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This study aimed to investigate the association between estimated dietary intake of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) and human sperm quality. This study cross-sectionally assessed the associations between estimated dietary intake of PCDD/Fs and sperm quality parameters in 200 participants aged 18-40 years from the Led-Fertyl study. Linear regression models, accounting for potential confounding variables, were employed to evaluate the relationships. To estimate the PCDD/Fs exposure, food frequency questionnaires and the latest data on PCDD/Fs concentrations in food, primarily from Spanish sources, were used. Our findings indicate that, in comparison to participants in the lowest tertile, those in the highest tertile (T3) of PCDD/Fs dietary intake exhibited significantly elevated body mass index, increased consumption of meat, fish and eggs, and decreased consumption of nuts. Furthermore, individuals in T3 demonstrated a higher percentage of sperm head abnormalities (4.65 % [0.10; 9.24]; p-trend= 0.037) and a corresponding increase per 1-SD increment in energy-adjusted total PCDD/Fs dietary intake (1.84 % [0.38; 3.68]). No significant associations for other sperm parameters were found. Minimal research exists on PCDD/F dietary exposure and human sperm quality. This study shows significant direct association between higher PCDD/Fs intake and the percentage of sperm head abnormalities which potentially may compromise human reproductive health., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Albert Salas Huetos reports was provided by Rovira i Virgili University. 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 © 2025 Elsevier Inc. All rights reserved.)

Bronchopulmonary dysplasia, the most prevalent chronic lung disease of prematurity, is often treated with glucocorticoids (GCs) such as dexamethasone (DEX), but their use is encumbered with several adverse somatic, metabolic, and neurologic effects. We previously reported that systemic delivery of the GC prodrug ciclesonide (CIC) in neonatal rats activated glucocorticoid receptor (GR) transcriptional responses in lung but did not trigger multiple adverse effects caused by DEX. To determine whether limited systemic metabolism of CIC was solely responsible for its enhanced safety profile, we treated neonatal rats with its active metabolite desisobutyryl-ciclesonide (Des-CIC). DEX but not Des-CIC caused a reduction in body weight as well as reduced insulin-like growth factor-1 serum levels and chronic hyperglycemia in neonatal rats. However, Des-CIC was as effective as DEX in reducing the expression of various bleomycin-induced proinflammatory cytokine mRNAs. In vitro studies with various cell types demonstrate the potent GR transactivation and transrepression activity of Des-CIC, although genome-wide transcriptomic analyses reveal differences in DEX vs. Des-CIC responses in neonatal rat lung and liver tissue. Des-CIC is a GR super-agonist as revealed by an in vitro coregulator peptide binding assay. In addition, molecular dynamics simulations revealed unique Des-CIC-dependent allosteric signaling pathways between specific residues in the GR ligand-binding domain and receptor surfaces interacting with coregulator peptides. Thus, Des-CIC is a potential novel selective GR modulator that could impart a favorable therapeutic index for CIC use for even modest durations of GC exposure which could have long-lasting adverse somatic, metabolic, or neurologic effects., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Background and Objectives : Proton Pump Inhibitors (PPIs) are the most effective agents for treating acid-related gastrointestinal disorders. The prescription of an intravenous (IV) formulation of PPIs has increased dramatically. The aims of this study were to assess the appropriateness of IV PPI use and to define the risk factors and outcomes associated with its inappropriate use. Materials and Methods : A case-control retrospective study included all the hospitalized patients who received IV PPIs was conducted. Patient health records were reviewed, data were collected covering the period of the individual patients' admission to the hospital until discharge or death, and over the 3-month post-discharge period. The appropriateness of the IV PPI use and the resulting clinical outcomes were analyzed. Results : Overall, 540 patients were analyzed. Among them, 130/540 (24%) had inappropriate PPI use in terms of indication, dosage, and duration of treatment vs. 410 patients who had appropriate indications. Two parameters were associated with inappropriate use: congestive heart failure (OR 1.77; p = 0.02) and prescription of IV PPIs by surgeons vs. internists (OR 1.53; p = 0.05). Conclusions : Inappropriate IV PPI use is still common in daily clinical practice. Significant predictors of inappropriate use were the presence of congestive heart failure, elderly age, current use of anticoagulants and antithromotics, and the cases managed by surgeons, naturally due to suspected upper gastrointestinal bleedings.

Articular masses comprise various disease entities including benign or malignant proliferative processes and other non-neoplastic processes such as infection, deposition diseases, vascular malformations, and other lesions. Many diseases that lead to intra-articular or para-articular masses have distinct imaging features, particularly on MRI. Radiologists can localize masses to the joint space by knowing the articular anatomy and can reach a suggested diagnosis by looking at precise imaging findings. In this review article, we first define the concept of articular space (intraarticular, para-articular) and the normal joint anatomy and histology. We provide a general and comprehensive approach for evaluation of articular lesions on MRI. We then describe specific imaging and histologic features of typical benign and malignant soft tissue articular neoplasms and some non-neoplastic mimickers; and provide a radio-pathologic correlation of the different described entities., Competing Interests: Declaration of competing interest The authors 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 B.V.)

Introduction: Preventing chronic diseases among children and adolescents requires a comprehensive approach. The Nutri-Score, a front-of-pack nutrition labeling system, may play an important role in public health by enhancing overall nutritional quality of dietary intake, a key modifiable risk factor. The aim of this study was to investigate the ability of the 2015 and 2023 NS-NPM to discriminate food consumption and nutrient intake in a population of French children and adolescents., Methods: Children and adolescents (6-17 years old) participating in the cross-sectional representative ESTEBAN survey conducted in mainland France were included. Food consumption was assessed with three repeated 24 h dietary recalls. To obtain a dietary score at the individual level, the Nutri-Score nutrient profiling model dietary index (NS-NPM DI) was computed as an energy-weighted mean using the 2015 and the 2023 NS-NPMs and categorized into quartiles. Linear contrasts were used to assess the linearity of the association between the indexes and the intakes., Results: 1279 participants (50.2 % boys and 49.8 % girls, mean age 11 years) were included in this study. Using the 2023 NS-NPM DI, participants with more favorable DI (lower NS-NPM DI) consumed higher amounts of fruits, vegetables, whole grain cereals, milk, poultry, fish and seafood and vegetable oils and lower amounts of, processed meat and sweetened foods. In addition, using the NS-NPM DI 2023, participants with more favorable DI (thus more favorable Nutri-Score) had higher intakes of proteins, fiber, vitamins and minerals, and lower intakes of lipids, SFA, MUFA and simple sugars. Compared to the NS-NPM DI 2015, with the updated algorithm, higher differences between quartiles were observed for tubers, fish and seafood, poultry, red meat, processed meat, vegetable oils and vitamin D and E, all in the expected direction (better discrimination)., Conclusion: The results of the present study suggest that the NS-NPM algorithm underlying Nutri-Score is a useful tool for characterizing the diet quality of children and adolescents. The updated version of this algorithm showed a more discriminatory ability when assessing some animal food groups and vitamin D and E, indicating that the revision of the Nutri-Score represents an improvement for public health purposes., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Salas-Salvadó reported being a nonpaid member of the scientific boards of the International Nut and Dried Fruit Foundation, Danone Institute International, and Fundación Eroski; receiving institutional grants from the International Nut and Dried Fruit Foundation; and receiving personal fees from Danone Institute Spain., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Pancreas transplantation, a crucial treatment for diabetes, is underutilized due to its invasiveness, strict criteria, organ scarcity, and limited centers. This highlights the need for enhanced public education and awareness through digital health platforms., Methods: We utilized Google's AI-driven, consensus-based model and Claude AI 3.0 Opus by Anthropic to analyze public perceptions of pancreas transplantation. The top 10 websites identified by Google as of April-May 2024 were reviewed, focusing on sentiment, consensus, content readability, and complexity to develop strategies for better public engagement and understanding using digital health technologies., Results: The top 10 websites, originating from the US and UK, showed a neutral and professional tone, targeting medical professionals and patients. Complex content was updated between 2021 and 2024, with a readability level suitable for high school to early college students. AI-driven analysis revealed strategies to increase public interest and understanding, including incorporating patient stories, simplifying medical jargon, utilizing visual aids, emphasizing quality of life improvements, showcasing research progress, facilitating patient outreach, promoting community engagement, partnering with influencers, and regularly updating content through digital health platforms., Conclusion: To increase interest in pancreas transplantation in the era of connected health, we recommend integrating real patient experiences, simplifying medical content, using visual explanations, emphasizing post-transplant quality-of-life improvements, highlighting recent research, providing outreach opportunities, encouraging community connections, partnering with influencers, and keeping information current through digital health technologies. These methods aim to make pancreas transplantation more accessible and motivating for a diverse audience, supporting informed decision-making., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Garcia Valencia, Thongprayoon, Jadlowiec, Mao, Miao, Leeaphorn, Suppadungsuk, Csongradi, Budhiraja, Khoury, Vaitla and Cheungpasitporn.)

Background: Cardiac implantable electronic devices (CIEDs), including pacemakers, have undeniably revolutionized the treatment of cardiac conditions. However, just like any other treatment or intervention some significant challenges can be encountered in CIEDs, mainly, CIED infections. With reported incidence rates ranging from 1 % to 15 % these infections can pose lead to dangerous complications. Our case report presents an occurrence of late-onset pacemaker endocarditis, which despite proper antibiotic therapy required an open-heart surgery as the only curative option., Case Presentation: Our patient is a 50-year-old female known to have a pacemaker implanted twenty years ago, she presented with fever and purulent discharge from her pacemaker site. After thorough investigations, diagnostic tests confirmed a Serratia marcescens infection and despite antibiotic treatment, the patient's symptoms persisted, an echocardiography revealed tricuspid valve involvement with vegetations. Surgical intervention, by complete removal of the old and new pacemaker leads, tricuspid valvuloplasty, and installation of an epicardial pacemaker, was performed., Conclusion: Our case highlights the rarity and complexity of Serratia marcescens-related pacemaker endocarditis and all CIEDs in general, while emphasizing the importance of interdisciplinary management to optimize patient outcomes. Early diagnosis, prompt treatment, and comprehensive surgical approaches are essential in managing CIED infections and achieving successful outcomes., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Georgio EL KOUBAYATI reports was provided by Lebanese University. 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., (© 2024 The Author(s).)

Both genetic and environmental factors contribute to multiple sclerosis (MS) risk. Infection with the Epstein-Barr virus (EBV) is the strongest environmental risk factor, and HLA-DR15 is the strongest genetic risk factor for MS. We employed computational methods and in vitro assays for CD4 T cell activation to investigate the DR15-restricted response to EBV. Using a machine learning-based HLA ligand predictor, the EBV glycoprotein B (gB) was predicted to be enriched in epitopes restricted to presentation by DRB1*15:01. In DR15-positive individuals, two epitopes comprised the major CD4 T cell response to gB. Surprisingly, the expression of recombinant gB in a DR15-homozygous B cell line or primary autologous B cells elicited a CD4 T cell response, indicating that intracellular gB was loaded onto HLA class II molecules. By deleting the signal sequence of gB, we determined that this pathway for direct activation of CD4 T cells was dependent on trafficking to the endoplasmic reticulum (ER) within the B cell. We screened seven recombinant EBV antigens from the ER compartment for immune responses in DR15-negative vs. DR15-homozygous individuals. In addition to gB, gH was a key CD4 T cell target in individuals homozygous for DR15. Compared to non-DR15 controls, DR15-homozygotes had significantly higher T cell responses to both gB and gH but not to EBV latent or lytic antigens overall. Responses to gB and gH were slightly elevated in DR15 homozygotes with MS. Our results link MS environmental and genetic risk factors by demonstrating that HLA-DR15 dictates CD4 T cell immunity to EBV antigens., Competing Interests: Competing interests statement:The authors declare no competing interest.

Aims: Nuts are nutrient-dense foods touted for their health-promoting effects, especially regarding cardiovascular health, yet inconsistencies in the literature remain in relation to their effect on blood lipids. Hence, a systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to determine the effect of nut intake on blood lipids., Data Synthesis: MEDLINE-PubMed and Cochrane databases were searched. 113 unique trials met eligibility criteria (n = 8060 adults with various health status) assessing the effect of a median daily dose of 45.5 g/d of nuts compared to a non-nut control on blood lipid outcomes met inclusion criteria. Overall, nut consumption resulted in moderate reductions in total cholesterol (mean difference, -0.14 mmol/L [95 % confidence interval, -0.18 to -0.10 mmol/L]) and LDL-C (-0.12 mmol/L [-0.14 to -0.09 mmol/L]), with small reductions in triglycerides (-0.05 mmol/L [-0.07 to -0.03 mmol/L]), TC:HDL-C (-0.11 [-0.16 to -0.06]), LDL-C:HDL-C (-0.19 [-0.24 to -0.12]), and apolipoprotein B (-0.04 g/L [-0.06 to -0.02 g/L]). There was no significant impact on HDL-cholesterol or other assessed measures. Certainty of evidence was high for apolipoprotein A, and generally moderate/low for all other outcomes. Sensitivity analysis did not change the evidence on the main outcomes. Significant effect modifications in subgroup analysis were shown for most of the lipid parameters assessed. None of these subgroup effects altered the evidence of heterogeneity for any primary outcome., Conclusions: Current evidence provides a good indication that consuming nuts may advantageously affect blood lipids in adults with a mix of health status., Prospero Registration: PROSPERO identifier, CRD42022358688., Competing Interests: Declaration of competing interest S.K.N. is a volunteer member of the not-for-profit group Plant-Based Canada. J.S.-S. reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, the European Commission, the USA National Institutes of Health; receiving consulting fees or travel expenses from Instituto Danone and Abbott Laboratories, receiving nonfinancial support from Patrimonio Comunal Olivarero, the Almond Board of California, Pistachio Growers and Borges S.A; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation; and personal fees from Instituto Danone; Serving in the Board of Danone Institute International. None of these organizations had any role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. All other authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Benign prostatic hyperplasia (BPH) is a condition generally associated with advanced age in men that can be accompanied by bothersome lower urinary tract symptoms (LUTS) including intermittency, weak stream, straining, urgency, frequency, and incomplete bladder voiding. Pharmacotherapies for LUTS/BPH include alpha-blockers, which relax prostatic and urethral smooth muscle and 5ɑ-reductase inhibitors such as finasteride, which can block conversion of testosterone to dihydrotestosterone thereby reducing prostate volume. Celecoxib is a cyclooxygenase-2 inhibitor that reduces inflammation and has shown some promise in reducing prostatic inflammation and alleviating LUTS for some men with histological BPH. However, finasteride and celecoxib can reduce mitochondrial function in some contexts, potentially impacting their efficacy for alleviating BPH-associated LUTS., Methods: To determine the impact of these pharmacotherapies on mitochondrial function in prostate tissues, we performed immunostaining of mitochondrial Complex I (CI) protein NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) and inflammatory cells on BPH specimens from patients naïve to treatment, or who were treated with celecoxib and/or finasteride for 28 days, as well as prostate tissues from male mice treated with celecoxib or vehicle control for 28 days. Quantification and statistical correlation analyses of immunostaining were performed., Results: NDUFS3 immunostaining was decreased in BPH compared to normal adjacent prostate. Patients treated with celecoxib and/or finasteride had significantly decreased NDUFS3 in both BPH and normal tissues, and no change in inflammatory cell infiltration compared to untreated patients. Mice treated with celecoxib also displayed a significant decrease in NDUFS3 immunostaining and no change in inflammatory cell infiltration., Conclusions: These findings suggest that celecoxib and/or finasteride are associated with an overall decrease in NDUFS3 levels in prostate tissues but do not impact the presence of inflammatory cells, suggesting a decline in mitochondrial CI function in the absence of enhanced inflammation. Given that BPH has recently been associated with increased prostatic mitochondrial dysfunction, celecoxib and/or finasteride may exacerbate existing mitochondrial dysfunction in some BPH patients thereby potentially limiting their overall efficacy in providing metabolic stability and symptom relief., (© 2024 The Author(s). The Prostate published by Wiley Periodicals LLC.)

The primary pre-neoplastic lesion of the lower esophagus in the vicinity of the gastroesophageal junction (GEJ) is any Barrett's esophageal lesions (BE), and esophageal neoplasia has increased in the US population with predispositions (Caucasian males, truncal obesity, age, and GERD). The responses to BE are endoscopic and screening cytologic programs with endoscopic ablation of various forms. The former have not been proven to be cost-effective and there are mixed results for eradication. A fresh approach is sorely needed. We prospectively followed 2229 mostly male veterans at high risk for colorectal cancer in a 27-year longitudinal long-term study, collecting data on colorectal neoplasia development and other preneoplastic lesions, including BE and spontaneous regression (SR). Another cross-sectional BE study at a similar time period investigated antigenic changes at the GEJ in both BE glandular and squamous mucosa immunohistochemistry and the role of inflammation. Ten of the prospective cohort (21.7%) experienced SR out of a total of forty-six BE patients. Significant differences between SR and stable BE were younger age ( p < 0.007); lower platelet levels ( p < 0.02); rectal p87 elevation in SR ( p < 0.049); a reduced innate immune system (InImS) FEREFF ratio (ferritin: p87 colonic washings) ( p < 0.04). Ancillary testing showed a broad range of neoplasia biomarkers. InImS markers may be susceptible to intervention using commonplace and safe medical interventions and encourage SR.

Calcium channel blockers are generally considered safe for use during pregnancy. They have several indications, including second-line therapy for lowering blood pressure and tocolytic therapy. We present the case of a 24-year-old woman, G1P0, with a twin gestation at 22 weeks, who presented with acute respiratory distress. Her symptoms occurred shortly after starting nifedipine as tocolytic therapy. Investigations revealed signs of volume overload and pulmonary edema. Extensive cardiac and infectious workups were normal. Obstetrical ultrasound did not show any signs of ovarian hyperstimulation syndrome. Based on these findings, she was diagnosed with acute pulmonary edema following tocolytic therapy with oral nifedipine. Nifedipine was stopped, and intravenous furosemide was started, resulting in rapid clinical improvement. We are reporting this case to raise awareness of this rare but life-threatening adverse event associated with nifedipine use in pregnant patients., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Khattab et al.)

Objectives: The evidence on water intake in the prevention of kidney function decline is scarce at population level in well-being individuals at high cardiovascular risk. Therefore, we aimed to longitudinally evaluate the associations between total water intake and subtypes and kidney function, through estimated-Glomerular Filtration Rate (eGFR)., Methods: Three-year prospective analysis conducted in 1986 older adults (aged 55-75 year) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus study. Water intake was assessed using validated beverage and food frequency questionnaires. Serum creatinine-based eGFR (SCr-based eGFR; ml/min/1.73 m 2 ) was estimated using the CKD-EPI equation at baseline, one-year and 3-years of follow-up. Mixed-effects linear regression models were fitted to evaluate the associations between baseline total water intake and subtypes, and SCr-based eGFR over 3-years of follow-up., Results: Participants in the highest baseline tertile of total water intake, plain water and water from all fluids showed a lower decrease in SCr-based eGFR after 3-years of follow-up, compared to those in the lowest tertile. Participants with the highest tap water consumption showed a lower SCr-based eGFR decline after 1-year and 3-years of follow-up, in comparerd to participants in the lowest intake category (T3 vs. T1: β: 1.4 ml/min/1.73 m 2 ; 95%CI: 0.5-2.3, β: 1.0; 95%CI: 0.1-2.0, respectively)., Conclusions: Plain water rather than other water sources, and especially tap water, was associated with lower kidney function decline assessed through eGFR over 3-years of follow-up, in older individuals at high cardiovascular risk., Trial Registration: ISRCTN89898870. Retrospectively registered on 24 July 2014., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Bats are recognized as the natural reservoir of several zoonotic viruses that pose a threat to public health worldwide. In our recent reports we describe the identification of a novel poxvirus, IsrRAPXV, in Egyptian fruit bats. This poxvirus is associated with high morbidity and mortality in bats., Methods: Herein, we describe the identification of poxvirus in a female patient hospitalized with systemic symptoms and severe painful skin lesions on her hands. We performed qPCR, whole genome sequencing and phylogenetic analysis to identify and characterize this poxvirus as the etiologic agent., Results: The patient interacted with wounded and sick bats as a volunteer in a bat shelter run by the Israel bat sanctuary organization. Samples collected from the patient's skin lesions were positive for the presence of IsrRAPXV by PCR. Additionally, phylogenetic analysis showed that this virus is identical to IsrRAPXV originally described by us as the causative agent of skin lesions in fruit bats., Conclusions: Our finding suggest that IsrRAPXV is zoonotic and therefore veterinarians and volunteers working in bats shelter should meticulously follow the guidelines of working with bats and use required personal protective equipment., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. 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.)

Background: Alcohol-associated liver disease (ALD) is the most common indication for liver transplantation in the United States. Alcohol use disorder (AUD) treatment is recommended in all patients with ALD and AUD, but it remains underutilized., Aims: To identify predictors of AUD treatment and to assess 30-day readmission, return to drinking, and 1-year transplant-free survival., Methods: Retrospective single-center cohort study of consecutive patients hospitalized with ALD and AUD between 2018 and 2020. Patients who died or were lost to follow-up at 90 days after hospitalization were excluded. AUD treatment was defined as receiving medication or participating in residential, outpatient, or support groups within 90 days of discharge., Results: One hundred nine patients were included. Mean age was 51.7 years, and 63% were male. Fifty-six (51%) patients received AUD treatment, and 23 (21%) patients received more than one treatment. Predictors of AUD treatment were younger age (OR, 1.07 [95% CI, 1.04-1.12]; P < 0.001), gastroenterology/hepatology consult (AOR, 8.54 [95% CI, 2.55-39.50]; P = 0.0002), addiction psychiatry consult (AOR, 2.77 [95% CI, 1.16-6.84]; P = 0.02), and a brief AUD intervention (AOR, 18.19 [95% CI, 3.36-339.07]; P = 0.0001). Cirrhosis decompensation, MELD-Na score, and insurance status were not associated with treatment. Thirty-one patients (28.4%) were readmitted, and 29 (26.6%) remained abstinent 30 days from discharge. Patients who received treatment had improved transplant-free survival (HR, 0.44, P = 0.04)., Conclusion: A brief intervention on AUD had the strongest association with receiving AUD treatment in our cohort. Further efforts to incorporate brief interventions when offering AUD treatment to patients with ALD may be beneficial., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 American Society of Addiction Medicine.)

Despite advancements in treatment strategies, the mortality from colorectal cancer (CRC) remains high. Evidence suggests that aspirin (ASA) may have a protective effect on CRC incidence and metastasis through various mechanisms. The 2016 to 2020 National Inpatient Sample was used to identify adult patients (age above 18 y) with the principal diagnosis of CRC. Patients were stratified into 2 groups based on ASA use. The outcomes studied were in-hospital mortality and rates of total, gastrointestinal (GI), non-GI, and lymphoid metastasis. A multivariate logistic regression analysis was performed to evaluate the impact of ASA use on outcomes after adjusting for patient demographics, comorbidities, and the Elixhauser Comorbidity Index (ECI). Of the 814,270 patients, 88,620 (10.8%) used ASA, with the majority being aged above 65 years (78%), male (57%), white (77.6%), and had Medicare insurance (74.5%). There was a higher prevalence of Diabetes mellitus, Hypertension, Chronic pulmonary disease, Coronary artery disease, Chronic kidney disease, Chronic heart failure, Obesity, and Smoking among aspirin users than among non-ASA users. Patients who used ASA had a lower prevalence of total (47.3% vs. 32.5%, P<0.001), GI (22.2% vs. 32.4%, P<0.001), non-GI (9.9% vs. 15.3%, P<0.001), and lymphoid (9.3% vs. 10.9%, P<0.001) metastasis compared with those who did not use ASA. After adjusting for confounding factors, patients with ASA use had lower odds of total (aOR: 0.75, 95% CI: 0.72-0.78, P<0.001), GI (aOR: 0.74, 95% CI: 0.71-0.77, P<0.001), non-GI (aOR: 0.72, 95% CI: 0.68-0.77, P<0.1), and statistically insignificant odds of lymphoid (aOR: 0.95, 95% CI: 0.90-1.00, P=0.098) metastasis. The use of ASA is associated with a decrease in the prevalence of metastasis among individuals diagnosed with CRC, but additional studies are required to elucidate the mechanism and duration of therapy needed to be effective., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: High intake of ultraprocessed foods (UPFs) has been associated with higher cardiometabolic risk in adults; however, the evidence in children is limited., Objective: To investigate the association between UPF consumption and cardiometabolic risk factors in the Childhood Obesity Risk Assessment Longitudinal Study (CORALS)., Design, Setting, and Participants: This baseline cross-sectional analysis was conducted using the data of CORALS participants recruited between March 22, 2019, and June 30, 2022. Preschool children (aged 3-6 years) were recruited from schools and centers in 7 cities in Spain. Inclusion criteria included informed consent signed by parents or caregivers and having a completed a set of questionnaires about the child's prenatal history at home. Exclusion criteria included low command of Spanish or unstable residence., Exposure: Energy-adjusted UPF consumption (in grams per day) from food frequency questionnaires and based on the NOVA food classification system., Main Outcomes and Measures: Age- and sex-specific z scores of adiposity parameters (body mass index [BMI], fat mass index, waist-to-height ratio, and waist circumference) and cardiometabolic parameters (diastolic and systolic blood pressure, fasting plasma glucose, homeostasis model assessment for insulin resistance, high-density and low-density lipoprotein cholesterol, and triglycerides) were estimated using linear regression models., Results: Of 1509 enrolled CORALS participants, 1426 (mean [SD] age, 5.8 [1.1] years; 698 boys [49.0%]) were included in this study. Mothers of children with high UPF consumption were younger, had a higher BMI, were more likely to have overweight or obesity, and had lower education levels and employment rates. Compared with participants in the lowest tertile of energy-adjusted UPF consumption, those in the highest tertile showed higher z scores of BMI (β coefficient, 0.20; 95% CI, 0.05-0.35), waist circumference (β coefficient, 0.20; 95% CI, 0.05-0.35), fat mass index (β coefficient, 0.17; 95% CI, 0.00-0.32), and fasting plasma glucose (β coefficient, 0.22; 95% CI, 0.06-0.37) and lower z scores for HDL cholesterol (β coefficient, -0.19; 95% CI, -0.36 to -0.02). One-SD increments in energy-adjusted UPF consumption were associated with higher z scores for BMI (β coefficient, 0.11; 95% CI, 0.05-0.17), waist circumference (β coefficient, 0.09; 95% CI, 0.02-0.15), fat mass index (β coefficient, 0.11; 95% CI, 0.04-1.18), and fasting plasma glucose (β coefficient, 0.10; 95% CI, 0.03-0.17) and lower HDL cholesterol (β coefficient, -0.07; 95% CI, -0.15 to -0.00). Substituting 100 g of UPFs with 100 g of unprocessed or minimally processed foods was associated with lower z scores of BMI (β coefficient, -0.03; 95% CI, -0.06 to -0.01), fat mass index (β coefficient, -0.03; 95% CI, -0.06 to 0.00), and fasting plasma glucose (β coefficient, -0.04; 95% CI, -0.07 to -0.01)., Conclusions and Relevance: These findings suggest that high UPF consumption in young children is associated with adiposity and other cardiometabolic risk factors, highlighting the need for public health initiatives to promote the replacement of UPFs with unprocessed or minimally processed foods.

Background: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food., Objective: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study., Methods: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI., Results: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [β-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m 2 (0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up., Discussion: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up., Competing Interests: Declaration of competing interest The authors 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The Lebanese population has faced numerous stressors due to multiple crises in the past four years. This study aims to measure the perceived stress of the Lebanese population, identify the coping mechanisms being used, and determine whether they are associated with their stress levels. A cross-sectional study of 205 individuals randomly selected from Beirut was conducted. Frequency distribution, descriptive analysis, and multivariable cumulative logit models were used to determine the associations between coping mechanisms and perceived stress. Our results indicated that 95.4% of our population had moderate to high perceived stress levels. Problem-focused coping was the most adopted mechanism and was associated with a statistically significant lower stress level, whereas avoidant coping was associated with a statistically significant higher stress level. Our study can pave the way for raising awareness on the importance of managing stress with adaptive coping mechanisms., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Hazem Iaali et al.)

Background: Pancreas transplantation is a crucial surgical intervention for managing diabetes, but it faces challenges such as its invasive nature, stringent patient selection criteria, organ scarcity, and centralized expertise. Despite the steadily increasing number of pancreas transplants in the United States, there is a need to understand global trends in interest to increase awareness of and participation in pancreas and islet cell transplantation., Methods: We analyzed Google Search trends for "Pancreas Transplantation" and "Islet Cell Transplantation" from 2004 to 14 November 2023, assessing variations in search interest over time and across geographical locations. The Augmented Dickey-Fuller (ADF) test was used to determine the stationarity of the trends ( p < 0.05)., Results: Search interest for "Pancreas Transplantation" varied from its 2004 baseline, with a general decline in peak interest over time. The lowest interest was in December 2010, with a slight increase by November 2023. Ecuador, Kuwait, and Saudi Arabia showed the highest search interest. "Islet Cell Transplantation" had its lowest interest in December 2016 and a more pronounced decline over time, with Poland, China, and South Korea having the highest search volumes. In the U.S., "Pancreas Transplantation" ranked 4th in interest, while "Islet Cell Transplantation" ranked 11th. The ADF test confirmed the stationarity of the search trends for both procedures., Conclusions: "Pancreas Transplantation" and "Islet Cell Transplantation" showed initial peaks in search interest followed by a general downtrend. The stationary search trends suggest a lack of significant fluctuations or cyclical variations. These findings highlight the need for enhanced educational initiatives to increase the understanding and awareness of these critical transplant procedures among the public and professionals.

Purpose: To evaluate the effect of cheek retractors on the accuracy of capturing peripheral borders in totally edentulous digital scans by comparing the conventional impression technique to digital scans made using two different cheek retractors., Material and Methods: Sixteen edentulous maxillary impressions were made using three techniques: the conventional impression technique, using modeling thermoplastic compound and zinc oxide eugenol paste; the digital intraoral scanning technique using the DIO scan retractor (DIO); and using the Br.nemark lip retractor (BRAN). The control impressions of each patient were poured, scanned using a desktop scanner, then transferred into a three-dimensional analysis software. DIO and BRAN groups were scanned using an intraoral scanner, imported, and superimposed using best fit algorithm on the corresponding control. The root mean square for the whole surface and for particular interest regions were calculated to assess the degree of trueness. The patients' perceptions of the impression techniques were the secondary outcomes. Statistical analyses were performed using the one sample T-test and Wilcoxon test (α=.05)., Results: Significant discrepancies were found for BRAN and DIO compared to the control. No significant discrepancies were found when comparing RMS of BRAN and DIO at different regions. Scan retractors had a significant impact on patient satisfaction, with patients preferring DIO., Conclusions: Edentulous intraoral scans made using cheek retractors had similar deviations when compared to each other but diverged from the conventional impression in edentulous maxilla. Patient preferences for intraoral scans over conventional impressions were confirmed., Clinical Implications: The use of different retracting methods during intraoral scanning of totally edentulous maxillary arches does not affect the peripheral border registration.

At some institutions, musculoskeletal and general radiologists rather than neuroradiologists are responsible for reading magnetic resonance imaging (MRI) of the spine. However, neurological findings, especially intrathecal ones, can be challenging. Intrathecal neurological findings in the spine can be classified by location (epidural, intradural extramedullary, and intramedullary) or etiology (tumor, infection, inflammatory, congenital). In this paper, we provide a succinct review of the intrathecal neurological findings that can be seen on MRI of the spine, primarily by location and secondarily by etiology, in order that this may serve as a helpful guide for musculoskeletal and general radiologists when encountering intrathecal neurological pathologies., (© 2023. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Proinflammatory cytokines, such as (IL: interleukin) IL-6 and IL-17A, and complement fixation are critical in the immunopathogenesis of neuromyelitis optica spectrum disorders (NMOSD). Blocking the IL-6 receptor or the C5 complement pathway reduces relapse risk. However, the role of interleukin (IL)-6 and complement in aquaporin-4 (AQP4) autoimmunity remains unclear. To investigate the role of the anti-AQP4 immunoglobulin (AQP4-IgG)/AQP4 immunocomplex on the induction and profile of ex vivo cytokine and surface marker expression in peripheral blood mononuclear cells (PBMC) culture. Isolated PBMCs obtained from 18 patients with AQP4-IgG-seropositive-NMOSD (8 treatment-naive, 10 rituximab-treated) or ten healthy controls were cultured with AQP4-immunocomplex with or without complement. Changes in PBMC surface markers and cytokine expression were profiled using flow cytometry and ELISA. PBMCs derived from treatment-naive NMOSD patients stimulated with a complex mixture of serum complement proteins produced significant elevations of IL-17A and IL-6. Rituximab-treated patients also exhibited higher IL-6 but not IL-17A release. IL-6 and IL-17A elevations are not observed without complement. Co-stimulation of PBMCs with AQP4-IgG/AQP4 immunocomplex and complement prompts a Th17-biased response consistent with the inflammatory paradigm observed in NMOSD. A possible inflammation model is proposed via antigen-specific autoreactive peripheral blood cells, including NK/NKT cells., (© 2024. The Author(s).)

Background: Reflecting on the existing literature on suicidal ideation and Avoidant/Restrictive Food Intake Disorder (ARFID), this article investigates the complex relationship between them, hypothesizing about the possibility of dysmorphic concerns, being a mediator linking ARFID to suicidal ideation., Methods: Using a snowball sampling approach, a survey was created on Google Forms and circulated across messaging applications and social media networks (WhatsApp, Instagram, Messenger). The sample involved 515 participants recruited between February and March 2023. The questionnaire included the following scales: Nine-items Avoidant/Restrictive Food Intake Disorder screen (NIAS), Dysmorphic Concern Questionnaire (DCQ), and Columbia-Suicide Severity Rating Scale (C-SSRS). When filling the questionnaire, respondents were warned that they can experience distress when answering certain questions and received information about mental health services. Five hundred fifteen adults participated in this study, with a mean age of 27.55 ± 10.92 years and 60.1% females., Results: After adjusting over potential confounders (i.e., age, education, marital status, and household crowding index), analyses showed that dysmorphic concerns fully mediated the association between avoidant restrictive eating and suicidal ideation. Higher avoidant restrictive eating was significantly associated with more dysmorphic concerns, and higher dysmorphic concerns were significantly associated with the presence of suicidal ideation. Finally, avoidant restrictive eating was not significantly associated with suicidal ideation., Conclusion: This study highlights the potential indirect link between ARFID and suicidal ideation mediated by dysmorphic concerns. While no direct connection was observed between ARFID and suicidal ideation, the presence of dysmorphic concerns appeared to be a crucial factor in amplifying the risk of suicidal ideation in individuals with ARFID. This emphasizes the importance of addressing dysmorphic concerns alongside ARFID treatment to enhance mental health interventions and outcomes., (© 2024. The Author(s).)

Disseminated histoplasmosis is a rare complication of infection due to Histoplasma capsulatum . Typically, histoplasmosis is self-limiting and asymptomatic in infected individuals with immunocompetence. Disseminated disease, however, can arise in high-risk populations with primary or acquired cellular immunodeficiency including HIV/AIDS, transplant recipients, and those undergoing immunosuppressive therapy. Here we describe a unique case of extrapulmonary gastrointestinal histoplasmosis by infiltrative Peyer's patch disease with bone marrow involvement in a transgender HIV-infected woman., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: To assess volumetrically, the impact of vertical facial growth types (VGFT) on the retromolar area as a bone donor site MATERIAL AND METHODS: 60 cone beam computed tomography (CBCT) scans of adult individuals were classified in three groups according to their SN-GoGn angle: hypodivergent group (hG) (33.33%), normodivergent group (NG) (30%) and hyperdivergent group (HG) (36.67%). Total harvestable bone volume and surface (TBV and TBS respectively), total cortical and cancellous bone volume (TCBV and TcBV respectively) and the percentage of cortical and cancellous bone volume (CBV and cBV respectively) were evaluated., Results: The whole sample showed a mean TBV of 1220.99±448.81mm³ and a mean TBS of 940.29±259.93mm². Statistically significant differences were found between the different outcome variables and the vertical growth patterns (p<0.001). TBS differs for the different vertical growth patterns with the highest mean of TBS observed in the hG group. TBV also significantly differs between the different vertical growth patterns (p<0.001) with the highest mean observed for the hG individuals. Significant differences in percentages of cBV and CBV were present between the hyper-divergent groups and the other groups (p<0.001) with the hyper-divergent group having the lowest percentage of CBV and the highest percentage of cBV., Conclusion: hypodivergent individuals tend to have thicker bone blocks that can be used in onlay technique while thinner bone blocks harvested from hyperdivergent and normodivergent individuals can be used in three-dimensional grafting approach., Competing Interests: Declaration of Competing Interest The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Objectives: To assess the implant position (IP), the interradicular septum width (ISW) and radiographic bone to implant contact (BIC), when simulating an immediate implant placement in first and second mandibular molars., Study Design: 75 patients (150 sites) were studied using cone beam computed tomography scans (CBCT) and computer aided design software. Implants were placed in a prosthetically driven position; subsequently, IP and BIC were digitally calculated. Linear ISW was also analyzed at 2, 4 and 6mm apically to the highest septal bony peak. Multiple linear regressions were performed to assess relationships between BIC and the different predictive variables. Additionally, the receiver operating characteristics (ROC) curve was used to create a model for BIC based on the ISW at 2mm., Results: BIC in implants replacing first molars was the highest at the septal (S) position when compared to those in septal-mesial (S-M) position (p-value 0.001). As for the second molar, the highest percentage of BIC was recorded at the septal (S) position, followed by those in S-M and mesial (M) positions (p<0.001)., Conclusion: According to the proposed classification, clinician must consider the ISW and IP when placing immediate implant in the first and second mandibular molar sites. When tackling first molars, S position is predominant, while S-M position is the most common in the second molars. ISW at 2mm should be at least respectively 2mm and 2.5mm at the first and second molar sites to achieve 50% of BIC., Competing Interests: Declaration of Competing Interest The authors 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 © 2023 Elsevier Masson SAS. All rights reserved.)

Purpose: (1) Describe imaging utilization and findings within two weeks of the 2020 Beirut blast according to the mechanism of injury, (2) determine the appropriate imaging modality per organ/system, and (3) describe changes in the workflow of a radiology department to deal with massive crises., Materials and Methods: Two hundred sixty patients presented to the largest emergency department in Beirut and underwent imaging within 2 weeks of the blast. In this retrospective study, patients were divided into early (1) and late (2) imaging groups. Patients' demographic, outcome, type and time of imaging studies, body parts imaged, and mechanism and types of injuries were documented., Results: Two hundred five patients in group 1 underwent 502 and 55 patients in group 2 underwent 145 imaging studies. Tertiary blast injuries from direct impact and falling objects were the most common type of injuries followed by secondary (shrapnel) injuries. Both types of injuries affected mostly the head and neck and upper extremities. Plain radiographs were adequate for the extremities and CT for the head and neck. A regularly updated and practiced emergency plan is essential to mobilize staff and equipment and efficiently deliver radiology services during crises., Conclusion: Because the powerful Beirut blast occurred at the port located in the periphery of the city, most injuries seen on imaging were of the upper extremities and head and neck caused by the severe blast wind or penetrating shrapnel and resulted from people using their arms to protect their heads and bodies from direct impact and falling objects., (© 2023. The Author(s), under exclusive licence to American Society of Emergency Radiology (ASER).)

Introduction: A multitude of evidence supports the consumption of a higher quantity of vegetables and fruits for their cardiovascular benefits. Nonetheless, the extent to which variety is associated with cardiovascular health remains unclear., Objective: To conduct a systematic review and meta-analysis of observational studies (prospective cohort and cross-sectional studies) assessing the role of a variety of vegetable and fruit consumption in cardiovascular morbidity and mortality in adults., Data Sources: MEDLINE-PubMed, Cochrane databases, and reference lists were searched through March 2023., Data Extraction: Two independent reviewers extracted data and assessed the risk of bias (National Heart, Lung, and Blood Institute Tool and Newcastle-Ottawa Scale)., Data Analysis: Data were pooled (fixed and random [DerSimonian and Laird] effects for <5 and ≥5 study comparisons, respectively), and heterogeneity was assessed using the Cochran Q statistic and quantified (I 2 statistic). The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used to assess the overall certainty of the evidence. Five cross-sectional (n = 45,761) and seven prospective studies (n = 253,422) met the eligibility criteria. Greater variety of vegetable and fruit consumption was prospectively related to decreased all-cause mortality (risk ratio, 0.89 [95% CI, 0.82-0.97], seven study comparisons, n = 196,925), while no significant associations were observed with assessed cardiovascular-related mortality or morbidity. For all outcomes, the certainty of the evidence was graded as "low" or "very low" owing to inconsistency and/or imprecision., Conclusions: Overall, this study shows that greater variety in vegetable and fruit consumption may reduce all-cause mortality and highlights the need for additional studies with a higher degree of evidence to better understand its role in cardiovascular health.

Background: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability., Objectives: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use., Design: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome., Methods: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models., Results: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO 2 eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced., Conclusions: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection., Trial Registration: ISRCTN, ISRCTN89898870. Registered 05 September 2013, http://www.isrctn.com/ISRCTN89898870., Competing Interests: Declaration of competing interest This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects leaded by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to MÁM-G.; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 and the AICO/2021/347 grants from the Generalitat Valenciana; the SEMERGEN grant. J.S-S is partially supported by ICREA under the ICREA Academia programme. C.B. was granted by Juan de la Cierva grant. P.M.G. was granted by the Specialist Postdoctoral program of the Consejería de Salud y Familias, Junta de Andalucía (Spain). None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication. J.S.-S. reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, the European Commission, the USA National Institutes of Health; receiving consulting fees or travel expenses from Eroski Foundation and Instituto Danone, receiving nonfinancial support from Hojiblanca, Patrimonio Comunal Olivarero, the California Almond Board of California, Pistachio Growers and Borges S.A; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and personal fees from Instituto Danone Spain; Serving in the Board of Danone Institute International. D.C. reported receiving grants from Instituto de Salud Carlos III. R.E. reported receiving grants from Instituto de Salud Carlos III, Fundación Dieta Meditarránea and Cerveza y Salud and olive oil for the trial from Fundación Patrimonio Comunal Olivarero and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes in Albuquerque, Milano and Tokyo, Pernod Ricard, Fundación Dieta Mediterránea (Spain), Wine and Culinary International Forum and Lilly Laboratories; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories. The rest of the authors have declared that no competing interests exist. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Bloodstream infections (BSIs) are the most common infectious complication in patients who receive allogeneic hematopoietic stem-cell transplants (allo-HSCTs). Polymorphonuclear neutrophils (PMNs) are quantified to monitor the susceptibility to BSIs; however, their degree of activation is not. We previously identified a population of primed PMNs (pPMNs) with distinct markers of activation representing approximately 10% of PMNs in circulation. In this study, we investigate whether susceptibility to BSIs is related to the proportion of pPMNs rather than strictly PMN counts., Methods: In this prospective observational study, we used flow cytometry to assess pPMNs in blood and oral rinse samples collected from patients receiving an allo-HSCT over the course of their treatment. We used the proportion of pPMNs in the blood on day 5 post-transplant to categorize patients into a high- or a low-pPMN group (>10% or <10% pPMNs). These groups were then used as a predictor of BSIs., Results: A total of 76 patients were enrolled in the study with 36 in the high-pPMN group and 40 in the low-pPMN group. Patients in the low-pPMN group had lower expression of PMN activation and recruitment markers and displayed a delay in PMN repopulation of the oral cavity after the transplant. These patients were more susceptible to BSIs compared with patients in the high-pPMN group with an odds ratio of 6.5 (95% confidence interval, 2.110-25.07; P = .002)., Conclusions: In patients who receive an allo-HSCT, having <10% pPMNs early in the post-transplant phase can be an independent predictor of BSI in allo-HSCT patients., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet., Aims: To assess the association between MetS severity and amount of carbon dioxide (CO 2 ) emitted in an adult population., Design: Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS)., Methods: Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO 2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score., Results: Higher glycaemia levels were found in people with higher CO 2 emissions. The risk of having high severe MetS was related to high CO 2 emissions., Conclusions: Low CO 2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet., Trial Registration: ISRCTN, ISRCTN89898870 . Registered 05 September 2013., (© 2023. The Author(s).)

Introduction: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited., Objective: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population., Methods: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models., Results: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (β-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (β-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015)., Conclusion: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results., Competing Interests: Declaration of competing interest The authors 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 © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Interpretive front-of-pack labels (FoPLs) are supported by World Health Organization as an important policy tool to promote healthy diets. At present, various FoPLs formats co-exist in the European Union (EU). However, as part of the Farm to Fork strategy published in 2020, the European Commission stated that it would propose a single mandatory FoPL. The aim of this study was to analyze Spanish consumers' preference and objective understanding of Nutri-Score and NutrInform, two FoPLs that are currently the subject of debate in the EU., Methods: In a representative sample of 1026 Spanish adults (50% women, mean age ± SD = 46 ± 14 years), objective understanding was assessed by asking participants to identify the healthiest food products in three food categories (breakfast products, breakfast cereals and added fats). The preference dimensions were tested by asking participants about the perceived helpfulness of the FoPL in discriminating the nutritional quality of food products (subjective understanding) and their overall assessment of the FoPL's ease of use, informativeness, trust and liking (perception)., Results: In terms of objective understanding, Nutri-Score was significantly associated with an increase in consumers' ability to identify healthier food products across all food categories compared with NutrInform [OR (odds ratio) = 19.1 [14.2-25.7], P < 0.0001]. On the preference dimension, Nutri-Score was perceived as significantly easier to use and was more liked than NutrInform (standardized principal component analysis dimension, respectively, 0.32 ± 1.58 vs. -0.29 ± 1.66, P < 0.0001 and 0.080 ± 1.18 vs. -0.072 ± 1.17, P = 0.039)., Conclusions: This study provides new evidence to support Nutri-Score in comparison with NutrInform in Spanish consumers, on both objective understanding and preference aspects., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Public Health Association.)

A major concern for cardiac arrest (CA) survivors is the manifestation of long-term cognitive impairments. Physical exercise (PE) is a well-established approach to improve cognitive functions under certain pathological conditions. We previously showed that PE post-CA mitigates cognitive deficits, but the underlying mechanisms remain unknown. To define neuroprotective mechanisms, we analyzed whether PE post-CA protects neurons involved in memory. We first performed a contextual fear conditioning (CFC) test to confirm that PE post-CA preserves memory in rats. We then conducted a cell-count analysis and determined the number of live cells in the hippocampus, and septal and thalamic nuclei, all areas involved in cognitive functions. Lastly, we performed RNA-seq to determine PE post-CA effect on gene expression. Following CA, exercised rats had preserved CFC memory than sham PE animals. Despite this outcome, PE post-CA did not protect hippocampal cells from dying. However, PE ameliorated cell death in septal and thalamic nuclei compared to sham PE animals, suggesting that these nuclei are crucial in mitigating cognitive decline post-CA. Interestingly, PE affected regulation of genes related to neuroinflammation, plasticity, and cell death. These findings reveal potential mechanisms whereby PE post-CA preserves cognitive functions by protecting septal and thalamic cells via gene regulation.

In a rat model, following exposure to rat folate receptor alpha antibodies (FRαAb) during gestation, FRαAb accumulates in the placenta and the fetus and blocks folate transport to the fetal brain and produces behavioral deficits in the offspring. These deficits could be prevented with folinic acid. Therefore, we sought to evaluate folate transport to the brain in young rat pups and determine what effect FRαAb has on this process, to better understand the folate receptor autoimmune disorder associated with cerebral folate deficiency (CFD) in autism spectrum disorders (ASD). When injected intraperitoneally (IP), FRαAb localizes to the choroid plexus and blood vessels including the capillaries throughout the brain parenchyma. Biotin-tagged folic acid shows distribution in the white matter tracts in the cerebrum and cerebellum. Since these antibodies can block folate transport to the brain, we orally administered various folate forms to identify the form that is better-absorbed and transported to the brain and is most effective in restoring cerebral folate status in the presence of FRαAb. The three forms of folate, namely folic acid, D,L-folinic acid and levofolinate, are converted to methylfolate while L-methylfolate is absorbed as such and all are efficiently distributed to the brain. However, significantly higher folate concentration is seen in the cerebrum and cerebellum with levofolinate in the presence or absence of FRαAb. Our results in the rat model support testing levofolinate to treat CFD in children with ASD.

Stimulation of the inflammatory reflex (IR) is a promising strategy to treat systemic inflammatory disorders. However, this strategy is hindered by the cost and side effects of traditional IR activators. Recently, oral intake of sodium bicarbonate (NaHCO3) has been suggested to activate the IR, providing a safe and inexpensive alternative. Critically, the mechanisms whereby NaHCO3 might achieve this effect and more broadly the pathways underlying the IR remain poorly understood. Here, we argue that the recognition of NaHCO3 as a potential IR activator presents exciting clinical and research opportunities. To aid this quest, we provide an integrative review of our current knowledge of the neural and cellular pathways mediating the IR and discuss the status of physiological models of IR activation. From this vantage point, we derive testable hypotheses on potential mechanisms whereby NaHCO3 might stimulate the IR and compare NaHCO3 with classic IR activators. Elucidation of these mechanisms will help determine the therapeutic value of NaHCO3 as an IR activator and provide new insights into the IR circuitry., Competing Interests: Declaration of Competing Interest The authors declare that they do not have any conflicts of interest (financial or otherwise) related to the data presented in this manuscript., (Copyright © 2022. Published by Elsevier Ltd.)

Turmeric is a common herbal supplement used for its possible anti-inflammatory and other properties. It is marketed as safe with few reports of major adverse effects directly related to oral supplementation. We report a case of turmeric supplement-induced liver injury in a 49-year-old woman admitted with elevated aspartate aminotransferase and alanine aminotransferase with no history of liver disease or alcohol use disorder. Thus, this case re-emphasizes the importance of evaluating herbal and dietary supplements as potential drug-induced liver injury causes., (© 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

The prevalence of coronary artery anomalies has been increasing due to the increasing usage of coronary angiography. There is a paucity of literature concerning management of viral-induced myocarditis in patients with anomalous coronary artery. We present a very unusual case of a 44-year-old man with anomalous origin of the left circumflex artery from the proximal ostium of the right coronary artery who was admitted for COVID-19-induced myocarditis. He presented with signs of heart failure and coronary angiography revealed the left circumflex artery with a separate ostium originating from the proximal right coronary artery. He was treated medically with Bisoprolol, Perindopril Arginine, Rivaroxaban, and Furosemide. His condition improved rapidly and he resumed regular life within 1 month. Coexistence of cardiac disease such as viral-induced myocarditis with an underlying anomalous origin of the coronary artery is challenging to spot and can lead to worse outcomes in case of misdiagnosis and inaccurate management., Competing Interests: Conflicts of interest: No conflicts of interest declared concerning the publication of this article., (Copyright© 2022 The authors.)

Objectives: To identify individual and clinical risk factors of aggressiveness, including exposure to different forms of childhood trauma, in a sample of Lebanese patients with schizophrenia., Methods: A total of 131 patients diagnosed with schizophrenia participated in this cross-sectional study., Results: Higher physical (Beta = 0.24, p < 0.001) and sexual (Beta = 0.29, p = 0.003) abuse, alcohol drinking (Beta = 1.46, p = 0.008), having a history of head trauma (Beta = 1.10, p = 0.041), and male gender (Beta = -1.59, p = 0.009) were significantly associated with higher mean aggression scores., Practical Implications: Our investigation of the factors linked to aggressiveness in patients with schizophrenia complement those of earlier findings, showing that the relationship between interacting individual and environmental risk factors and later aggressiveness is quite complex, and needs further longitudinal and prospective studies., (© 2022 Wiley Periodicals LLC.)

Background: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm-NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure., Materials and Methods: Dietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55-75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models., Results: Compared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (β coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; <0.001; 6.27 [2.46, 10.09]; <0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60]; <0.001; 1.19 [0.89, 1.50]; <0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown., Conclusion: This prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure., Competing Interests: JSS served on the board of the International Nut and Dried Fruit Council and receives grant support through this institution. He also served in the Executive Committee of the Instituto Danone, Spain, and on the Scientific Committee of the Danone International Institute. He received research support from the Patrimonio Comunal Olivarero, Spain, and Borges S.A., Spain. He received consulting fees or travel expenses from Eroski Foundation, the Instituto Danone, Spain, Mundipharma and Abbot Laboratories. ER reports grants, personal fees, non-financial support, and others from California Walnut Commission and Alexion, personal fees, non-financial support, and others from Ferrer International and Danone, and personal fees from Amarin, other than the submitted study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khoury, Gómez-Donoso, Martínez, Martínez-González, Corella, Fitó, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, León-Acuña, Tinahones, Santos-Lozano, Serra-Majem, Massó Guijarro, Tur, Martín Sánchez, Pintó, Delgado-Rodríguez, Matía-Martín, Vidal, Vázquez, Daimiel, Ros, Bes-Rastrollo, Barragan, Castañer, Torres-Peña, Notario-Barandiaran, Muñoz-Bravo, Abete, Prohens, Cano-Ibáñez, Tojal Sierra, Fernández-García, Sayon-Orea, Pascual, Sorli, Zomeño, Peña-Orihuela, Signes-Pastor, Basterra-Gortari, Schröeder, Salas Salvadó and Babio.)

Background: Genetic mutations underlying familial Alzheimer's disease (AD) were identified decades ago, but the field is still in search of transformative therapies for patients. While mouse models based on overexpression of mutated transgenes have yielded key insights in mechanisms of disease, those models are subject to artifacts, including random genetic integration of the transgene, ectopic expression and non-physiological protein levels. The genetic engineering of novel mouse models using knock-in approaches addresses some of those limitations. With mounting evidence of the role played by microglia in AD, high-dimensional approaches to phenotype microglia in those models are critical to refine our understanding of the immune response in the brain., Methods: We engineered a novel App knock-in mouse model (App SAA ) using homologous recombination to introduce three disease-causing coding mutations (Swedish, Arctic and Austrian) to the mouse App gene. Amyloid-β pathology, neurodegeneration, glial responses, brain metabolism and behavioral phenotypes were characterized in heterozygous and homozygous App SAA mice at different ages in brain and/ or biofluids. Wild type littermate mice were used as experimental controls. We used in situ imaging technologies to define the whole-brain distribution of amyloid plaques and compare it to other AD mouse models and human brain pathology. To further explore the microglial response to AD relevant pathology, we isolated microglia with fibrillar Aβ content from the brain and performed transcriptomics and metabolomics analyses and in vivo brain imaging to measure energy metabolism and microglial response. Finally, we also characterized the mice in various behavioral assays., Results: Leveraging multi-omics approaches, we discovered profound alteration of diverse lipids and metabolites as well as an exacerbated disease-associated transcriptomic response in microglia with high intracellular Aβ content. The App SAA knock-in mouse model recapitulates key pathological features of AD such as a progressive accumulation of parenchymal amyloid plaques and vascular amyloid deposits, altered astroglial and microglial responses and elevation of CSF markers of neurodegeneration. Those observations were associated with increased TSPO and FDG-PET brain signals and a hyperactivity phenotype as the animals aged., Discussion: Our findings demonstrate that fibrillar Aβ in microglia is associated with lipid dyshomeostasis consistent with lysosomal dysfunction and foam cell phenotypes as well as profound immuno-metabolic perturbations, opening new avenues to further investigate metabolic pathways at play in microglia responding to AD-relevant pathogenesis. The in-depth characterization of pathological hallmarks of AD in this novel and open-access mouse model should serve as a resource for the scientific community to investigate disease-relevant biology., (© 2022. The Author(s).)

Food fortification and folic acid supplementation during pregnancy have been implemented as strategies to prevent fetal malformations during pregnancy. However, with the emergence of conditions where folate metabolism and transport are disrupted, such as folate receptor alpha autoantibody (FRαAb)-induced folate deficiency, it is critical to find a folate form that is effective and safe for pharmacologic dosing for prolonged periods. Therefore, in this study, we explored the absorption and tissue distribution of folic acid (PGA), 5-methyl-tetrahydrofolate (MTHF), l-folinic acid (levofolinate), and d,l-folinic acid (Leucovorin) in adult rats. During absorption, all forms are converted to MTHF while some unconverted folate form is transported into the blood, especially PGA. The study confirms the rapid distribution of absorbed folate to the placenta and fetus. FRαAb administered, also accumulates rapidly in the placenta and blocks folate transport to the fetus and high folate concentrations are needed to circumvent or overcome the blocking of FRα. In the presence of FRαAb, both Leucovorin and levofolinate are absorbed and distributed to tissues better than the other forms. However, only 50% of the leucovorin is metabolically active whereas levofolinate is fully active and generates higher tetrahydrofolate (THF). Because levofolinate can readily incorporate into the folate cycle without needing methylenetetrahydrofolate reductase (MTHFR) and methionine synthase (MS) in the first pass and is relatively stable, it should be the folate form of choice during pregnancy, other disorders where large daily doses of folate are needed, and food fortification.

Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare and distinct type of hepatocellular carcinoma that frequently presents in an advanced stage in younger patients with no underlying liver disease. Currently, there is a limited understanding of factors that impact outcomes in FL-HCC., Aim: To characterize the survival of FL-HCC by age, race, and surgical intervention., Methods: This is a retrospective study of The Surveillance, Epidemiology, and End Results database. We identified patients with FL-HCC between 2000-2018 by using an ICD-O-3 site code C22.0 and a histology code 8171/3: Hepatocellular carcinoma, fibrolamellar. In addition, demographics, tumor characteristics, types of surgical procedure, stages, and survival data were obtained. We conducted three separate survival analyses by age groups; ≤ 19, 20-59, and ≥ 60-year-old, and race; White, Black, Hispanic, Asian and Pacific islanders (API), and surgical types; Wedge resection or segmental resection, lobectomy, extended lobectomy (lobectomy + locoregional therapy or resection of the other lobe), and transplant. The Chi-Square test analyzed categorical variables, and continuous variables were examined using the Mann-Whitney U test. The Kaplan-Meier survival curve was used to compare survival. Multivariate analysis was done with Cox regression analysis., Results: We identified 225 FL-HCC patients with a mean age of 36.9. Overall median survival was 34 (95%CI: 27-41) mo. Patients ≤ 19-years-old had more advanced disease with positive lymph nodes status. However, they received more surgical interventions such as a wedge, segmental resection, lobectomy, extended lobectomy, and transplant. Survival for ≤ 19 was 85 (95%CI: 37-137) mo, age 20-59 was 29 (95%CI: 18-41) mo, and age ≥ 60 years was 12 (95%CI: 7-31) mo ( P < 0.001). There were no differences in stage, lymph node status, metastasis status, and surgical treatment among races. The median survival were; Whites had 39 (95%CI: 29-63), Blacks 26 (95%CI: 5-92), Hispanics 31 (95%CI: 11-54), and APIs 28 (95%CI: 5-39) mo ( P = 0.28). Of 225 patients, 111 FL-HCC patients had surgical procedures. Median survivals for a wedge or segmental resection was 112 (95%CI: 78-NA), lobectomy was 92 (95%CI: 57-NA), extended lobectomy was 54 (95%CI: 23-NA), and a transplant was 63 (95%CI: 20-NA) mo ( P < 0.001). The median survival was better in patients who had surgical treatments regardless of lymph nodes or metastasis status ( P < 0.001)., Conclusion: FL-HCC occurs in a primarily younger population, but survival can be prolonged despite the aggressive disease. There were no racial differences in the survival of FL-HCC; however, Asians with FL-HCC tended to be older than in other races. Surgical treatment provided better survival even in those patients with nodal disease or metastases. Although future studies are needed to explore other therapies for FL-HCC, surgical options should be considered in all cases of FL-HCC unless contraindicated., Competing Interests: Conflict-of-interest statement: Wong LL is a speaker bureau for Eisai. All other authors do not have any conflicts of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Acute kidney injury (AKI) in deceased donors is not associated with graft failure (GF). We hypothesize that hemodynamic AKI (hAKI) comprises the majority of donor AKI and may explain this lack of association., Methods: In this ancillary analysis of the Deceased Donor Study, 428 donors with available charts were selected to identify those with and without AKI. AKI cases were classified as hAKI, intrinsic (iAKI), or mixed (mAKI) based on majority adjudication by three nephrologists. We evaluated the associations between AKI phenotypes and delayed graft function (DGF), 1-year eGFR and GF. We also evaluated differences in urine biomarkers among AKI phenotypes., Results: Of the 291 (68%) donors with AKI, 106 (36%) were adjudicated as hAKI, 84 (29%) as iAKI and 101 (35%) as mAKI. Of the 856 potential kidneys, 669 were transplanted with 32% developing DGF and 5% experiencing GF. Median 1-year eGFR was 53 (IQR: 41-70) ml/min/1.73m2. Compared to non-AKI, donors with iAKI had higher odds DGF [aOR (95%CI); 4.83 (2.29, 10.22)] and had lower 1-year eGFR [adjusted B coefficient (95% CI): -11 (-19, -3) mL/min/1.73 m2]. hAKI and mAKI were not associated with DGF or 1-year eGFR. Rates of GF were not different among AKI phenotypes and non-AKI. Urine biomarkers such as NGAL, LFABP, MCP-1, YKL-40, cystatin-C and albumin were higher in iAKI., Conclusion: iAKI was associated with higher DGF and lower 1-year eGFR but not with GF. Clinically phenotyped donor AKI is biologically different based on biomarkers and may help inform decisions regarding organ utilization., Competing Interests: The authors have declared that no competing interests exist.

Expandable endoprostheses provide a limb salvage option for skeletally immature patients with bone sarcoma of the lower extremities. Initial reports of the Repiphysis prosthesis were encouraging; however, medium-term follow-up revealed high complication rates. We report on the long-term follow-up of a cohort of patients treated with the Repiphysis prosthesis. Eleven patients were included in the study. Data collected included sex, age at surgery, duration of follow-up, site of disease, histologic diagnosis, number of lengthening sessions, amount lengthened, postoperative complications, endoprosthetic failure, mode of endoprosthetic failure, duration from index surgery to failure and to revision, type of revision surgery and final limb-length discrepancy. The average duration of follow-up from the time of surgery was 180 months (range, 144-215 months). Fifteen Repiphysis implants were used in 11 patients. All implants failed with an average time from surgery to failure of 36 months (range, 3-72 months). Twenty-four complications were observed: one wound dehiscence, two deep infections, 18 mechanical failures, implant collapse with destruction of proximal tibia epiphysis in two and one periprosthetic proximal femur fracture with dislodgement of the stem. Despite being an option for limb salvage, the Repiphysis prosthesis has a high rate of mechanical failure and need for revision, similar to other expandable implants. The authors, therefore, recommend full disclosure of the potential short- and long-term complications and need for revision, as well as alternative treatment options if their use is considered. Level of evidence: IV (Therapeutic)., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The human brain vasculature is of great medical importance: its dysfunction causes disability and death 1 , and the specialized structure it forms-the blood-brain barrier-impedes the treatment of nearly all brain disorders 2,3 . Yet so far, we have no molecular map of the human brain vasculature. Here we develop vessel isolation and nuclei extraction for sequencing (VINE-seq) to profile the major vascular and perivascular cell types of the human brain through 143,793 single-nucleus transcriptomes from 25 hippocampus and cortex samples of 9 individuals with Alzheimer's disease and 8 individuals with no cognitive impairment. We identify brain-region- and species-enriched genes and pathways. We reveal molecular principles of human arteriovenous organization, recapitulating a gradual endothelial and punctuated mural cell continuum. We discover two subtypes of human pericytes, marked by solute transport and extracellular matrix (ECM) organization; and define perivascular versus meningeal fibroblast specialization. In Alzheimer's disease, we observe selective vulnerability of ECM-maintaining pericytes and gene expression patterns that implicate dysregulated blood flow. With an expanded survey of brain cell types, we find that 30 of the top 45 genes that have been linked to Alzheimer's disease risk by genome-wide association studies (GWASs) are expressed in the human brain vasculature, and we confirm this by immunostaining. Vascular GWAS genes map to endothelial protein transport, adaptive immune and ECM pathways. Many are microglia-specific in mice, suggesting a partial evolutionary transfer of Alzheimer's disease risk. Our work uncovers the molecular basis of the human brain vasculature, which will inform our understanding of overall brain health, disease and therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)