Ecosystem engineers enhance the multifunctionality of an urban novel ecosystem: Population persistence and ecosystem resilience since the 1980s.

In degraded urban habitats, nature-based solutions aim to enhance ecosystem functioning and service provision. Bivalves are increasingly reintroduced to urban environments to enhance water quality through biofiltration, yet their long-term sustainability remains uncertain. Following the restoration of the disused South Docks in Liverpool in the 1980s, natural colonization of mussels rapidly improved dock-basin water quality and supported diverse taxa, including other filter feeders. While the initial colonization phase has been well documented, there has been limited published research since the mid-1990s, despite ongoing routine water quality monitoring. Here, we assessed the long-term persistence of mussel populations, their associated biodiversity, and physico-chemical parameters of the water in Queens and Albert Docks by comparing historical (1980s to 1990s) and contemporary data from follow-up surveys (2012,2022). Following an initial period of poor water quality (high contamination and turbidity, low oxygen), the natural colonization of mussels from Albert Dock in 1988 extended throughout the South Docks. By the mid-1990s, the environment of the South Docks and its mussel populations had stabilized. The dock walls were dominated by mussels which provided important complex secondary substrate for invertebrates and macroalgae. Surveys conducted in 2012 and 2022 confirmed the continued dominance of mussels and estimates of mussel biofiltration rates confirm that mussels are continuing to contribute to maintaining water quality. A decline in salinity was observed in both docks in 2022, with evidence of recovery. While these ecosystems appear relatively stable, careful management of the hydrological regime is crucial to ensuring the persistence of mussels and resilient ecosystem service provision through biofiltration.

Women with Schizophrenia: Beyond Psychosis.

Although women with schizophrenia face significant lifelong challenges due to their diagnosis and sex-related issues, those challenges are seldom taken into consideration in their medical treatment and general care. In order to report the needs and desires of a group of women with schizophrenia, we conducted a series of semistructured interviews with nine women diagnosed with schizophrenia and attending outpatient clinics at the Hospital Del Salvador in Valparaíso. Our qualitative study followed a phenomenological design. Using ATLAS.ti software, we performed a content analysis of the interview transcripts, developed a coding frame for each major topic addressed in the interviews, and triangulated the results. Despite presenting with psychotic symptoms, some women received different diagnoses. Although acknowledging the benefits of medication, women also reported concerns about weight gain and body image. All women reported experiences with stigma and self-stigma related to the diagnosis of schizophrenia, and most had experienced childhood trauma, including sexual abuse, parental violence, and/or bullying. Young women with schizophrenia also feared that if they become mothers, then their children might also have schizophrenia and/or that they would be unable to adequately care for them. Women with schizophrenia have different experiences and play different roles in society beyond their psychoses, an understanding that should integrated into more personalized treatments for schizophrenia that consider individual characteristics and needs.

Role of the polyamine transporter PotABCD during biofilm formation by Streptococcus pneumoniae.

Streptococcus pneumoniae is a bacterium of great global importance, responsible for more than one million deaths per year. This bacterium is commonly acquired in the first years of life and colonizes the upper respiratory tract asymptomatically by forming biofilms that persist for extended times in the nasopharynx. However, under conditions that alter the bacterial environment, such as viral infections, pneumococci can escape from the biofilm and invade other niches, causing local and systemic disease of varying severity. The polyamine transporter PotABCD is required for optimal survival of the organism in the host. Immunization of mice with recombinant PotD can reduce subsequent bacterial colonization. PotD has also been suggested to be involved in pneumococcal biofilm development. Therefore, in this study we aimed to elucidate the role of PotABCD and polyamines in pneumococcal biofilm formation. First, the formation of biofilms was evaluated in the presence of exogenous polyamines-the substrate transported by PotABCD-added to culture medium. Next, a potABCD-negative strain was used to determine biofilm formation in different model systems using diverse levels of complexity from abiotic surface to cell substrate to in vivo animal models and was compared with its wild-type strain. The results showed that adding more polyamines to the medium stimulated biofilm formation, suggesting a direct correlation between polyamines and biofilm formation. Also, deletion of potABCD operon impaired biofilm formation in all models tested. Interestingly, more differences between wild-type and mutant strains were observed in the more complex model, which emphasizes the significance of employing more physiological models in studying biofilm formation.

Inflammatory bowel disease genomics, transcriptomics, proteomics and metagenomics meet artificial intelligence.

Various extrinsic and intrinsic factors such as drug exposures, antibiotic treatments, smoking, lifestyle, genetics, immune responses, and the gut microbiome characterize ulcerative colitis and Crohn's disease, collectively called inflammatory bowel disease (IBD). All these factors contribute to the complexity and heterogeneity of the disease etiology and pathogenesis leading to major challenges for the scientific community in improving management, medical treatments, genetic risk, and exposome impact. Understanding the interaction(s) among these factors and their effects on the immune system in IBD patients has prompted advances in multi-omics research, the development of new tools as part of system biology, and more recently, artificial intelligence (AI) approaches. These innovative approaches, supported by the availability of big data and large volumes of digital medical datasets, hold promise in better understanding the natural histories, predictors of disease development, severity, complications and treatment outcomes in complex diseases, providing decision support to doctors, and promising to bring us closer to the realization of the "precision medicine" paradigm. This review aims to provide an overview of current IBD omics based on both individual (genomics, transcriptomics, proteomics, metagenomics) and multi-omics levels, highlighting how AI can facilitate the integration of heterogeneous data to summarize our current understanding of the disease and to identify current gaps in knowledge to inform upcoming research in this field.

A Public Mid-Density Genotyping Platform for Hexaploid Sweetpotato (Ipomoea batatas [L.] Lam).

Small public breeding programs focused on specialty crops have many barriers to adopting technology, particularly creating and using genetic marker panels for genomic-based decisions in selection. Here, we report the creation of a DArTag panel of 3120 loci distributed across the sweetpotato (Ipomoea batatas [L.] Lam) genome for molecular-marker-assisted breeding and genomic prediction. The creation of this marker panel has the potential to bring cost-effective and rapid genotyping capabilities to sweetpotato breeding programs worldwide. The open access provided by this platform will allow the genetic datasets generated on the marker panel to be compared and joined across projects, institutions, and countries. This genotyping resource has the power to make routine genotyping a reality for any breeder of sweetpotato.

Combined hyperglycemic crises in adult patients already exist in Latin America / Las crisis hiperglucémicas combinadas en pacientes adultos ya existen en Latinoamérica

INTRODUCTION: Diabetes mellitus is one of the most common diseases worldwide, with a high morbidity and mortality rate. Its prevalence has been increasing, as well as its acute complications, such as hyperglycemic crises. Hyperglycemic crises can present with combined features of diabetic ketoacidosis and hyperosmolar state. However, their implications are not fully understood. OBJECTIVE: To describe the characteristics, outcomes, and complications of the diabetic population with hyperglycemic crises and to value the combined state in the Latin American population. MATERIALS AND METHODS: Retrospective observational study of all hyperglycemic crises treated in the intensive care unit of the Fundación Valle del Lili between January 1, 2015, and December 31, 2020. Descriptive analysis and prevalence ratio estimation for deaths were performed using the robust Poisson regression method. RESULTS: There were 317 patients with confirmed hyperglycemic crises, 43 (13.56%) with diabetic ketoacidosis, 9 (2.83%) in hyperosmolar state, and 265 (83.59%) with combined diabetic ketoacidosis and hyperosmolar state. Infection was the most frequent triggering cause (52.52%). Fatalities due to ketoacidosis occurred in four patients (9.30%) and combined diabetic ketoacidosis/hyperosmolar state in 22 patients (8.30%); no patient had a hyperosmolar state. Mechanical ventilation was associated with death occurrence (adjusted PR = 1.15; 95 % CI 95 = 1.06 - 1.24). CONCLUSIONS: The combined state was the most prevalent presentation of the hyperglycemic crisis, with a mortality rate similar to diabetic ketoacidosis. Invasive mechanical ventilation was associated with a higher occurrence of death.

Introducción. La diabetes mellitus es una de las enfermedades más frecuentes en todo el mundo, con una tasa elevada de morbimortalidad. Su prevalencia ha ido en aumento y, también, sus complicaciones agudas, como las crisis hiperglucémicas. Las crisis hiperglucémicas pueden presentar características combinadas de cetoacidosis diabética y estado hiperosmolar. Aún no se conocen completamente sus implicaciones. Objetivo. Describir las características, los resultados y las complicaciones de la población diabética con crisis hiperglucémicas, y valorar el estado mixto en la población latinoamericana. Materiales y métodos. Se trata de un estudio observacional retrospectivo de pacientes con crisis hiperglucémicas atendidos en la unidad de cuidados intensivos de la Fundación Valle del Lili, entre el 1º de enero de 2015 y el 31 de diciembre de 2020. Se realizó un análisis descriptivo y se estimó la razón de prevalencia para muerte mediante el método de regresión de Poisson. Resultados. Se incluyeron 317 pacientes con crisis hiperglucémica confirmada, 43 (13,56 %) con cetoacidosis diabética, 9 (2,83 %) en estado hiperosmolar y 265 (83,59 %) en estado mixto. La causa desencadenante más frecuente fue la infección (52,52 %). Cuatro pacientes fallecieron por cetoacidosis (9,30 %), 22 (8,30 %), por un estado mixto; ninguno se encontraba en estado hiperosmolar. La asistencia respiratoria mecánica se asoció con la muerte (razón de prevalencia ajustada = 1,15; IC95%: 1,06-1,24). Conclusiones. El estado combinado fue la presentación más prevalente de la crisis hiperglucémica, con una tasa de mortalidad similar a la de la cetoacidosis diabética, y la asistencia respiratoria mecánica invasiva se asoció con una mayor ocurrencia de muerte.

Opportunistic omnivory impairs the use of the Atlantic blue crab Callinectes sapidus as a trace metal biomonitor in invaded Mediterranean coastal waters.

The contribution of non-indigenous species to the transfer of contaminants in invaded food webs represents an active research area. Here we measured trace metals and CN stable isotopes in five populations of the invasive Atlantic blue crab Callinectes sapidus and in baseline bivalve species from Spain, Italy and Greece. They were used to estimate trophic transfer effects and the trophic position and isotopic niche of C. sapidus. Maximum trophic transfer effects occurred where the crab showed the largest isotopic niches and highest trophic positions; furthermore, the consistency of trace metal profiles between bivalves and crabs co-varied with the trophic position of the latters. Omnivory may influence the success of an invasive species, but also limit its effectiveness for biomonitoring. However, our results indicated that stable isotopes analysis provides a clarifying background where to cast patterns of contamination of the blue crab as well as of other omnivorous biomonitor species.

Recent advances in the therapeutic potential of cathelicidins.

The alarming increase in antimicrobial resistance in the last decades has prompted the search for alternatives to control infectious diseases. Antimicrobial peptides (AMPs) represent a heterogeneous class of molecules with ample antibacterial, antiviral, and antifungal effects. They can be found in many organisms, including all classes of vertebrates, providing a valuable source of new antimicrobial agents. The unique properties of AMPs make it harder for microbes develop resistance, while their immunomodulatory properties and target diversity reinforce their translational use in multiple diseases, from autoimmune disorders to different types of cancer. The latest years have witnessed a vast number of studies evaluating the use of AMPs in therapy, with many progressing to clinical trials. The present review explores the recent developments in the medicinal properties of cathelicidins, a vast family of AMPs with potent antimicrobial and immunomodulatory effects. Cathelicidins from several organisms have been tested in disease models of viral and bacterial infections, inflammatory diseases, and tumors, with encouraging results. Combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. However, there are still important limitations, such as the toxicity of many cathelicidins to healthy host cells and low stability in vivo. The recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics. Furthermore, a better understanding of the mechanisms of cathelicidin action in vivo and their synergy with other host molecules will contribute to the development of safer, highly effective therapies.

Deciphering Microbial Composition in Patients with Inflammatory Bowel Disease: Implications for Therapeutic Response to Biologic Agents.

Growing evidence suggests that alterations in the gut microbiome impact the development of inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC). Although IBD often requires the use of immunosuppressant drugs and biologic therapies to facilitate clinical remission and mucosal healing, some patients do not benefit from these drugs, and the reasons for this remain poorly understood. Despite advancements, there is still a need to develop biomarkers to help predict prognosis and guide treatment decisions. The aim of this study was to investigate the gut microbiome of IBD patients using biologics to identify microbial signatures associated with responses, following standard accepted criteria. Microbiomes in 66 stool samples from 39 IBD patients, comprising 20 CD and 19 UC patients starting biologic therapies, and 29 samples from healthy controls (HCs) were prospectively analyzed via NGS and an ensemble of metagenomics analysis tools. At baseline, differences were observed in alpha and beta metrics among patients with CD, UC and HC, as well as between the CD and UC groups. The degree of dysbiosis was more pronounced in CD patients, and those with dysbiosis exhibited a limited response to biological drugs. Pairwise differential abundance analyses revealed an increasing trend in the abundance of an unannotated genus from the Clostridiales order, Gemmiger genus and an unannotated genus from the Rikenellaceae family, which were consistently identified in greater abundance in HC. The Clostridium genus was more abundant in CD patients. At baseline, a greater abundance of the Odoribacter and Ruminococcus genera was found in IBD patients who responded to biologics at 14 weeks, whereas a genus identified as SMB53 was more enriched at 52 weeks. The Collinsella genus showed a higher prevalence among non-responder IBD patients. Additionally, a greater abundance of an unclassified genus from the Barnesiellaceae family and one from Lachnospiraceae was observed in IBD patients responding to Vedolizumab at 14 weeks. Our analyses showed global microbial diversity, mainly in CD. This indicated the absence or depletion of key taxa responsible for producing short-chain fatty acids (SCFAs). We also identified an abundance of pathobiont microbes in IBD patients at baseline, particularly in non-responders to biologic therapies. Furthermore, specific bacteria-producing SCFAs were abundant in patients responding to biologics and in those responding to Vedolizumab.

Urbanization and scorpion stings in Manaus, the largest metropolis in the Brazilian Amazon.

This study analyzed a total of 260 confirmed scorpion stings reported in the city of Manaus, in the Brazilian Amazon, from 1990 to 2020. Cases were mapped according to the GPS location of their occurrence and plotted on a satellite image of the city. The stings generally occurred close to green areas, and the hotspots of stings moved north as city grew into that direction over time. Spatial analysis shows that scorpion stings mostly occur in poor, recently urbanized areas. The rapid and unplanned urbanization of originally forested areas, without offering adequate infrastructure and services, creates favorable conditions for infestation by scorpions and increases the risk of scorpion stings.

Repeated human leukocyte antigens eplets, importance of typing the partner.

INTRODUCTION: Antibody-mediated rejection (AMR) is the most common cause of immune-mediated allograft failure after kidney transplant and impacts allograft survival. Previous sensitization is a major risk factor for development of donor specific antibodies (DSA). AMR can have a wide range of clinical features such as impaired kidney function, proteinuria/hypertension or can be subclinical. HLA molecules have specific regions of antigens binding antibodies called epitopes and eplets are considered essential components responsible for immune recognition. We present a patient with subclinical AMR 1 week post transplantation. CASE REPORT: A 48-year-old, caucasian woman with end-stage kidney disease (ESKD) secondary to autosomal dominant polycystic kidney disease (ADPKD) on peritoneal dialysis was registered in deceased donor waitlist. She was a hypersensitized patient from 3 prior pregnancies with a calculated panel reactive antibody of 93,48%. She was transplanted through kidney paired exchange donation with no evidence of DSA pre transplantation. Surgery and post-op were unremarkable with excellent and immediate graft function. Per protocol DSA levels on the 5th day was DR1 of 3300 MFI, with an increase in MFI by day 13 with 7820 MFI and a new B41 1979MFI. Allograft kidney biopsy findings were diagnostic of AMR and she was treated with immunoglobulin and plasmapheresis. As early onset AMR post transplantation was observed an anamnestic response was hypothesized from a previous exposure to allo-HLA. We decided to type her husband, her son's father, which was presented with DSA. Mismatch eplet analysis revealed a shared 41 T and 67LQ eplets between the donor and husband, responsible for the reactivity and new HLA class I B41 and HLA class II DR1 DSA, respectively. DISCUSSION: Shared eplets between the patient husband and donor was responsible for the alloimmune response and early development of DSAs. This case highlights the importance of early monitoring DSA levels in highly sensitized patients after transplant in order to promptly address and lower inflammatory damage. Mismatch eplet analysis can provide a thorough and precise evaluation of immune compatibility providing a useful technique to immune risk stratification, donor selection and post-transplant immunosuppressive therapy and monitoring.

Integrative geriatric assessment. A narrative review of the scales and their use in Ecuador

This study aims to describe the main tools for integrative geriatric assessment and their use in Ecuador. We performed a narrative review with a comprehensive and systematic literature search. 261 original articles were obtained from the primary search, and after the discrimination by the researchers, 76 articles were included in the final analysis. Integrative geriatric assessments cover different areas, including cognitive function, affective function, nutritional status and functionality, and seve-ral tools that are used worldwide for this purpose. In Ecuador, a deeper analysis of their use is required to evaluate their diagnostic efficacy and applicability to impro-ve health outcomes for the elderly population.

Este estudio tiene como objetivo describir las principales herramientas de evalua-ción integral geriátrica y su uso en el Ecuador. Realizamos una revisión narrativa con una búsqueda bibliográfica exhaustiva y sistemática. De la búsqueda primaria se obtuvieron 261 artículos originales, y luego de la discriminación por parte de los investigadores, se incluyeron 76 artículos en el análisis final. La evaluación ge-riátrica cubre diferentes áreas, incluida la función cognitiva, la función afectiva, el estado nutricional y la funcionalidad, y se utilizan varias herramientas en todo el mundo para este propósito. En Ecuador se requiere un análisis más profundo de su uso para evaluar su eficacia diagnóstica y aplicabilidad con el fin de mejorar los resultados de salud de la población adulta mayor.

The role of the brain renin-angiotensin system in Parkinson´s disease.

The renin-angiotensin system (RAS) was classically considered a circulating hormonal system that regulates blood pressure. However, different tissues and organs, including the brain, have a local paracrine RAS. Mutual regulation between the dopaminergic system and RAS has been observed in several tissues. Dysregulation of these interactions leads to renal and cardiovascular diseases, as well as progression of dopaminergic neuron degeneration in a major brain center of dopamine/angiotensin interaction such as the nigrostriatal system. A decrease in the dopaminergic function induces upregulation of the angiotensin type-1 (AT1) receptor activity, leading to recovery of dopamine levels. However, AT1 receptor overactivity in dopaminergic neurons and microglial cells upregulates the cellular NADPH-oxidase-superoxide axis and Ca2+ release, which mediate several key events in oxidative stress, neuroinflammation, and α-synuclein aggregation, involved in Parkinson's disease (PD) pathogenesis. An intraneuronal antioxidative/anti-inflammatory RAS counteracts the effects of the pro-oxidative AT1 receptor overactivity. Consistent with this, an imbalance in RAS activity towards the pro-oxidative/pro-inflammatory AT1 receptor axis has been observed in the substantia nigra and striatum of several animal models of high vulnerability to dopaminergic degeneration. Interestingly, autoantibodies against angiotensin-converting enzyme 2 and AT1 receptors are increased in PD models and PD patients and contribute to blood-brain barrier (BBB) dysregulation and nigrostriatal pro-inflammatory RAS upregulation. Therapeutic strategies addressed to the modulation of brain RAS, by AT1 receptor blockers (ARBs) and/or activation of the antioxidative axis (AT2, Mas receptors), may be neuroprotective for individuals with a high risk of developing PD or in prodromal stages of PD to reduce progression of the disease.

Impact of treatment adherence and inhalation technique on asthma outcomes of pediatric patients: a longitudinal study.

Introduction: We aimed to evaluate the longitudinal relationships, both at between- and within-person levels, that adherence to inhaled corticosteroid-based maintenance treatment and inhalation technique present with symptom control, exacerbations, and health-related quality of life (HRQoL) in children and adolescents with asthma. Methods: Participants (6-14 years old) from the ARCA (Asthma Research in Children and Adolescents) cohort-a prospective, multicenter, observational study (NCT04480242)-were followed for a period from 6 months to 5 years via computer-assisted telephone interviews and a smartphone application. The Medication Intake Survey-Asthma (MIS-A) was administered to assess the implementation stage of adherence, and the Inhalation Technique Questionnaire (InTeQ) was used to assess the five key steps when using an inhaler. Symptom control was measured with the Asthma Control Questionnaire (ACQ), and HRQL was measured with the EQ-5D and the Patient-Reported Outcomes Measurement Information System-Pediatric Asthma Impact Scale (PROMIS-PAIS). Multilevel longitudinal mixed models were constructed separately with symptom control, exacerbation occurrence, EQ-5D, and PROMIS-PAIS as the dependent variables. Results: Of the 360 participants enrolled, 303 (1,203 interviews) were included in the symptom control and exacerbation analyses, 265 (732) in the EQ-5D, and 215 (617) in the PROMIS-PAIS. Around 60% of participants were male subjects, and most of them underwent maintenance treatment with inhaled corticosteroids plus long-acting ß-agonists in a fixed dose (73.3%). Within-person variability was 83.6% for asthma control, 98.6% for exacerbations, 36.4% for EQ-5D, and 49.1% for PROMIS-PAIS. At the within-person level, patients with higher adherence had better symptom control (p = 0.002) and HRQoL over time (p = 0.016). Patients with a better inhalation technique reported worse HRQoL simultaneously (p = 0.012), but they showed better HRQoL in future assessments (p = 0.012). The frequency of reliever use was associated with symptom control (p < 0.001), exacerbation occurrence (p < 0.001), and HRQoL (p = 0.042); and boys were more likely to present better symptom control and HRQoL than girls. Conclusion: Our results confirm longitudinal associations at the within-person level of the two indicators of quality use of inhalers: for adherence to maintenance treatment with symptom control and HRQoL, and for the inhalation technique with HRQoL. Although treatment adherence was shown to be excellent, a third of the participants reported a suboptimal inhalation technique, highlighting the need for actions for improving asthma management of the pediatric population.

Satisfactory mid-term clinical outcomes of endoscopic tenotomy for iliopsoas tendinopathy following total hip arthroplasty.

PURPOSE: To report 5-year outcomes of endoscopic iliopsoas tenotomy in patients with iliopsoas tendinopathy following total hip arthroplasty (THA) and determine whether clinical scores are associated with cup position. METHODS: Patients who underwent endoscopic iliopsoas tenotomy for iliopsoas tendinopathy following THA (2014-2017) were contacted. Indications for endoscopic iliopsoas tenotomy after THA were groin pain during active hip flexion, exclusion of other causes of groin pain, and no pain relief after 6 months of conservative treatment. Pretenotomy cup inclination and anteversion were measured on radiographs; axial and sagittal cup overhang were measured on computed tomography (CT) scans. Oxford hip score (OHS), modified Harris hip score (mHHS), and groin pain were assessed. RESULTS: The initial cohort comprised 16 men (17 hips) and 31 women (32 hips), aged 60.7 ± 10.6 years. Cup inclination and anteversion were, respectively, 46.2 ± 6.2° and 14.6 ± 8.4°, while axial and sagittal cup overhang were, respectively, 4.4 ± 4.0 mm and 6.9 ± 4.5 mm. At ≥5 years follow-up, four hips underwent cup and stem revision, two underwent isolated cup revision and one underwent secondary iliopsoas tenotomy. OHS improved by 23 ± 10 and mHHS improved by 31 ± 16. Posttenotomy groin pain was slight in 20.0%, mild in 17.5% and moderate in 12.5%. Regression analyses revealed that net change in mHHS decreased with sagittal cup overhang (ß = -3.1; 95% confidence interval [CI] = -4.6 to -1.7; p < 0.001), but that there were no associations between cup position and net change in OHS. CONCLUSIONS: Endoscopic iliopsoas tenotomy provides good mid-term clinical outcomes in patients with iliopsoas tendinopathy following THA. Furthermore, improvements in mHHS were found to decrease with increasing sagittal cup overhang, in cases for which adequate preoperative imaging was available. LEVEL OF EVIDENCE: Level IV.

No Differences in Clinical Outcomes Between Hip Arthroscopy With Versus Without Capsular Closure in Patients With Cam- or Mixed-Type Femoroacetabular Impingement: A Randomized Controlled Trial.

PURPOSE: To compare 2-year clinical outcomes of primary hip arthroscopy with versus without capsular closure after interportal capsulotomy in patients with cam- or mixed-type femoroacetabular impingement (FAI). METHODS: Patients with cam- or mixed-type FAI undergoing primary hip arthroscopy with interportal capsulotomy were prospectively enrolled in this randomized controlled trial (RCT) and allocated into either capsular closure or no capsular closure groups. Patients were blinded to group allocation. Clinical outcomes were assessed preoperatively and at 2-year follow-up using the 12-item International Hip Outcome Tool (iHOT-12), modified Harris Hip Score (mHHS), and 6 subsections of the Copenhagen Hip and Groin Outcome Score (HAGOS). Complications and reoperations were noted. RESULTS: Eighty-four patients (100 hips) were enrolled, 49 hips in the capsular closure group and 51 in the no capsular closure group, with no significant differences in age (28.5 ± 7.5 vs 30.4 ± 8.4, P = .261), body mass index (23.5 ± 3.0 vs 23.4 ± 1.9, P = .665), and sex distribution (female: 10.2% vs 13.7%, P = .760). Four patients were lost to follow-up (2.0% vs 5.9%, P = .618) and 6 had reoperations (6.1% vs 5.9%, P = 1.000), which left 45 hips per group for clinical assessment. There were no significant differences between groups in the net change of iHOT-12 (28.3 ± 19.6 vs 32.5 ± 22.7, P = .388), mHHS (7.6 ± 13.1 vs 7.5 ± 10.2, P = .954), and subsections of HAGOS (P > .05). Complication rates were also similar between groups (P > .05). CONCLUSIONS: The present RCT compared primary hip arthroscopy with versus without capsular closure after interportal capsulotomy in a male-dominated, non-dysplastic, non-arthritic cohort with cam- or mixed-type FAI and found no significant differences in patient-reported clinical outcomes, complication rates, or reoperation rates. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

RND3 Potentiates Proinflammatory Activation through NOTCH Signaling in Activated Macrophages.

Macrophage activation is a complex process with multiple control elements that ensures an adequate response to the aggressor pathogens and, on the other hand, avoids an excess of inflammatory activity that could cause tissue damage. In this study, we have identified RND3, a small GTP-binding protein, as a new element in the complex signaling process that leads to macrophage activation. We show that RND3 expression is transiently induced in macrophages activated through Toll receptors and potentiated by IFN-γ. We also demonstrate that RND3 increases NOTCH signaling in macrophages by favoring NOTCH1 expression and its nuclear activity; however, Rnd3 expression seems to be inhibited by NOTCH signaling, setting up a negative regulatory feedback loop. Moreover, increased RND3 protein levels seem to potentiate NFκB and STAT1 transcriptional activity resulting in increased expression of proinflammatory genes, such as Tnf-α, Irf-1, or Cxcl-10. Altogether, our results indicate that RND3 seems to be a new regulatory element which could control the activation of macrophages, able to fine tune the inflammatory response through NOTCH.