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Obesity is a multifactorial, chronic, progressive and recurrent disease considered a public health issue worldwide and an important determinant of disability and death. In Spain, its current prevalence in the adult population is about 24% and an estimated prevalence in 2035 of 37%. Obesity increases the probability of several diseases linked to higher mortality such as diabetes, cardiovascular disease, hyperlipidemia, arterial hypertension, non-alcoholic fatty liver disease, several types of cancer, or obstructive sleep apnea. On the other hand, although the incidence of inflammatory bowel disease (IBD) is stabilizing in Western countries, its prevalence already exceeds 0.3%. Paralleling to general population, the current prevalence of obesity in adult patients with IBD is estimated at 15-40%. Obesity in patients with IBD could entail, in addition to its already known impact on disability and mortality, a worse evolution of the IBD itself and a worse response to treatments. The aim of this document, performed in collaboration by four scientific societies involved in the clinical care of severe obesity and IBD, is to establish clear and concise recommendations on the therapeutic possibilities of severe or typeIII obesity in patients with IBD. The document establishes general recommendations on dietary, pharmacological, endoscopic, and surgical treatment of severe obesity in patients with IBD, as well as pre- and post-treatment evaluation., (Copyright © 2024 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: Non-suicidal self-injury (NSSI) is highly prevalent among adolescents. However, knowledge about the possible factors that might precede and influence its development remains scarce., Objective: Our goal is to examine the impact of adverse childhood events, and more specifically of different types of childhood maltreatment (CM) in adolescent NSSI. This involves performing a systematic review and meta-analysis of the different CM subtypes (physical and emotional neglect, physical and emotional abuse, sexual abuse) in clinical and non-clinical samples of adolescents with NSSI., Participants and Methods: A digital search of the PsycInfo, PubMed and Web of Science platforms for articles published up to June 2022 was performed. The search terms were "self harm", "non-suicidal self-injury", "childhood maltreatment" and "adolescents"., Results: Forty-six articles that fit the research objectives were included in the study, which covered a total of 1,505,430 adolescents, of whom 560,337 belonged to the NSSI group, while 945,093 were in the control group. The results describe strong positive associations between all CM subtypes and NSSI, especially with emotional abuse (odds ratio [OR] 2.91, 95 % CI 2.37-3.56) and sexual abuse (OR 2.72, 95 % CI 2.12-3.48), in clinical and non-clinical samples of adolescents., Conclusions: The experience of CM, and especially emotional and/or sexual abuse, seems to be associated with a greater risk of developing NSSI in adolescence. Therefore, early identification and detection of children who have suffered or are suffering these forms of CM are of vital importance for instigating psychotherapeutic treatments that can minimize the risk of developing NSSI in adolescence., Competing Interests: Declaration of competing interest The autors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Skin identity is controlled by intrinsic features of the epidermis and dermis and their interactions. Modifying skin identity has clinical potential, such as the conversion of residual limb and stump (nonvolar) skin of amputees to pressure-responsive palmoplantar (volar) skin to enhance prosthesis use and minimize skin breakdown. Greater keratin 9 ( KRT9 ) expression, higher epidermal thickness, keratinocyte cytoplasmic size, collagen length, and elastin are markers of volar skin and likely contribute to volar skin resiliency. Given fibroblasts' capacity to modify keratinocyte differentiation, we hypothesized that volar fibroblasts influence these features. Bioprinted skin constructs confirmed the capacity of volar fibroblasts to induce volar keratinocyte features. A clinical trial of healthy volunteers demonstrated that injecting volar fibroblasts into nonvolar skin increased volar features that lasted up to 5 months, highlighting a potential cellular therapy.

A series of square-planar palladium and platinum compounds with cis -blocking phosphanes and terminal azobenzene ligands [M(dppp)(azo) 2 ](OTf) 2 (azo = CN(C 6 H 4 )-N═N-(C 6 H 4 )CN ( iso-cyano ), CN(C 6 H 4 )-N═N-(C 6 H 5 ) ( iso-Ph )) and [{M 2 (tpbz)}(azo) 4 ](OTf) 4 (azo = CN(C 6 H 4 )-N═N-(C 6 H 5 ) ( iso-Ph )) have been synthesized and fully characterized. Similarly to the uncoordinated ligands, the new coordination compounds have shown to be photochemically active with respect to their trans-to-cis isomerization process. Their cis-to-trans back spontaneous reaction have been studied as a function of solvent, temperature and pressure and the corresponding activation parameters determined in order to investigate the mechanism of these transformations. The results obtained are indicative of the operation of a rotational mechanism with no cooperativity between the azo ligands attached to the same metal. Density functional theory calculations have been carried out in order to estimate the relative energies of the different photoisomers for the theoretical interpretation of the experimental data.

Significance: The skin's mechanical properties are tightly regulated. Various pathologies can affect skin stiffness, and understanding these changes is a focus in tissue engineering. Ex vivo skin scaffolds are a robust platform for evaluating the effects of various genetic and molecular interactions on the skin. Transforming growth factor-beta ( TGF - β ) is a critical signaling molecule in the skin that can regulate the amount of collagen and elastin in the skin and, consequently, its mechanical properties., Aim: This study investigates the biomechanical properties of bio-engineered skin scaffolds, focusing on the influence of TGF - β , a signaling molecule with diverse cellular functions., Approach: The TGF - β receptor I inhibitor, galunisertib, was employed to assess the mechanical changes resulting from dysregulation of TGF - β . Skin scaffold samples, grouped into three categories (control, TGF - β -treated, and TGF - β + galunisertib-treated), were prepared in two distinct culture media-one with aprotinin (AP) and another without. Two optical elastography techniques, namely wave-based optical coherence elastography (OCE) and Brillouin microscopy, were utilized to quantify the biomechanical properties of the tissues., Results: Results showed significantly higher wave speed (with AP, p < 0.001 ; without AP, p < 0.001 ) and Brillouin frequency shift (with AP, p < 0.001 ; without AP, p = 0.01 ) in TGF - β -treated group compared with the control group. The difference in wave speed between the control and TGF - β + galunisertib with ( p = 0.10 ) and without AP ( p = 0.36 ) was not significant. Moreover, the TGF - β + galunisertib-treated group exhibited lower wave speed without and with AP and reduced Brillouin frequency shift than the TGF - β -treated group without AP, further strengthening the potential role of TGF - β in regulating the mechanical properties of the samples., Conclusions: These findings offer valuable insights into TGF - β -induced biomechanical alterations in bio-engineered skin scaffolds, highlighting the potential of OCE and Brillouin microscopy in the development of targeted therapies in conditions involving abnormal tissue remodeling and fibrosis., (© 2024 The Authors.)

Introduction: hemorrhoidal disease and anal fissure are the two most frequent entities within benign anal pathology, both of which have a negative impact on quality of life. To date, there is no specific questionnaire in Spanish to assess the impact on quality of life in patients suffering from these conditions., Objective: the aim of this study was to validate a questionnaire in Spanish for this purpose, adapting it to our daily clinical practice., Material and Methods: the HEMO-FISS-Quality of Life Questionnaire (HEMO-FISS-CdV) is the Spanish version of the original HEMO-FISS-Quality of Life Questionnaire (HEMO-FISS-QoL) by Abramowitz. The questionnaire consists of 23 items organized in four dimensions (physical, psychological, defecation and sexuality). The reliability of the new tool was assessed by determining internal consistency using Cronbach's alpha and Guttman's coefficient. It was also correlated with the quality of life questionnaire SF12 Health Questionnaire version 2 (SF12v2)., Results: the Cronbach's alpha obtained for our questionnaire (HEMO-FISS-CdV) was 0.951 (CI 95 % ± 0.016), with a range between 0.935 and 0.967. The Guttman two-half coefficient had a value of 0.910. Patients with internal hemorrhoids, anal fissure or both had higher values on the HEMO-FISS-CdV questionnaire than patients without internal hemorrhoids, and these differences were significant (p < 0.05)., Conclusion: both diseases have a negative impact on quality of life. The HEMO-FISS-CdV provides a tool in Spanish that easily and specifically assesses the impact of hemorrhoidal disease and anal fissure on quality of life.

Objectives: Patients with syndromic heritable thoracic aortic diseases (sHTAD) who underwent prophylactic aortic root replacement are at high risk of distal aortic events, but the underlying mechanisms are poorly understood. This prospective, longitudinal study aims to assess the impact of valve-sparing aortic root replacement (VSARR) on aortic fluid dynamics and biomechanics in these patients, and to examine whether they present altered haemodynamics or biomechanics prior to surgery compared to sHTAD patients with no indication for surgery (sHTAD-NSx) and healthy volunteers (HV)., Methods: Sixteen patients with Marfan or Loeys-Dietz syndrome underwent two 4D flow CMR studies before (sHTAD-preSx) and after VSARR (sHTAD-postSx). Two age, sex and BSA matched cohorts of 40 HV and 16 sHTAD-NSx patients with available 4D flow CMR, were selected for comparison. In-plane rotational flow (IRF), systolic flow reversal ratio (SFRR), wall shear stress (WSS), pulse wave velocity (PWV) and aortic strain were analysed in the ascending (AscAo) and descending aorta (DescAo)., Results: All patients with sHTAD presented altered haemodynamics and increased aortic stiffness (p<0.05) compared to HV, both in the AscAo (median PWV 7.4 in sHTAD-NSx; 6.8 in sHTAD-preSx; 4.9m/s in HV) and DescAo (median PWV 9.1 in sHTAD-NSx; 8.1 in sHTAD-preSx; 6.3m/s in HV). Patients awaiting VSARR had markedly reduced in-plane (median IRF -2.2 vs 10.4 cm 2 /s in HV, p=0.001), but increased through-plane flow rotation (median SFRR 7.8 vs 3.8% in HV, p=0.002), and decreased WSS (0.36 vs 0.47N/m 2 in HV, p=0.004) in the proximal DescAo. After VSARR, proximal DescAo in-plane rotational flow (p=0.010) and circumferential WSS increased (p=0.011), no longer differing from HV, but through-plane rotational flow, axial WSS and stiffness remained altered. Patients in which aortic tortuosity was reduced after surgery showed greater post-surgical increase in IRF compared to those in which tortuosity increased (median IRF increase 18.1 vs 3.3cm²/s, p=0.047). Most AscAo flow alterations were restored to physiological values after VSARR., Conclusions: In patients with sHTAD, VSARR partially restores downstream fluid dynamics to physiological levels. However, some flow disturbances and increased stiffness persist in the proximal DescAo. Further longitudinal studies are needed to evaluate whether persistent alterations contribute to post-surgical risk., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Arturo Evangelista reports financial support was provided by Carlos III Health Institute. Gisela Teixido-Tura reports financial support was provided by Carlos III Health Institute. Jose Rodriguez-Palomares reports financial support was provided by Spanish Ministry of Science, Innovation and Universities. Jose Rodriguez-Palomares reports financial support was provided by Spanish Society of Cardiology. Gisela Teixido-Tura reports financial support was provided by Spanish Society of Cardiology. Andrea Guala reports financial support was provided by La Caixa Foundation. Juan Garrido-Oliver reports financial support was provided by Secretaria d’Universitats i Recerca del Departament de Recerca i Universitats de la Generalitat de Catalunya i del Fons Europeu Social Plus. Ignacio Ferreira Gonzalez reports financial support was provided by Spanish Ministry of Science, Innovation and Universities. Kevin M Johnson reports a relationship with General Electric Healthcare that includes: non-financial support. Oliver Wieben reports a relationship with General Electric Healthcare that includes: non-financial support. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Dental implants offer an effective solution for partial and total edentulism, but mechanical and biological complications exist. Furthermore, high occlusal loads challenge implants and lead to potential failures. This review focuses on impact testing in contrast to incremental and static tests, an underexplored aspect of assessing daily loads on implants, bringing to light potential complications. The review examines studies employing impact forces to assess implant-supported prostheses and natural teeth properties, highlighting their significance in dental research. A systematic search following PRISMA guidelines identified 21 relevant articles out of 224, emphasizing studies employing impact forces to evaluate various aspects of dental implant treatments. The diverse applications of impact forces in dental research were categorized into tooth structure, restorative materials, interface evaluation, implant properties, and finite element models. Some studies showed the significance of impact forces in assessing stress distribution, shock absorption, and biomechanical response. Impact testing is a critical tool for understanding the daily forces on implants. Despite diverse experimental approaches, a lack of standardized protocols complicates the systematization of the results and, therefore, the conclusions. This review highlights the need for consistent methodologies in impact testing studies for future research on implant-supported prostheses.

Spontaneous preterm birth (PTB) affects around 11% of births, posing significant risks to neonatal health due to the inflammation at the fetal-maternal interface (FMi). This inflammation disrupts immune tolerance during pregnancy, often leading to PTB. While organ-on-a-chip (OOC) devices effectively mimic the physiology, pathophysiology, and responses of FMi, their relatively low throughput limits their utility in high-throughput testing applications. To overcome this, we developed a three-dimensional (3D)-printed model that fits in a well of a 96-well plate and can be mass-produced while also accurately replicating FMi, enabling efficient screening of drugs targeting FMi inflammation. Our model features two cell culture chambers (maternal and fetal cells) interlinked via an array of microfluidic channels. It was thoroughly validated, ensuring cell viability, metabolic activity, and cell-specific markers. The maternal chamber was exposed to lipopolysaccharides (LPS) to induce an inflammatory state, and proinflammatory cytokines in the culture supernatant were quantified. Furthermore, the efficacy of anti-inflammatory inhibitors in mitigating LPS-induced inflammation was investigated. Results demonstrated that our model supports robust cell growth, maintains viability, and accurately mimics PTB-associated inflammation. This high-throughput 3D-printed model offers a versatile platform for drug screening, promising advancements in drug discovery and PTB prevention.

Background: Trimodulin (human polyvalent immunoglobulin [Ig] M ~ 23%, IgA ~ 21%, IgG ~ 56% preparation) has previously been associated with a lower mortality rate in a subpopulation of patients with severe community-acquired pneumonia on invasive mechanical ventilation (IMV) and with clear signs of inflammation. The hypothesis for the ESsCOVID trial was that trimodulin may prevent inflammation-driven progression of severe coronavirus disease 2019 (COVID-19) to critical disease or even death., Methods: Adults with severe COVID-19 were randomised to receive intravenous infusions of trimodulin or placebo for 5 consecutive days in addition to standard of care. The primary efficacy endpoint was a composite of clinical deterioration (Days 6-29) and 28-day all-cause mortality (Days 1-29)., Results: One-hundred-and-sixty-six patients received trimodulin (n = 84) or placebo (n = 82). Thirty-three patients died, nine during the treatment phase. Overall, 84.9% and 76.5% of patients completed treatment and follow-up, respectively. The primary efficacy endpoint was reported in 33.3% of patients on trimodulin and 34.1% of patients on placebo (P = 0.912). No differences were observed in the proportion of patients recovered on Day 29, days of invasive mechanical ventilation, or intensive care unit-free days. Rates of treatment-emergent adverse events were comparable. A post hoc analysis was conducted in patients with early systemic inflammation by excluding those with high CRP (> 150 mg/L) and/or D-dimer (≥ 3 mg/L) and/or low platelet counts (< 130 × 10 9 /L) at baseline. Forty-seven patients in the trimodulin group and 49 in the placebo group met these criteria. A difference of 15.5 percentage points in clinical deterioration and mortality was observed in favour of trimodulin (95% confidence interval: -4.46, 34.78; P = 0.096)., Conclusion: Although there was no difference in the primary outcome in the overall population, observations in a subgroup of patients with early systemic inflammation suggest that trimodulin may have potential in this setting that warrants further investigation. ESSCOVID WAS REGISTERED PROSPECTIVELY AT CLINICALTRIALS.GOV ON OCTOBER 6, 2020.: NCT04576728., (© 2024. The Author(s).)

Family GH1 glycosyl hydrolases are ubiquitous in prokaryotes and eukaryotes and are utilized in numerous industrial applications, including bioconversion of lignocelluloses. In this study, hyperacidophilic archaeon Cuniculiplasma divulgatum (S5T=JCM 30642T) was explored as a source of novel carbohydrate-active enzymes. The genome of C. divulgatum encodes three GH1 enzyme candidates, from which CIB12 and CIB13 were heterologously expressed and characterized. Phylogenetic analysis of CIB12 and CIB13 clustered them with β-glucosidases from genuinely thermophilic archaea including Thermoplasma acidophilum, Picrophilus torridus, Sulfolobus solfataricus, Pyrococcus furiosus, and Thermococcus kodakarensis. Purified enzymes showed maximal activities at pH 4.5-6.0 (CIB12) and 4.5-5.5 (CIB13) with optimal temperatures at 50°C, suggesting a high-temperature origin of Cuniculiplasma spp. ancestors. Crystal structures of both enzymes revealed a classical (α/β)8 TIM-barrel fold with the active site located inside the barrel close to the C-termini of β-strands including the catalytic residues Glu204 and Glu388 (CIB12), and Glu204 and Glu385 (CIB13). Both enzymes preferred cellobiose over lactose as substrates and were classified as cellobiohydrolases. Cellobiose addition increased the biomass yield of Cuniculiplasma cultures growing on peptides by 50%, suggesting that the cellobiohydrolases expand the carbon substrate range and hence environmental fitness of Cuniculiplasma., (© The Author(s) 2024. Published by Oxford University Press on behalf of FEMS.)

Background : Body dissatisfaction (BD) has been consistently linked to adverse consequences on mental health and overall well-being, and is recognized as a significant contributing factor in the initiation and persistence of eating disorders (EDs). Empirical evidence has demonstrated that an elevated body mass index (BMI) and media influence and pressure about a thin ideal heighten the risk of subsequent BD. Moreover, suggestibility, a propensity to accept and act upon messages without critical evaluation, has been shown to be positively associated with greater susceptibility to the influence of sociocultural messages that endorse the thin ideal. This study aimed to assess whether suggestibility moderates the association between BMI and BD in women. Methods : A total of 117 women completed assessments using the Eating Disorder Inventory-3 (EDI-3) BD subscale and the Suggestibility Inventory, which encompasses a general suggestibility index and a subscale that evaluates susceptibility to influence by others. We conducted moderation analyses employing the PROCESS macro, with BMI as the central predictor, BD as the outcome variable, and suggestibility and its subscale as moderators. Results : The findings revealed statistically significant positive moderating interactions for both the general suggestibility index and susceptibility to influence by others. Specifically, women who exhibited high levels of suggestibility and susceptibility to influence by others demonstrated a more pronounced increase in BD as their BMI increased. Conclusions: These outcomes are in line with the sociocultural model of EDs, suggesting that greater susceptibility to external influences amplifies the impact of societal pressures to conform to thin ideals.

A mesophilic, hyperacidophilic archaeon, strain M1 T , was isolated from a rock sample from Vulcano Island, Italy. Cells of this organism were cocci with an average diameter of 1 µm. Some cells possessed filaments. The strain grew in the range of temperatures between 15 and 52 °C and pH 0.5-4.0 with growth optima at 40 °C and pH 1.0. Strain M1 T was aerobic and chemoorganotrophic, growing on complex substrates, such as casamino acids, trypticase, tryptone, yeast and beef extracts. No growth at expenses of oxidation of elemental sulphur or reduced sulphur compounds, pyrite, or ferrous sulphate was observed. The core lipids were glycerol dibiphytanyl glycerol tetraether lipids (membrane spanning) with 0 to 4 cyclopentane moieties and archaeol, with trace amounts of hydroxy archaeol. The dominant quinone was MK-7 : 7. The genome size of M1 T was 1.67 Mbp with a G+C content of 39.76 mol%, and both characteristics were well within the common range for Thermoplasmatales . The phylogenetic analysis based on 16S rRNA gene sequence placed the strain M1 T within the order Thermoplasmatales with sequence identities of 90.9, 90.3 and 90.5% to the closest SSU rRNA gene sequences from organisms with validly published names, Thermoplasma acidophilum , Thermoplasma volcanium and Thermogymnomonas acidicola , respectively. Based on the results of our genomic, phylogenetic, physiological and chemotaxonomic studies, we propose that strain M1 T (=DSM 116605 T =JCM 36570 T ) represents a new genus and species, Oxyplasma meridianum gen. nov., sp. nov., within the order Thermoplasmatales .

Irritability worsens prognosis and increases mortality in individuals with Attention-Deficit and Hyperactivity Disorder (ADHD) and/or Borderline Personality Disorder (BPD). However, treatment options are still insufficient. The aim of this randomized, double blind, placebo-controlled study was to investigate the superiority of a synbiotic over placebo in the management of adults with ADHD and/or BPD and high levels of irritability. The study was conducted between February 2019 and October 2020 at three European clinical centers located in Hungary, Spain and Germany. Included were patients aged 18-65 years old diagnosed with ADHD and/or BPD and high levels of irritability (i.e., an Affectivity Reactivity Index (ARI-S) ≥ 5, plus a Clinical Global Impression-Severity Scale (CGI-S) score ≥ 4). Subjects were randomized 1(synbiotic):1(placebo); the agent was administered each day, for 10 consecutive weeks. The primary outcome measure was end-of-treatment response (i.e., a reduction ≥ 30 % in the ARI-S total score compared to baseline, plus a Clinical Global Impression-Improvement (CGI-I) total score of < 3 (very much, or much improved) at week 10). Between-treatment differences in secondary outcomes, as well as safety were also investigated. Of the 231 included participants, 180 (90:90) were randomized and included in the intention-to-treat-analyses. Of these, 117 (65 %) were females, the mean age was 38 years, ADHD was diagnosed in 113 (63 %), BPD in 44 (24 %), both in 23 (13 %). The synbiotic was well tolerated. At week 10, patients allocated to the synbiotic experienced a significantly higher response rate compared to those allocated to placebo (OR: 0.2, 95 % CI:0.1 to 0.7; P = 0.01). These findings suggest that that (add-on) treatment with a synbiotic may be associated with a clinically meaningful improvement in irritability in, at least, a subgroup of adults with ADHD and/or BPD. A superiority of the synbiotic over placebo in the management of emotional dysregulation (-3.6, 95 % CI:-6.8 to -0.3; P = 0.03), emotional symptoms (-0.6, 95 % CI:-1.2 to -0.05; P = 0.03), inattention (-1.8, 95 % CI: -3.2 to -0.4; P = 0.01), functioning (-2.7, 95 % CI: -5.2 to -0.2; P = 0.03) and perceived stress levels (-0.6, 95 % CI: -1.2 to -0.05; P = 0.03) was also suggested. Higher baseline RANK-L protein levels were associated with a significantly lower response rate, but only in the synbiotic group (OR: 0.1, 95 % CI: -4.3 to - 0.3, P = 0.02). In the placebo group, higher IL-17A levels at baseline were significantly associated with a higher improvement in in particular, emotional dysregulation (P = 0.04), opening a door for new (targeted) drug intervention. However, larger prospective studies are warranted to confirm the findings. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03495375., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Arteaga-Henríquez reported receiving personal fees from Janssen outside the submitted work. Dr. Bitter reported receiving consulting fees from Gedeon Richter and Janssen/Janssen-Cilag; speaker’s honoraria from Gedeon Richter, Hikma Pharmaceuticals, Janssen/Janssen-Cilag, KRKA, Lundbeck, and Medichem Pharmaceuticals Inc. by Unilab; research grant from Gedeon Richter; royalties from Oxford University Press. Dr. Reif reported receiving personal fees from Medice, Shire/Takeda, SAGE/Biogen, Boehringen Ingelheimm, Janssen, and Cyclerion outside the submitted work. Dr. Ramos-Quiroga reported being on the speakers’ bureau and/or having acted as a consultant for Janssen Cilag, Novartis, Shire, Takeda, Bial, Shionogi, Sincrolab, Novartis, BMS, Medice, Rubió, Uriach, Technofarma and Rafo, received travel awards (air tickets + hotel) from Janssen-Cilag, Rubió, Shire, Takeda, Shionogi, Bial and Medice for taking part in psychiatric meetings, outside the submitted work. No other disclosures were reported., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

In 1977 Weiss and Grimes, by means of mass spectrometry and 1 H and 11 B NMR spectroscopy, proposed two structures (I and II) for the ferraborane (η 5 -C 5 H 5 )Fe(B 5 H 10 ), isoelectronic with ferrocene. In this work, by means of high-level quantum-chemical computations, we confirm the experimental structures of the two isomers with their corresponding energies, and assign the reported 1 H and 11 B NMR chemical shifts. A striking result from this study is the planarization (3D→2D) of the B 5 H 10 - ligand - an unknown isolated anion, isoelectronic with aromatic cyclopentadienyl anion C 5 H 5 - - when attached to the (η 5 -C 5 H 5 )Fe + moiety, thus resulting in a more stable ferraborane isomer II., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

Background and Objectives: Individuals with epilepsy have increased risk of suicidal ideation (SI) and behaviors when compared with the general population. This relationship has remained largely unexplored in adolescents. We investigated the prevalence of suicidality in adolescents with newly diagnosed focal epilepsy within 4 months of treatment initiation and over the following 36 months., Methods: This was a post hoc analysis of the enrollment and follow-up data from the Human Epilepsy Project, an international, multi-institutional study that enrolled participants between 2012 and 2017. Participants enrolled were 11-17 years of age within 4 months of treatment initiation for focal epilepsy. We used data from the Columbia Suicide Severity Rating Scale (C-SSRS), administered at enrollment and over the 36-month follow-up period, along with data from medical records., Results: A total of 66 adolescent participants were enrolled and completed the C-SSRS. At enrollment, 14 (21%) had any lifetime SI and 5 (8%) had any lifetime suicidal behaviors (SBs). Over the following 36 months, 6 adolescents reported new onset SI and 5 adolescents reported new onset SB. Thus, the lifetime prevalence of SI within this population increased from 21% to 30% (14-20 adolescents), and the lifetime prevalence of SB increased from 8% to 15% (5-10)., Discussion: The prevalence of suicidality in adolescents with newly diagnosed focal epilepsy reported in our study is consistent with previous findings of significant suicidality observed in epilepsy. We identify adolescents as an at-risk population at the time of epilepsy diagnosis and in the following years.

The rat has long served as a valuable animal model in implant dentistry and orthopedics, particularly in studying the interactions between biomaterials and bone tissue. The rat's tibia is frequently chosen due to its easy surgical access through thin tissue layers (skin and muscle) and the flattened shape of its medial face, facilitating the surgical insertion of intraosseous devices. Additionally, this model enables the induction of specific diseases, mimicking various clinical conditions to assess biological responses to different implant conditions like geometry, surface texture, or biological cues. However, despite its robust cortical structure, certain intraosseous devices may require adaptations in design and size for successful implantation. Therefore, establishing standardized surgical methods for manipulating both soft and hard tissues in the implantation region is essential for ensuring proper implant or screw device placement, particularly in fields like implant dentistry and orthopedics. This study included eighty Sprague Dawley rats divided into two groups based on their respective diseases: Group 1 with osteoporosis and Group 2 with Type 2 Diabetes. Implantations were performed at 4 weeks and 12 weeks, with the same surgeon following a consistent surgical technique. A positive biological response was observed, indicating complete osseointegration of all implants placed. These results validate the success of the surgical protocol, which can be replicated for other studies and serve as a benchmark for the biomaterials community. Notably, osseointegration values remained stable at both 4 weeks and 12 weeks for both disease models, demonstrating a durable integration of the implant over time and emphasizing the establishment of an intimate bone connection as early as 4 weeks.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely tied to obesity. The degree ranges from steatosis (MASL) and steatohepatitis (MASH) to liver cirrhosis. PCSK9 controls cholesterol and lipid particle transport to the liver. PCSK9 might interfere with the pathophysiology of MASLD and bariatric surgery (BS) outcomes of patients with MASLD., Objectives: Evaluate the relationship between serum and hepatic PCSK9 levels with the degree of MASLD and the metabolic outcome of BS., Setting: University Hospital, Spain., Methods: A total of 110 patients with obesity undergoing BS were classified according to liver histology as controls, MAS, and MASH. PCSK9 levels in serum were measured before and 6 months after BS using enzyme-linked immunosorbent assay. PCSK9 protein and mRNA levels in liver tissue were analyzed by immunohistochemistry and reverse transcriptase-polymerase chain reaction, respectively., Results: Hepatic PCSK9 protein levels were diminished in MASL and MASH compared with patients without MASLD and showed a strong negative association with MASLD severity scores. Liver PCSK9 mRNA was higher in MASH compared with controls and MASL and showed positive associations with MASLD severity scores. There were no differences in serum PCSK9 pre or postBS between the groups. Pre- and postsurgery serum PCSK9 positively correlated with cholesterol fold-changes and body mass index (BMI), cholesterol, and low-density lipoprotein -cholesterol fold-changes, respectively. PCSK9 fold-change positively correlated with BMI changes and was the sole variable explaining BMI fold changes in a regression model., Conclusions: PCSK9 mRNA and protein in the liver might be associated with the degree of MASLD. Serum PCSK9 may be associated with cholesterol and/or BMI fold changes. Serum changes of PCSK9 after BS could explain BMI loss outcome., (Copyright © 2024 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Surgical ciliated cysts occur mainly in the maxillae after radical maxillary sinus surgery; they rarely develop in the mandible. This study aims to gather information on all the characteristics of patients suffering from mandibular surgical ciliated cysts. This article also reports two new cases., Methods: PubMed, Google Scholar and the International Clinical Trials Registry Platform were explored until 13 December 2022 for articles regarding mandibular surgical ciliated cysts. Maxillary ciliated cysts were excluded., Results: Fourteen original articles were included in a total of 16 cases. Maxillofacial surgeries are the first aetiology (94.4%). Surgical ciliated cysts of the mandibular region show a 1.25:1 male-to-female ratio with a protracted time to diagnosis (range: 2-56 years). Most patients are symptomatic (77.8%). Typically, radiology shows a radiolucency lesion (88.9%) and histology describes pseudostratified ciliated columnar epithelium. Enucleation has always been described as the treatment., Discussion: All results were case reports, thus a low level of evidence studies. Mandibular surgical ciliated cysts should be considered in patients presenting a mandibular swelling or radiolucency lesion with a maxillofacial surgery history. Meticulous surgical techniques can aid in the prevention of this lesion., (© 2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.)

Objectives: This study assessed the transparency and replicability of exercise-based interventions following bariatric surgery by evaluating the content reporting of exercise-based clinical trials., Design: The study design of the present article is a systematic review., Data Sources: PubMed, Scopus, Web of Sciences, PsycINFO, and Cochrane were searched from their inception to May 2023., Eligibility Criteria: Eligible studies were clinical trials including exercise interventions in participants following bariatric surgery. There were 28 unique exercise interventions. Two independent reviewers applied the exercise prescription components of Frequency, Intensity, Time, and Type (FITT; four items) and the Consensus on Exercise Reporting Template (CERT; 19 items). Exercise interventions were organized into four major exercise components: aerobic training, resistance training, concurrent training, and "others.", Results: The FITT assessment revealed that 53% of the trials did not report the training intensity, whereas 25% did not indicate the duration of the major exercise component within the training session. The mean CERT score was 5 out of a possible score of 19. No studies reached CERT score >10, while 13 out of the total 19 CERT items were not adequately reported by ≥75% of the studies., Conclusion: This study highlights that the exercise interventions following bariatric surgery are poorly reported, non-transparent, and generally not replicable. This precludes understanding the dose-response association of exercise and health-related effects and requires action to improve this scientific field., (© 2024 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Chronic pain and depression are frequently comorbid conditions associated with significant health care and social costs. This study examined the cost-utility and cost-effectiveness of videoconference-based group forms of Acceptance and Commitment Therapy (ACT) and Behavioral Activation Therapy for Depression (BATD), as a complement to treatment-as-usual (TAU), for patients with chronic low back pain (CLBP) plus depressive symptoms, compared to TAU alone. A trial-based economic evaluation (n = 234) was conducted from a governmental and health care perspective with a time horizon of 12 months. Primary outcomes were the Brief Pain Inventory-Interference Scale (BPI-IS) and Quality Adjusted Life Year. Compared to TAU, ACT achieved a significant reduction in total costs (d = .47), and BATD achieved significant reductions in indirect (d = .61) and total costs (d = .63). Significant improvements in BPI-IS (d = .73 and d = .66, respectively) and Quality Adjusted Life Year scores (d = .46 and d = .28, respectively) were found in ACT and BATD compared to TAU. No significant differences in costs and outcomes were found between ACT and BATD. In the intention-to-treat analyses, from the governmental and health care perspective, no significant differences in cost reduction and incremental effects were identified in the comparison between ACT, BATD, and TAU. However, in the complete case analysis, significant incremental effects of ACT (∆BPI-IS = -1.57 and -1.39, respectively) and BATD (∆BPI-IS = -1.08 and -1.04, respectively) compared with TAU were observed. In the per-protocol analysis, only the significant incremental effects of ACT (∆BPI-IS = -1.68 and -1.43, respectively) compared to TAU were detected. In conclusion, ACT and BATD might be efficient options in the management of CLBP plus comorbid depression symptoms as compared to usual care. However, no clear difference was found in the comparison between the 2 active therapies regarding cost-effectiveness or cost-utility. PERSPECTIVE: The economic evaluation of psychological therapies for the management of complex conditions can be used in decision-making and resource allocation. This study provides evidence that ACT and BATD are more effective and involve a greater reduction in costs than usual care in the management of CLBP plus comorbid depressive symptoms. TRIAL NUMBER: NCT04140838., (Copyright © 2024 United States Association for the Study of Pain, Inc. Published by Elsevier Inc. All rights reserved.)

Social cognition (SC) and executive function (EF) have been described as important variables for social functioning and recovery of patients with psychosis. However, the relationship between SC and EF in first-episode psychosis (FEP) deserves further investigation, especially focusing on gender differences., Aims: To investigate the relationship between EF and different domains of SC in FEP patients and to explore gender differences in the relationship between these domains., Methods: A cross-sectional study of 191 patients with new-onset psychosis recruited from two multicenter clinical trials. A comprehensive cognitive battery was used to assess SC (Hinting Task, Face Test and IPSAQ) and EF (TMT, WSCT, Stroop Test and digit span - WAIS-III). Pearson correlations and linear regression models were performed., Results: A correlation between Theory of Mind (ToM), Emotional Recognition (ER) and EF was found using the complete sample. Separating the sample by gender showed different association profiles between these variables in women and men., Conclusions: A relationship between different domains of SC and EF is found. Moreover, women and men presented distinct association profiles between EF and SC. These results should be considered in order to improve the treatment of FEP patients and designing personalized interventions by gender., (Copyright © 2024 Sociedad Española de Psiquiatría y Salud Mental (SEPSM). Published by Elsevier España S.L.U. All rights reserved.)

This work provides psychometric data on the validity and reliability of the Spanish adaptation of the Pet Bereavement Questionnaire (PBQ), as well as information on the intensity of bereavement in the Spanish population. The study evaluated 333 Spanish participants of legal age (M = 31.5; SD = 11.6), mostly women (76.3%). Confirmatory factor analysis (CFA) tested the adequacy of three different structures present in literature, finding better fit indexes for a model that kept the original three-factor structure (grief, guilt, and anger) but rearranged 2 of the 16 items. Around 70% of participants reported signs of intense bereavement on the grief scale, with higher means among women. The results confirm adequate psychometric qualities of the PBQ, offering healthcare professionals a tool to evaluate bereavement intensity after the loss of a companion animal in Spanish samples.

Purpose: This study aimed to examine health-related quality of life (HRQoL) in head and neck cancer patients at 1 and 5 years after successful treatment of their tumors, and to explore the usefulness of 2 instruments for assessing the need of dental care services., Methods: This cross-sectional pilot study included 20 adult patients with head and neck cancer who completed the Functional Assessment of Cancer Therapy-Head and Neck (FACT H&N) Symptom Index and the European Organization for Research and Treatment of Cancer Quality of Life Head and Neck Module (EORTC QLQ-H&N43) after 1 and 5 years of treatment., Results: Mean (standard deviation, SD) scores of the FACT H&N Symptom Index were higher (better HRQoL) at 5 years than at 1 year (24.1 [4.4] vs. 21.1 [6.4]; p = 0.236). Only three of the ten items of FACT H&N (swallow, pain in mouth/throat or neck, and solid foods) evaluated oral health. In the EORTC QLQ-H&N43 questionnaire, scores were lower at 5 years (better HRQoL) in almost all multi- and single-item symptoms. This questionnaire includes four multi-item scales (pain in the mouth, social eating, swallowing, and problems with teeth) measuring dental and orthodontic needs., Conclusion: HRQoL in patients with head and neck cancer improved with the length of follow-up. The EORTC QLQ-H&N43 has more items addressing oral health compared to the FACT H&N Symptom Index and may be more adequate to assess the need of dental therapy in clinical practice., (© 2024. The Author(s).)

Context: Metabolic dysfunction-associated steatotic liver disease (MASLD) is characterized by the intracellular lipid accumulation in hepatocytes. Excess caloric intake and high-fat diets are considered to significantly contribute to MASLD development., Objective: To evaluate the hepatic and serum fatty acid (FA) composition in patients with different stages of MASLD, and their relationship with FA dietary intake and MASLD-related risk factors., Methods: This was a case-control study in patients with obesity undergoing bariatric surgery at a university hospital between January 2020 and December 2021. Participants were distributed in 3 groups: no MASLD (n = 26), steatotic liver disease (n = 33), and metabolic dysfunction-associated steatohepatitis (n = 32). Hepatic and serum FA levels were determined by gas chromatography-mass spectrometry. Nutritional status was evaluated using validated food frequency questionnaires. The hepatic expression of genes involved in FA metabolism was analyzed by reverse transcription quantitative polymerase chain reaction., Results: The hepatic, but not serum, FA profiles were significantly altered in patients with MASLD compared with those without MASLD. No differences were observed in FA intake between the groups. Levels of C16:0, C18:1, and the C18:1/C18:0 ratio were higher, while C18:0 levels and C18:0/C16:0 ratio were lower in patients with MASLD, being significantly different between the 3 groups. Hepatic FA levels and ratios correlated with histopathological diagnosis and other MASLD-related parameters. The expression of genes involved in the FA metabolism was upregulated in patients with MASLD., Conclusion: Alterations in hepatic FA levels in MASLD patients were due to enhancement of de novo lipogenesis in the liver., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Patient and public involvement (PPI) has become an essential part of health research. There is a need for genuine involvement in order to ensure that research is relevant to patients. This can then improve the quality, relevance, and impact of health research, while at the same time reducing wasted research and in doing so bringing science and society closer together. Despite the increasing attention for this involvement, it is not yet common practice to report on proposed activities. An article reporting planned PPI could provide guidance and inspiration for the wider academic community in future activities. Therefore, this current article aims to describe the way in which PPI principles are incorporated in the research project called "Quality of Life in Oncology: measuring what matters for cancer patients and survivors in Europe (EUonQoL)." This project aims to develop a new set of questionnaires to enable cancer patients to assess their quality of life, entitled the EUonQoL-Kit., Methods: The first step is to recruit cancer patients and their informal caregivers as co-researchers in order to train them to collaborate with the researchers. Based on their skills and preferences, they are then assigned to several of the project's work packages. Their individual roles, tasks, and responsibilities regarding the work packages, to which they have been assigned, are evaluated and adapted when necessary. The impact of their involvement is evaluated by both the researchers and co-researchers., Discussion: PPI is a complex and dynamic process. As such, the overall structure of the research may be defined while at the same time leaving room for certain aspects to be filled in later. Our research is, we believe, relevant as co-researcher involvement in such a large European project as EUonQoL is a new development., (© 2024. The Author(s).)

This study aimed to investigate obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: 15 rats were fed with a standard diet (SD-rats), and 15 rats were fed with a high-fat diet (HFD-rats). After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD-rats gained significantly more weight (55.8% vs. 29.2%; p < 0.001) and albuminuria (10,384.04 ng/mL vs. 5845.45 ng/mL; p < 0.001) compared to SD-rats. HFD-rats exhibited early stages of ORG, with predominant mesangial matrix increase and podocyte hypertrophy (PH). These lesions correlated with differentially expressed (DE) genes and miRNAs. Functional analysis showed that miR-205, which was DE in both the kidneys and urine of HFD-rats, negatively regulated the PTEN gene, promoting lipid endocytosis in podocytes. The downregulation of PTEN was proved through a higher PTEN/nephrin ratio in the SD-rats and the presence of lipid vacuoles in HFD-podocytes. This study has found a specific targetome of miRNAs and gene expression in early stages of ORG. Also, it emphasizes the potential value of miR-205 as a urinary biomarker for detecting podocyte injury in ORG, offering a tool for early diagnosis, and opening new avenues for future therapeutic research of obesity-related glomerulopathy.

Context: A Conceptual DFT (CDFT) study has been carry out to analyse the coupling reactions of the simplest amine (CH 3 NH 2 ), alcohol (CH 3 OH), and thiol (CH 3 SH) compounds with CO 2 to form the corresponding adducts CH 3 NHCO 2 H, CH 3 OCO 2 H, and CH 3 SCO 2 H. The reaction mechanism takes place in a single step comprising two chemical events: nucleophilic attack of the non-metallic heteroatoms to CO 2 followed by hydrogen atom transfer (HAT). According to our calculations, the participation of an additional nucleophilic molecule as HAT assistant entails important decreases in activation electronic energies. In such cases, the formation of a six-membered ring in the transition state (TS) reduces the angular stress with respect to the non-assisted paths, characterised by four-membered ring TSs. Through the analysis of the energy and reaction force profiles along the intrinsic reaction coordinate (IRC), the ratio of structural reorganisation and electronic rearrangement for both activation and relaxation energies has been computed. In addition, the analysis of the electronic chemical potential and reaction electronic flux profiles confirms that the highest electronic activity as well as their changes take place in the TS region. Finally, the distortion/interaction model using an energy decomposition scheme based on the electron density along the reaction coordinate has been carried out and the relative energy gradient (REG) method has been applied to identify the most important components associated to the barriers., Methods: The theoretical calculation were performed with Gaussian-16 scientific program. The B3LYP-D3(BJ)/aug-cc-pVDZ level was used for optimization of the minima and TSs. IRC calculations has also been carried out connecting the TS with the associated minima. Conceptual-DFT (CDFT) calculations have been carried out with the Eyringpy program and in-house code. The distortion/interaction model along the reaction coordinate have used the decomposition scheme of Mandado et al. and the analysis of the importance of each components have been done with the relative energy gradient (REG) method., (© 2024. The Author(s).)

Background: Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase., Methods: We performed a retrospective analysis on a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of 2 tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF)., Results: After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia, advanced atrioventricular block, heart failure, and cardiogenic shock. In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p<0.001), without differences in stroke incidence (10.1% vs. 9.3%)., Conclusions: As a conclusion, patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-year follow-up, they exhibit a high risk of AF recurrence and mortality, with no significant differences in stroke incidence., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Importance: There is a need for representative research on serious adverse outcomes following discharge from psychiatric hospitalization., Objective: To compare rates of premature death, suicide, and nonlethal intentional self-harm after psychiatric discharge with rates in the general population and investigate associations of these outcomes with relevant variables associated with the index psychiatric hospitalization., Design, Setting, and Participants: This retrospective cohort study included all residents from Catalonia, Spain (7.6 million population), who had psychiatric hospitalizations between January 1, 2014, and December 31, 2018, and were older than 10 years at the index (first) hospitalization. Follow-up was until December 31, 2019. Statistical analysis was performed from December 1, 2022, through April 11, 2024., Exposures: Socioeconomic status, psychiatric diagnoses, duration of index hospitalization, and number of previous psychiatric hospitalizations., Main Outcomes and Measures: Postdischarge premature death (ie, all-cause death before age 70 years) and suicide (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] code range X60-X84), identified using mortality data, and postdischarge nonlethal intentional self-harm, identified using electronic health record and self-harm case register data. Standardized mortality ratios (SMRs) compared rates of premature death and suicide between the cohort and the general population. Fully adjusted, multivariable, cause-specific Cox proportional hazards regression models for the 3 outcomes were fitted., Results: A total of 49 108 patients discharged from psychiatric hospitalization were included (25 833 males [52.6%]; mean [SD] age at discharge, 44.2 [18.2] years). During follow-up, 2260 patients (4.6%) died prematurely, 437 (0.9%) died by suicide, and 4752 (9.7%) had an episode of nonlethal intentional self-harm. The overall SMR for premature death was 7.5 (95% CI, 7.2-7.9). For suicide, SMR was 32.9 (95% CI, 29.9-36.0) overall and was especially high among females (47.6 [95% CI, 40.2-54.9]). In fully adjusted sex-stratified hazard models, postdischarge premature death was associated with cognitive disorders (adjusted hazard ratio [AHR], 2.89 [95% CI, 2.24-3.74] for females; 2.59 [95% CI, 2.17-3.08] for males) and alcohol-related disorders (AHR, 1.41 [95% CI, 1.18-1.70] for females; 1.22 [95% CI, 1.09-1.37] for males). Postdischarge suicide was associated with postdischarge intentional self-harm (AHR, 2.83 [95% CI, 1.97-4.05] for females; 3.29 [95% CI, 2.47-4.40] for males), with depressive disorders (AHR, 2.13 [95% CI, 1.52-2.97]) and adjustment disorders (AHR, 1.94 [95% CI, 1.32-2.83]) among males, and with bipolar disorder among females (AHR, 1.94 [95% CI, 1.21-3.09]). Postdischarge intentional self-harm was associated with index admissions for intentional self-harm (AHR, 1.95 [95% CI, 1.73-2.21] for females; 2.62 [95% CI, 2.20-3.13] for males) as well as for adjustment disorders (AHR, 1.48 [95% CI, 1.33-1.65] for females; 1.99 [95% CI, 1.74-2.27] for males), anxiety disorders (AHR, 1.24 [95% CI, 1.10-1.39] for females; 1.36 [95% CI, 1.18-1.58] for males), depressive disorders (AHR, 1.54 [95% CI, 1.40-1.69] for females; 1.80 [95% CI, 1.58-2.04] for males), and personality disorders (AHR, 1.59 [95% CI, 1.46-1.73] for females; 1.43 [95% CI, 1.28-1.60] for males)., Conclusions and Relevance: In this cohort study of patients discharged from psychiatric hospitalization, risk for premature death and suicide was significantly higher compared with the general population, suggesting individuals discharged from psychiatric inpatient care are a vulnerable population for premature death and suicidal behavior.

Interleukin-6 (IL-6) has been long considered a key player in cancer cachexia. It is believed that sustained elevation of IL-6 production during cancer progression causes brain dysfunctions, which ultimately result in cachexia. However, how peripheral IL-6 influences the brain remains poorly understood. Here we show that neurons in the area postrema (AP), a circumventricular structure in the hindbrain, is a critical mediator of IL-6 function in cancer cachexia in male mice. We find that circulating IL-6 can rapidly enter the AP and activate neurons in the AP and its associated network. Peripheral tumor, known to increase circulating IL-6, leads to elevated IL-6 in the AP, and causes potentiated excitatory synaptic transmission onto AP neurons and AP network hyperactivity. Remarkably, neutralization of IL-6 in the brain of tumor-bearing mice with an anti-IL-6 antibody attenuates cachexia and the hyperactivity in the AP network, and markedly prolongs lifespan. Furthermore, suppression of Il6ra, the gene encoding IL-6 receptor, specifically in AP neurons with CRISPR/dCas9 interference achieves similar effects. Silencing Gfral-expressing AP neurons also attenuates cancer cachectic phenotypes and AP network hyperactivity. Our study identifies a central mechanism underlying the function of peripheral IL-6, which may serve as a target for treating cancer cachexia., (© 2024. The Author(s).)

A 3D bioprinted neurovascular unit (NVU) model is developed to study glioblastoma (GBM) tumor growth in a brain-like microenvironment. The NVU model includes human primary astrocytes, pericytes and brain microvascular endothelial cells, and patient-derived glioblastoma cells (JHH-520) are used for this study. Fluorescence reporters are used with confocal high content imaging to quantitate real-time microvascular network formation and tumor growth. Extensive validation of the NVU-GBM model includes immunostaining for brain relevant cellular markers and extracellular matrix components; single cell RNA sequencing (scRNAseq) to establish physiologically relevant transcriptomics changes; and secretion of NVU and GBM-relevant cytokines. The scRNAseq reveals changes in gene expression and cytokines secretion associated with wound healing/angiogenesis, including the appearance of an endothelial mesenchymal transition cell population. The NVU-GBM model is used to test 18 chemotherapeutics and anti-cancer drugs to assess the pharmacological relevance of the model and robustness for high throughput screening., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Background: Clinical trials showed the efficacy of 300 mg/4 weeks of omalizumab (OMA) during 6 months in patients with severe chronic spontaneous urticaria (CSU). Nevertheless, in real life, many patients require higher doses and/or longer treatment. This study assesses the real-life performance of OMA in severe CSU and identifies factors associated with the response., Methods: CSU patients eligible for OMA were recruited prospectively. Clinical data and a blood test were collected before OMA initiation. Urticaria Activity Score 7 (UAS7) was calculated at baseline and every 3 months during OMA treatment. CSU control was defined as UAS7 <7 points. This work was partially sponsored by OMA manufacturer., Results: Eighty-nine adults (19.1% males) with severe CSU were recruited. Median duration of CSU prior to OMA initiation was 2 years, and median severity by UAS7 at baseline was 24 points (range 10-42 points). OMA controlled 94.4% of patients, but 17.9% of responders required doses >300 mg/4 weeks. A blood basophil count >20 cells/μL (OR 13.33; 95% CI 3.32-52.63; p < .001) and the absence of hypothyroidism (OR 3.65; 95% CI 0.78-16.95; p = .099) were identified as predictive factors to achieve control with 300 mg/4 weeks. Twelve patients were able to stop OMA during the study (responders in remission, RR). RR had received OMA for a median of 29 months (12-53 months). Conversely, 32 patients had been on OMA for >29 months at the end of the study (active responders, AR). AR had received OMA for a median of 45 months (30-100 months). There were no significant differences in clinical or analytical factors between RR and AR patients., Conclusions: Low blood basophil count and the presence of hypothyroidism might serve as biomarkers for the controller dose of OMA in severe CSU patients., (© 2024 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Neurosciences clinical trials continue to have notoriously high failure rates. Appropriate outcomes selection in early clinical trials is key to maximizing the likelihood of identifying new treatments in psychiatry and neurology. The field lacks good standards for designing outcome strategies, therefore The Outcomes Research Group was formed to develop and promote good practices in outcome selection. This article describes the first published guidance on the standardization of the process for clinical outcomes in neuroscience. A minimal step process is defined starting as early as possible, covering key activities for evidence generation in support of content validity, patient-centricity, validity requirements and considerations for regulatory acceptance. Feedback from expert members is provided, regarding the risks of shortening the process and examples supporting the recommended process are summarized. This methodology is now available to researchers in industry, academia or clinics aiming to implement consensus-based standard practices for clinical outcome selection, contributing to maximizing the efficiency of clinical research., Competing Interests: Disclosures Silvia Zaragoza Domingo Developed EPICOG-SCH Brief Cognitive Battery in Schizophrenia and provided services as consultant to pharma industry (Sanofi-Genzyme and Jazz Pharmaceuticals in different periods 2018-23). Jordi Alonso, Montserrat Ferrer, Peter Annas, Chris Edgar, Manuel de Gracia, Georg Dorffner, Brian Harel, Jan Kottner, Amy Pinkham and Daniella Tinoco, Maria T. Acosta, Larry Alphs, John Harrison and Judith Jaeger have no conflicts of interest. For Florence Butlen-Ducuing and Pavel Balabanov, the views expressed in this document are the personal views of the authors and may not be understood or quoted as being made for or reflecting the position of the European Medicines Agency (EMA) or any of its committees or working parties. Anna-Karin Berger is employed by Lundbeck A/S. Kim I. Bishop is the principal of Global Pharma Consultancy, LLC, a provider of CNS and cognitive psychopharmacology services with a particular focus on executive functioning. William P. Horan is an employee of and holds equity in Karuna Therapeutics. Christian Yavorksy is the Chief Scientific Officer at Valis Bioscience and reports no conflicts of interest. Monica Vance is the Chief Executive Officer of Santium Media Corporation and reports no conflicts of interest, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Lymphoepithelioma-like gastric adenocarcinoma is characterised by a large reactive lymphoplasmacytic infiltrate in the stroma and islets of undifferentiated cells, which express intense and widespread Epstein-Barr virus (EBV). This tumour type has higher survival rates than other gastric cancers, a more proximal location and less lymphatic spread. Our aim is to describe the clinical and pathological characteristics of our series of lymphoepithelioma-like gastric adenocarcinoma. We selected patients who underwent surgery for gastric adenocarcinoma lymphoepithelioma-like variant from 2014 onwards. The results of the following variables were collected: age (years), sex, pre-diagnostic clinical time (months), gastric tumour location, endoscopic biopsy histology, surgical technique, in situ hybridisation for EBER region (Epstein-Barr virus-associated non-coding RNA), microsatellite instability, degree of differentiation, level of resection, tumour size (cm), TNM T value, lymphadenopathy/resected node ratio, overall survival (months) and vital status. Our experience in the lymphoepithelioma-like variant presents as an advanced gastric cancer, possibly related to long-standing prediagnostic symptoms. It behaves as a tumour with expansive local growth with little capacity for lymphatic or metastatic involvement, which could be explained by the prominent intratumoral lymphoid stroma that acts as an antimetastatic barrier.

The molecular mechanisms underlying seizure generation remain elusive, yet they are crucial for developing effective treatments for epilepsy. The current study shows that inhibiting c-Abl tyrosine kinase prevents apoptosis, reduces dendritic spine loss, and maintains N-methyl-d-aspartate (NMDA) receptor subunit 2B (NR2B) phosphorylated in in vitro models of excitotoxicity. Pilocarpine-induced status epilepticus (SE) in mice promotes c-Abl phosphorylation, and disrupting c-Abl activity leads to fewer seizures, increases latency toward SE, and improved animal survival. Currently, clinically used c-Abl inhibitors are non-selective and have poor brain penetration. The allosteric c-Abl inhibitor, neurotinib, used here has favorable potency, selectivity, pharmacokinetics, and vastly improved brain penetration. Neurotinib-administered mice have fewer seizures and improved survival following pilocarpine-SE induction. Our findings reveal c-Abl kinase activation as a key factor in ictogenesis and highlight the impact of its inhibition in preventing the insurgence of epileptic-like seizures in rodents and humans., Competing Interests: Declaration of interests Neurotinib is under patent WO2019/173761 A1., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Information on the microbiome's human pathways and active members that can affect SARS-CoV-2 susceptibility and pathogenesis in the salivary proteome is very scarce. Here, we studied a unique collection of samples harvested from April to June 2020 from unvaccinated patients., Methods: We compared 10 infected and hospitalized patients with severe (n = 5) and moderate (n = 5) coronavirus disease (COVID-19) with 10 uninfected individuals, including non-COVID-19 but susceptible individuals (n = 5) and non-COVID-19 and nonsusceptible healthcare workers with repeated high-risk exposures (n = 5)., Results: By performing high-throughput proteomic profiling in saliva samples, we detected 226 unique differentially expressed (DE) human proteins between groups (q-value ≤ 0.05) out of 3376 unambiguously identified proteins (false discovery rate ≤ 1%). Major differences were observed between the non-COVID-19 and nonsusceptible groups. Bioinformatics analysis of DE proteins revealed human proteomic signatures related to inflammatory responses, central cellular processes, and antiviral activity associated with the saliva of SARS-CoV-2-infected patients (p-value ≤ 0.0004). Discriminatory biomarker signatures from human saliva include cystatins, protective molecules present in the oral cavity, calprotectins, involved in cell cycle progression, and histones, related to nucleosome functions. The expression levels of two human proteins related to protein transport in the cytoplasm, DYNC1 (p-value, 0.0021) and MAPRE1 (p-value, 0.047), correlated with angiotensin-converting enzyme 2 (ACE2) plasma activity. Finally, the proteomes of microorganisms present in the saliva samples showed 4 main microbial functional features related to ribosome functioning that were overrepresented in the infected group., Conclusion: Our study explores potential candidates involved in pathways implicated in SARS-CoV-2 susceptibility, although further studies in larger cohorts will be necessary., (© 2024. The Author(s).)

Background: The taxonomy of the hymenopteran parasitoid subfamily Charipinae (Hymenoptera: Cynipoidea: Figitidae) has, until recently, been in a state of chaos. While this situation has improved significantly in recent years, most of the efforts were focused on morphological data of typically old specimens. Here, we present the first integrative approach to describe the diversity of the genus Phaenoglyphis Förster, 1869 from north-western Europe., New Information: For seven (of a total of 17) species, we provide DNA barcode data. Phaenoglyphisbelizini Pujade-Villar, 2018 and Phaenoglyphisevenhuisi Pujade-Villar & Paretas-Martínez, 2006 are recorded for the first time from Germany. All DNA barcodes and specimen data were added to the publicly available GBOL and BOLD reference database. The presence of a 6 bp long deletion in the CO1 barcode region that is characteristic to the genus and unique amongst Figitidae supports the monophyly of Phaenoglyphis ., (Jonathan Vogel, Ralph S. Peters, Jesús Selfa, Mar Ferrer-Suay.)

The hymenopteran subfamily Charipinae (Cynipoidea: Figitidae) consist of a group of parasitic wasps that are exclusive hyperparasitoids of Hemipteran. The species boundaries in Charipinae have historically been unclear. While diagnostic morphological features have been established for the stepwise separation of species, it is recommended to confirm those limits using molecular data. Here, we focus on the genera Alloxysta Förster, 1869 and Phaenoglyphis Förster, 1869, both of which contain species that are hyperparasitoids of aphids. We sequenced three genes (mitochondrial COI and 16S rDNA, and nuclear ITS2 rDNA) from specimens that were identified as belonging to five species: Alloxysta brevis (Thomson, 1862), A. castanea (Hartig, 1841), A. ramulifera (Thomson, 1862), A. victrix (Westwood, 1833), and Phaenoglyphis villosa (Hartig, 1841). The phylogeny resulting from concatenating these genes supported the species status of the five morphologically identified taxa, with P. villosa nested within Alloxysta . Our study thus indicates that these molecular markers can successfully distinguish charipine species, and also indicates that the genera Alloxysta and Phaenoglyphis may be more closely related than previously hypothesized. We also present the first estimates of genetic distances for these species. Future studies that include more species, loci, and/or genomic data will complement our research and help determine species relationships within the Charipinae subfamily.

Research on the biology of fetal-maternal barriers has been limited by access to physiologically relevant cells, including trophoblast cells. In this study, we describe the development of a human term placenta-derived cytotrophoblast immortalized cell line (hPTCCTB) derived from the basal plate. Human-term placenta-derived cytotrophoblast immortalized cell line cells are comparable to their primary cells of origin in terms of morphology, marker expression, and functional responses. We demonstrate that these can transform into syncytiotrophoblast and extravillous trophoblasts. We also compared the hPTCCTB cells to immortalized chorionic trophoblasts (hFM-CTC), trophoblasts of the chorionic plate, and BeWo cells, choriocarcinoma cell lines of conventional use. Human-term placenta-derived cytotrophoblast immortalized cell line and hFM-CTCs displayed more similarity to each other than to BeWos, but these differ in syncytialization ability. Overall, this study (1) demonstrates that the immortalized hPTCCTB generated are cells of higher physiological relevance and (2) provides a look into the distinction between the spatially distinct placental and fetal barrier trophoblasts cells, hPTCCTB and hFM-CTC, respectively., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: Detecting occult cancer in patients with unprovoked venous thromboembolism (VTE) remains a significant challenge. Our objective was to investigate the potential predictive role of coagulation-related biomarkers in the diagnosis of occult malignancies., Methods: We conducted a nested case-control study with a 1-year prospective cohort of 214 patients with unprovoked VTE, with a focus on identifying occult cancer. At the time of VTE diagnosis, we measured various biomarkers, including soluble P-selectin (sP-selectin), dimerized plasmin fragment D (D-dimer), platelets, leukocytes, hemoglobin, total extracellular vesicles (EVs), EVs expressing tissue factor on their surface (TF+EVs), and EVs expressing P-selectin on their surface (Psel+EVs) in all participants., Results: We observed statistically significant increased levels of sP-selectin (P = .015) in patients with occult cancer. Despite an increase in Psel+EVs, TF+EVs, D-dimer, and platelets within this group, however, no significant differences were found. When sP-selectin exceeded 62 ng/mL and D-dimer surpassed 10,000 µg/L, the diagnosis of occult cancer demonstrated a specificity of up to 91% (95% CI, 79.9%-96.7%)., Conclusions: The combination of sP-selectin and D-dimer can be a valuable biomarker in detecting occult cancer in patients with unprovoked VTE. Further research is necessary to ascertain whether easily measurable biomarkers such as sP-selectin and D-dimer can effectively distinguish between patients who have VTE with and without hidden malignancies., (© American Society for Clinical Pathology, 2024.)

Background and Aims: Bariatric surgery is effective for treating type 2 diabetes (T2D) in patients with obesity, although a significant proportion of these patients do not achieve diabetes remission after the surgery even after significant weight loss and metabolic improvement. C-peptide is a valuable marker of beta cell function and insulin secretion, but renal function must be considered when interpreting measurements in patients with T2D. The study aims to investigate the association of serum levels of C-peptide adjusted for creatinine with diabetes remission and glycemic target achievement after bariatric surgery in patients with obesity and T2D., Methods and Results: Prospective data from a cohort of 84 patients with obesity and T2D submitted to Roux-en-Y gastric bypass (RYGB) were collected at baseline and at least a 6-month follow up. A multivariate binomial regression model showed that Ln(C-peptide/creatinine) and age were significantly associated with 6-month T2D remission. The area under the curve for the receiver operating characteristic analysis (AUROC) to predict remission was 0.87, and more accurate than the AUROC based on C-peptide levels alone (0.75). The same model was also able to predict achieving an HbA1c target of 7 % (53 mmol/mol) (AUROC 0.96)., Conclusion: In conclusion, Ln(C-peptide/creatinine) ratio could be a useful tool in predicting T2D remission and target achievement after RYGB surgery, providing a more accurate reflection of beta cell function in bariatric patients., Competing Interests: Declaration of competing interest The authors declare no potential conflict of interests with the present study., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Purpose: Functional problems such as incontinence and sexual dysfunction after radical prostatectomy (RP) are important outcomes to evaluate surgical quality in prostate cancer (PC) care. Differences in survival after RP between countries are known, but differences in functional outcomes after RP between providers from different countries are not well described., Methods: Data from a multinational database of patients with PC (nonmetastatic, treated by RP) who answered the EPIC-26 questionnaire at baseline (before RP, T0) and 1 year after RP (T1) were used, linking survey data to clinical information. Casemix-adjusted incontinence and sexual function scores (T1) were calculated for each country and provider on the basis of regression models and then compared using minimally important differences (MIDs)., Results: A total of 21,922 patients treated by 151 providers from 10 countries were included. For the EPIC-26 incontinence domain, the median adjusted T1 score of countries was 76, with one country performing more than one MID (for incontinence: 6) worse than the median. Eighteen percent of the variance ( R 2 ) of incontinence scores was explained by the country of the providers. The median adjusted T1 score of sexual function was 33 with no country performing perceivably worse than the median (more than one MID worse), and 34% ( R 2 ) of the variance of the providers' scores could be explained by country., Conclusion: To our knowledge, this is the first comparison of functional outcomes 1 year after surgical treatment of patients with PC between different countries. Country is a relevant predictor for providers' incontinence and sexual function scores. Although the results are limited because of small samples from some countries, they should be used to enhance cross-country initiatives on quality improvement in PC care.