Safety and Immunogenicity of a ChAd155-Vectored Respiratory Syncytial Virus Vaccine in Infants 6-7 Months of age: A Phase 1/2 Randomized Trial.

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections in infants. This phase 1/2, observer-blind, randomized, controlled study assessed the safety and immunogenicity of an investigational chimpanzee-derived adenoviral vector RSV vaccine (ChAd155-RSV, expressing RSV F, N, and M2-1) in infants. METHODS: Healthy 6- to 7-month-olds were 1:1:1-randomized to receive 1 low ChAd155-RSV dose (1.5 × 1010 viral particles) followed by placebo (RSV_1D); 2 high ChAd155-RSV doses (5 × 1010 viral particles) (RSV_2D); or active comparator vaccines/placebo (comparator) on days 1 and 31. Follow-up lasted approximately 2 years. RESULTS: Two hundred one infants were vaccinated (RSV_1D: 65; RSV_2D: 71; comparator: 65); 159 were RSV-seronaive at baseline. Most solicited and unsolicited adverse events after ChAd155-RSV occurred at similar or lower rates than after active comparators. In infants who developed RSV infection, there was no evidence of vaccine-associated enhanced respiratory disease (VAERD). RSV-A neutralizing titers and RSV F-binding antibody concentrations were higher post-ChAd155-RSV than postcomparator at days 31, 61, and end of RSV season 1 (mean follow-up, 7 months). High-dose ChAd155-RSV induced stronger responses than low-dose, with further increases post-dose 2. CONCLUSIONS: ChAd155-RSV administered to 6- to 7-month-olds had a reactogenicity/safety profile like other childhood vaccines, showed no evidence of VAERD, and induced a humoral immune response. Clinical Trials Registration. NCT03636906.

The abundant fraction of soil microbiomes regulates the rhizosphere function in crop wild progenitors.

The rhizosphere influence on the soil microbiome and function of crop wild progenitors (CWPs) remains virtually unknown, despite its relevance to develop microbiome-oriented tools in sustainable agriculture. Here, we quantified the rhizosphere influence-a comparison between rhizosphere and bulk soil samples-on bacterial, fungal, protists and invertebrate communities and on soil multifunctionality across nine CWPs at their sites of origin. Overall, rhizosphere influence was higher for abundant taxa across the four microbial groups and had a positive influence on rhizosphere soil organic C and nutrient contents compared to bulk soils. The rhizosphere influence on abundant soil microbiomes was more important for soil multifunctionality than rare taxa and environmental conditions. Our results are a starting point towards the use of CWPs for rhizosphere engineering in modern crops.

Phase 3 Safety and Efficacy of AZD1222 (ChAdOx1 nCoV-19) Covid-19 Vaccine.

BACKGROUND: The safety and efficacy of the AZD1222 (ChAdOx1 nCoV-19) vaccine in a large, diverse population at increased risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the United States, Chile, and Peru has not been known. METHODS: In this ongoing, double-blind, randomized, placebo-controlled, phase 3 clinical trial, we investigated the safety, vaccine efficacy, and immunogenicity of two doses of AZD1222 as compared with placebo in preventing the onset of symptomatic and severe coronavirus disease 2019 (Covid-19) 15 days or more after the second dose in adults, including older adults, in the United States, Chile, and Peru. RESULTS: A total of 32,451 participants underwent randomization, in a 2:1 ratio, to receive AZD1222 (21,635 participants) or placebo (10,816 participants). AZD1222 was safe, with low incidences of serious and medically attended adverse events and adverse events of special interest; the incidences were similar to those observed in the placebo group. Solicited local and systemic reactions were generally mild or moderate in both groups. Overall estimated vaccine efficacy was 74.0% (95% confidence interval [CI], 65.3 to 80.5; P<0.001) and estimated vaccine efficacy was 83.5% (95% CI, 54.2 to 94.1) in participants 65 years of age or older. High vaccine efficacy was consistent across a range of demographic subgroups. In the fully vaccinated analysis subgroup, no severe or critical symptomatic Covid-19 cases were observed among the 17,662 participants in the AZD1222 group; 8 cases were noted among the 8550 participants in the placebo group (<0.1%). The estimated vaccine efficacy for preventing SARS-CoV-2 infection (nucleocapsid antibody seroconversion) was 64.3% (95% CI, 56.1 to 71.0; P<0.001). SARS-CoV-2 spike protein binding and neutralizing antibodies increased after the first dose and increased further when measured 28 days after the second dose. CONCLUSIONS: AZD1222 was safe and efficacious in preventing symptomatic and severe Covid-19 across diverse populations that included older adults. (Funded by AstraZeneca and others; ClinicalTrials.gov number, NCT04516746.).

Assessing the Relationship between Radiology Department Research Funding and Institutional Community Inclusion and Investment.

Background Health care access disparities and lack of inclusion in clinical research have been well documented for marginalized populations. However, few studies exist examining the research funding of institutions that serve historically underserved groups. Purpose To assess the relationship between research funding awarded to radiology departments by the National Institutes of Health (NIH) and Lown Institute Hospitals Index rankings for inclusivity and community benefit. Materials and Methods This retrospective study included radiology departments awarded funding from the NIH between 2017 and 2021. The 2021 Lown Institute Hospitals Index rankings for inclusivity and community benefit were examined. The inclusivity metric measures how similar a hospital's patient population is to the surrounding community in terms of income, race and ethnicity, and education level. The community benefit metric measures charity care spending, Medicaid as a proportion of patient revenue, and other community benefit spending. Linear regression and Pearson correlation coefficients (r values) were used to evaluate the relationship between aggregate NIH radiology department research funding and measures of inclusivity and community benefit. Results Seventy-five radiology departments that received NIH funding ranging from $195 000 to $216 879 079 were included. A negative correlation was observed between the amount of radiology department research funding received and institutional rankings for serving patients from racial and/or ethnic minorities (r = -0.34; P < .001), patients with low income (r = -0.44; P < .001), and patients with lower levels of education (r = -0.46; P < .001). No correlation was observed between the amount of radiology department research funding and institutional rankings for charity care spending (r = -0.19; P = .06), community investment (r = -0.04; P = .68), and Medicaid as a proportion of patient revenue (r = -0.10; P = .22). Conclusion Radiology departments that received more NIH research funding were less likely to serve patients from racial and/or ethnic minorities and patients who had low income or lower levels of education. © RSNA, 2024 See also the editorial by Mehta and Rosen in this issue.

Yeast diversity in open agave fermentations across Mexico.

Yeasts are a diverse group of fungal microorganisms that are widely used to produce fermented foods and beverages. In Mexico, open fermentations are used to obtain spirits from agave plants. Despite the prevalence of this traditional practice throughout the country, yeasts have only been isolated and studied from a limited number of distilleries. To systematically describe the diversity of yeast species from open agave fermentations, here we generate the YMX-1.0 culture collection by isolating 4524 strains from 68 sites with diverse climatic, geographical, and biological contexts. We used MALDI-TOF mass spectrometry for taxonomic classification and validated a subset of the strains by ITS and D1/D2 sequencing, which also revealed two potential novel species of Saccharomycetales. Overall, the composition of yeast communities was weakly associated with local variables and types of climate, yet a core set of six species was consistently isolated from most producing regions. To explore the intraspecific variation of the yeasts from agave fermentations, we sequenced the genomes of four isolates of the nonconventional yeast Kazachstania humilis. The genomes of these four strains were substantially distinct from a European isolate of the same species, suggesting that they may belong to different populations. Our work contributes to the understanding and conservation of an open fermentation system of great cultural and economic importance, providing a valuable resource to study the biology and genetic diversity of microorganisms living at the interface of natural and human-associated environments.

Serum biomarker levels predict disability progression in patients with primary progressive multiple sclerosis.

BACKGROUND: We aimed to investigate the potential of serum biomarker levels to predict disability progression in a multicentric real-world cohort of patients with primary progressive multiple sclerosis (PPMS). METHODS: A total of 141 patients with PPMS from 18 European MS centres were included. Disability progression was investigated using change in Expanded Disability Status Scale (EDSS) score over three time intervals: baseline to 2 years, 6 years and to the last follow-up. Serum levels of neurofilament light chain (sNfL), glial fibrillar acidic protein (sGFAP) and chitinase 3-like 1 (sCHI3L1) were measured using single-molecule array assays at baseline. Correlations between biomarker levels, and between biomarkers and age were quantified using Spearman's r. Univariable and multivariable linear models were performed to assess associations between biomarker levels and EDSS change over the different time periods. RESULTS: Median (IQR) age of patients was 52.9 (46.4-58.5) years, and 58 (41.1%) were men. Median follow-up time was 9.1 (7.0-12.6) years. Only 8 (5.7%) patients received treatment during follow-up. sNfL and sGFAP levels were moderately correlated (r=0.43) and both weakly correlated with sCHI3L1 levels (r=0.19 and r=0.17, respectively). In multivariable analyses, levels of the three biomarkers were associated with EDSS changes across all time periods. However, when analysis was restricted to non-inflammatory patients according to clinical and radiological parameters (n=64), only sCHI3L1 levels remained associated with future EDSS change. CONCLUSIONS: Levels of sNfL, sGFAP and sCHI3L1 are prognostic biomarkers associated with disability progression in patients with PPMS, being CHI3L1 findings less dependent on the inflammatory component associated with disease progression.

Thermoelectric Performance of Hybrid Inorganic/Organic Composites Based on PEDOT:PSS/Tin(II) Oxide.

PEDOT: PSS(poly(3,4-ethylenedioxylthiophene):poly(styrenesulfonate))-based composites often exhibit remarkable characteristics regarding high electrical conductivity and great processability, being a suitable candidate for thermoelectric (TE) applications. To increase its performance, PEDOT:PSS is commonly blended with scarce and toxic inorganic compounds based on Se, Te or Bi. In this work we propose the use of one p-type metal oxide semiconductor (MOs): tin(II) oxide (SnO), motivated by its abundance and low toxicity. Hybrid PEDOT:PSS/SnO composites were obtained by firstly blending Ethylene glycol (EG) with PEDOT:PSS and then by adding p-type SnO, previously synthesized by a chemical route. The mixture was deposited via spin-coating onto glass substrates. The Power Factor (PF) of the composites increased by a factor of 300 with the combined EG/SnO composition.

Association of Benzodiazepine Prescription With Short-Term Prognosis in Elderly Patients Attended in Emergency Department: Results From the EDEN PROJECT.

AIM: Benzodiazepine prescription is a growing phenomenon among the elderly population. However, information related to the frequency of these drugs among the elderly population attending in emergency departments (ED) and its impact over prognosis is scarce. The aim of this study is to assess the prevalence of benzodiazepine prescription and to analyze its association with short-term prognosis in elderly patients attended in ED. METHODS: A retrospective analysis of the EDEN (Emergency Department Elderly in Need) cohort was conducted. This registry included all elderly patients attending in 52 Spanish EDs for any condition, between April 1st and 7th in 2019. Socio-demographic data, comorbidities, and medication were recorded by consulting the patient's electronic health records. The assessed outcomes consisted on new ED visit, hospitalization, and mortality at 30 days after the first ED visit, associated with the use of benzodiazepines at baseline in comparison with no prescription of benzodiazepines. Crude and adjusted logistic regression analyses including patient's comorbidities were performed. Two sensitivity analyses were performed considering concomitant prescription of other central nervous system depressants as well as direct discharge from the ED. RESULTS: 25 557 patients were evaluated (mean age 78 [IQR: 71-84]). 7865 (30.8%) patients were taken benzodiazepines at admission. After adjustment for comorbidities and other central nervous system drugs, benzodiazepine prescription was associated with ED revisit [OR: 1.10 (95%CI: 1.03-1.18)]. Similar results were found in the sensitivity analysis, eliminating patients with central nervous depressors [OR: 1.11 (1.03-1.25)] and patients discharged to home [OR: 1.13 (1.04-1.23)]. No association was found between the use of these drugs and new hospitalizations [OR: 0.90 (0.77-1.05)] or mortality 30 days after discharge [OR: 1.01 (0.88-1.18)]. The results held for all three outcomes in the sensitivity analyses. CONCLUSION: The use of benzodiazepines is a frequent phenomenon among the elderly population attended in the ED, being associated with an increased risk of new visits to the emergency room, but not with an increased risk of 30-day hospitalization or mortality.

Effects of COVID-19 Pandemic on the Diagnosis of Melanoma and Keratinocyte Carcinomas: a Systematic Review and Meta-analysis.

Since December 2019, the COVID-19 pandemic has profoundly affected healthcare. The real effects of the COVID-19 pandemic on skin cancer are still unclear, more than 3 years later. This study aims to summarise the pandemic's impact on skin cancer diagnosis and outcome. A systematic review and meta-analysis was conducted, selecting studies comparing skin cancer diagnosis and prognosis post-pandemic with pre-pandemic data. A total of 27 papers were reviewed including 102,263 melanomas and 271,483 keratinocyte carcinomas. During the initial pandemic months (January-July 2020), melanoma surgeries dropped by 29.7% and keratinocyte carcinomas surgeries by 50.8%. Early pandemic tumours exhibited greater thickness and stage. In a long-term period beyond the initial months, melanoma surgeries decreased by 9.3%, keratinocyte carcinomas by 16.6%. No significant differences were observed in the Breslow thickness of melanomas after the start of the pandemic (mean difference 0.06, 95% confidence interval -0.46, 0.58). Melanomas operated on post-pandemic onset had an increased risk of ulceration (odds ratio 1.35, 95% confidence interval 1.22-1.50). Keratinocyte carcinomas showed increased thickness and worsened stage post-pandemic. However, studies included were mostly retrospective and cross-sectional, reporting diverse data. This review indicates that the pandemic likely caused delays in skin cancer diagnosis and treatment, potentially impacting patient outcomes.

Collateral effects of Coping Power on caregiver symptoms of depression and long-term changes in child behavior.

A large body of research demonstrates positive impacts of the Coping Power Program as a preventive intervention for youth behavioral outcomes, but potential collateral effects for caregivers is less known. The current study examined whether the youth-focused Coping Power Program can have a secondary impact on caregiver self-reported symptoms of depression and in turn result in longer-term impacts on child disruptive behavior problems including aggression, conduct problems and hyperactivity. Data from 360 youth/caregiver pairs across 8 waves of data (grades 4 through 10) were analyzed. We used two methodological approaches to (a) assess indirect effects in the presence of potential bidirectionality using timepoint-to-timepoint dynamic effects under Autoregressive Latent Trajectory modeling and (b) estimate scale scores in the presence of measurement non-invariance. Results showed that individually delivered Coping Power (ICP) produced greater direct effects on conduct problems and indirect effects on general externalizing and hyperactivity (through reductions in caregiver self-reported symptoms of depression), compared to group Coping Power (GCP). In comparison to GCP, ICP produced similar direct effects on reductions in caregiver depression. Child-focused prevention interventions can have an indirect impact on caregiver depression, which later shows improvements in longer-term reductions for child disruptive problems.

Development and validation of a new anthropometric equation to predict fat mass percentage in a white Spanish population.

OBJECTIVE: (1) To develop a new regression equation for estimating fat mass percentage (%FM) from anthropometric measurements in a heterogeneous Caucasian population and (2) to compare it with the Durnin and Womersley equation, which is one of the most used anthropometric equations for fat mass assessment. DESIGN: Body mass, stature, and four skinfolds (biceps, triceps, subscapular, and supracrestal) were assessed by an accredited anthropometrist, according to the International Society for Advancement in Kinanthropometry. Participants completed a dual-energy X-ray absorptiometry (DXA) whole-body scan to determine their %FM. A new anthropometric equation to estimate %FM was developed using multiple forward regression analyses with DXA as the reference method. Tests for the accuracy of the different equations included mean differences, coefficient of determination, standard error of the estimate (SEE), concordance correlation coefficient (CCC), and Bland-Altman plots. SETTING: Spain. PARTICIPANTS: Two hundred and eighteen healthy Caucasian participants aged 18-65 years participated in this cross-sectional study. RESULTS: Our proposed equation explained 89.9% of the variance in the DXA-derived %FM, with a low random error (SEE = 3.00%), a very strong agreement (CCC = 0.93), no fixed or proportional bias, and a relatively low individual variability (5.84%). However, the Durnin and Womersley equations obtained a fixed bias of -3.65% when compared to DXA and a greater individual variability (6.74%). CONCLUSIONS: The proposed equation can accurately estimate %FM in a heterogeneous Caucasian population with a wide age range (18-65 years). Additionally, the Durnin and Womersley equation was inadequate when applied to our participants.

Short-term outcomes of a multicentre prospective study using a "visible" polyvinylidene fluoride onlay mesh for the prevention of midline incisional hernia.

INTRODUCTION: Prophylactic meshes in high-risk patients prevent incisional hernias, although there are still some concerns about the best layer to place them in, the type of fixation, the mesh material, the significance of the level of contamination, and surgical complications. We aimed to provide answers to these questions and information about how the implanted material behaves based on its visibility under magnetic resonance imaging (MRI). METHOD: This is a prospective multicentre observational cohort study. Preliminary results from the first 3 months are presented. We included general surgical patients who had at least two risk factors for developing an incisional hernia. Multivariate logistic regression was used. A polyvinylidene fluoride (PVDF) mesh loaded with iron particles was used in an onlay position. MRIs were performed 6 weeks after treatment. RESULTS: Between July 2016 and June 2022, 185 patients were enrolled in the study. Surgery was emergent in 30.3% of cases, contaminated in 10.7% and dirty in 11.8%. A total of 5.6% of cases had postoperative wound infections, with the requirement of stoma being the only significant risk factor (OR = 7.59, p = 0.03). The formation of a seroma at 6 weeks detected by MRI, was associated with body mass index (OR = 1.13, p = 0.02). CONCLUSIONS: The prophylactic use of onlay PVDF mesh in midline laparotomies in high-risk patients was safe and effective in the short term, regardless of the type of surgery or the level of contamination. MRI allowed us to detect asymptomatic seromas during the early process of integration. STUDY REGISTRATION:  This protocol was registered at ClinicalTrials.gov (NCT03105895).

Neuroendoscopic access to the third ventricle in patients with narrow foramen of monro without stenosis/obstruction: role of foraminoplasty.

OBJECT: One of the critical steps for the success of intraventricular neuroendoscopic procedures is the entry into the third ventricle and passage of the endoscopy system through the foramen of Monro (FM). A diameter larger than that of the instrument used is considered a prerequisite for safely performing the technique, as damage to this structure can lead to alterations in the fornix and vascular structures. When the foramen diameter is narrow and there is no obstruction/stenosis, the role of foraminoplasty in reducing the risk of complications has not been adequately assessed in the literature. METHODS: A review of endoscopic procedures conducted at our center since 2018 was undertaken. Cases in which preoperative imaging indicated a FM diameter < 6 mm and foraminoplasty technique was applied were examined to determine the technical and functional success of the procedure. The technical success was determined by completing the neuroendoscopic procedure with the absence of macroscopic lesions in the various structures comprising the foramen and without complications in the follow-up imaging tests. Functional success was defined as the absence of cognitive/memory alterations during the 3-month postoperative follow-up. Additionally, a review of the various forms of foraminoplasty described in the literature is conducted. RESULTS: In our cohort, six patients were identified with a preoperative FM diameter < 6 mm without obstruction or stenosis. Foraminoplasty was planned for these cases to facilitate various intraventricular neuroendoscopic procedures. In all instances, the technique was successfully performed without causing macroscopic damage to the structures comprising the foramen. Follow-up visits included various cognitive tests to assess potential sequelae related to microscopic damage to the fornix. None of the patients exhibited anomalies. CONCLUSION: Foraminoplasty in patients with a narrow FM without signs of stenosis/obstruction is a useful technique to reduce the risk of complications during the passage of the endoscopy system through this structure, enabling the safe performance of neuroendoscopic procedures.

Tendon Lengthening Surgery for Elbow Flexion Contractures in Brachial Plexus Birth Palsy.

PURPOSE: Flexion contracture of the elbow is a common deformity associated with brachial plexus birth palsy and is often managed with preventive night orthoses. For severe cases, however, surgical interventions may become necessary. This study evaluated the effectiveness of surgically releasing elbow flexion contractures exceeding 30° through partial tenotomy of the brachialis and biceps brachii muscles, along with a division of the lacertus fibrosus. METHODS: We performed 36 anterior elbow releases on patients with injury to the upper trunk (C5-C6) of the brachial plexus and elbow flexion contractures between 30° and 80°. All releases involved lacertus fibrosus section and partial lengthening of the distal portion of the brachialis tendon. In severe cases, biceps brachii tenotomy was also performed. All participants had a minimum follow-up of 12 months and preoperative elbow flexion strength of at least grade 4 on the British Medical Research Council scale, with no deformities in the shape of the ulnohumeral joint or radial head subluxation. RESULTS: Following a mean follow-up of 41 months, the average extension gain was 31° (range, 10°-50°). All patients maintained their flexion strength. Except for two participants with weaker triceps, the mean elbow extension gain was sustained throughout the follow-up period. There were no major or minor complications or reinterventions in the study. CONCLUSIONS: Partial tenotomy of the brachialis and biceps brachii muscles, coupled with lacertus fibrosus section, is an effective treatment for elbow contractures exceeding 30° flexion. This method is successful in individuals with a functioning triceps brachii and elbow extension strength of at least grade 3 on the British Medical Research Council scale. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Design and Characterization of a Wearable Inertial Measurement Unit.

The utilization of inertial measurement units as wearable sensors is proliferating across various domains, such as health care, sports, and rehabilitation. This expansion has produced a market of devices tailored to accommodate very specific ranges of operational demands. Simultaneously, this growth is creating opportunities for the development of a new class of devices more oriented towards general-purpose use and capable of capturing both high-frequency signals for short-term, event-driven motion analysis and low-frequency signals for extended monitoring. For such a design, which combines flexibility and low cost, a rigorous evaluation of the device in terms of deviation, noise levels, and precision is essential. This evaluation is crucial for identifying potential improvements and refining the design accordingly, yet it is rarely addressed in the literature. This paper presents the development process of such a device. The results of the design process demonstrate acceptable performance in optimizing energy consumption and storage capacity while highlighting the most critical optimizations needed to advance the device towards the goal of a smart, general-purpose unit for human motion monitoring.

Correlation between Molecular Docking and the Stabilizing Interaction of HOMO-LUMO: Spirostans in CHK1 and CHK2, an In Silico Cancer Approach.

Checkpoint kinases 1 and 2 (CHK1 and CHK2) are enzymes that are involved in the control of DNA damage. At the present time, these enzymes are some of the most important targets in the fight against cancer since their inhibition produces cytotoxic effects in carcinogenic cells. This paper proposes the use of spirostans (Sp), natural compounds, as possible inhibitors of the enzymes CHK1 and CHK2 from an in silico analysis of a database of 155 molecules (S5). Bioinformatics studies of molecular docking were able to discriminate between 13 possible CHK1 inhibitors, 13 CHK2 inhibitors and 1 dual inhibitor for both enzymes. The administration, distribution, metabolism, excretion and toxicity (ADMETx) studies allowed a prediction of the distribution and metabolism of the potential inhibitors in the body, as well as determining the excretion routes and the appropriate administration route. The best inhibition candidates were discriminated by comparing the enzyme-substrate interactions from 2D diagrams and molecular docking. Specific inhibition candidates were obtained, in addition to studying the dual inhibitor candidate and observing their stability in dynamic molecular studies. In addition, Highest Occupied Molecular Orbital-Lowest Unoccupied Molecular Orbital (HOMO-LUMO) interactions were analyzed to study the stability of interactions between the selected enzymes and spirostans resulting in the predominant gaps from HOMOCHKs to LUMOSp (Highest Occupied Molecular Orbital of CHKs-Lowest Unoccupied Molecular Orbital of spirostan). In brief, this study presents the selection inhibitors of CHK1 and CHK2 as a potential treatment for cancer using a combination of molecular docking and dynamics, ADMETx predictons, and HOMO-LUMO calculation for selection.

Response to Fingolimod in Multiple Sclerosis Patients Is Associated with a Differential Transcriptomic Regulation.

Fingolimod is an immunomodulatory sphingosine-1-phosphate (S1P) analogue approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). The identification of biomarkers of clinical responses to fingolimod is a major necessity in MS to identify optimal responders and avoid the risk of disease progression in non-responders. With this aim, we used RNA sequencing to study the transcriptomic changes induced by fingolimod in peripheral blood mononuclear cells of MS-treated patients and their association with clinical response. Samples were obtained from 10 RRMS patients (five responders and five non-responders) at baseline and at 12 months of fingolimod therapy. Fingolimod exerted a vast impact at the transcriptional level, identifying 7155 differentially expressed genes (DEGs) compared to baseline that affected the regulation of numerous signaling pathways. These DEGs were predominantly immune related, including genes associated with S1P metabolism, cytokines, lymphocyte trafficking, master transcription factors of lymphocyte functions and the NF-kB pathway. Responder and non-responder patients exhibited a differential transcriptomic regulation during treatment, with responders presenting a higher number of DEGs (6405) compared to non-responders (2653). The S1P, NF-kB and TCR signaling pathways were differentially modulated in responder and non-responder patients. These transcriptomic differences offer the potential of being exploited as biomarkers of a clinical response to fingolimod.

Comparative Brain Proteomic Analysis between Sham and Cerebral Ischemia Experimental Groups.

Sham control groups are essential in experimental animal studies to reduce the influence of surgical intervention. The intraluminal filament procedure is one of the most common models of middle cerebral artery occlusion (MCAO) used in the study of brain ischemia. However, a sham group is usually not included in the experimental design of these studies. In this study, we aimed to evaluate the relevance of the sham group by analyzing and comparing the brain protein profiles of the sham and MCAO groups. In the sham group, 98 dysregulated proteins were detected, compared to 171 in the ischemic group. Moreover, a comparative study of protein profiles revealed the existence of a pool of 57 proteins that appeared to be dysregulated in both sham and ischemic animals. These results indicated that the surgical procedure required for the intraluminal occlusion of the middle cerebral artery (MCA) induces changes in brain protein expression that are not associated with ischemic lesions. This study highlights the importance of including sham control groups in the experimental design, to ensure that surgical intervention does not affect the therapeutic target under study.

Comparative study on sexual dysfunction in alopecia areata: prevalence and associated factors.

BACKGROUND AND OBJECTIVES: Alopecia areata (AA) impairs quality of life. However, there is no evidence on the impact of this disease in terms of sexual dysfunction (SD). The aim of the present study was to assess the prevalence of SD and possible associated factors in a cohort of patients with AA. PATIENTS AND METHODS: A cross-sectional study was conducted in a cohort of AA patients matched with healthy controls. Sexual function was assessed using a numerical scale and gender-specific questionnaires. RESULTS: A total of 60 patients with AA and 60 healthy controls were included. The prevalence of SD was higher in women with AA than in healthy controls and in men with AA (p < 0.05). Female SD was associated with younger age, shorter duration of illness and higher rates of anxiety and depression (p < 0.05). Male SD was associated with older age and greater severity of AA (p < 0.05). CONCLUSIONS: Women with AA appear to have higher rates of SD than healthy controls and men with AA. Similarly, the factors associated with SD differ between men and women, with mood disturbance being of greater relevance in women, whereas disease severity seems to play a key role in men.

The Benefits of an Integral HAMMAM Experience Combining Hydrotherapy and Swedish Massage on Pain, Subjective Well-Being and Quality of Life in Women with Endometriosis-Related Chronic Pelvic Pain: A Randomized Controlled Trial.

Background and Objectives: To evaluate the effectiveness of an integral HAMMAM experience, a 4-week therapeutic program that combined hydrotherapy and Swedish massage, applied in a multisensorial immersive environment, on pain, well-being and quality of life (QoL) in women with endometriosis-related chronic pelvic pain that is unresponsive to conventional treatment. Materials and Methods: This randomized controlled trial included 44 women with endometriosis. They were randomly allocated to either the 'HAMMAM' group (n = 21) or to a control group (n = 23). The primary outcome, pain intensity, was evaluated using numeric rating scales (NRSs). The secondary outcomes were pain interference, pain-related catastrophic thoughts, pressure pain thresholds (PPTs), subjective well-being, functional capacity and QoL, which were evaluated using the brief pain inventory (BPI), the pain catastrophizing scale (PCS), algometry, the subjective well-being scale-20 (EBS-20), the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) and the Endometriosis Health Profile-30 Questionnaire (EHP-30), respectively. The primary and secondary outcomes were measured at the baseline and after the intervention. The statistical (between-group analyses of covariance) and clinical effects were analyzed by the intention to treat. Results: The adherence rate was 100.0% and the mean (± standard deviation) satisfaction was 9.71 ± 0.46 out of 10. No remarkable health problems were reported during the trial. The 'HAMMAM' intervention improved dysmenorrhea and dyspareunia after the intervention with large and moderate effect sizes, respectively. Improvements in pain interference during sleep and PPTs in the pelvic region were also observed in women allocated to the 'HAMMAM' group. No effects were observed in catastrophizing thoughts, well-being nor QoL, except for the sleep subscale. Conclusions: A 4-week program of an integral 'HAMMAM' experience combining hydrotherapy and massage in a multisensorial immersive environment is a feasible and effective intervention to alleviate pain during menstruation and sexual intercourse as well as pain interference with sleep in women with endometriosis.