Clinical characteristics and impact on patient-reported outcomes and quality of life of people with ambulatory secondary progressive multiple sclerosis: Discover study.

BACKGROUND: People with secondary progressive multiple sclerosis (pwSPMS) experience increasing disability, which impacts negatively on their health-related quality of life (HRQoL). Our aims were to assess the impact of secondary progressive multiple sclerosis (SPMS) on functional status and HRQoL and describe the clinical profile in this population. METHODS: DISCOVER is an observational, cross-sectional, multicenter study with retrospective data collection in real-world clinical practice in Spain. Sociodemographic and clinical variables, functional and cognitive scales, patient-reported outcomes (PROs), and direct healthcare, and non-healthcare and indirect costs were collected. RESULTS: A total of 297 evaluable pwSPMS with a EDSS score between 3-6.5 participated: 62.3 % were female and 18.9 % had active SPMS. At the study visit, 77 % of them presented an Expanded Disability Scale Score (EDSS) of 6-6.5. Nearly 40 % did not receive any disease-modifying treatment. Regarding the working situation, 61.6 % were inactive due to disability. PROs: 99.3 % showed mobility impairment in EuroQoL-5 Dimensions-5 Levels, and about 60 % reported physical impact on the Multiple Sclerosis Impact Scale-29. Fatigue was present in 76.1 %, and almost 40 % reported anxiety or depression. The Symbol Digit Modalities Test was used to assess cognitive impairment; 80 % of the patients were below the mean score. Participants who presented relapses two years before and had high EDSS scores had a more negative impact on HRQoL. PwSPMS with a negative impact on HRQoL presented a higher cost burden, primarily due to indirect costs. CONCLUSIONS: PwSPMS experience a negative impact on their HRQoL, with a high physical impact, fatigue, cognitive impairment, and a high burden of indirect costs.

Atypical noncontiguous TSC2/PKD1 gene deletions presenting as tuberous sclerosis/polycystic kidney disease contiguous gene syndrome.

Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are genetically distinct disorders typically associated with pathogenic variants in TSC1 and TSC2 for the former and PKD1 and PKD2 for the latter. TSC2 and PKD1 lie adjacent to each other, and large deletions comprising both genes lead to TSC2/PKD1 contiguous gene deletion syndrome (CGS). In this study, we describe a young female patient exhibiting symptoms of TSC2/PKD1 CGS in which genetic analysis disclosed two noncontiguous partial gene deletions in TSC2 and PKD1 that putatively are responsible for the manifestations of the syndrome. Further analysis revealed that both deletions appear to be de novo on the maternal chromosome, presumably with a germline origin. Despite extensive analysis, no maternal chromosomal rearrangement triggering these pathogenic variants was detected. This case elucidates a unique pathogenesis for TSC2/PKD1 CGS, diverging from the common contiguous deletions typically observed, marking the first reported instance of TSC2/PKD1 CGS caused by independent, functionally significant partial gene deletions.

Infective Endocarditis Due to Corynebacterium jeikeium: Four Case Reports and Narrative Review of the Literature.

Corynebacterium jeikeium, a pleomorphic Gram-positive bacillus, is a common component of the cutaneous microbiota, usually considered as a contaminant, with little pathogenic potential. However, its role in various types of infections, such as bacteremia, sepsis, endocarditis (IE) and infection of prosthetic material is gradually being proven. Few cases of IE due to Corynebacterium jeikeium have been described in the literature. The aim of this article was to describe four cases of IE due to Corynebacterium jeikeium diagnosed in our hospital between May 2021 and April 2022, as well as to conduct a narrative review of the literature on this entity. After analysis, we highlight that 65.6% were men, 81.3% were valve or intravascular device carriers, and IE cases presented early, before one year after surgery. The most affected valve was the aortic valve (68.8%), followed by the mitral valve (21.1%). Valve replacement was performed in 65.6% of cases, and the most commonly used antibiotic was vancomycin (68.8%) at a dose of 15 mg/kg/12 h. With respect to prognosis, the overall mortality rate was 21.9%. The comparative results between our series and the literature review were similar except for a higher mortality rate (50%) and the use of dalbavancin in the treatment. We go on to review previously reported cases, along with four cases described in our hospital, of C. jeikeium endocarditis and will discuss various aspects of C. jeikeium infection, focusing on microbiology, pathophysiology, and treatment.

Systemic testosterone for the treatment of female sexual interest and arousal disorder (FSIAD) in the postmenopause.

INTRODUCTION: Female sexual interest and arousal disorder (FSIAD) is the most prevalent female sexual dysfunction in the postmenopause. OBJECTIVE: The aim of this review is to provide a summary of the currently available evidence on the use of testosterone in the treatment of FSIAD in postmenopausal women. METHODS: A narrative review on the topic was performed. Only randomized controlled trials (RCTs) and systematic reviews and meta-analysis were considered. 123 articles were screened, 105 of them assessed for eligibility, and finally 9 were included in qualitative synthesis following the PRISMA declaration. RESULTS: Current evidence recommends, with moderate therapeutic benefit, the use of systemic transdermal testosterone within the premenopausal physiological range in postmenopausal women with Hypoactive Sexual Desire Disorder (HSDD), the previous entity for low desire dysfunction, not primarily related to modifiable factors or comorbidities such as relationship or mental health problems. The available evidence is based on studies with heterogeneity on their design (different testosterone doses, routes of administration, testosterone use in combination and alone, sexual instruments of measurement). There is no data indicating severe short-term adverse effects, although long-term safety data is lacking. CONCLUSIONS: Despite having testosterone as a valuable tool, therapeutic strategies are lacking in the pharmacological field of HSDD/FSIAD. Neuroimaging studies could provide valuable information regarding the sexual desire substrate and suggest the potential application of already approved drugs for women with a good safety profile. The use of validated instruments for HSDD in postmenopausal women, considering the level of distress, is necessary to be able to draw robust conclusions on the evaluated treatments.

The Evolving Field of Dental Sleep Medicine.

Dental sleep medicine is a dynamic field focused on the relationship between oral health and sleep disorders, particularly sleep apnea. Dentists play a crucial role in diagnosing and treating sleep-related breathing issues. As awareness of the impact of sleep on overall health grows, the field is evolving rapidly with advancements in technology, diagnostic tools, and treatment modalities. Interdisciplinary collaboration between dentists, sleep physicians, and other health care professionals is becoming increasingly important. The integration of innovative approaches and a patient-centric focus make dental sleep medicine a pivotal player in addressing the complex interplay between oral health and sleep quality.

Synthesis of biocompatible hydrogel of alginate-chitosan enriched with iron sulfide nanocrystals.

This work aimed to synthesize and characterize a biocompatible hydrogel of alginate and chitosan enriched with iron sulfide nanocrystals. Three concentrations of iron sulfide nanocrystals (FeS2NCs) 0.03905, 0.0781, and 0.2343 mg/ml were used. Gel swelling was determined using phosphate-buffered saline solution at 1, 2, 4, 6, 24, 48, and 72 h. The microstructure, the morphology, and the elastic strength were determined by optical microscopy, scanning electron microscopy, and rheological studies, respectively. The functional groups were identified through Fourier Transform Infrared spectroscopy. Biocompatibility was determined in a murine model; after seven days of subdermal inoculation, histological sections stained with H&E were analyzed, and then histopathological features were evaluated. All the compounds obtained showed a loss modulus lower than the storage modulus. The 0.2343 mg/ml FeS2NCs hydrogel showed higher swelling than the control. In the in vivo evaluation, no adverse effects were found. The presence of FeS2NCs was well tolerated in the subcutaneous tissue of mice, according to histopathological analysis. The hydrogels synthesized with added FeS2NCs demonstrate a swelling ratio of 150 %, rheologically exhibiting gel-like behavior rather than viscous liquids. Furthermore, they did not present any adverse effects on the subcutaneous tissue.

Prevalence and Characteristics of Sleep Disorders in Children Aged 7-17: Insights from Parental Observations at the Dental Office.

Sleep disorders (SD) in children is a topic of great relevance due to their impact on a child's general health. This has led us to study their prevalence and the factors that disturb them in the developing population. Using a validated Likert-type questionnaire, different behaviors observed by the parents during the different phases of their children's sleep were evaluated during the last 6 months. A total of 206 children between the ages of 7 and 17 who attended a dental office participated in the study. The prevalence of SD was 47.6%. There were no significant differences regarding the SD in relation to sex (p = 0.796). The mean total score for children aged 7 to 11 years old was 42.3 (±14.25) compared to 45.44 (±15.51) for the group consisting of children aged 12 to 17 years old, reporting a statistically significant difference among both age groups (p = 0.01). The most frequent disorder was related to initiating and maintaining sleep (64.9%) while the least prevalent were the respiratory sleep disorders (27.2%). Given the high prevalence of these disorders, it is necessary to intercept them during childhood and establish educational guidelines in this regard throughout primary care.

Antimicrobial and Cytotoxic Effect of Positively Charged Nanosilver-Coated Silk Sutures.

Sutures are a crucial component of surgical procedures, serving to close and stabilize wound margins to promote healing. However, microbial contamination of sutures can increase the risk of surgical site infections (SSI) due to colonization by pathogens. This study aimed to tackle SSI by synthesizing positively charged silver nanoparticles (P-AgNPs) and using them to produce antimicrobial sutures. The P-AgNPs were reduced and stabilized using polyethylenimine (PEI), a cationic branched polymer. The physiochemical characteristics of P-AgNPs were confirmed from the surface plasmon resonance (SPR) peak at 419 nm, spherical morphology with a particle size range of 8-10 nm, PEI functional groups on NPs, a hydrodynamic diameter of 12.3 ± 2.4 nm, and a zeta potential of 31.3 ± 6 mV. Subsequently, the surfaces of silk sutures were impregnated with P-AgNPs at different time intervals (24, 48, and 96 h) using an ex situ method. Scanning electron microscopy (SEM) and tensile strength studies were conducted to determine the coating and durability of the NP-coated sutures. The NPs were quantified on sutures using inductively coupled plasma optical emission spectrophotometry (ICP-OES), which was in the range of 1-5 µg. Primarily, antimicrobial activity was studied using three microorganisms (Candida albicans, Streptococcus mutans, and Staphylococcus aureus) for both P-AgNPs and suture-coated P-AgNPs using the agar diffusion method. The results showed that only the NPs and NP-coated sutures exhibited enhanced antimicrobial effects against bacteria and fungi. Finally, the cytotoxicity of the sutures was investigated using stem cells from the apical papilla (SCAPs) for 24 h, which exhibited more than 75% cell viability. Overall, the results indicate that NP-coated sutures can potentially be used as antimicrobial sutures to diminish or inhibit SSI in postoperative or general surgery patients.

Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution.

Knockout of the ORF8 protein has repeatedly spread through the global viral population during SARS-CoV-2 evolution. Here we use both regional and global pathogen sequencing to explore the selection pressures underlying its loss. In Washington State, we identified transmission clusters with ORF8 knockout throughout SARS-CoV-2 evolution, not just on novel, high fitness viral backbones. Indeed, ORF8 is truncated more frequently and knockouts circulate for longer than for any other gene. Using a global phylogeny, we find evidence of positive selection to explain this phenomenon: nonsense mutations resulting in shortened protein products occur more frequently and are associated with faster clade growth rates than synonymous mutations in ORF8. Loss of ORF8 is also associated with reduced clinical severity, highlighting the diverse clinical impacts of SARS-CoV-2 evolution.

A multi-site cultural and linguistic adaptation of a hypospadias decision aid for Latinx communities.

INTRODUCTION: Latinx, Spanish-speaking (LSS) patients are more likely to experience decisional conflict and regret about healthcare decisions than non-Hispanic, white, English-speaking patients. OBJECTIVE: To adapt the Hypospadias Hub (Hub), a rigorously developed and tested web-based decision aid (DA), for LSS parents. METHODS: Guided by the Ecological Validity Model (EVM), a heuristic framework was followed to culturally adapt the Hub (see Extended Summary Figure). In stage 1, recommendations were obtained from a focus group with members of the institution's Latinx Community Review Board (Latinx CRB) and semi-structured interviews with pediatricians with Latinx-focused practices. In stage 2, preliminary cultural modifications were made, the Hub was translated into Spanish, and a second focus group with the Latinx CRB was convened to review the revised Hub. In stage 3, semi-structured interviews with LSS parents of healthy boys (i.e., without hypospadias) ≤ 5 years old were conducted to identify any cultural adaptations and/or usability issues regarding the revised Hub. In stage 4, based on parents' feedback, final revisions to the Hub were made. The focus groups and parent interviews were conducted in Spanish; then, the recordings were professionally transcribed in Spanish and translated into English. Interviews with pediatricians were conducted in English; then, the recordings were professionally transcribed. Three coders conducted a qualitative content analysis to identify areas for revision. Changes were applied iteratively. RESULTS: Participants included 3 Latinx CRB members (2 women, 1 did not disclose gender; mean age = 48.3, SD = 21.2), 3 non-Latinx pediatricians (2 women, 1 man; mean age = 49.6, SD = 9.1), and 5 Latinx mothers (mean age = 34.0, SD = 1.26). Participants recommended: 1) featuring video testimonials from Latinx families or including Spanish voice-overs/subtitles; 2) diversifying racial/ethnic/geographic representation and including extended families in photographs/illustrations; 3) adding information about health insurance coverage and circumcision, 4) reassuring parents that the condition is not their fault, 5) considering cultural values (e.g., reliance on expert advice), and 6) clarifying medical terminology. Feedback related to seven EVM dimensions: concepts, content, context, goals, language, metaphors, and methods. DISCUSSION: Participants perceived the Hub to be informative in guiding parents' treatment decisions. Revisions were reasonable and acceptable for a linguistic and cultural adaptation for LSS parents. CONCLUSIONS: We identified and implemented preliminary cultural modifications to the Hub and applied user-centered design methods to test and revise the website. The product is a culturally appropriate DA for LSS parents. Next, English and Spanish-versions of the Hub will be tested in a randomized controlled trial.

Gender disparities in kidney replacement therapies and transplantation in Colombia.

BACKGROUND: In chronic kidney disease (CKD), there are historical inequities in multiple stages of the pathway for organ transplantation. Women have been recognized as disadvantaged within this process even after several efforts. Therefore, we aimed to analyze the prevalence and incidence of CKD by gender and their access to Kidney replacement therapy (KRT) in Colombia. METHODS: A cross-sectional study based on secondary analysis of national information on CKD, hypertension, diabetes, waiting list, deceased, and living donor transplantation between 2015 and 2020. RESULTS: In Colombia, 4.934.914 patients were diagnosed with hypertension, diabetes, or CKD. 60,64% were female, with a mean age of 63.84 years (SD 14,36). Crude incidence for hypertension (10.85 vs. 7.21 /1000 inhabitants), diabetes mellitus (3.77 vs. 2.98 /1000 inhabitants), and CKD (4 vs. 2 /1000 inhabitants) was higher for females. Crude incidence for KRT was 86.45 cases /100.0000 inhabitants. In 2020, 2978 patients were on the waiting list, 44% female. There were 251 deaths on the waiting list, 38% female. This year, 517 kidney transplants were performed, and only 40% were female. CONCLUSION: In Colombia, there are proportionally more females with CKD and precursor comorbidities. Nevertheless, there are fewer females on the waiting list and transplanted annually.

Correlative light-electron microscopy methods to characterize the ultrastructural features of the replicative and dormant liver stages of Plasmodium parasites.

BACKGROUND: The infection of the liver by Plasmodium parasites is an obligatory step leading to malaria disease. Following hepatocyte invasion, parasites differentiate into replicative liver stage schizonts and, in the case of Plasmodium species causing relapsing malaria, into hypnozoites that can lie dormant for extended periods of time before activating. The liver stages of Plasmodium remain elusive because of technical challenges, including low infection rate. This has been hindering experimentations with well-established technologies, such as electron microscopy. A deeper understanding of hypnozoite biology could prove essential in the development of radical cure therapeutics against malaria. RESULTS: The liver stages of the rodent parasite Plasmodium berghei, causing non-relapsing malaria, and the simian parasite Plasmodium cynomolgi, causing relapsing malaria, were characterized in human Huh7 cells or primary non-human primate hepatocytes using Correlative Light-Electron Microscopy (CLEM). Specifically, CLEM approaches that rely on GFP-expressing parasites (GFP-CLEM) or on an immunofluorescence assay (IFA-CLEM) were used for imaging liver stages. The results from P. berghei showed that host and parasite organelles can be identified and imaged at high resolution using both CLEM approaches. While IFA-CLEM was associated with more pronounced extraction of cellular content, samples' features were generally well preserved. Using IFA-CLEM, a collection of micrographs was acquired for P. cynomolgi liver stage schizonts and hypnozoites, demonstrating the potential of this approach for characterizing the liver stages of Plasmodium species causing relapsing malaria. CONCLUSIONS: A CLEM approach that does not rely on parasites expressing genetically encoded tags was developed, therefore suitable for imaging the liver stages of Plasmodium species that lack established protocols to perform genetic engineering. This study also provides a dataset that characterizes the ultrastructural features of liver stage schizonts and hypnozoites from the simian parasite species P. cynomolgi.

Spanish Translation and Cultural Adaptations of Physical Therapy Parent Educational Materials for Use in Neonatal Intensive Care.

Background: A paucity of Spanish language, culturally relevant parent education materials in the healthcare setting results in suboptimal care for Latinx families and further perpetuates health disparities. The purpose of this article is to describe the process for Spanish translation and cultural adaptations to parent education materials of a parent-centered physical therapy program designed to support maternal mental health and infant development during Neonatal Intensive Care (NICU). Methods: Two bilingual physical therapy (PT) students translated educational materials from English to Spanish and were proofread by a professional translator. Next, we conducted a materials review with 5 members of the Latine Community Review Board (CRB), a "standing" advisory group of natively Spanish-speaking, Latine North Carolinians who contract with research teams under the coordination of the Inclusive Science Program (ISP) of the North Carolina Translational and Clinical Sciences Institute (NC TraCS). Review session recruitment, facilitation, and data analysis were conducted by bilingual NC TraCS project managers and the primary investigator for the main feasibility study. Readability analyses were performed at the final stage of translation and adaptation. Results: Themes from CRB review sessions for improvement included to 1) use parent-friendly language, 2) use the plural masculine form of gendered language for caregivers to include all gender identities in this neonatal context, 3) address challenges with direct translation, and 4) use written education materials to supplement in-person, hands-on training with parents and their infants. All translated materials received a grade level of 5 on the Crawford grade-level index. Conclusion: Based on CRB feedback and readability analysis, the translation and cultural-adaptation process resulted in comprehensible written parent education materials for Spanish-speaking families. Review meetings with the CRB reinforced the need for Spanish materials in the healthcare setting. Further assessment of these materials with Spanish-speaking families in the NICU setting is needed.

Iatrogenic rectal perforation due to application of topical treatment in a patient with ulcerative colitis: a rare complication.

Rectal perforations due to topical treatments (enemas or foams) are unusual complications and they have been mostly reported in the use of barium enemas or in elderly patients with constipation. Very little has been reported about perforations secondary to topical treatment in patients with ulcerative colitis. We present the case of a patient with ulcerative colitis who suffered a rectal perforation complicated with a superinfected collection after the application of topical mesalazine foam.

Ketamine for Pain in Sickle Cell Disease Reduces Opioid Usage.

CONTEXT: Pain attributable to sickle cell disease (SCD) is often unpredictable, recurrent, and requires complex treatments. Subanesthetic ketamine infusion has been studied in other diseases and disorders, but there is still limited data on its efficacy in pain management for SCD. OBJECTIVES: The primary objective is to determine if subanesthetic ketamine infusion reduces pain scores and opioid requirements in hospitalized pediatric patients with SCD. RESULTS: Forty-six admissions among 22 patients between February 2018 and December 2019 were analyzed. We observed decrease in pain scores within 24 hours of ketamine initiation in 34 of 46 admissions (mean pain score per patient before ketamine initiation: 2.2-9.7, mean pain score per patient after ketamine initiation: 0-9.7; P < .05). We observed a decrease in pain scores in the remaining 12 admissions after greater than 24 hours of ketamine initiation. Opioid usage declined after ketamine infusion, with a difference of means in oral morphine equivalents before and after ketamine of 122.8 mg/day. The side effects observed with ketamine infusion included hallucinations in 11 (23.9%) admissions. Only four (8.7%) admissions required cessation of the infusion due to side effects. The readmission rate at two weeks and four weeks after first ketamine infusion was the same (12.5%) at both time points. For all patients in the cohort, the introduction of ketamine into pain regimens did not reduce the number of admissions in the year following ketamine initiation relative to the year prior. CONCLUSION: In pediatric patients with SCD, subanesthetic ketamine was safe as a continuous infusion and effectively reduced both pain scores and opioid requirements.

Brain Atrophy and Physical and Cognitive Disability in Multiple Sclerosis.

Introduction: Brain atrophy is associated with physical disability in multiple sclerosis (MS), but there is a great variability between different studies and methodologies, and its use is still limited to research projects. We aimed to analyze the relationship between several volumetric measurements and physical disability and cognitive functioning in MS patients in a clinical practice setting. Methods: This is a cross-sectional study. A total of 41 patients (31 relapsing-remitting MS, 6 secondary-progressive MS, and 4 primary-progressive MS) were included. Whole brain volume (WBV), gray matter volume (GMV), and T2 lesion load (T2L) were obtained using Icometrix® software. Physical disability was measured with the Expanded Disability Status Scale (EDSS), and cognitive status was evaluated with the brief repeatable battery of neuropsychological tests (BRB-N). The relationship between brain volumes and EDSS was analyzed through linear multivariate regression. The association between volumetry measurements and the number of affected cognitive domains was studied with negative binomial regression. Results: GMV was associated with age (b=-1.7, P=0.014) and with EDSS (b=-7.55, P=0.013). T2L was associated with EDSS (b=2.29, P=0.032). The number of affected cognitive domains was associated with clinical phenotype, worse in primary progressive MS (PPMS). There was not correlations between cognitive impairment and cerebral volumes. Conclusion: Brain atrophy measurement is feasible in clinical practice setting, and it is helpful in monitoring the EDSS progression. Primary progressive phenotype is associated with greater risk of cognitive dysfunction. Highlights: The T2 lesion load is associated with physical disability in patients with multiple sclerosis (MS).The gray matter volume is associated with age and physical disability in patients with MS.There is no significant correlation between cognitive impairment and cerebral volumes in patients with MS. Plain Language Summary: Conventional magnetic resonance imaging (MRI) is still used for diagnosing and monitoring multiple sclerosis (MS). Analysis of Brain volumes including Whole brain volume (WBV), gray matter volume (GMV), and T2 lesion load (T2L) allows the evaluation of its neurodegenerative mechanisms. Robust evidence links brain atrophy with disability in MS. This study aims to analyze the relationship between advanced MRI sequences and physical disability and cognitive functioning in MS patients. According to the results, T2L was associated with physical disability and GMV was associated with age and physical disability. There was no significant correlation between cognitive impairment and cerebral volumes in patients with MS.

Trauma-informed care in school-based health centers: A mixed methods study of behavioral health screening and services.

An explanatory, parallel mixed method design was used to examine trauma screening and behavioral health service rates in urban school-based health centers (SBHCs) and SBHC personnel's experiences providing culturally responsive, trauma-informed care. Logistic regressions were performed with electronic medical records from N = 4,794 patients ages 12-22 receiving care in a SBHC using trauma screening rates and service use as dependent variables. Quantitative analyses were supplemented with semistructured interviews with medical providers and behavioral health clinicians (N = 9) from eight SBHCs. The overall trauma screening rate across the SBHCs was 69.2%. Screening rates were higher for older and Spanish-speaking youth. The rate of behavioral health use was 32.9%, with higher rates among students screened for trauma at a prior medical visit, recent immigrant, and female youth. This suggests that trauma screening is feasible and facilitates access. Additionally, English-speaking youth were more likely to use behavioral health services than Spanish-speakers. Qualitative analyses suggested a strong sense of mission, collaboration, and beliefs that trauma screening facilitated access to care all facilitated trauma-focused screening. Barriers included staffing shortages and language translation challenges. Analysis also highlighted the importance of culturally responsive practices (e.g., interpreters, culture-specific assessment tools, knowledge of population needs). Mixed methods integrative analysis highlighted the ways in which barriers and facilitators aligned with the overall rates of access to screening and behavioral health care, and factors that helped the SBHCs tailor care to diverse youth. Limitations and implications for practice are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

MicroRNAs Associated with Disability Progression and Clinical Activity in Multiple Sclerosis Patients Treated with Glatiramer Acetate.

MicroRNAs (miRNAs) are promising biomarkers in multiple sclerosis (MS). This study aims to investigate the association between a preselected list of miRNAs in serum with therapeutic response to Glatiramer Acetate (GA) and with the clinical evolution of a cohort of relapsing-remitting MS (RRMS) patients. We conducted a longitudinal study for 5 years, with cut-off points at 2 and 5 years, including 26 RRMS patients treated with GA for at least 6 months. A total of 6 miRNAs from a previous study (miR-9.5p, miR-126.3p, mir-138.5p, miR-146a.5p, miR-200c.3p, and miR-223.3p) were selected for this analysis. Clinical relapse, MRI activity, confirmed disability progression (CDP), alone or in combination (No Evidence of Disease Activity-3) (NEDA-3), and Expanded Disability Status Scale (EDSS), were studied. After multivariate regression analysis, miR-9.5p was associated with EDSS progression at 2 years (ß = 0.23; 95% CI: 0.04-0.46; p = 0.047). Besides this, mean miR-138.5p values were lower in those patients with NEDA-3 at 2 years (p = 0.033), and miR-146a.5p and miR-126.3p were higher in patients with CDP progression at 2 years (p = 0.044 and p = 0.05 respectively. These results reinforce the use of microRNAs as potential biomarkers in multiple sclerosis. We will need more studies to corroborate these data and to better understand the role of microRNAs in the pathophysiology of this disease.

Evaluation of the biological responses of silver nanoparticles synthesized using Pelargonium x hortorum extract.

Silver nanoparticles (AgNPs) are one of the widely studied nanomaterials for diverse biomedical applications, in particular, as antimicrobial agents to kill bacteria, fungi, and viruses. In this report, AgNPs were synthesized using a geranium (Pelargonium x hortorum) leaves extract and tested for their antimicrobial and cytotoxic activity and reactive oxygen species (ROS) production. Using green biosynthesis, the leaves extract was employed as a reducing and stabilizing agent. Synthesis parameters like reaction time and precursor (silver nitrate AgNO3) volume final were modified, and the products were tested against Streptococcus mutans. For the first time, the metabolomic analysis of extract, we have identified more than 50 metabolites. The UV-Vis analysis showed a peak ranging from 410-430 nm, and TEM confirmed their nearly spherical morphology for all NPs. The antimicrobial activity of the NPs revealed a minimum inhibitory concentration (MIC) of 10 µg mL-1. Concerning cytotoxicity, a dose-time-dependent effect was observed with a 50% cellular cytotoxicity concentration (CC50) of 4.51 µg mL-1 at 24 h. Interestingly, the cell nuclei were visualized using fluorescence microscopy, and no significant changes were observed. These results suggest that synthesized spherical AgNPs are promising potential candidates for medical applications.