Low prevalence of microplastic contamination in the bottom sediments and deep-sea waters of the Bransfield Strait, Antarctica.

Despite the remoteness of the Antarctic continent and Southern Ocean, microplastic (MPs) contamination has been evidenced in recent years. However, the deep-sea compartments of the Southern Ocean are yet to be investigated. In the present study, we conducted a baseline MP assessment of the deep-sea waters and bottom sediments of the Bransfield Strait, Antarctica. A low abundance of suspected MPs was found. The average MP abundances in bottom sediments and water samples were 0.09 MPs/g (range of 0 to 0.2 MPs/g) and 7.00 MPs/L (range of 0 to 16 MPs/L), respectively. The majority of the particles were fibers identified as cellulose, although polyethylene terephthalate (PET) and polyacrylonitrile (PAN) was also detected. These results suggest low MP contamination levels in the Southern Ocean's deepest environmental compartments. However, future studies must aim to investigate the smallest MP fractions and, if possible, nanoplastic (<1 µm) contamination in these remote compartments.

Effect of enamel deproteinization with 5.25% sodium hypochlorite on the bond strength of orthodontic brackets. An experimental study.

Background: In the search for alternatives to increase the bond strength of brackets, when necessary, this study proposes to apply the enamel deproteinization protocol to eliminate the proteins in the surface enamel to achieve better etching patterns and thereby increase bond strength. The aim of this study was to evaluate the effect of sodium hypochlorite as a deproteinizing agent on the bond strength of metal brackets. Material and Methods: Forty bovine teeth were randomly and equally divided into two groups. The experimental group (n=20) underwent a deproteinization treatment with sodium hypochlorite at 5.25% for 60 seconds prior to acid etching of the enamel with 37% phosphoric acid and bracket bonding with Transbond XTTM resin. The control group (n=20) underwent enamel etching with 37% phosphoric acid and bracket bonding with Transbond XTTM resin. Shear strength and the adhesive remnant index were evaluated and the Students t and Chi-square tests were used (P<0.05). Results: The bond strength values of the control group (27.72±6.42 Mpa) were not significantly lower compared to the experimental group (29.21± 7.96 Mpa) (p=0.259). The adhesive remnant index showed a similar behavior in both groups, with the amount of adhesive remaining on the enamel being less than 50% in most samples of both the control and experimental group. Conclusions: Deproteinization treatment of bovine tooth enamel with 5.25% sodium hypochlorite for 60 seconds prior to enamel acid etching does not improve the bond strength of a resin in orthodontic bracket bonding. Key words:Deproteinization, sodium hypochlorite, bracket bonding, orthodontics.

Autonomic dysfunction as manifestation of ICANS: A case report.

RATIONALE: Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy is a successful treatment for B-cell malignancies associated with cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cardiovascular toxicities have also been reported in this setting. However, there is scarce data regarding development of autonomic disorders after CAR-T cell therapy. PATIENT CONCERNS: We report a case with a patient with non-Hodgkin B-cell lymphoma, refractory to 2 prior lines of immunochemotherapy, treated with CAR-T therapy. DIAGNOSES: Orthostatic hypotension secondary to autonomic dysfunction was diagnosed as manifestation of ICANS. INTERVENTIONS: The patient received metilprednisolone 1000 mg IV daily for 3 days and anakinra 100 mg IV every 6h. OUTCOMES: The vast majority of autonomic symptoms ceased and 4 months after CAR-T therapy, autonomic dysfunction was resolved. LESSONS: New-onset autonomic dysfunction can occur as manifestation of ICANS in patients who experience persistent neurologic and cardiovascular symptoms after resolution of acute neurotoxicity and should be early recognized. Differences in differential diagnosis, mechanisms and treatment approaches are discussed.

Controlled comparison evaluation of the soothing effect of 3 cosmetic products on skin discomfort induced by an irritant chemical agent (capsaicin).

BACKGROUND: Sensitive skin is a highly prevalent problem. The objective of the study was to assess whether the tested products are effective and safe in terms of improving the symptoms of sensitive skin. METHODS: A clinical randomized split-face study was carried out on 24 healthy female subjects. Three cosmetic combinations were tested versus vehicle: product A (Solía Thermal Spring Water-TSW-from Cantabria, Spain + diatom algae-P. tricornutum-extract), product B (Solía TSW + diatom algae extract + Annona cherimola Fruit Extract) and product C (Solía TSW + diatom algae extract + Annona cherimola Fruit Extract + niacinamide). Prior to each application of the study Product (A, B, or C)/vehicle, 10% of aqueous solution of capsaicin to induce skin irritation was applied, mimicking the symptoms of sensitive skin. Stinging and burning sensations were evaluated at different time points. RESULTS: All three tested products A, B, and C showed to act better in calming the symptoms induced by capsaicin when compared to the vehicle. CONCLUSIONS: The tested products would be an interesting option for treating stinging and burning sensations in sensitive skin patients.

Association between exposure to perfluoroalkyl substances (PFAS) and endometriosis in the ENDEA case-control study.

BACKGROUND: Perfluoroalkyl substances (PFAS) are environmental contaminants present in a wide range of consumer products and frequently detected in drinking water. They have been linked to adverse reproductive health outcomes in women, but there is limited human evidence on the association of PFAS exposure with endometriosis. OBJECTIVE/AIM: To explore the association between plasma concentrations of several PFAS, considered individually and as a mixture, and the risk of endometriosis in women of childbearing age. METHODS: Between 2018 and 2020, 42 patients with endometriosis and 90 controls undergoing abdominal surgery were recruited at two public hospitals in Granada, Spain. The presence or absence of endometriosis was ascertained by laparoscopic inspection of the pelvis and biopsy of suspected lesions (histological diagnosis). Concentrations of 10 PFAS were quantified in plasma samples from participants. Unconditional logistic regression was employed to examine associations of individual PFAS and summed concentrations of short (∑SC) and long-chain (∑LC) PFAS with odds of endometriosis, and quantile g-computation was used to assess their mixture effect. RESULTS: In models adjusted for age, schooling, and parity, perfluorotridecanoic acid (PFTrDA) was associated with higher odds of endometriosis (odds ratio [OR] = 1.74; 95 % CI = 1.11-2.73 per 2-fold increase in plasma concentrations), while marginally significant associations were found for perfluorohexane sulfonate (PFHxS) (OR = 1.45, 95 % CI = 0.94-2.21) and ∑SC PFAS (OR = 1.48; 95 % CI = 0.96-2.30). No associations were found for the remaining PFAS. The PFAS mixture was non-significantly associated with 1.7-fold higher odds of endometriosis (95 % CI = 0.73-3.80), with perfluorononanoic acid (PFNA), PFHxS, and PFTrDA being the major contributors to this effect. CONCLUSIONS: These findings suggest that exposure to certain PFAS may increase the odds of endometriosis. However, given the modest sample size, further studies are warranted to verify these results.

Evaluation of the i-gel® Plus supraglottic airway device in elective surgery: a prospective international multicentre study.

BACKGROUND: The i-gel® Plus is a modified version of the i-gel® supraglottic airway device. It contains a wider drainage port; a longer tip; ramps inside the breathing channel; and an additional port for oxygen delivery. There has been no prospective evaluation of this device in clinical practice. METHODS: This international, multicentre, prospective cohort study aimed to evaluate the performance of the i-gel Plus in adult patients undergoing elective procedures under general anaesthesia. The primary outcome was overall insertion success rate, defined as the ability to provide effective airway management through the device from insertion until the end of the surgical procedure. Secondary outcomes included device performance and incidence of postoperative adverse events. Data from the first 1000 patients are reported. RESULTS: In total, 1012 patients were enrolled; 12 forms were excluded from the final analysis due to incomplete data leaving 1000 included patients (545 female). Overall insertion success rate was 98.6%, with a first-attempt success rate of insertion of 88.2%. A significant difference between females and males was seen for the overall success rate (97.4% vs. 99.6% respectively) but not for first-attempt successful insertion. Mean (SD) oropharyngeal seal pressure was 32 (7) cmH2O. The only independent factor that increased the risk of first-attempt failure was low operator experience. Complications included desaturation < 85% in 0.6%; traces of blood on the device in 7.4%; laryngospasm in 0.5%; and gastric contents inside the bowl in 0.2% of patients. CONCLUSIONS: The i-gel Plus appears to be an effective supraglottic airway device that is associated with a high insertion success rate and a reasonably low incidence of complications.

The Role of Functional Deficits, Depression, and Cognitive Symptoms in the Perceived Loneliness of Older Adults in Mexico City.

The world is aging and experiencing loneliness. Functional impairment in instrumental activities of daily living (IADL) in older people (OP) with mild neurocognitive disorder (MNCD) predicts loneliness. After the pandemic, there was an increase in perceived loneliness. We explored the association between loneliness, depression, deficits in IADL, and cognitive symptoms among OP. From February to December 2023, using a cross-sectional design, we interviewed probable cases with mild cognitive impairment and caregivers in two public facilities. We administered the UCLA Loneliness Scale v3, Lawton IADL Scale, Mini-Mental State Examination (MMSE), and Yesavage's Geriatric Depression Scale. Samples were matched: 85 per group, 82.4% were women, married (52.95%), and mean age of 69.17 (±6.93) years. In our study, 30% displayed moderate to high levels of perceived loneliness. Multivariate analysis showed loneliness was associated with depression, low levels of IADL, and older age, but not with cognitive symptoms, which explained 22% of the total variance (F 165) = 16.99, (p < 0.001). Targeting symptoms and behaviors that could be modified (i.e., depression and functionality) can improve feelings of perceived loneliness and have an impact on morbidity and mortality with which it is associated.

Adult Pompe disease: Analysis of 13 patients. / Enfermedad de Pompe del adulto: análisis de 13 pacientes.

INTRODUCTION: Pompe Disease (PD) is a lysosomal disorder caused by a deficiency of the enzyme acid alpha-glucosidase (GAA), primarily manifesting as a progressive myopathy with early respiratory involvement. Enzyme replacement therapy (ERT) is available since 2006. MATERIALS AND METHODS: We describe 13 patients with partial GAA deficiency, followed at Hospital 12 de Octubre, 8 of whom were receiving treatment. RESULTS: 8 patients exhibit symptoms, all with late onset. They display axial and proximal weakness predominantly in the lower limbs but maintain autonomous gait. Five patients require non-invasive mechanical ventilation due to respiratory insufficiency. All symptomatic patients receive ERT, and in 7/8 (87.5%), there is a decline in motor and pulmonary function after an average of 8.25 years of treatment (baseline and post-treatment FVC and 6MWT mean 86.6% vs 70.8% and 498 vs 430 meters, respectively). CONCLUSION: Not all patients with partial GAA deficiency experience symptoms of PD, and symptomatic patients, despite ERT with recombinant alpha-glucosidase, mostly experience a gradual decline in motor and respiratory function.

Antidiabetic drugs in Parkinson's disease.

This review explores the intricate connections between type 2 diabetes (T2D) and Parkinson's disease (PD), both prevalent chronic conditions that primarily affect the aging population. These diseases share common early biochemical pathways that contribute to tissue damage. This manuscript also systematically compiles potential shared cellular mechanisms between T2D and PD and discusses the literature on the utilization of antidiabetic drugs as potential therapeutic options for PD. This review encompasses studies investigating the experimental and clinical efficacy of antidiabetic drugs in the treatment of Parkinson's disease, along with the proposed mechanisms of action. The exploration of the benefits of antidiabetic drugs in PD presents a promising avenue for the treatment of this neurodegenerative disorder.

Cortisol/Cortisone Ratio in Youth with Obesity One Year Following Sleeve Gastrectomy.

Background: Glucocorticoid metabolites are associated with body composition measures and are altered with weight status. Metabolic and bariatric surgery (MBS) results in significant changes in weight and body composition. However, MBS effects on glucocorticoid metabolites are unknown. Objective: To evaluate (i) changes in the cortisol/cortisone ratio in youth with obesity 12 months after sleeve gastrectomy (SG) compared with nonsurgical controls with obesity (NS), and (ii) associations of these changes with body composition changes. Methods: A total of 38 participants 13-25 years old with obesity (29 female) were followed for 12 months. Half underwent SG, and the other half were followed with routine care (nonsurgical, NS). Fasting blood was assessed for cortisol and cortisone using liquid chromatography-mass spectroscopy as part of metabolomic analysis, and the cortisol/cortisone ratio was calculated. A single-slice MRI of the abdomen was performed to assess subcutaneous and visceral adipose tissue (SAT, VAT). Hepatic steatosis was assessed by computed tomography (CT). Results: SG did not differ from NS for baseline clinical characteristics, other than the mean age (SG 18.0 ± 0.46 vs. NS 16.6 ± 0.50 years, P = 0.041), BMI (BMI, 47.23 ± 1.5 vs. 41.32 ± 1.1 kg/m2, P = 0.003) weight and VAT, which were higher in SG. Significant reductions were noted over 12 months in BMI, BMI z-score, VAT, and SAT within the SG versus NS groups (P ≤ 0.001). Over 12 months, groups did not differ for changes in cortisol/cortisone ratio after controlling for age at baseline (P = 0.293). The ratio trended to decrease within the SG group [-1.40 (-5.08, 0.06), P = 0.080], particularly among those that had completed puberty (P = 0.048). No associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Conclusions: The cortisol/cortisone ratio trended to decrease 12 months following SG. However, no associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Studies with larger numbers of participants are necessary to confirm these findings.

Evaluation of the Effectiveness of Eugenol and MS-222 as Anesthetics in Zebrafish in Repeated Exposures and Post-Anesthesia Behaviour.

The increasing use of the zebrafish (Danio rerio) in scientific experiments has made it necessary to implement anesthesia protocols guaranteeing minimum pain and suffering for these animals and ensuring the reliability of the results obtained from their research. Therefore, we aimed to compare the effectiveness of two anesthetics, eugenol and MS-222, in consecutive administrations and evaluate the zebrafish behaviour after repeated anesthesia. Thus, several zebrafish were anaesthetized with eugenol, MS-222, and buffered MS-222 three times repeatedly with a 24-h interval between each exposure. The induction and recovery periods were also timed. Their swimming frequency was determined after each exposure to assess their behaviour after the anesthesia. Anesthesia induction was quicker with eugenol compared to MS-222. However, eugenol presented longer recovery times, which were prolonged after each exposure. Also, the swimming frequency was reduced after each anesthesia with eugenol. The buffered version of MS-222 was more efficacious than the non-buffered one. Both versions of MS-222 did not affect the swimming frequency. Based on these findings, we recommend the utilization of MS-222 buffered rather than eugenol when repeated, brief-duration anesthesia is necessitated for a study.

Development and Evaluation of a Software Designed by a Nursing and Technology Team to Assess the Health Status of Adults over 65 Years of Age / Desarrollo y evaluación de un software diseñado por un equipo de enfermería y tecnología para la valoración del estado de salud de los adultos mayores de 65 año / Desenvolvimento e avaliação de um software desenvolvido por uma equipe de enfermagem e tecnologia para avaliação do estado de saúde de adultos com mais de 65 anos

Objective. This work sought to develop the Actuasalud platformas a useful tool for nursing that permits assessing health, in term of frailty, in population over 65 years of age. Methods. For the design and development of Actuasalud, two working groups were formed: one from nursing with different profiles, to identify the scientific content and a computer science group responsible for the software programming and development. Both teams adapted the scientific content to the technology so that the tool would allow for population screening with detection of health problems and frailty states. Results. The software was developed in three large blocks that include all the dimensions of frailty: a) sociodemographic variables, b) comorbidities, and c) assessment tools of autonomy-related needs that evaluate the dimensions of frailty. At the end of the evaluation, a detailed report is displayed through bar diagram with the diagnosis of each of the dimensions assessed. The assessment in the participating elderly showed that 44.7% (n = 38) of the population was considered not frail, and 55.3%; (n = 47) as frail. Regarding associated pathologies, high blood pressure (67.1%; n = 57), osteoarthritis and/or arthritis (55.3%; n = 47), diabetes (48.2%; n = 41) and falls during the last year (35.3%; n = 30) were highlighted. Conclusion.Actuasalud is an application that allows nursing professionals to evaluate frailty and issue a quick diagnosis with ordered sequence,which helps to provide individualized care to elderly individuals according to the problems detected during the evaluation.

Objetivo. Desarrollar la plataforma Actuasalud como una herramienta útil para enfermería que permita evaluar la salud, en términos de fragilidad, en población mayor de 65 años. Métodos. Para el diseño y desarrollo de Actuasalud,se constituyeron dos grupos de trabajo: uno de enfermería con diferentes perfiles para identificar el contenido científico y uno informático que se responsabilizó de la programación y desarrollo del software. Ambos equipos adaptaron el contenido científico a la tecnología de manera que la herramienta permitiese hacer un cribado poblacional con detección de problemas de salud y estados de fragilidad. Resultados. Se desarrolló el software en tres grandes bloques que incluyen todas las dimensiones de fragilidad: a) variables sociodemográficas, b) comorbilidades y c) herramientas de evaluación de necesidades relacionadas con la autonomía que evalúan las dimensiones de fragilidad. Al finalizar la evaluación, se visualiza un informe detallado mediante diagrama de barras con el diagnóstico de cada una de las dimensiones evaluadas. La evaluación en los mayores participantes mostró que el 44.7% (n = 38) de la población se consideró como no frágil, y un 55.3%; (n = 47) como frágiles. En cuanto a las patologías asociadas, destacaron hipertensión arterial (67,1 %; n = 57), artrosis y/o artritis (55.3%; n = 47), diabetes (48.2 %; n = 41) y caídas en el último año (35,3 %; n = 30). Conclusión.Actuasalud es una aplicación que permite a los profesionales de enfermería evaluar fragilidad y emitir un diagnóstico de forma ágil con secuencia ordenada que ayuda a brindar cuidados individualizados a personas mayores de acuerdo los problemas detectados en la evaluación.

Objetivo. Desenvolver a plataforma Actuasalud como uma ferramenta útil para a enfermagem que permite avaliar a saúde, em termos de fragilidade, numa população com mais de 65 anos. Métodos. Para a concepção e desenvolvimento do Actuasalud foram formados dois grupos de trabalho: um grupo de enfermagem com perfis diferentes, para identificar o conteúdo científico, e um grupo de informática que foi responsável pela programação e desenvolvimento do software. Ambas as equipas adaptaram o conteúdo científico à tecnologia para que a ferramenta permitisse o rastreio da população para detectar problemas de saúde e estados de fragilidade. Resultados. O software foi desenvolvido em três grandes blocos que incluem todas as dimensões da fragilidade: a) variáveis sociodemográficas, b) comorbidades ec) instrumentos de avaliação de necessidades relacionadas à autonomia que avaliam as dimensões da fragilidade. Ao final da avaliação é apresentado um relatório detalhado através de um diagrama de barras com o diagnóstico de cada uma das dimensões avaliadas. A avaliação nos idosos mostrou que 44.7% (n=38) da população foi considerada não frágil e 55.3%; (n=47) como frágil. Quanto às patologias associadas, destacaram-se a hipertensão arterial (67.1%; n=57), a osteoartrite e/ou artrite (55.3%; n=47), a diabetes (48.2%; n=41) e as quedas no último ano (35.3%; n=30). Conclusão. Actuasalud é um aplicativo que permite ao profissional de enfermagem avaliar a fragilidade e emitir um diagnóstico de forma ágil e com sequência ordenada que auxilia no atendimento individualizado ao idoso de acordo com os problemas detectados na avaliação.

Body image, illness uncertainty and symptom clusters in surgically treated breast cancer survivors: An exploratory factor analysis and correlational study.

PURPOSE: To determine the relationship among body image, illness uncertainty, and symptom clusters in surgically treated breast cancer survivors. METHODS: A correlational, descriptive study was conducted in a convenience sample of 60 women surgically treated breast cancer survivors recruited in a private hospital and a survivor center. A questionnaire of sociodemographic characteristics, MUIS-C Scale, and QLQ-C30 and Module BR-23 were used. Variable characteristics and associations were analyzed with descriptive statistics and Pearson correlation coefficient, and exploratory factor analysis using unweighted least squares and Promax rotation was used for symptom clustering. RESULTS: A three-factor structure was found: an anxiety symptom cluster, a breast symptom cluster, and an arm symptoms, depression, and fatigue symptom cluster, explaining 46,47% of the variance. Significant correlations were found among body image and illness uncertainty (r = -0,390, p < 0,01), body image and the anxiety symptom cluster (r = 0,613, p < 0,01), illness uncertainty and the anxiety symptom cluster (r = -0,421, p < 0,01), the breast symptom cluster (r = -0,425, p < 0,01), and the arm symptoms - depression - fatigue symptom cluster (r = -0,443, p < 0,01). CONCLUSION: The relationships among all variables were statistically significant. Nurses providing care to BC survivors need to address the multidimensionality of the symptom experience and its correlates to better assist their patients. Further research is needed to elucidate the biopsychosocial underpinnings of those relationships.

Data Model for the Comprehensive Management of Biobanks and Its Contribution to Personalized Medicine.

Biobanks are infrastructures essential for research involving multi-disciplinary teams and an increasing number of stakeholders. In the field of personalized medicine, biobanks play a key role through the provision of well-characterized and annotated samples protecting at the same time the right of donors. The Andalusian Public Health System Biobank (SSPA Biobank) has implemented a global information management system made up of different modules that allow for the recording, traceability and monitoring of all the information associated with the biobank operations. The data model, designed in a standardized and normalized way according to international initiatives on data harmonization, integrates the information necessary to guarantee the quality of results from research, benefiting researchers, clinicians and donors.

Measurement of iron absorption and iron gains from birth to 6 months in breastfed and formula-fed infants using iron isotope dilution.

Little is known about iron kinetics in early infancy. We administered stable iron isotopes to pregnant women and used maternal-fetal iron transfer to enrich newborn body iron. Dilution of enriched body iron by dietary iron with natural isotopic composition was used to assess iron kinetics from birth to 6 months. In breastfed (BF, n = 8), formula-fed (FF, n = 7), or mixed feeding (MF, n = 8) infants, median (interquartile range) iron intake was 0.27, 11.19 (10.46-15.55), and 4.13 (2.33-6.95) mg/day; iron absorbed was 0.128 (0.095-0.180), 0.457 (0.374-0.617), and 0.391 (0.283-0.473) mg/day (BF versus FF, P < 0.01); and total iron gains were 0.027 (-0.002-0.055), 0.349 (0.260-0.498), and 0.276 (0.175-0.368) mg/day (BF versus FF, P < 0.001; BF versus MF, P < 0.05). Isotope dilution can quantify long-term iron absorption and describe the trajectory of iron depletion during early infancy.

Influence of Impaired Upper Extremity Motor Function on Static Balance in People with Chronic Stroke.

BACKGROUND: Stroke is a leading cause of disability, especially due to an increased fall risk and postural instability. The objective of this study was to analyze the impact of motor impairment in the hemiparetic UE on static balance in standing, in subject with chronic stroke. METHODS: Seventy adults with chronic stroke, capable of independent standing and walking, participated in this cross-sectional study. The exclusion criteria included vestibular, cerebellar, or posterior cord lesions. The participants were classified based on their UE impairment using the Fugl-Meyer Assessment of Motor Recovery after Stroke (FMA-UE). A posturographic evaluation (mCTSIB) was performed in the standing position to analyze the center of pressure (COP) displacement in the mediolateral (ML) and anteroposterior (AP) axes and its mean speed with eyes open (OE) and closed (EC) on stable and unstable surfaces. RESULTS: A strong and significant correlation (r = -0.53; p < 0.001) was observed between the mediolateral (ML) center of pressure (COP) oscillation and the FMA-UE, which was particularly strong with eyes closed [r(EO) = 0.5; r(EC) = 0.54]. The results of the multiple linear regression analysis indicated that the ML oscillation is influenced significantly by the FMA-Motor, and specifically by the sections on UE, wrist, coordination/speed, and sensation. CONCLUSIONS: The hemiparetic UE motor capacity is strongly related to the ML COP oscillation during standing in individuals with chronic stroke, with a lower motor capacity associated with a greater instability. Understanding these relationships underpins the interventions to improve balance and reduce falls in people who have had a stroke.

Melatonin synergistically potentiates the effect of methylprednisolone on reducing neuroinflammation in the experimental autoimmune encephalomyelitis mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease of unknown etiology characterized by infiltration of encephalitogenic cells in the central nervous system (CNS) resulting in the presence of multifocal areas of demyelination leading to neurodegeneration. The infiltrated immune cells population is composed mainly of effector CD4+ and CD8+ T lymphocytes, B cells, macrophages, and dendritic cells that secrete pro-inflammatory factors that eventually damage myelin leading to axonal damage. The most common clinical form of MS is relapsing-remitting (RR), characterized by neuroinflammatory episodes followed by partial or total recovery of neurological deficits. The first-line treatment for RRMS relapses is a high dose of glucocorticoids, especially methylprednisolone, for three to five consecutive days. Several studies have reported the beneficial effects of melatonin in the context of neuroinflammation associated with MS or experimental autoimmune encephalomyelitis (EAE), the preclinical model for MS. Therefore, the objective of this study was to evaluate the effect of the combined treatment of melatonin and methylprednisolone on the neuroinflammatory response associated with the EAE development. This study shows for the first time the protective synergistic effect of co-treatment with melatonin and methylprednisolone on reducing the severity of EAE by decreasing CD4 lymphocytes, B cells, macrophages and dendritic cells in the CNS, as well as modulating the population of infiltrated T and B cells toward regulatory phenotypes to the detriment of pro-inflammatory effector functions. In addition to the potentiation of the protective role of methylprednisolone, treatment with melatonin from the clinical onset of EAE improves the natural course of the EAE and the response to a subsequent treatment with methylprednisolone in a later relapse of the disease, pointing melatonin as potential therapeutic tool in combination with methylprednisolone for the treatment of relapses in MS.

A Novel Role for the Histone Demethylase JMJD3 in Mediating Heroin-Induced Relapse-Like Behaviors.

BACKGROUND: Epigenetic changes that lead to long-term neuroadaptations following opioid exposure are not well understood. We examined how histone demethylase JMJD3 in the nucleus accumbens (NAc) influences heroin seeking after abstinence from self-administration. METHODS: Male Sprague Dawley rats were trained to self-administer heroin. Western blotting and quantitative polymerase chain reaction were performed to quantify JMJD3 and bone morphogenetic protein (BMP) pathway expression in the NAc (n = 7-11/group). Pharmacological inhibitors or viral expression vectors were microinfused into the NAc to manipulate JMJD3 or the BMP pathway member SMAD1 (n = 9-11/group). The RiboTag capture method (n = 3-5/group) and viral vectors (n = 7-8/group) were used in male transgenic rats to identify the contributions of D1- and D2-expressing medium spiny neurons in the NAc. Drug seeking was tested by cue-induced response previously paired with drug infusion. RESULTS: Levels of JMJD3 and phosphorylated SMAD1/5 in the NAc were increased after 14 days of abstinence from heroin self-administration. Pharmacological and virus-mediated inhibition of JMJD3 or the BMP pathway attenuated cue-induced seeking. Pharmacological inhibition of BMP signaling reduced JMJD3 expression and H3K27me3 levels. JMJD3 bidirectionally affected seeking: expression of the wild-type increased cue-induced seeking whereas expression of a catalytic dead mutant decreased it. JMJD3 expression was increased in D2+ but not D1+ medium spiny neurons. Expression of the mutant JMJD3 in D2+ neurons was sufficient to decrease cue-induced heroin seeking. CONCLUSIONS: JMJD3 mediates persistent cellular and behavioral adaptations that underlie heroin relapse, and this activity is regulated by the BMP pathway.