bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical, Genetic, and Histological Characterization of Patients with Rare Neuromuscular and Mitochondrial Diseases Presenting with Different Cardiomyopathy Phenotypes
Authors: Monda Emanuele , Lioncino Michele , Caiazza Martina , Simonelli Vincenzo , Nesti Claudia , Rubino Marta , Perna Alessia , Mauriello Alfredo , Budillon Alberta , Pota Vincenzo , Bruno Giorgia , Varone Antonio , Nigro Vincenzo , Santorelli Filippo Maria , Pacileo Giuseppe , Russo Maria Giovanna , Frisso Giulia , Sampaolo Simone , Limongelli Giuseppe
Published: May 2023

Cardiomyopathies are mostly determined by genetic mutations affecting either cardiac muscle cell structure or function. Nevertheless, cardiomyopathies may also be part of complex clinical phenotypes in the spectrum of neuromuscular (NMD) or mitochondrial diseases (MD). The aim of this study is to describe the clinical, molecular, and histological characteristics of a consecutive cohort of patients with cardiomyopathy associated with NMDs or MDs referred to a tertiary cardiomyopathy clinic. Consecutive patients with a definitive diagnosis of NMDs and MDs presenting with a cardiomyopathy phenotype were described. Seven patients were identified: two patients with ACAD9 deficiency (Patient 1 carried the c.1240C>T (p.Arg414Cys) homozygous variant in ACAD9; Patient 2 carried the c.1240C>T (p.Arg414Cys) and the c.1646G>A (p.Ar549Gln) variants in ACAD9); two patients with MYH7-related myopathy (Patient 3 carried the c.1325G>A (p.Arg442His) variant in MYH7; Patient 4 carried the c.1357C>T (p.Arg453Cys) variant in MYH7); one patient with desminopathy (Patient 5 carried the c.46C>T (p.Arg16Cys) variant in DES); two patients with mitochondrial myopathy (Patient 6 carried the m.3243A>G variant in MT-TL1; Patient 7 carried the c.253G>A (p.Gly85Arg) and the c.1055C>T (p.Thr352Met) variants in MTO1). All patients underwent a comprehensive cardiovascular and neuromuscular evaluation, including muscle biopsy and genetic testing. This study described the clinical phenotype of rare NMDs and MDs presenting as cardiomyopathies. A multidisciplinary evaluation, combined with genetic testing, plays a main role in the diagnosis of these rare diseases, and provides information about clinical expectations, and guides management.
Molecular Mechanisms Determining the Role of Bacteria from the Genus Azospirillum in Plant Adaptation to Damaging Environmental Factors
Authors: Gureeva Maria V. , Gureev Artem P.
Published: May 2023

Agricultural plants are continuously exposed to environmental stressors, which can lead to a significant reduction in yield and even the death of plants. One of the ways to mitigate stress impacts is the inoculation of plant growth-promoting rhizobacteria (PGPR), including bacteria from the genus Azospirillum, into the rhizosphere of plants. Different representatives of this genus have different sensitivities or resistances to osmotic stress, pesticides, heavy metals, hydrocarbons, and perchlorate and also have the ability to mitigate the consequences of such stresses for plants. Bacteria from the genus Azospirillum contribute to the bioremediation of polluted soils and induce systemic resistance and have a positive effect on plants under stress by synthesizing siderophores and polysaccharides and modulating the levels of phytohormones, osmolytes, and volatile organic compounds in plants, as well as altering the efficiency of photosynthesis and the antioxidant defense system. In this review, we focus on molecular genetic features that provide bacterial resistance to various stress factors as well as on Azospirillum-related pathways for increasing plant resistance to unfavorable anthropogenic and natural factors.
TULA Proteins in Men, Mice, Hens, and Lice: Welcome to the Family
Authors: Tsygankov Alexander Y.
Published: May 2023

The two members of the UBASH3/STS/TULA protein family have been shown to critically regulate key biological functions, including immunity and hemostasis, in mammalian biological systems. Negative regulation of signaling through immune receptor tyrosine-based activation motif (ITAM)- and hemITAM-bearing receptors mediated by Syk-family protein tyrosine kinases appears to be a major molecular mechanism of the down-regulatory effect of TULA-family proteins, which possess protein tyrosine phosphatase (PTP) activity. However, these proteins are likely to carry out some PTP-independent functions as well. Whereas the effects of TULA-family proteins overlap, their characteristics and their individual contributions to cellular regulation also demonstrate clearly distinct features. Protein structure, enzymatic activity, molecular mechanisms of regulation, and biological functions of TULA-family proteins are discussed in this review. In particular, the usefulness of the comparative analysis of TULA proteins in various metazoan taxa, for identifying potential roles of TULA-family proteins outside of their functions already established in mammalian systems, is examined.
The Epigenetics of Migraine
Authors: Zobdeh Farzin , Eremenko Ivan I. , Akan Mikail A. , Tarasov Vadim V. , Chubarev Vladimir N. , Schiöth Helgi B. , Mwinyi Jessica
Published: May 2023

Migraine is a complex neurological disorder and a major cause of disability. A wide range of different drug classes such as triptans, antidepressants, anticonvulsants, analgesics, and beta-blockers are used in acute and preventive migraine therapy. Despite a considerable progress in the development of novel and targeted therapeutic interventions during recent years, e.g., drugs that inhibit the calcitonin gene-related peptide (CGRP) pathway, therapy success rates are still unsatisfactory. The diversity of drug classes used in migraine therapy partly reflects the limited perception of migraine pathophysiology. Genetics seems to explain only to a minor extent the susceptibility and pathophysiological aspects of migraine. While the role of genetics in migraine has been extensively studied in the past, the interest in studying the role of gene regulatory mechanisms in migraine pathophysiology is recently evolving. A better understanding of the causes and consequences of migraine-associated epigenetic changes could help to better understand migraine risk, pathogenesis, development, course, diagnosis, and prognosis. Additionally, it could be a promising avenue to discover new therapeutic targets for migraine treatment and monitoring. In this review, we summarize the state of the art regarding epigenetic findings in relation to migraine pathogenesis and potential therapeutic targets, with a focus on DNA methylation, histone acetylation, and microRNA-dependent regulation. Several genes and their methylation patterns such as CALCA (migraine symptoms and age of migraine onset), RAMP1, NPTX2, and SH2D5 (migraine chronification) and microRNA molecules such as miR-34a-5p and miR-382-5p (treatment response) seem especially worthy of further study regarding their role in migraine pathogenesis, course, and therapy. Additionally, changes in genes including COMT, GIT2, ZNF234, and SOCS1 have been linked to migraine progression to medication overuse headache (MOH), and several microRNA molecules such as let-7a-5p, let-7b-5p, let-7f-5p, miR-155, miR-126, let-7g, hsa-miR-34a-5p, hsa-miR-375, miR-181a, let-7b, miR-22, and miR-155-5p have been implicated with migraine pathophysiology. Epigenetic changes could be a potential tool for a better understanding of migraine pathophysiology and the identification of new therapeutic possibilities. However, further studies with larger sample sizes are needed to verify these early findings and to be able to establish epigenetic targets as disease predictors or therapeutic targets.
IL-10-Engineered Dendritic Cells Modulate Allogeneic CD8+ T Cell Responses
Authors: Fortunato Marta , Amodio Giada , Gregori Silvia
Published: May 2023

Tolerogenic dendritic cells (tolDC) play a central role in regulating immune homeostasis and in promoting peripheral tolerance. These features render tolDC a promising tool for cell-based approaches aimed at inducing tolerance in T-cell mediated diseases and in allogeneic transplantation. We developed a protocol to generate genetically engineered human tolDC overexpressing IL-10 (DCIL-10) by means of a bidirectional lentiviral vector (LV) encoding for IL-10. DCIL-10 promote allo-specific T regulatory type 1 (Tr1) cells, modulate allogeneic CD4+ T cell responses in vitro and in vivo, and are stable in a pro-inflammatory milieu. In the present study, we investigated the ability of DCIL-10 to modulate cytotoxic CD8+ T cell responses. We demonstrate that DCIL-10 reduces allogeneic CD8+ T cell proliferation and activation in primary mixed lymphocyte reactions (MLR). Moreover, long-term stimulation with DCIL-10 induces allo-specific anergic CD8+ T cells without signs of exhaustion. DCIL-10-primed CD8+ T cells display limited cytotoxic activity. These findings indicate that stable over-expression of IL-10 in human DC leads to a population of cells able to modulate cytotoxic allogeneic CD8+ T cell responses, overall indicating that DCIL-10 represent a promising cellular product for clinical applications aimed at inducing tolerance after transplantation.
Editorial for the IJMS Special Issue “Progress in Understanding of Cardiac Arrhythmia Mechanisms and Antiarrhythmic Targets”
Authors: Tribulova Narcis
Published: May 2023

Cardiac rhythm disorders, in particular life-threatening ventricular fibrillation and stroke-provoking fibrillation of the atria, are a permanent focus of both clinical and experimental cardiologists [...]
New 5-Hydroxycoumarin-Based Tyrosyl-DNA Phosphodiesterase I Inhibitors Sensitize Tumor Cell Line to Topotecan
Authors: Khomenko Tatyana M. , Zakharenko Alexandra L. , Kornienko Tatyana E. , Chepanova Arina A. , Dyrkheeva Nadezhda S. , Artemova Anastasia O. , Korchagina Dina V. , Achara Chigozie , Curtis Anthony , Reynisson Jóhannes , Volcho Konstantin P. , Salakhutdinov Nariman F. , Lavrik Olga I.
Published: May 2023

Tyrosyl-DNA-phosphodiesterase 1 (TDP1) is an important enzyme in the DNA repair system. The ability of the enzyme to repair DNA damage induced by a topoisomerase 1 poison such as the anticancer drug topotecan makes TDP1 a promising target for complex antitumor therapy. In this work, a set of new 5-hydroxycoumarin derivatives containing monoterpene moieties was synthesized. It was shown that most of the conjugates synthesized demonstrated high inhibitory properties against TDP1 with an IC50 in low micromolar or nanomolar ranges. Geraniol derivative 33a was the most potent inhibitor with IC50 130 nM. Docking the ligands to TDP1 predicted a good fit with the catalytic pocket blocking access to it. The conjugates used in non-toxic concentration increased cytotoxicity of topotecan against HeLa cancer cell line but not against conditionally normal HEK 293A cells. Thus, a new structural series of TDP1 inhibitors, which are able to sensitize cancer cells to the topotecan cytotoxic effect has been discovered.
Transcriptome Profile of the Rat Adrenal Gland: Parenchymal and Interstitial Cells
Authors: Tyczewska Marianna , Sujka-Kordowska Patrycja , Szyszka Marta , Jopek Karol , Blatkiewicz Małgorzata , Malendowicz Ludwik , Rucinski Marcin
Published: May 2023

The homeostasis of the adrenal gland plays a decisive role in its proper functioning, both in non-stressful conditions and under the influence of various types of stress. This consists of interactions between all types of cells that make up the organ, including parenchymal and interstitial cells. The amount of available information on this subject in the rat adrenal glands under non-stressful conditions is insufficient; the aim of the research was to determine the expression of marker genes for rat adrenal cells depending on their location. The material for the study consisted of adrenal glands taken from intact adult male rats that were separated into appropriate zones. Transcriptome analysis by means of Affymetrix® Rat Gene 2.1 ST Array was used in the study, followed by real-time PCR validation. Expression analysis of interstitial cell marker genes revealed both the amount of expression of these genes and the zone in which they were expressed. The expression of marker genes for fibroblasts was particularly high in the cells of the ZG zone, while the highest expression of specific macrophage genes was observed in the adrenal medulla. The results of this study, especially with regard to interstitial cells, provide a so far undescribed model of marker gene expression of various cells, both in the cortex and medulla of the sexually mature rat adrenal gland. The interdependence between parenchymal and interstitial cells creates a specific microenvironment that is highly heterogeneous within the gland with respect to some of the interstitial cells. This phenomenon most likely depends on the interaction with the differentiated parenchymal cells of the cortex, as well as the medulla of the gland.
Frankia alni Carbonic Anhydrase Regulates Cytoplasmic pH of Nitrogen-Fixing Vesicles
Authors: Pujic Petar , Carro Lorena , Fournier Pascale , Armengaud Jean , Miotello Guylaine , Dumont Nathalie , Bourgeois Caroline , Saupin Xavier , Jame Patrick , Selak Gabriela Vuletin , Alloisio Nicole , Normand Philippe
Published: May 2023

A phyloprofile of Frankia genomes was carried out to identify those genes present in symbiotic strains of clusters 1, 1c, 2 and 3 and absent in non-infective strains of cluster 4. At a threshold of 50% AA identity, 108 genes were retrieved. Among these were known symbiosis-associated genes such as nif (nitrogenase), and genes which are not know as symbiosis-associated genes such as can (carbonic anhydrase, CAN). The role of CAN, which supplies carbonate ions necessary for carboxylases and acidifies the cytoplasm, was thus analyzed by staining cells with pH-responsive dyes; assaying for CO2 levels in N-fixing propionate-fed cells (that require a propionate-CoA carboxylase to yield succinate-CoA), fumarate-fed cells and N-replete propionate-fed cells; conducting proteomics on N-fixing fumarate and propionate-fed cells and direct measurement of organic acids in nodules and in roots. The interiors of both in vitro and nodular vesicles were found to be at a lower pH than that of hyphae. CO2 levels in N2-fixing propionate-fed cultures were lower than in N-replete ones. Proteomics of propionate-fed cells showed carbamoyl-phosphate synthase (CPS) as the most overabundant enzyme relative to fumarate-fed cells. CPS combines carbonate and ammonium in the first step of the citrulline pathway, something which would help manage acidity and NH4+. Nodules were found to have sizeable amounts of pyruvate and acetate in addition to TCA intermediates. This points to CAN reducing the vesicles’ pH to prevent the escape of NH3 and to control ammonium assimilation by GS and GOGAT, two enzymes that work in different ways in vesicles and hyphae. Genes with related functions (carboxylases, biotin operon and citrulline-aspartate ligase) appear to have undergone decay in non-symbiotic lineages.
Response of Phenolic Compounds in Lippia graveolens Kunth Irrigated with Aquaculture Wastewater and Steiner Solution
Authors: Nieto-Ramírez María Isabel , Feregrino-Pérez Ana Angélica , Aguirre Becerra Humberto , Parra-Pacheco Benito , Oviedo-Olvera Mónica Vanessa , García-Trejo Juan Fernando
Published: May 2023

Lippia graveolens is one of the most important aromatic species in Mexico due to antioxidant and antibiotic activities reported in its essential oil. The aim of this work was to assess the effect of irrigation with aquaculture wastewater and salicylic acid addition on the production of phenolic compounds in L. graveolens. L. graveolens plants (14) were irrigated with aquaculture wastewater and (14) using Steiner solution for 28 days; at the same time, salicylic acid was exogenously applied at 0.0 (control), 0.5 and 1.0 mM concentrations in both treatments at 5 and 19 experimental days. The total phenolic content was measured by Folin–Ciocalteu, the flavonoid content was determined by the aluminum chloride method, and the antioxidant capacity was measured by DPPH and FRAP assays. The results showed an increase in the total phenolic and flavonoid content in plants irrigated with aquaculture wastewater solution (17.25 ± 2.35 to 38.16 ± 4.47 mg eq GA·g⁻1 W). The antioxidant capacity was higher in plants irrigated with Steiner solution (98.52 mg eq T·g⁻1 W). In conclusion, L. graveolens irrigated with aquaculture wastewater leads to an increase in the total phenolic content and Steiner-solution antioxidant capacity in plants.
Knee Arthrodesis with a Modular Silver-Coated Endoprosthesis for Infected Total Knee Arthroplasty with Extensive Bone Loss: A Retrospective Case-Series Study
Authors: Savvidou Olga D. , Kaspiris Angelos , Goumenos Stavros , Trikoupis Ioannis , Melissaridou Dimitra , Kalogeropoulos Athanasios , Serenidis Dimitris , Georgoulis Jim-Dimitris , Lianou Ioanna , Koulouvaris Panagiotis , Papagelopoulos Panayiotis J.
Published: May 2023

Introduction: Knee arthrodesis is a limb salvage intervention for persistent periprosthetic joint infection (PJI) when revision total knee arthroplasty fails. Conventional arthrodesis techniques are associated with the increased rate of complications, especially in patients with extensive bone loss and extensor tendon deficiency. Methods: Eight patients with a modular silver-coated arthrodesis implant after failed exchange arthroplasty for infection, were retrospectively reviewed. All patients had significant bone loss, while 5 displayed extensor tendon deficiency. Survivorship, complications, leg length discrepancy, median Visual Analogue Scale (VAS) and Oxford Knee score (OKS) were evaluated. Results: The median follow up was 32 months (range 24–59 months). The survivorship rate of the prosthesis was 86% during the minimum time of follow up of 24 months. In one patient recurrence of the infection was observed and above-knee amputation was performed. The median postoperative leg length discrepancy was 2.07 ± 0.67 cm. Patients were able to ambulate with mild or no pain. The median VAS and OKS was 2.14 ± 0.9 and 34.7 ± 9.3, respectively. Conclusions: The results of our study demonstrated that knee arthrodesis with a silver coated arthrodesis implant, performed for persistent PJI in patients with significant bone loss and extensor tendon deficit, provided a stable construct, allowed eradication of infection and was associated with good functional outcome.
Plasma-Metanephrines in Patients with Autoimmune Addison’s Disease with and without Residual Adrenocortical Function
Authors: Åkerman Anna-Karin , Sævik Åse Bjorvatn , Thorsby Per Medbøe , Methlie Paal , Quinkler Marcus , Jørgensen Anders Palmstrøm , Höybye Charlotte , Debowska Aleksandra J. , Nedrebø Bjørn Gunnar , Dahle Anne Lise , Carlsen Siri , Tomkowicz Aneta , Sollid Stina Therese , Nermoen Ingrid , Grønning Kaja , Dahlqvist Per , Grimnes Guri , Skov Jakob , Finnes Trine , Wahlberg Jeanette , Holte Synnøve Emblem , Simunkova Katerina , Kämpe Olle , Husebye Eystein Sverre , Øksnes Marianne , Bensing Sophie
Published: May 2023

Purpose: Residual adrenocortical function, RAF, has recently been demonstrated in one-third of patients with autoimmune Addison’s disease (AAD). Here, we set out to explore any influence of RAF on the levels of plasma metanephrines and any changes following stimulation with cosyntropin. Methods: We included 50 patients with verified RAF and 20 patients without RAF who served as controls upon cosyntropin stimulation testing. The patients had abstained from glucocorticoid and fludrocortisone replacement > 18 and 24 h, respectively, prior to morning blood sampling. The samples were obtained before and 30 and 60 min after cosyntropin stimulation and analyzed for serum cortisol, plasma metanephrine (MN), and normetanephrine (NMN) by liquid-chromatography tandem-mass pectrometry (LC-MS/MS). Results: Among the 70 patients with AAD, MN was detectable in 33%, 25%, and 26% at baseline, 30 min, and 60 min after cosyntropin stimulation, respectively. Patients with RAF were more likely to have detectable MN at baseline (p = 0.035) and at the time of 60 min (p = 0.048) compared to patients without RAF. There was a positive correlation between detectable MN and the level of cortisol at all time points (p = 0.02, p = 0.04, p < 0.001). No difference was noted for NMN levels, which remained within the normal reference ranges. Conclusion: Even very small amounts of endogenous cortisol production affect MN levels in patients with AAD.
Plasma Rich in Growth Factors as an Adjuvant Agent in Non-Penetrating Deep Sclerectomy
Authors: Rodríguez-Calvo Pedro P. , Rodríguez-Uña Ignacio , Fernández-Vega-Cueto Andrés , Sánchez-Ávila Ronald M. , Anitua Eduardo , Merayo-Lloves Jesús
Published: May 2023

Background: The purpose of this study is to evaluate the utility and safety of plasma rich in growth factors immunosafe eye drops (is-ePRGF) in the postoperative treatment of non-penetrating deep sclerectomy (NPDS). Methods: This is a case–control study in patients with open-angle glaucoma. Group one (control) was not treated with is-ePRGF, while group two (is-ePRGF) was treated (four times a day for four months). Postoperative evaluations were performed at one day, one month, three months and six months. The main outcomes were: intraocular pressure (IOP), microcysts in blebs with AS-OCT and the number of hypotensive eye drops. Results: Preoperatively, group one (n = 48 eyes) and group two (n = 47 eyes) were similar in age (71.5 ± 10.7 vs. 70.9 ± 10.0 years; p = 0.68), IOP (20.6 ± 10.2 vs. 23.0 ± 9.0 mmHg; p = 0.26) and number of hypotensive drugs (2.7 ± 0.8 vs. 2.8 ± 0.9; p = 0.40). The IOP at six months dropped to 15.0 ± 8.0 mmHg (IOP reduction: −27.2%) and 10.9 ± 4.3 mmHg (IOP reduction: −52.6%) for group one and group two, respectively (p < 0.01). At six months, blebs with microcysts were 62.5% (group one) and 76.7% (group two). Postoperative complications were observed in 12 eyes (25%) for group one and in 5 eyes (11%) for group two (p = 0.06). No specific complications related to the use of is-ePRGF were identified. Conclusions: Topical is-ePRGF seems to reduce IOP and the rate of complications in the medium term after NPDS, so it can be considered as a possible safe adjuvant to achieve surgical success.
The Role of Corticosteroid Nasal Irrigations in the Management of Chronic Rhinosinusitis: A State-of-the-Art Systematic Review
Authors: Calvo-Henriquez Christian , Viera-Artiles Jaime , Rodriguez-Iglesias Miguel , Rodriguez-Rivas Paula , Maniaci Antonino , Yáñez Miguel Mayo , Martínez-Capoccioni Gabriel , Alobid Isam
Published: May 2023

Chronic rhinosinusitis (CRS) is a highly prevalent condition. CRS is usually managed with intranasal corticosteroids, useful both before as well as after endoscopic sinus surgery (ESS). However, the greatest drawback of these low-volume sprays is the inadequate delivery into the paranasal sinuses, even after ESS. Recent studies have shown that high-volume steroid nasal rinse (HSNR) has a significantly better penetration of the paranasal sinuses. The purpose of this state-of-the-art review is to systematically overview the current literature about the role of nasal rinses with steroids in CRS. Four authors examined four databases (Embase, Pubmed, Scielo, Cochrane). This review identified 23 studies answering 5 research questions. It included 1182 participants, 722 cases, and 460 controls. Available evidence suggests a potential positive effect of HSNR, which seems to be higher in CRS with nasal polyps. More well-designed studies are needed in order to obtain solid conclusions. The evidence is solid regarding the safety of this treatment modality in the short and long-term. We expect that this lack of severe negative effects will facilitate the acceptance of this treatment modality and the development of future studies.
The Relationship between Body Image, Disability and Mental Health in Patients with Multiple Sclerosis
Authors: Lo Buono Viviana , Bonanno Lilla , Corallo Francesco , Cardile Davide , D’Aleo Giangaetano , Rifici Carmela , Sessa Edoardo , Quartarone Angelo , De Cola Maria Cristina
Published: May 2023

Background: Multiple sclerosis is a progressive degenerative disorder that frequently involves the development of physical and emotional changes, including loss of limb function or sensitivity, sexual dysfunction, and cognitive and mood alterations. It is likely that these alterations lead to changes in body aspects. However, knowledge about body image perception in multiple sclerosis is lacking. Purpose: The present study investigated the relationship between body image perception and its correlation with a disability, neuropsychiatric symptoms, and self-esteem. Methods: A total of 100 outpatients with relapsing-remitting multiple sclerosis underwent neurological assessment using the Expanded Disability Status Scale. Participants also completed the Body Image Scale (BIS), Rosenberg Self-Esteem Scale (RSES), and Symptom Checklist-90-Revised (SCL-90-R). Results: We found a significant positive correlation between body image and disability (r = 0.21; p = 0.03), body image and self-esteem (r = −0.52; p < 0.001), body image and somatization (r = 0.44; p < 0.001), body image and depression (r = 0.57; p < 0.001), and body image and anxiety (r = 0.5; p < 0.001). Conclusions: The body is considered one of the main parts of a person’s identity. Dissatisfaction with one’s own body changes the general evaluation of the “self”. The body image construct has important health outcomes and should be studied more in patients with multiple sclerosis.
Short-Term Outcomes in Patients Undergoing Virtual/Ghost Ileostomy or Defunctioning Ileostomy after Anterior Resection of the Rectum: A Meta-Analysis
Authors: Zizzo Maurizio , Morini Andrea , Zanelli Magda , Tumiati David , Sanguedolce Francesca , Palicelli Andrea , Mereu Federica , Ascani Stefano , Fabozzi Massimiliano
Published: May 2023

Background and Objectives: Anterior rectal resection (ARR) represents one of the most frequently performed methods in colorectal surgery, mainly carried out for rectal cancer (RC) treatment. Defunctioning ileostomy (DI) has long been chosen as a method to “protect” colorectal or coloanal anastomosis after ARR. However, DI does not rule out risks of more or less serious complications. A proximal intra-abdominal closed-loop ileostomy, the so-called virtual/ghost ileostomy (VI/GI), could limit the number of DIs and the associated morbidity. Materials and Methods: We performed a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. Meta-analysis was performed by use of RevMan [Computer program] Version 5.4. Results: The five included comparative studies (VI/GI or DI) covering an approximately 20-year study period (2008–2021). All included studies were observational ones and originated from European countries. Meta-analysis indicated VI/GI as significantly associated with lower short-term morbidity rates related to VI/GI or DI after primary surgery (RR: 0.21, 95% CI: 0.07–0.64, p = 0.006), fewer dehydration (RR: 0.17, 95% CI: 0.04–0.75, p = 0.02) and ileus episodes after primary surgery (RR: 0.20, 95% CI: 0.05–0.77, p = 0.02), fewer readmissions after primary surgery (RR: 0.17, 95% CI: 0.07–0.43, p = 0.0002) and readmissions after primary surgery plus stoma closure surgery (RR: 0.14, 95% CI: 0.06–0.30, p < 0.00001) than the DI group. On the contrary, no differences were identified in terms of AL after primary surgery, short-term morbidity after primary surgery, major complications (CD ≥ III) after primary surgery and length of hospital stay after primary surgery. Conclusions: Given the significant biases among meta-analyzed studies (small overall sample size and the small number of events analyzed, in particular), our results require careful interpretation. Further randomized, possibly multi-center trials may be of paramount importance in confirming our results.
Effects on Right Ventricular Function One Year after COVID-19-Related Pulmonary Embolism
Authors: Ilardi Federica , Crisci Mario , Calabrese Cecilia , Scognamiglio Anna , Arenga Fortunato , Manzo Rachele , Mariniello Domenica F. , Allocca Valentino , Annunziata Anna , D’Andrea Antonello , Merenda Raffaele , Monda Vittorio , Esposito Giovanni , Fiorentino Giuseppe
Published: May 2023

The aim of this study was to investigate the presence of subclinical cardiac dysfunction in recovered coronavirus disease 2019 (COVID-19) patients, who were stratified according to a previous diagnosis of pulmonary embolism (PE) as a complication of COVID-19 pneumonia. Out of 68 patients with SARS-CoV-2 pneumonia followed up for one year, 44 patients (mean age 58.4 ± 13.3, 70% males) without known cardiopulmonary disease were divided in two groups (PE+ and PE−, each comprising 22 patients) and underwent clinical and transthoracic echocardiographic examination, including right-ventricle global longitudinal strain (RV-GLS), and RV free wall longitudinal strain (RV-FWLS). While no significant differences were found in the left- or right-heart chambers’ dimensions between the two study groups, the PE+ patients showed a significant reduction in RV-GLS (−16.4 ± 2.9 vs. −21.6 ± 4.3%, p < 0.001) and RV-FWLS (−18.9 ± 4 vs. −24.6 ± 5.12%, p < 0.001) values compared to the PE- patients. According to the ROC-curve analysis, RV-FWLS < 21% was the best cut-off with which to predict PE diagnosis in patients after SARS-CoV-2 pneumonia (sensitivity 74%, specificity 89%, area under the curve = 0.819, p < 0.001). According to the multivariate logistic regression model, RV-FWLS < 21% was independently associated with PE (HR 34.96, 95% CI:3.24–377.09, p = 0.003) and obesity (HR 10.34, 95% CI:1.05–101.68, p = 0.045). In conclusion, in recovered COVID-19 patients with a history of PE+, there is a persistence of subclinical RV dysfunction one year after the acute phase of the disease, detectable by a significant impairment in RV-GLS and RV-FWLS. A reduction in RV-FWLS of lower than 21% is independently associated with COVID-related PE.
Effect of Psychosocial Interventions for Individuals Who Underwent Arthroscopy in Femoroacetabular Impingement: A Randomized Controlled Trial
Authors: You Mingke , Yang Shuoyao , Li Jian , Chen Gang
Published: May 2023

Purpose: The purpose of this protocol was to discover the connection between patients with non-surgical pain or other discomfort and their psychosocial status. Cognitive behavior therapy will be used, which we verified will determine the effect and feasibility of postoperative rehabilitation processes. Materials and Methods: This study will include 200 patients ranging from 18 to 60 years old who have underwent or will undergo FAI arthroscopy in the West China Hospital Sports Medicine Center from 2023 to 2026. A standardized prospective single-center parallel-group randomized controlled trial will be used for these participants. The participants will be divided into intervention (telephone versus face-to-face versus music versus floatation) and control groups. The follow-up periods will be measured pre-operatively, as well as postoperatively at 1, 3, and 6 months. The primary outcomes will include the modified Harris Hip Score (mHHS) and the Visual Analogic Score (VAS), and the secondary outcomes will include the range of motion (ROM), the Huaxi Emotional-distress Index (HEI), and the depression, anxiety, and stress scale (DASS-21 scale). Furthermore, the Patient Health Questionnaire-9 (PHQ-9) and a Short-Form 12 (SF-12) questionnaire will also be evaluated. Discussion: This study will evaluate the clinical and cost-effectiveness of different types of psychosocial-therapy-based rehabilitation methods designed to improve the quality of life of FAI patients with persistent symptoms.
A New Face of Fibrin-Associated Large B-Cell Lymphoma: Epstein–Barr Virus-Positive Breast Implant-Associated Diffuse Large B-Cell Lymphoma
Authors: Martin de Bustamante Jose Manuel , Mendoza Ana , López-Muñoz Samuel , García-Fernández Eugenia , Gómez-Prieto Pilar , Jiménez-Yuste Victor
Published: May 2023

Recently, there have been reports of what could be a new lymphoproliferative entity: breast implant-associated Epstein–Barr virus positive (EBV+) diffuse large B-cell lymphoma (EBV+ BIA-DLBCL). The new World Health Organization classification has categorized it as fibrin-associated large B-cell lymphomas (FA-LBCLs); therefore, it could be referred to as breast implant-associated fibrin-associated large B-cell lymphomas (BIA-FA-LBCLs). Although the association between breast implants and lymphomas has been known since the mid-1990s, it has been almost exclusively breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Here, we describe the first case of BIA-FA-LBCL at our center, with a literature review of the clinical features, diagnosis and treatment approach of this lymphoma. We also explore the differential diagnosis of BIA-FA-LBCL, highlighting the diagnostic challenges and the reasons that have led these lymphomas to being labeled as a new face of FA-LBCL.
Treatment Strategy of Fractured Osteochondroma in the Young Athlete’s Knee
Authors: Futani Hiroyuki , Kawaguchi Takayuki , Sawai Tatsuo , Tachibana Toshiya
Published: May 2023

Purpose: The main purpose of this study was to compare the clinical outcome of surgery versus observation in young athletes with fractured osteochondromas in the knee. The secondary aim was to evaluate displacement versus non-displacement fractures with regards to functional recovery. Methods: A retrospective analysis was performed in young athletes with fractures of osteochondromas in the knee. In the surgery group, resection of the osteochondromas was performed due to pain persisting at 4 weeks after injury. In contrast, patients with pain diminishing within 4 weeks after injury were observed without surgery. Displacement was defined as a gap widening of ≥1 mm between fragments, or translation of >50% of the distal fragment in relation to the proximal fragment. The time to return to the original sport was compared between groups. Results: The study sample was composed of 21 patients with a mean age of 12 years (range 9–16 years). There were 14 patients in the surgery group and 7 patients in the observation group. There were 10 patients (71%) with displacement and 4 patients (29%) with non-displacement fractures in the surgery group. Surgery was required more frequently in displacement than in non-displacement fracture patients (p = 0.01). The mean time to return to the original sport was 2.1 ± 1.1 and 7.2 ± 4.1 weeks in the surgery and observation groups, respectively (p < 0.01). Conclusions: Surgical excision is preferable in a young athlete’s knee presenting with displacement of fractured osteochondromas due to disabling symptoms and in order to allow them to return faster to original sports activities.
Mindful Coping Power Effects on Children’s Autonomic Nervous System Functioning and Long-Term Behavioral Outcomes
Authors: Boxmeyer Caroline L. , Stager Catanya G. , Miller Shari , Lochman John E. , Romero Devon E. , Powell Nicole P. , Bui Chuong , Qu Lixin
Published: May 2023

Mindful Coping Power (MCP) was developed to enhance the effects of the Coping Power (CP) preventive intervention on children’s reactive aggression by integrating mindfulness training into CP. In prior pre–post analyses in a randomized trial of 102 children, MCP improved children’s self-reported anger modulation, self-regulation, and embodied awareness relative to CP but had fewer comparative effects on parent- and teacher-reported observable behavioral outcomes, including reactive aggression. It was hypothesized that MCP-produced improvements in children’s internal awareness and self-regulation, if maintained or strengthened over time with ongoing mindfulness practice, would yield improvements in children’s observable prosocial and reactive aggressive behavior at later time points. To appraise this hypothesis, the current study examined teacher-reported child behavioral outcomes at a one-year follow-up. In the current subsample of 80 children with one-year follow-up data, MCP produced a significant improvement in children’s social skills and a statistical trend for a reduction in reactive aggression compared with CP. Further, MCP produced improvements in children’s autonomic nervous system functioning compared with CP from pre- to post-intervention, with a significant effect on children’s skin conductance reactivity during an arousal task. Mediation analyses found that MCP-produced improvements in inhibitory control at post-intervention mediated program effects on reactive aggression at the one-year follow-up. Within-person analyses with the full sample (MCP and CP) found that improvements in respiratory sinus arrhythmia reactivity were associated with improvements in reactive aggression at the one-year follow-up. Together, these findings indicate that MCP is an important new preventive tool to improve embodied awareness, self-regulation, stress physiology, and observable long-term behavioral outcomes in at-risk youth. Further, children’s inhibitory control and autonomic nervous system functioning emerged as key targets for preventive intervention.
Unravelling the Clinical Co-Morbidity and Risk Factors Associated with Agenesis of the Corpus Callosum
Authors: Smith Callum J. , Smith Zoey G. , Rasool Hania , Cullen Katie , Ghosh Meghana , Woolley Thomas E. , Uzun Orhan , Loh Ne Ron , Tucker David , Syed Yasir Ahmed
Published: May 2023

Agenesis of the Corpus Callosum (ACC) can result in multiple neurological deficits including social and behavioural issues. However, the underlying aetiology, clinical co-morbidity and the contributing risk factors remain elusive, resulting in inaccurate prognosis and delayed therapy. The main objective of this study was to comprehensively describe the epidemiology and clinical co-morbidity associated with patients diagnosed with ACC. The secondary objective was to identify the factors that contribute towards increased risk for ACC. For this, we analysed 22 years (1998–2020) of clinical data across the whole of Wales, UK collected through the Congenital Anomaly Register & Information Service (CARIS) and Public Health Wales (PHW). Our results demonstrate that complete ACC (84.1%) was the prevalent subtype, in comparison to partial ACC. Further, ventriculomegaly/hydrocephalus (26.37%) and ventricular septal defect (21.92%) were identified to be the most prevalent neural malformation (NM) and congenital heart disorder (CHD) in our cohort. Although 12.7% of subjects with ACC had both an NM and CHD, we found no significant association between them (χ2 (1, n = 220) = 3.84, p = 0.33). We found socioeconomic deprivation and increased maternal age contributed towards an increased risk for ACC. To the best of our knowledge, this study for the first time defines the clinical phenotypes and the factors that contribute to ACC within the Welsh population. These findings will be of value to both patients and healthcare professionals, who may take preventative or remedial measures.
Acute Bacterial Meningitis in Healthy Adult Patients: A Prospective Cohort Study
Authors: Pomar Virginia , Benito Natividad , Duch Pol , Colomé Marc , Rivera Alba , Domingo Pere
Published: May 2023

Spontaneous bacterial meningitis (BM) is more common among patients with underlying conditions, but its characteristics in previously healthy patients are not well described. We analyzed the time trends of BM in terms of characteristics, and outcomes in patients without comorbidities. Patients and methods: Single-center, prospective observational cohort study of 328 adults with BM hospitalized in a tertiary university hospital in Barcelona (Spain). We compared the features of infections diagnosed in 1982–2000 and 2001–2019. The main outcome measure was in-hospital mortality. Results: The median age of the patients increased from 37 to 45 years. Meningococcal meningitis significantly diminished (56% versus 31%, p < 0.000) whereas listerial meningitis increased (1.2% versus 8%, p = 0.004). Systemic complications were more common in the second period, although mortality did not vary significantly between periods (10.4% versus 9.2%). However, after adjusting for relevant variables, infection in the second period was associated with lower risk death. Conclusions: Adult patients without underlying comorbidities that developed BM in recent years were older and more likely to have pneumococcal or listerial infections and systemic complications. In-hospital death was less likely in the second period, after adjusting for risk factors of mortality.
When Characteristics of Clinical Trials Require Per-Protocol as Well as Intention-to-Treat Outcomes to Draw Reliable Conclusions: Three Examples
Authors: Scheim David E. , Aldous Colleen , Osimani Barbara , Fordham Edmund J. , Hoy Wendy E.
Published: May 2023

Under exceptional circumstances, including high rates of protocol non-compliance, per-protocol (PP) analysis can better indicate the real-world benefits of a medical intervention than intention-to-treat (ITT) analysis. Exemplifying this, the first randomized clinical trial (RCT) considered found that colonoscopy screenings were marginally beneficial, based upon ITT analysis, with only 42% of the intervention group actually undergoing the procedure. However, the study authors themselves concluded that the medical efficacy of that screening was a 50% reduction in colorectal cancer deaths among that 42% PP group. The second RCT found a ten-fold reduction in mortality for a COVID-19 treatment drug vs. placebo by PP analysis, but only a minor benefit by ITT analysis. The third RCT, conducted as an arm of the same platform trial as the second RCT, tested another COVID-19 treatment drug and reported no significant benefit by ITT analysis. Inconsistencies and irregularities in the reporting of protocol compliance for this study required consideration of PP outcomes for deaths and hospitalizations, yet the study coauthors refused to disclose them, instead directing inquiring scientists to a data repository which never held the study’s data. These three RCTs illustrate conditions under which PP outcomes may differ significantly from ITT outcomes and the need for data transparency when these reported or indicated discrepancies arise.
Multimodality Imaging and Biomarker Approach to Characterize the Pathophysiology of Heart Failure in Left Ventricular Non-Compaction with Preserved Ejection Fraction
Authors: Visoiu Ionela-Simona , Rimbas Roxana Cristina , Nicula Alina Ioana , Mihaila-Baldea Sorina , Magda Stefania Lucia , Mihalcea Diana Janina , Hayat Memis , Luchian Maria Luiza , Chitroceanu Alexandra Maria , Vinereanu Dragos
Published: May 2023

Left ventricular non-compaction (LVNC) with preserved ejection fraction (EF) is still a controverted entity. We aimed to characterize structural and functional changes in LVNC with heart failure with preserved EF (HFpEF). Methods: We enrolled 21 patients with LVNC and HFpEF and 21 HFpEF controls. For all patients, we performed CMR, speckle tracking echocardiography (STE), and biomarker assessment for HFpEF (NT-proBNP), for myocardial fibrosis (Galectin-3), and for endothelial dysfunction [ADAMTS13, von Willebrand factor, and their ratio]. By CMR, we assessed native T1 and extracellular volume (ECV) for each LV level (basal, mid, and apical). By STE, we assessed longitudinal strain (LS), globally and at each LV level, base-to-apex gradient, LS layer by layer, from epicardium to endocardium, and transmural deformation gradient. Results: In the LVNC group, mean NC/C ratio was 2.9 ± 0.4 and the percentage of NC myocardium mass was 24.4 ± 8.7%. LVNC patients, by comparison with controls, had higher apical native T1 (1061 ± 72 vs. 1008 ± 40 ms), diffusely increased ECV (27.2 ± 2.9 vs. 24.4 ± 2.5%), with higher values at the apical level (29.6 ± 3.8 vs. 25.2 ± 2.8%) (all p < 0.01); they had a lower LS only at the apical level (−21.4 ± 4.4 vs. −24.3 ± 3.2%), with decreased base-to-apex gradient (3.8 ± 4.7 vs. 6.9 ± 3.4%) and transmural deformation gradient (3.9 ± 0.8 vs. 4.8 ± 1.0%). LVNC patients had higher NT-proBNP [237 (156–489) vs. 156 (139–257) pg/mL] and Galectin-3 [7.3 (6.0–11.5) vs. 5.6 (4.8–8.3) ng/mL], and lower ADAMTS13 (767.3 ± 335.5 vs. 962.3 ± 253.7 ng/mL) and ADAMTS13/vWF ratio (all p < 0.05). Conclusion: LVNC patients with HFpEF have diffuse fibrosis, which is more extensive at the apical level, explaining the decrease in apical deformation and overexpression of Galectin-3. Lower transmural and base-to-apex deformation gradients underpin the sequence of myocardial maturation failure. Endothelial dysfunction, expressed by the lower ADAMTS13 and ADAMTS13/vWF ratio, may play an important role in the mechanism of HFpEF in patients with LVNC.
Recent Advancements in Electrospun Chitin and Chitosan Nanofibers for Bone Tissue Engineering Applications
Authors: Ganesh S Shree , Anushikaa Ramprasad , Swetha Victoria Venkadesan Sri , Lavanya Krishnaraj , Shanmugavadivu Abinaya , Selvamurugan Nagarajan
Published: May 2023

Treatment of large segmental bone loss caused by fractures, osteomyelitis, and non-union results in expenses of around USD 300,000 per case. Moreover, the worst-case scenario results in amputation in 10% to 14.5% of cases. Biomaterials, cells, and regulatory elements are employed in bone tissue engineering (BTE) to create biosynthetic bone grafts with effective functionalization that can aid in the restoration of such fractured bones, preventing amputation and alleviating expenses. Chitin (CT) and chitosan (CS) are two of the most prevalent natural biopolymers utilized in the fields of biomaterials and BTE. To offer the structural and biochemical cues for augmenting bone formation, CT and CS can be employed alone or in combination with other biomaterials in the form of nanofibers (NFs). When compared with several fabrication methods available to produce scaffolds, electrospinning is regarded as superior since it enables the development of nanostructured scaffolds utilizing biopolymers. Electrospun nanofibers (ENFs) offer unique characteristics, including morphological resemblance to the extracellular matrix, high surface-area-to-volume ratio, permeability, porosity, and stability. This review elaborates on the recent strategies employed utilizing CT and CS ENFs and their biocomposites in BTE. We also summarize their implementation in supporting and delivering an osteogenic response to treat critical bone defects and their perspectives on rejuvenation. The CT- and CS-based ENF composite biomaterials show promise as potential constructions for bone tissue creation.