The enterovirus genome can be translated in an IRES-independent manner that requires the initiation factors eIF2A/eIF2D.

RNA recombination in positive-strand RNA viruses is a molecular-genetic process, which permits the greatest evolution of the genome and may be essential to stabilizing the genome from the deleterious consequences of accumulated mutations. Enteroviruses represent a useful system to elucidate the details of this process. On the biochemical level, it is known that RNA recombination is catalyzed by the viral RNA-dependent RNA polymerase using a template-switching mechanism. For this mechanism to function in cells, the recombining genomes must be located in the same subcellular compartment. How a viral genome is trafficked to the site of genome replication and recombination, which is membrane associated and isolated from the cytoplasm, is not known. We hypothesized that genome translation was essential for colocalization of genomes for recombination. We show that complete inactivation of internal ribosome entry site (IRES)-mediated translation of a donor enteroviral genome enhanced recombination instead of impairing it. Recombination did not occur by a nonreplicative mechanism. Rather, sufficient translation of the nonstructural region of the genome occurred to support subsequent steps required for recombination. The noncanonical translation initiation factors, eIF2A and eIF2D, were required for IRES-independent translation. Our results support an eIF2A/eIF2D-dependent mechanism under conditions in which the eIF2-dependent mechanism is inactive. Detection of an IRES-independent mechanism for translation of the enterovirus genome provides an explanation for a variety of debated observations, including nonreplicative recombination and persistence of enteroviral RNA lacking an IRES. The existence of an eIF2A/eIF2D-dependent mechanism in enteroviruses predicts the existence of similar mechanisms in other viruses.

Self-Healing Polymeric Soft Actuators.

Natural evolution has provided multicellular organisms with sophisticated functionalities and repair mechanisms for surviving and preserve their functions after an injury and/or infection. In this context, biological systems have inspired material scientists over decades to design and fabricate both self-healing polymeric materials and soft actuators with remarkable performance. The latter are capable of modifying their shape in response to environmental changes, such as temperature, pH, light, electrical/magnetic field, chemical additives, etc. In this review, we focus on the fusion of both types of materials, affording new systems with the potential to revolutionize almost every aspect of our modern life, from healthcare to environmental remediation and energy. The integration of stimuli-triggered self-healing properties into polymeric soft actuators endow environmental friendliness, cost-saving, enhanced safety, and lifespan of functional materials. We discuss the details of the most remarkable examples of self-healing soft actuators that display a macroscopic movement under specific stimuli. The discussion includes key experimental data, potential limitations, and mechanistic insights. Finally, we include a general table providing at first glance information about the nature of the external stimuli, conditions for self-healing and actuation, key information about the driving forces behind both phenomena, and the most important features of the achieved movement.

Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) constitute a recently discovered bone-marrow-derived cell type useful for dealing with neuroinflammatory disorders. However, these cells are only formed during inflammatory conditions from immature myeloid cells (IMCs) that acquire immunosuppressive activity, thus being commonly gathered from diseased animals. Then, to obtain a more clinically feasible source, we characterized IMCs directly derived from healthy bone marrow and proved their potential immunosuppressive activity under pathological conditions in vitro. We then explored their neuroprotective potential in a model of human cerebellar ataxia, the Purkinje Cell Degeneration (PCD) mouse, as it displays a well-defined neurodegenerative and neuroinflammatory process that can be also aggravated by invasive surgeries. METHODS: IMCs were obtained from healthy bone marrow and co-cultured with activated T cells. The proliferation and apoptotic rate of the later were analyzed with Tag-it Violet. For in vivo studies, IMCs were transplanted by stereotactic surgery into the cerebellum of PCD mice. We also used sham-operated animals as controls of the surgical effects, as well as their untreated counterparts. Motor behavior of mice was assessed by rotarod test. The Purkinje cell density was measured by immunohistochemistry and cell death assessed with the TUNEL technique. We also analyzed the microglial phenotype by immunofluorescence and the expression pattern of inflammation-related genes by qPCR. Parametric tests were applied depending on the specific experiment: one or two way ANOVA and Student's T test. RESULTS: IMCs were proven to effectively acquire immunosuppressive activity under pathological conditions in vitro, thus acting as MDSCs. Concerning in vivo studios, sham-operated PCD mice suffered detrimental effects in motor coordination, Purkinje cell survival and microglial activation. After intracranial administration of IMCs into the cerebellum of PCD mice, no special benefits were detected in the transplanted animals when compared to untreated mice. Nonetheless, this transplant almost completely prevented the impairments caused by the surgery in PCD mice, probably by the modulation of the inflammatory patterns. CONCLUSIONS: Our work comprise two main translational findings: (1) IMCs can be directly used as they behave as MDSCs under pathological conditions, thus avoiding their gathering from diseased subjects; (2) IMCs are promising adjuvants when performing neurosurgery.

Response Rate, Acceptability and Effectiveness of an Intervention Offering HIV/STI Testing Via Apps Among Gay, Bisexual, and Other Men Who Have Sex With Men in Barcelona, Spain, from 2016 to 2020.

We evaluated the response rate, acceptability, and effectiveness of a preventive programme offering rapid HIV and other STI testing, as well as sexual counselling to gay, bisexual, and other men who have sex with men (GBMSM) via dating apps over a 4-year period. The programme was carried out in 9 out of the 10 districts in the city of Barcelona, Spain. The response rate was defined as the proportion of people responding to the message sent, acceptability as the proportion of those responding favourably, and effectiveness as the proportion of users requesting a test. We performed univariate analysis and multivariate logistic regression in relation with the response rate, acceptability and effectiveness. A total of 5,254 messages were send to different users. The response rate was 33.1% (n = 1,741), acceptability was 86.2% (n = 1,500), and effectiveness was 10.1% (n = 532). The factors associated with user response were recent connection to the app (aOR = 1.85; CI:1.39-2.46) and the presence of a profile photograph (aOR = 1.34; CI:1.11-1.64). Acceptability was associated with recent connection to the app (aOR = 1.98; CI:1.09-3.58). Effectiveness was associated with lower reported age (aOR = 0.98; CI:0.97-0.99), contact before 14:00 (aOR = 2.47; CI: 1.77-3.46), and recent connection to the app (aOR = 4.89; CI:1.98-12.08). Effectiveness was also greater in districts that were more disadvantaged or had fewer sexual health services. This study demonstrates that the use of these apps is an acceptable and effective method of prevention and sexual health promotion in GBMSM in this setting and identifies the associated factors that could guide such interventions.

Highly efficient and reusable CuAu nanoparticles supported on crosslinked chitosan hydrogels as a plasmonic catalyst for nitroarene reduction.

The synthesis of CuAu-based monometallic (MNPs) and bimetallic nanoparticles (BNPs) supported on chitosan-based hydrogels for their application as catalysts is presented. The hydrogels consisted of chitosan chains cross-linked with tripolyphosphate (TPP) in the form of beads with an approximate average diameter of 1.81 mm. The MNPs and BNPs were obtained by the adsorption of metallic ions and their subsequent reduction with hydrazine, achieving a metallic loading of 0.297 mmol per gram of dry sample, with average nanoparticle sizes that were found between 2.6 and 4.4 nm. Both processes, metal adsorption and the stabilization of the nanoparticles, are mainly attributed to the participation of chitosan hydroxyl, amine and amide functional groups. The materials revealed important absorption bands in the visible region of the light spectra, specifically between 520 and 590 nm, mainly attributed to LSPR given the nature of the MNPs and BNPs inside the hydrogels. Subsequently, the hydrogels were evaluated as catalysts against the reduction of 4-nitrophenol (4NP) into 4-aminophenol (4AP), followed by UV-visible spectroscopy. The kinetic advance of the reaction revealed important improvements in the catalytic activity of the materials by synergistic effect of BNPs and plasmonic enhancement under visible light irradiation, given the combination of metals and the light harvesting properties of the nanocomposites. Finally, the catalytic performance of hydrogels containing BNPs CuAu 3:1 showed an important selectivity, recyclability and reusability performance, due to the relevant interaction of the BNPs with the chitosan matrix, highlighting the potential of this nanocomposite as an effective catalyst, with a potential environmental application.

Trends in Sexual Health of Gay, Bisexual, and Other Men Who Have Sex with Men, and Transgender Individuals: Apps Driven Testing Program for HIV and Other STIs in Barcelona, Spain (2016-2023).

Gay, bisexual and other men who have sex with men (GBMSM) and transgender individuals face heightened risks of HIV and other sexually transmitted infections (STIs). Surveillance within these populations is critical, and community testing services play a pivotal role in preventing and controlling HIV and STIs. This study investigates the trends in HIV, syphilis and hepatitis C (HCV) infections among participants in an apps-driven rapid test program from 2016 to 2023 in Barcelona, Spain, examining associated factors. Trend analysis utilized Wilcoxon-type test and associated factors were determined through multivariate logistic analysis. The prevalence of new HIV diagnosis was 1.81% (CI 1.18-2.64), active syphilis was 3.37% (CI 2.46-4.50) and acute HCV was 0.40% (CI 0.11-1.02). While infection rates showed no significant changes, there was significant increasing in sex work and chemsex and decreasing in condom use. Additionally, a peak in dating apps use for sex and a specific reduction in number of sexual partners were observed in 2020. Factors associated with HIV diagnoses included migrant status (aOR = 11.19; CI 2.58-48.53) and inconsistent condom use during the previous 12 months (aOR = 3.12; CI 1.02-9.51). For syphilis, associated factors were migrant status (aOR = 2.46; CI 1.14-5.29), inconsistent condom use (aOR = 3.38; CI 1.37-8.36), and chemsex practice during the previous 12 months (aOR = 2.80; CI 1.24-6.30). Our findings emphasize the need for tailored interventions, including culturally sensitive outreach for migrants and comprehensive strategies addressing substance use in sexual contexts. Technological innovations and targeted educational initiatives could reduce the burden of HIV and STIs within the GBMSM and transgender communities, providing valuable insights for public health strategies.

Common Oral Conditions: A Review.

Importance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are 3 of the most common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. Observations: In a meta-analysis of 26 population-based cohort and cross-sectional studies, the global prevalence of dry mouth symptoms was 23% (95% CI, 18% to 28%), placing individuals at risk of oral candidiasis, dental caries, dysgeusia, masticatory/speech impairment, and oropharyngeal dysphagia. Dry mouth is associated with using more than 3 oral medications per day (odds ratio [OR], 2.9 [95% CI, 1.4 to 6.2]), head and neck radiation, and Sjögren disease. Symptoms may include difficulty swallowing and speaking, thirst, and halitosis. Dry mouth is associated with an 11.5% (95% CI, 3.6% to 27%) higher risk of oral candidiasis, based on a meta-analysis of 6 observational cohorts. Management of dry mouth includes mechanical salivary stimulants, oral moisturizers, and/or systemic sialagogues. Oral candidiasis is an opportunistic fungal infection caused by overgrowth of the Candida genus with C albicans, which accounts for 76.8% of infections. The prevalence of oral candidiasis is higher in patients who are immunosuppressed, for example, those with HIV (35% [95% CI, 28% to 42%]) and those with salivary gland hypofunction (OR, 3.02 [95% CI, 1.73 to 5.28]). Common risk factors associated with oral candidiasis include use of antibiotics (P = .04) and oral mucosal disorders such as lichen planus. Oral burning and dysgeusia are common symptoms of oral candidiasis. Treatment includes addressing risk factors and use of topical and/or systemic antifungal medications. Recurrent aphthous stomatitis is characterized by symptomatic round or oval oral ulcers, which are covered by a gray-white fibrin layer and encircled by an erythematous ring. A meta-analysis of 10 case-controlled studies revealed an increased risk of recurrent aphthous stomatitis associated with polymorphism of IL-1ß (+3954C/T) (OR, 1.52 [95% CI, 1.07 to 2.17]) and IL-1ß (-511C/T) (OR, 1.35 [95% CI, 1.09 to 1.67]). Another meta-analysis of 9 case-control studies reported that patients with recurrent aphthous stomatitis had a higher frequency of nutritional deficiencies, including vitamin B12 (OR, 3.75 [95% CI, 2.38 to 5.94]), folic acid (OR, 7.55 [95% CI, 3.91 to 14.60]), and ferritin (OR, 2.62 [95% CI, 1.69 to 4.06]). Recurrent aphthous stomatitis can be associated with systemic diseases. A meta-analysis of 21 case-control studies revealed that celiac disease is associated with a higher incidence of recurrent aphthous stomatitis (25% vs 11%; OR, 3.79 [95% CI, 2.67 to 5.39]; P <.001). Topical corticosteroids are first-line agents to manage recurrent aphthous stomatitis; however, systemic medications may be necessary in more severe cases. Conclusions and Relevance: Dry mouth, oral candidiasis, and recurrent aphthous ulcers are common oral conditions that may be associated with patient discomfort, decreased quality of life, and morbidity. First-line treatment includes over-the-counter sialagogues for dry mouth, topical antifungals for oral candidiasis, and topical corticosteroids for aphthous ulcers. Oral conditions that do not improve with first-line treatment may require treatment with systemic medications.

Nanostructured Transition Metal Oxides on Carbon Fibers for Supercapacitor and Li-Ion Battery Electrodes: An Overview.

Nowadays, owing to the new technological and industrial requirements for equipment, such as flexibility or multifunctionally, the development of all-solid-state supercapacitors and Li-ion batteries has become a goal for researchers. For these purposes, the composite material approach has been widely proposed due to the promising features of woven carbon fiber as a substrate material for this type of material. Carbon fiber displays excellent mechanical properties, flexibility, and high electrical conductivity, allowing it to act as a substrate and a collector at the same time. However, carbon fiber's energy-storage capability is limited. Several coatings have been proposed for this, with nanostructured transition metal oxides being one of the most popular due to their high theoretical capacity and surface area. In this overview, the main techniques used to achieve these coatings-such as solvothermal synthesis, MOF-derived obtention, and electrochemical deposition-are summarized, as well as the main strategies for alleviating the low electrical conductivity of transition metal oxides, which is the main drawback of these materials.

Convalescent Plasma Therapy in Severe COVID-19: A Pilot Study at the Beginning of the Pandemic Outbreak in Southern Chile.

Convalescent Plasma (CP) from patients who recovered from COVID-19 may present neutralizing antibodies against viral protein S of SARS-CoV-2 and emerged as a potential therapeutic alternative for patients with severe infection at the beginning of the COVID-19 pandemic breakout. Thus, this study aimed to evaluate the effect and safety of CP treatment in patients with severe COVID-19. METHODS: We designed a quasi-experimental study that included 156 patients with SARS-CoV-2 infection confirmed by RT-qPCR and severe symptoms who received CP. As a control group, we selected a historical cohort of 113 individuals admitted with COVID-19 and severe symptomatology before the starting date of the study. Clinical status and mortality during the study period were recorded. RESULTS: There were no adverse reactions to CP administration. In the CP group, days on mechanical ventilation were significantly lower than the control group (2.8±5.08 days vs. 4.7±6.19 days; p= 0.0081). Moreover, a significant difference was observed in the number of days stayed in the critical patient unit (CPU) in CP vs. controls (4.2±5.47 vs. 5.8±6.39 days, p= 0.0281). CONCLUSIONS: We observed no association between CP administration and survival at 14 days. Treatment with CP was safe and not associated with adverse events. In addition, using CP was associated with a reduction in both stay at the CPU and connection to mechanical ventilation.

The Role of Physical Exercise in the Prevention of Musculoskeletal Disorders in Manual Workers: A Systematic Review and Meta-Analysis.

Work-related musculoskeletal disorders (WMSDs) are the most common occupational health problem in the European Union. Physical exercise interventions have been investigated in the prevention of WMSDs in many sectors. Therefore, our aim was to assess the effect of physical exercise in manual workers for the primary and secondary prevention of WMSDs. We conducted a systematic search of the literature and papers were included if: the participants were adult employees exclusively engaged in manual labor tasks; non-acute physical exercise intervention; pain, disability, physical functioning, or health-related quality of life outcome, with pre-post intervention measurements. We retrieved 10419 unique records and included 23 studies. A random effect meta-analysis was conducted on the studies with a control group design, using a three level model to estimate the pooled effect for pain outcomes (g = 0.4339, 95% CI : 0.1267 - 0.7412, p < 0.01), and a two-level model for disability outcomes (g = 0.6279, 95% CI : 0.3983 - 0.8575, p < 0.0001). Subset analysis revealed a moderate-to-large effect on the VAS outcome (g = 0.5866, 95% CI: 0.3102 - 0.8630, p < 0.0001). Meta-regression on pain outcomes revealed a significant effect for sex, age, study quality, and body segments tested. The analyses on all outcomes except VAS showed substantial heterogeneity (I2pain = 93%, of which 72% at the study level, I2disability = 78%, and I2vas = 56%, of which 44% at the study level). Physical exercise programs seem to have a positive effect on pain and disability stemming from WRMSDs in manual workers.

Dual-mode colorimetric/fluorescent chemosensor for Cu2+/Zn2+ and fingerprint imaging based on rhodamine ethylenediamine bis(triazolyl silsesquioxane).

A novel dual functional and visual rhodamine ethylenediamine bis(triazolyl silsesquioxane) (RBS) chemosensor was successfully synthesized using "click" chemistry. The results have unambiguously demonstrated that RBS can act in fluorescent and colorimetric sensing of Cu2+ and Zn2+ by their respective coordination with triazole structures and, more importantly, it has also been found that triazole-amide of RBS could turn on chelation-enhanced fluorescence (CHEF) of Cu2+. Remarkably, the addition of Cu2+ triggered an enhanced fluorescent emission by 63.3-fold (ϕF = 0.41), while Zn2+ enhanced it 48.3-fold (ϕF = 0.29) relative to the original RBS (ϕF = 0.006) in acetonitrile (MeCN) solvent. The fluorescent limit of detection for Cu2+ and Zn2+ is similar and fall within 3.0 nM, while under colorimetric sensing the responses were 2.14 × 10-8 and 4.0 × 10-8 mol L-1, respectively. Moreover, the effective sensing profile of RBS and extended applications of RBS-Cu2+ and RBS-Zn2+ for fingerprinting detection and imaging were observed with adequate sensitivity, stability and legibility under the dual visual responses.

Innovative training modality for sacral neuromodulation (SNM): Patient-specific computerized tomography (CT) reconstructed 3D-printed training system: ICS School of Modern Technology novel training modality.

INTRODUCTION: Sacral neuromodulation (SNM) is an effective treatment of urinary and bowel dysfunction, including secondary to neurological disorders. The learning curve for the optimal electrode placement for SNM is steep, expensive, and limited by patient factors such as obesity and previous injuries. We aim to create a patient specific 3-dimensional (3D) model for successful SNM training. MATERIALS AND METHODS: A total of 26 urology residents who had different level of knowledge and experience were enrolled to the 3D SNM training program. The creation of 3D sacrum model has been started with evaluation of real patient computerized tomography images and creation of Digital Imaging and Communications in Medicine files. The segmented anatomic structures from the files then edited and stereolithographic files were generated for 3D-model prints via Mimics© software. The 3D-printed models were used for training and evaluation of participants during the SNM intervention was performed. The evaluation of 3D SNM model training was led by one mentor who is expert on SNM. RESULTS: On the preprinted 3D sacrum model all 26 participants were requested to perform the essential steps to complete a SNM procedure and individual procedure time was recorded. The mean and median scores were 18.8 and 19, respectively according to Likert scores (min 11 max 28). CONCLUSIONS: SNM is increasing in popularity as a treatment option with physicians and patients with refractory symptoms. Few experienced specialists exist, and more effective training methods are needed to tackle the increasing demand, and individual patient anatomy.

The effects of an 8-week hypopressive exercise training program on urinary incontinence and pelvic floor muscle activation: A randomized controlled trial.

BACKGROUND: Pelvic floor dysfunction and urinary incontinence are two of the most frequent gynecological problems, and pelvic floor muscle training is recommended as a first-line treatment, with new approaches such as hypopressive exercises. This study aimed to analyze the efficacy of an 8-week supervised training program of hypopressive exercises on pelvic floor muscle strength and urinary incontinence symptomatology. DESIGN: Blinded randomized controlled trial. SETTINGS: Women with pelvic floor dysfunction and urinary incontinence symptoms, aged 18-60 years. PARTICIPANTS: A total of 117 participants were randomly allocated to the hypopressive exercises group (n = 62) or a control group that received no intervention (n = 55) and completed the study. MAIN OUTCOME MEASURES: Clinical and sociodemographic data were collected, as well as pelvic floor muscle strength (using the Modified Oxford Scale); the genital prolapse symptoms, colorectal symptoms, and urinary symptoms (with the Pelvic Floor Distress Inventory [PFDI-20]); the impact of pelvic floor disorders (PFD) on women's lives (with the Pelvic Floor Impact Questionnaire [PFIQ-7]); and the severity of urinary incontinence symptoms (using the International Consultation on Incontinence Questionnaire [ICIQ]). RESULTS: The results showed an improvement in the hypopressive group in the pelvic floor muscle strength F (1117) = 89.514, p < 0.001, a significantly lower score for the PFIQ7 total score, t (112) = 28.895, p < 0.001 and FPDI20 t (112) = 7.037, p < 0.001 as well as an improvement in ICIQ-SF values after 8 weeks of intervention in comparison with the control group. CONCLUSIONS: After performing an 8-week of hipopressive exercises intervention, a decrease in pelvic floor disorders associated symptoms can be observed. In addition, pelvic floor muscle contractility is improved and a decrease in severity and symptoms associated with urinary incontinence has been reported.

Long-Term Functional Outcomes and Quality of Life after Male Transobturator-Retrourethral Sling Surgery.

INTRODUCTION: Post-prostatectomy urinary incontinence (PPUI) has an enormous impact in quality of life (QoL). Transobturator-rethrourethral sling (AdVanceTMXP sling) is a well-established treatment option although there is paucity of data on long-term outcomes. Our objective was to assess the long-term functional outcomes and QoL in a cohort of men undergoing AdVanceTMXP sling surgery. METHODS: Retrospective observational study of men undergoing AdVanceTMXP sling in a tertiary referral institution from August 2013 to July 2020. 55 patients met the inclusion criteria, with a minimum follow-up of 12 months. Main outcomes were pre- and post-operative daily pad use and scoring in the ICIQ-SF questionnaire. Post-operative complications were assessed following the Clavien-Dindo classification system. QoL and satisfaction with the procedure were assessed through direct interview. RESULTS: Mean number of pads prior to surgery was 3.1, and mean ICIQ-SF score was 13.5. After surgery, mean daily pads use went to 1.2, and mean ICIQ-SF dropped to 5. With a mean follow-up of 42.36 months, 21.8% patients did not use any pads/day and 76.4% achieved social continence (0-1 pad/day). We found no statistically significant differences in outcomes of patients with follow-up of <36 months, 36-48 months, and >48 months (p = 0.067). CONCLUSIONS: AdVanceTMXP sling implantation in men with PPUI improves urinary incontinence and QoL, and their results are sustained over time.

Oleoylethanolamide Treatment Modulates Both Neuroinflammation and Microgliosis, and Prevents Massive Leukocyte Infiltration to the Cerebellum in a Mouse Model of Neuronal Degeneration.

Neurodegenerative diseases involve an exacerbated neuroinflammatory response led by microglia that triggers cytokine storm and leukocyte infiltration into the brain. PPARα agonists partially dampen this neuroinflammation in some models of brain insult, but neuronal loss was not the triggering cause in any of them. This study examines the anti-inflammatory and immunomodulatory properties of the PPARα agonist oleoylethanolamide (OEA) in the Purkinje Cell Degeneration (PCD) mouse, which exhibits striking neuroinflammation caused by aggressive loss of cerebellar Purkinje neurons. Using real-time quantitative polymerase chain reaction and immunostaining, we quantified changes in pro- and anti-inflammatory markers, microglial density and marker-based phenotype, and overall leukocyte recruitment at different time points after OEA administration. OEA was found to modulate cerebellar neuroinflammation by increasing the gene expression of proinflammatory mediators at the onset of neurodegeneration and decreasing it over time. OEA also enhanced the expression of anti-inflammatory and neuroprotective factors and the Pparα gene. Regarding microgliosis, OEA reduced microglial density-especially in regions where it is preferentially located in PCD mice-and shifted the microglial phenotype towards an anti-inflammatory state. Finally, OEA prevented massive leukocyte infiltration into the cerebellum. Overall, our findings suggest that OEA may change the environment to protect neurons from degeneration caused by exacerbated inflammation.

Patients with Chronic Spinal Cord Injury Display a Progressive Alteration over the Years of the Activation Stages of the T Lymphocyte Compartment.

Spinal cord injury (SCI) is a serious medical condition associated with severe morbidities and disability. Chronic SCI patients present an enhanced susceptibility to infections and comorbidities with inflammatory pathogenesis. Chronic SCI appears to be associated with a systemic dysfunction of the immune system. We investigated the alteration of the pivotal CD4+ and CD8+ T lymphocytes in patients with chronic SCI at different years of evolution. A clinically homogenous population of 105 patients with chronic SCI (31 with time of evolution less than 5 years (SCI SP); 32 early chronic (SCI ECP) with time of evolution between 5 and 15 years; and 42 late chronic (SCI LCP) with time of evolution more than 15 years) and 38 healthy controls were enrolled. SCI ECP and SCI LCP patients showed significant CD4+ and CD8+ T lymphopenia, ascribed to a reduction in naïve and CM subsets. Furthermore, SCI ECP and SCI LCP patients showed a significant reduction in the expression of CD28 on CD8+ T lymphocytes. The expression of CCR6 by CD4+ T lymphocytes was decreased during the evolution of chronic SCI, but on CD8+ T lymphocytes, it was observed during the first 15 years of evolution. In conclusion, the chronic SCI course with severe damage to T lymphocytes mainly worsens over the years of disease evolution.

Patients with Chronic Spinal Cord Injury and a Long Period of Evolution Exhibit an Altered Cytokine Production by CD4 and CD8 T Cell Populations.

Spinal cord injury (SCI) is a disabling neurological condition coursing with serious multisystem affections and morbidities. Changes in immune cell compartments have been consistently reported in previous works, representing a critical point of study for understanding the pathophysiology and progression of SCI from acute to chronic stages. Some relevant variations in circulating T cells have been noticed in patients with chronic SCI, although the number, distribution, and function of these populations remain to be fully elucidated. Likewise, the characterization of specific T cell subpopulations and their related cytokine production can aid in understanding the immunopathological role of T cells in SCI progression. In this sense, the objective of the present study was to analyze and quantify the total number of different cytokine-producers T cells in the serum of patients with chronic SCI (n = 105) in comparison to healthy controls (n = 38) by polychromatic flow cytometry. Having this goal, we studied CD4 and CD8 lymphocytes as well as naïve, effector, and effector/central memory subpopulations. SCI patients were classified according to the duration of the lesion in chronic SCI with a short period of evolution (SCI-SP) (comprised between 1 and 5 years since initial injury), early chronic phase (SCI-ECP) (between 5 and 15 years since initial injury) and late-chronic phase (SCI-LCP) (>15 years since initial injury). Our results show that patients with chronic SCI exhibited an altered immune profile of cytokine-producer T cells, including CD4/CD8 naïve, effector, and memory subpopulations in comparison to HC. In particular, IL-10 and IL-9 production seems to be importantly altered, especially in patients with SCI-LCP, whereas changes in IL-17, TNF-α, and IFN-γ T cell populations have also been reported in this and other chronic SCI groups. In conclusion, our study demonstrates an altered profile of cytokine-producer T cells in patients with chronic SCI, with marked changes throughout the course of the disease. In more detail, we have observed significant variations in cytokine production by circulating naive, effector, and effector/central memory CD4 and CD8 T cells. Future studies should be directed to explore the possible clinical consequences of these changes or develop additional translational approaches in these groups of patients.

Lignin-Based Catalysts for C-C Bond-Forming Reactions.

Carbon-carbon (C-C) bond formation is the key reaction in organic synthesis to construct the carbon framework of organic molecules. The continuous shift of science and technology toward eco-friendly and sustainable resources and processes has stimulated the development of catalytic processes for C-C bond formation based on the use of renewable resources. In this context, and among other biopolymer-based materials, lignin has attracted scientific attention in the field of catalysis during the last decade, either through its acid form or as a support for metal ions and metal nanoparticles that drive the catalytic activity. Its heterogeneous nature, as well as its facile preparation and low cost, provide competitive advantages over other homogeneous catalysts. In this review, we have summarized a variety of C-C formation reactions, such as condensations, Michael additions of indoles, and Pd-mediated cross-coupling reactions that were successfully carried out in the presence of lignin-based catalysts. These examples also involve the successful recovery and reuse of the catalyst after the reaction.

Automated High-Throughput Method for the Fast, Robust, and Reproducible Enrichment of Newly Synthesized Proteins.

A high-throughput method was developed for the automated enrichment of newly synthesized proteins (NSPs), which are labeled metabolically by substituting methionine with the "click-able" analogue azidohomoalanine (AHA). A suitable conjugate containing a dibenzocyclooctyne (DBCO) group allows the specific selection of NSPs by a fast 1 h click chemistry-based reaction with AHA. Through an automated pipetting platform, the samples are loaded into streptavidin cartridges for the selective binding of the NSPs by means of a biotin bait contained in the conjugate. The enriched proteins are eluted by a reproducible chemical cleavage of the 4,4-dimethyl-2,6-dioxocyclohexylidene (Dde) group in the conjugate, which increases selectivity. The NSPs can be collected and digested in the same well plate, and the resulting peptides can be subsequently loaded for automated cleanup, followed by mass spectrometry analysis. The proposed automated method allows for the robust and effective enrichment of samples in 96-well plates in a period of 3 h. Our developed enrichment method was comprehensively evaluated and then applied to the proteomics analysis of the melanoma A375 cell secretome, after treatment with the cytokines interferon α (IFN-α) and γ (IFN-γ), resulting in the quantification of 283 and 263 proteins, respectively, revealing intricate tumor growth-supportive and -suppressive effects.

Marine heatwaves drive recurrent mass mortalities in the Mediterranean Sea.

Climate change is causing an increase in the frequency and intensity of marine heatwaves (MHWs) and mass mortality events (MMEs) of marine organisms are one of their main ecological impacts. Here, we show that during the 2015-2019 period, the Mediterranean Sea has experienced exceptional thermal conditions resulting in the onset of five consecutive years of widespread MMEs across the basin. These MMEs affected thousands of kilometers of coastline from the surface to 45 m, across a range of marine habitats and taxa (50 taxa across 8 phyla). Significant relationships were found between the incidence of MMEs and the heat exposure associated with MHWs observed both at the surface and across depths. Our findings reveal that the Mediterranean Sea is experiencing an acceleration of the ecological impacts of MHWs which poses an unprecedented threat to its ecosystems' health and functioning. Overall, we show that increasing the resolution of empirical observation is critical to enhancing our ability to more effectively understand and manage the consequences of climate change.