantify their behaviour and monitor their progress during therapy. This work aims to develop a quantitative model, to evaluate the attention response of children with ASD, during robotic-assistive therapeutic sessions. Previous attempts to quantify the attention response of autistic subjects during human-robot interaction tasks were limited to restrained child movements. Instead, we developed an accurate quantitative system to assess the attention of ASD children in unconstrained scenarios. Our approach combines gaze extraction (Gaze360 model) with the definition of angular Areas-of-Interest, to characterise periods of attention towards elements of interest in the therapy environment during the session. The methodology was tested with 12 ASD children, achieving a mean test accuracy of 79.5 %. Finally, the proposed attention index was consistent with the therapists' evaluation of patients, allowing a meaningful interpretation of the automatic evaluation. This encourages the future clinical use of the proposed system.

The nature of training in flavor preference learning determines the underlying associative structure.

Pairing a palatable flavor (US) with an initially neutral flavor cue (CS) results in an acquired conditioned preference for the latter. Two main associations have been proposed to explain the acquisition of flavor preferences: Flavor-Flavor and Flavor-Nutrient learning. Although the hedonic reaction triggered by US consumption has also been suggested as a possible additional component underlying acquired flavor preference, this issue has received little attention. Here we explored whether the amount of training to the CS-US compound can favor the formation of a Flavor-Hedonic reaction association using rats as subjects and sucrose as the US. We expected that the more exposure to the CS-US compound, the stronger the S-R type association. Since S-R associations are not sensitive to devaluation procedures, we used a Sensory-Specific Satiety procedure to devalue the US after conditioning and then measured preferences for the CS. On Experiment 1 with a short restrictive training (classic procedure), preference for the CS was decreased after devaluation of the US compared to the control condition. On Experiment 2, with short unrestrictive training, preference for the CS was again weakened. Experiment 3 with a long unrestrictive training, rats expressed preference for the CS regardless of the devaluation procedure. These results suggest that, as with an instrumental paradigm, extensive training in flavor preference learning undermines the US devaluation effect.

Curbing the major and growing threats from invasive alien species is urgent and achievable.

Although invasive alien species have long been recognized as a major threat to nature and people, until now there has been no comprehensive global review of the status, trends, drivers, impacts, management and governance challenges of biological invasions. The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services (IPBES) Thematic Assessment Report on Invasive Alien Species and Their Control (hereafter 'IPBES invasive alien species assessment') drew on more than 13,000 scientific publications and reports in 15 languages as well as Indigenous and local knowledge on all taxa, ecosystems and regions across the globe. Therefore, it provides unequivocal evidence of the major and growing threat of invasive alien species alongside ambitious but realistic approaches to manage biological invasions. The extent of the threat and impacts has been recognized by the 143 member states of IPBES who approved the summary for policymakers of this assessment. Here, the authors of the IPBES assessment outline the main findings of the IPBES invasive alien species assessment and highlight the urgency to act now.

Challenges in Psoriasis Research: A Systematic Review of Preclinical Models.

INTRODUCTION: Psoriasis is a chronic inflammatory skin disease with variable clinical presentation, multifactorial etiology and an immunogenetic basis. Several studies demonstrate that it results from a dysregulated interaction between skin keratinocytes, immune cells, and the environment that leads to a persistent inflammatory process modulated by cytokines and T cells. The development of new treatment options requires increased understanding of pathogenesis. However, the successful implementation of effective drugs requires well-characterized and highly available preclinical models that allow researchers to quickly and reproducibly determine their safety and efficacy. METHODS: A systematic search on PubMed and Scopus databases was performed and assessed to find appropriate articles about psoriasis models applying the key words previously defined. The PRISMA guidelines were employed. RESULTS: A total of 45 original articles were selected that met the selection criteria. Among these, there are articles on in vivo, in vitro, and ex vivo models, with the in vitro model being the majority due to its ease of use. Within animal models, the most widely used in recent years are chemically induced models using a compound known as imiquimod. However, the rest of the animal models used throughout the disease's research were also discussed. On the other hand, in vitro models were divided into two and three dimensions. The latter were the most used due to their similarity to human skin. Lastly, the ex vivo models were discussed, although they were the least used due to their difficulty in obtaining them. CONCLUSIONS: Therefore, this review summarizes the current preclinical models (in vivo, in vitro, and ex vivo), discussing how to develop them, their advantages, limitations, and applications. There are many challenges to improve the development of the different models. However, research in these in vitro model studies could reduce the use of animals. This is favored with the use of future technologies such as 3D bioprinting or organ-on-a-chip technologies.

NOS2 and COX-2 Co-Expression Promotes Cancer Progression: A Potential Target for Developing Agents to Prevent or Treat Highly Aggressive Breast Cancer.

Nitric oxide (NO) and reactive nitrogen species (RNS) exert profound biological impacts dictated by their chemistry. Understanding their spatial distribution is essential for deciphering their roles in diverse biological processes. This review establishes a framework for the chemical biology of NO and RNS, exploring their dynamic reactions within the context of cancer. Concentration-dependent signaling reveals distinctive processes in cancer, with three levels of NO influencing oncogenic properties. In this context, NO plays a crucial role in cancer cell proliferation, metastasis, chemotherapy resistance, and immune suppression. Increased NOS2 expression correlates with poor survival across different tumors, including breast cancer. Additionally, NOS2 can crosstalk with the proinflammatory enzyme cyclooxygenase-2 (COX-2) to promote cancer progression. NOS2 and COX-2 co-expression establishes a positive feed-forward loop, driving immunosuppression and metastasis in estrogen receptor-negative (ER-) breast cancer. Spatial evaluation of NOS2 and COX-2 reveals orthogonal expression, suggesting the unique roles of these niches in the tumor microenvironment (TME). NOS2 and COX2 niche formation requires IFN-γ and cytokine-releasing cells. These niches contribute to poor clinical outcomes, emphasizing their role in cancer progression. Strategies to target these markers include direct inhibition, involving pan-inhibitors and selective inhibitors, as well as indirect approaches targeting their induction or downstream effectors. Compounds from cruciferous vegetables are potential candidates for NOS2 and COX-2 inhibition offering therapeutic applications. Thus, understanding the chemical biology of NO and RNS, their spatial distribution, and their implications in cancer progression provides valuable insights for developing targeted therapies and preventive strategies.

Post-transplant cyclophosphamide compared to sirolimus/tacrolimus in reduced intensity conditioning transplants for patients with lymphoid malignancies.

Despite novel cellular and immunomodulatory therapies, allogeneic hematopoietic stem cell transplantation (HSCT) remains a treatment option for lymphoid malignancies. Post-transplant cyclophosphamide (PTCY) is increasingly employed for graft vs. host disease (GVHD) prophylaxis. This study aims to evaluate the safety and efficacy of PTCY in reduce intensity (RIC) HSCT for patients with lymphoid neoplasms compared to sirolimus with tacrolimus (SIR/TAC). The primary endpoint was to compare grade III-IV acute GVHD, severe chronic GVHD, and relapse-free survival (GRFS) between the two GVHD prophylaxis strategies. This study, conducted from January 2012 to December 2020, included 171 consecutive patients (82 in the PTCY and 89 in the SIR/TAC group). Results revealed a significantly decreased incidence of moderate and severe forms of chronic GVHD in PTCY cohort (5.8% [95% CI, 1.8 to 13.1]) versus the SIR/TAC cohort (39.6% [95% CI, 29.3 to 49.7] (p < 0.001)). Other outcomes, including GRFS (PTCY [45.9% (95% CI, 35.8-58.7)] and SIR/TAC groups [36.8% (95% CI, 28-48.4)], (p = 0.72)), non-relapse mortality (NRM), relapse and overall survival (OS) were similar in both groups. Interestingly, the failure to achieve GRFS was mainly attributed to GVHD in the SIR/TAC group, while disease relapse was the primary reason in the PTCY cohort.

Radiological insights into rheumatoid meningitis - a rare central nervous system manifestation of rheumatoid arthritis: a retrospective review of six cases.

BACKGROUND: The objective is to analyze and review the clinical, laboratory, and neuroimaging characteristics of rheumatoid meningitis (RM) in six patients with known rheumatoid arthritis (RA). METHODS: We performed a retrospective review of patients diagnosed with RM from August 2012 to June 2023. To identify the cases, we used medical term search engines and the hospital´s radiology case database. Clinical information and laboratory findings were gathered from the medical records. A neuroradiologist with five years of experience reviewed and analyzed the RM to determine the characteristics findings of RM. RESULTS: Six patients with RM are included. Seizures along with headaches were among the clinical signs that were documented. All the patients had high levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptides (ACPA) in the peripheral blood. Biopsy in two cases confirmed typical rheumatoid nodules. Leptomeningeal enhancement was found bilaterally in all cases and was predominantly found in the frontoparietal region. "Mismatch DWI/FLAIR" was found in five patients. Bilateral subdural collections could be found in two patients. Brain PET scan revealed increased metabolism in two cases. CONCLUSION: Rheumatoid meningitis is a rare complication of rheumatoid arthritis (RA) with challenging clinical diagnosis due to non-specific symptoms. This study highlights the importance of MR in detecting characteristic neuroimaging patterns, including "mismatch DWI/FLAIR", to aid in early diagnosis. Increased awareness of this condition may facilitate timely intervention and improve prognosis. These results still need to be verified by large studies.

Cellular Response of Adapted and Non-Adapted Tetrahymena thermophila Strains to Europium Eu(III) Compounds.

Europium is one of the most reactive lanthanides and humans use it in many different applications, but we still know little about its potential toxicity and cellular response to its exposure. Two strains of the eukaryotic microorganism model Tetrahymena thermophila were adapted to high concentrations of two Eu(III) compounds (EuCl3 or Eu2O3) and compared to a control strain and cultures treated with both compounds. In this ciliate, EuCl3 is more toxic than Eu2O3. LC50 values show that this microorganism is more resistant to these Eu(III) compounds than other microorganisms. Oxidative stress originated mainly by Eu2O3 is minimized by overexpression of genes encoding important antioxidant enzymes. The overexpression of metallothionein genes under treatment with Eu(III) compounds supports the possibility that this lanthanide may interact with the -SH groups of the cysteine residues from metallothioneins and/or displace essential cations of these proteins during their homeostatic function. Both lipid metabolism (lipid droplets fusing with europium-containing vacuoles) and autophagy are involved in the cellular response to europium stress. Bioaccumulation, together with a possible biomineralization to europium phosphate, seems to be the main mechanism of Eu(III) detoxification in these cells.

Polydatin and Nicotinamide Rescue the Cellular Phenotype of Mitochondrial Diseases by Mitochondrial Unfolded Protein Response (mtUPR) Activation.

Primary mitochondrial diseases result from mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) genes, encoding proteins crucial for mitochondrial structure or function. Given that few disease-specific therapies are available for mitochondrial diseases, novel treatments to reverse mitochondrial dysfunction are necessary. In this work, we explored new therapeutic options in mitochondrial diseases using fibroblasts and induced neurons derived from patients with mutations in the GFM1 gene. This gene encodes the essential mitochondrial translation elongation factor G1 involved in mitochondrial protein synthesis. Due to the severe mitochondrial defect, mutant GFM1 fibroblasts cannot survive in galactose medium, making them an ideal screening model to test the effectiveness of pharmacological compounds. We found that the combination of polydatin and nicotinamide enabled the survival of mutant GFM1 fibroblasts in stress medium. We also demonstrated that polydatin and nicotinamide upregulated the mitochondrial Unfolded Protein Response (mtUPR), especially the SIRT3 pathway. Activation of mtUPR partially restored mitochondrial protein synthesis and expression, as well as improved cellular bioenergetics. Furthermore, we confirmed the positive effect of the treatment in GFM1 mutant induced neurons obtained by direct reprogramming from patient fibroblasts. Overall, we provide compelling evidence that mtUPR activation is a promising therapeutic strategy for GFM1 mutations.