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.

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.

Validation of mutated CEBPA bZIP as a distinct prognosis entity in acute myeloid leukemia: a study by the Spanish PETHEMA registry.

Not available.

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.

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.

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.

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.

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).

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.

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.

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.

Relevance of Sociocultural Inequalities and Parents' Origins in Relation to the Oral Health of Preschoolers in Lanzarote, Spain.

Approaching inequalities to achieve health equity requires joint action. Early childhood caries affects disadvantaged population groups. The objective of this study was to determine the relevance of sociocultural inequalities and parental origin with respect to oral health in preschool children in Lanzarote. A transversal epidemiological study was carried out. Sociocultural data and information about parental origin were collected via a questionnaire. The decayed and filled teeth (dft), decayed teeth (dt), filled teeth (ft), restorative index (RI), plaque index (PI) and gingival index (GI) were obtained via an investigator's examination. Statistical analysis of the data indicated that children of semi-skilled manual workers (28.15%) had the highest prevalence of caries (46.9%). Additionally 43.7 of the mothers had second grade and first cycle studies. When relating the medium and high level of education, there were statistically significant differences in relation to the cod index (p = 0.046). When the origin was foreign (48.4%), preschoolers presented 10.7% more active or untreated caries than Spaniards (p = 0.038). Low socioeconomic cultural level and foreign origin is associated with a more deficient state of oral health in preschoolers. Oral health programs are needed to minimize social inequalities.

Predicting 5-year survival after kidney transplantation in Colombia using the survival benefit estimator tool.

INTRODUCTION: A complex relationship between donor and recipient characteristics influences kidney transplant (KT) success. A tool developed by Bae S. et al. (Survival Benefit Estimator, SBE) helps estimate post-KT survival. We aim to evaluate the predictive performance of the SBE tool in terms of 5-year patient survival after a kidney transplant. METHODS: A retrospective cohort study of all deceased-donor KT recipients between January 2009 to December 2021. A descriptive analysis of clinical and sociodemographic characteristics was performed. The SBE online tool was used to calculate the predicted patient survival (PPS) and the survival benefit at five years post-KT. Comparisons between predictive vs. actual patient survival were made using quintile subgroups. Three Cox regression models were built using PPS, EPTS, and KDPI. RESULTS: A total of 1145 recipients were evaluated. Mortality occurred in 157 patients. Patient survival was 86.2%. Predictive survival for patients if they remained on the waiting list was 70.6%. The PPS was 89.3%, which results in a survival benefit (SB) of 18.7% for our population. Actual survival rates were lower than the predicted ones across all the quintiles. In unadjusted analysis, PPS was a significant protective factor for mortality (HR 0.66), whereas EPTS (HR 8.9) and KDPI (HR 3.25) scores were significant risk factors. The discrimination of KDPI, PPS, and EPTS scores models were 0.59, 0.65, and 0.66, respectively. CONCLUSION: SBE score overestimated actual survival rates in our sample. The discrimination power of the score was moderate, although the utility of this tool may be limited in this specific population.

Computerized working memory training for hypertensive individuals with executive function impairment: a randomized clinical trial.

Background: Hypertension is associated with working memory (WM) impairment. However, the benefits of Cogmed WM training for the hypertensive population are unknown. Therefore, we aimed to evaluate Cogmed's effects on the WM performance of hypertensive individuals with executive function (EF) impairment. Methods: We included 40 hypertensive patients (aged 40-70 years, 68% female) with EF impairment. They were randomized in a 1:1 ratio to receive 10 weeks of adaptive Cogmed training or a non-adaptive control training based on online games. The primary outcome was the WM performance. The secondary outcomes were verbal memory, visuospatial ability, executive function, global cognition, and the neuronal activity measured using functional magnetic resonance imaging (fMRI) under two WM task conditions: low (memorization of 4 spatial locations) and high (memorization of 6 spatial locations). An intention-to-treat (ITT) and per-protocol (PP) analysis were performed. Results: Cogmed did not show a significant effect on WM or any other cognitive outcome post-training. However, under the WM-low load and WM-high load conditions of the fMRI, respectively, the Cogmed group had an activation decrease in the right superior parietal lobe (ITT and PP analyses) and left inferior frontal lobe (PP analysis) in comparison to the control group. Conclusion: The Cogmed showed no effects on the WM performance of hypertensive individuals with EF impairment. However, activation decreases were observed in frontoparietal areas related to the WM network, suggesting a more efficient neuronal activity after training.

Increased peripartum mortality associated with maternal subclinical malaria in Mozambique.

BACKGROUND: Plasmodium falciparum infection in pregnant women in sub-Saharan Africa is often asymptomatic. As these forms of malaria are often submicroscopic and difficult to diagnose by conventional methods (microscopy and/or rapid diagnostic test), diagnosis requires the use of molecular techniques such as polymerase chain reaction (PCR). This study analyses the prevalence of subclinical malaria and its association with adverse maternal and neonatal outcomes, a topic that has been scarcely evaluated in the literature. METHODS: A cross-sectional study was conducted using semi-nested multiplex PCR to assess the presence of P. falciparum in placental and peripheral blood of 232 parturient pregnant women at the Hospital Provincial de Tete, Mozambique between March 2017 and May 2019. Multivariate regressions were performed to assess the associations of maternal subclinical malaria with several maternal and neonatal outcomes after controlling for the presence of preeclampsia/eclampsia (PE/E) and HIV infection, as well as for other maternal and pregnancy characteristics. RESULTS: In total, 17.2% (n = 40) of the women studied had positive PCR for P. falciparum (7 in placental blood only, 3 in peripheral blood only). We found a significant association between subclinical malaria and a higher peripartum mortality risk, which persisted after controlling for maternal comorbidity and maternal and pregnancy characteristics (adjusted odds ratio: 3.50 [1.11-10.97]). In addition, PE/E and HIV infections were also significantly associated with several adverse maternal and neonatal outcomes. CONCLUSION: This study demonstrated the association of subclinical malaria, as well as of PE/E and HIV, in pregnant women with adverse maternal and neonatal outcomes. Therefore, molecular methods may be sensitive tools to identify asymptomatic infections that can reduce the impact on peripartum mortality and their contribution to sustained transmission of the parasite in endemic countries.

Hopelessness in Patients with Early-Stage Relapsing-Remitting Multiple Sclerosis.

Background: Hopelessness is a risk factor for depression and suicide. There is little information on this phenomenon among patients with relapsing-remitting multiple sclerosis (RRMS), one of the most common causes of disability and loss of autonomy in young adults. The aim of this study was to assess state hopelessness and its associated factors in early-stage RRMS. Methods: A multicenter, non-interventional study was conducted. Adult patients with a diagnosis of RRMS, a disease duration ≤ 3 years, and an Expanded Disability Status Scale (EDSS) score of 0-5.5 were included. The State-Trait Hopelessness Scale (STHS) was used to measure patients´ hopelessness. A battery of patient-reported and clinician-rated measurements was used to assess clinical status. A multivariate logistic regression analysis was conducted to determine the association between patients' characteristics and state hopelessness. Results: A total of 189 patients were included. Mean age (standard deviation-SD) was 36.1 (9.4) years and 71.4% were female. Median disease duration (interquartile range-IQR) was 1.4 (0.7, 2.1) years. Symptom severity and disability were low with a median EDSS (IQR) score of 1.0 (0, 2.0). A proportion of 65.6% (n=124) of patients reported moderate-to-severe hopelessness. Hopelessness was associated with older age (p=0.035), depressive symptoms (p=<0.001), a threatening illness perception (p=0.001), and psychological and cognitive barriers to workplace performance (p=0.029) in the multivariate analysis after adjustment for confounders. Conclusion: Hopelessness was a common phenomenon in early-stage RRMS, even in a population with low physical disability. Identifying factors associated with hopelessness may be critical for implementing preventive strategies helping patients to adapt to the new situation and cope with the disease in the long term.

Influence of the Severity of Osteogenesis Imperfecta on Cranial Measurements.

Osteogenesis Imperfecta (OI) is a disease that causes bone fragility and deformities, affecting both the cranial base and the craniocervical junction, and may lead to other neurological disorders. A retrospective cross-sectional study was carried out based on cephalometric analysis of the cranial base in a sample of patients with OI, in lateral skull radiographs and magnetic resonance imaging (MRI), comparing them with a sample of age-matched controls. When the different variables of the craniocervical junction were analyzed, significance was found in comparisons with the different age groups. All measurements of the variables studied stabilized as growth progressed. For most of the variables, the severity of the disease influences the measurements of the skull base, with statistically significant differences. Both age and severity of the disease are factors that directly influence the anatomy of the craniocervical junction in these patients and may serve as indicators in the early detection and prevention of other derived alterations.