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Study Question: Could sperm and leukocyte telomere length (TL) be associated with sperm quality parameters and reproductive health in men from the general population?, Summary Answer: A positive association between sperm and leukocyte TL with sperm concentration and total count has been demonstrated., What Is Known Already: Male factors account for almost half of cases of couple infertility, and shorter TLs have been observed in sperm from men with impaired sperm parameters. However, evidence in men from the general population is limited., Study Design Size Duration: A total of 200 volunteers of reproductive age were recruited between February 2021 and April 2023 to participate in the Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters (Led-Fertyl) cross-sectional study., Participants/materials Setting Methods: TLs in sperm and leukocytes were measured using quantitative polymerase chain reaction (qPCR) in 168 and 194 participants, respectively. Sperm parameters, including concentration, total count, motility, vitality, and morphology, were analyzed using a computer-assisted sperm analysis (CASA) SCA ® system according to the World Health Organization (WHO) 2010 guidelines. Multivariable regression models were performed to assess the associations between sperm and leukocyte TL, either in tertiles or as continuous variables, and sperm quality parameters while adjusting for potential confounders., Main Results and the Role of Chance: Participants in tertiles 2 (T2) and 3 (T3) of sperm TL showed a higher sperm concentration (β: 1.09; 95% CI: 0.09-2.09 and β: 2.06; 95% CI: 1.04-3.09 for T2 and T3, respectively; P -trend < 0.001), compared to those in the reference tertile (T1). Participants in the highest tertile of sperm TL showed higher total sperm count (β: 3.83; 95% CI: 2.08-5.58 for T3 vs T1; P -trend < 0.001). Participants in the top tertile of leukocyte TL showed higher sperm concentration (β: 1.49; 95% CI: 0.44-2.54 for T3 vs T1; P -trend = 0.004), and total count (β: 3.49; 95% CI: 1.62-5.35 for T3 vs T1; P -trend < 0.001) compared with participants in T1. These results remained consistent when sperm and leukocyte TL were modelled as continuous variables., Limitations Reasons for Caution: One limitation is the impossibility of establishing a cause-effect relationship due to the cross-sectional study design. Additionally, the sample size of the study cannot be considered large., Wider Implications of the Findings: Sperm and leukocyte TLs are associated with sperm quality parameters in the general population. Additional determinations and further studies with larger sample sizes are needed to clarify the mechanisms underlying these associations and to investigate the further implications., Study Funding/competing Interests: The Led-Fertyl study was supported by the Spanish government's official funding agency for biomedical research, Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS) and co-funded by the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' (PI21/01447), and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S., senior author of the present study, is partially supported by ICREA under the ICREA Academia program. M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI&#95;B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). All authors declare that they have no conflicts of interest., Trial Registration Number: N/A., Competing Interests: All authors declare that they have no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Study Question: Is ultra-processed food (UPF) consumption associated with semen quality parameters?, Summary Answer: Higher UPF consumption was inversely associated with total sperm count, sperm concentration, and total motility in men of reproductive age., What Is Known Already: The consumption of UPF, which has been rising during the last decades, has been demonstrated to be positively associated with several chronic diseases such as diabetes or cardiovascular diseases. However, the scientific evidence on its potential impact on semen quality remains notably limited., Study Design Size Duration: A cross-sectional analysis was conducted using data from 200 healthy men (mean age 28.4 ± 5.5 years) enrolled in the Led-Fertyl (Lifestyle and Environmental Determinants of Seminogram and Other Male Fertility-Related Parameters) study between February 2021 and April 2023., Participants/materials Setting Methods: UPF consumption (% of energy from UPF) was estimated according to the NOVA classification system using a validated 143-item semi-quantitative food frequency questionnaire. Total sperm count, sperm concentration, sperm vitality, total motility, progressive motility, and normal sperm forms were set as the main outcomes. Microscopic parameters were analyzed using a phase-contrast microscope and a computer-assisted sperm analysis (CASA) system. Semen samples were collected and tested according to World Health Organization 2010 standards. Multivariable linear regression models were fitted to estimate the associations between UPF tertile and semen quality parameters., Main Results and the Role of Chance: Sperm concentration ( β : -1.42 × 10 6 spz./ml; 95% CI: -2.72 to -0.12) and motility ( β : -7.83%; 95% CI: -15.16 to -0.51) were lower in participants in the highest tertile of UPF compared to the lowest. A similar association was observed for sperm count when UPF was analyzed per 10% increment of energy from UPF consumption ( β : -1.50 × 10 6 spz.; 95% CI: -2.83 to -0.17). Theoretically replacing 10% of energy from UPF consumption with 10% of energy from unprocessed or minimally processed food consumption was associated with a higher total sperm count, sperm concentration, total motility, progressive motility, and normal sperm forms., Limitations Reasons for Caution: Cross-sectional studies do not permit the drawing of causal inferences. Measurement errors and reporting bias cannot be entirely ruled out., Wider Implications of the Findings: This work suggests that consumption of UPF may have an impact on certain semen quality parameters. Furthermore, opting for unprocessed or minimally processed foods instead of UPFs could potentially benefit semen quality. If these results are replicated in future epidemiological studies with different long-term designs, these novel findings could provide valuable insights for updating or even designing preventive and interventional programs to address infertility among men of reproductive age., Study Funding/competing Interests: This study was supported by the Spanish government's official funding agency for biomedical research, ISCIII, through the Fondo de Investigación para la Salud (FIS), the European Union ERDF/ESF, 'A way to make Europe'/'Investing in your future' [PI21/01447], and the Diputació de Tarragona (2021/11-No.Exp. 8004330008-2021-0022642). J.S.-S. gratefully acknowledges the financial support of ICREA under the ICREA Academia program. C.V.-H. received a predoctoral grant from the Generalitat de Catalunya (2022 FI&#95;B100108). M.Á.M. was supported by the Sara Borrell postdoctoral fellowship (CD21/00045-Instituto de Salud Carlos III (ISCIII)). M.F.d.l.P. was supported by a predoctoral grant from the Rovira i Virgili University and Diputació de Tarragona (2020-PMF-PIPF-8). All authors have no conflict of interest to declare., Trial Registration Number: N/A., Competing Interests: All authors have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology.)

Over the past five decades, there have been multiple advances in the treatment of congenital heart defects, resulting in an increasing population of adults living with congenital heart disease (CHD). Despite improved survival, CHD patients often have residual haemodynamic sequelae and limited physiologic reserve and are at increased risk for acute decompensation with occurrence of arrhythmias, heart failure, and other medical conditions. Comorbidities occur more frequently and at an earlier age in CHD patients than in the general population. The management of the critically ill CHD patient requires an understanding of the unique aspects of congenital cardiac physiology as well as the recognition of other organ systems that may be involved. Certain patients may be candidates for mechanical circulatory support, and goals of care should be established with advanced care planning., Competing Interests: Conflict of interest: A.M.V. is supported by the Sarah M. Liamos Fund for Adult Congenital Heart Disease Research., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Lung pneumatoceles represent a potential life-threatening complication of pneumonia in infants, especially when they do not spontaneously reabsorb. In this category of patients, scientific literature lacks and no consensus guidelines for management have been proposed. Imaging plays a key role in the diagnosis, characterization, and follow-up of pneumatoceles. Image-guided percutaneous drainage can be considered a safe and effective treatment in children, although it is not widely recognized in newborns and infants. The aim of this case series review is to describe the main CT features of complicated or persistent pneumatoceles in infants and to highlight the potential role of image-guided percutaneous drainage as an effective approach for their treatment. Successful management of four infants affected by pneumonia-related pneumatoceles with percutaneous drainage is presented., (© 2022 The Authors. Published by the British Institute of Radiology.)

The Ebola virus is a deadly human pathogen responsible for several outbreaks in Africa. Its genome encodes the 'large' L protein, an essential enzyme that has polymerase, capping and methyltransferase activities. The methyltransferase activity leads to RNA co-transcriptional modifications at the N7 position of the cap structure and at the 2'-O position of the first transcribed nucleotide. Unlike other Mononegavirales viruses, the Ebola virus methyltransferase also catalyses 2'-O-methylation of adenosines located within the RNA sequences. Herein, we report the crystal structure at 1.8 Å resolution of the Ebola virus methyltransferase domain bound to a fragment of a camelid single-chain antibody. We identified structural determinants and key amino acids specifically involved in the internal adenosine-2'-O-methylation from cap-related methylations. These results provide the first high resolution structure of an ebolavirus L protein domain, and the framework to investigate the effects of epitranscriptomic modifications and to design possible antiviral drugs against the Filoviridae family., (© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Amyotrophic lateral sclerosis is characterized by the degeneration of upper and lower motor neurons, yet an increasing number of studies in both mouse models and patients with amyotrophic lateral sclerosis suggest that altered metabolic homeostasis is also a feature of disease. Pre-clinical and clinical studies have shown that modulation of energy balance can be beneficial in amyotrophic lateral sclerosis. However, the capacity to target specific metabolic pathways or mechanisms requires detailed understanding of metabolic dysregulation in amyotrophic lateral sclerosis. Here, using the superoxide dismutase 1, glycine to alanine substitution at amino acid 93 (SOD1 G93A ) mouse model of amyotrophic lateral sclerosis, we demonstrate that an increase in whole-body metabolism occurs at a time when glycolytic muscle exhibits an increased dependence on fatty acid oxidation. Using myotubes derived from muscle of amyotrophic lateral sclerosis patients, we also show that increased dependence on fatty acid oxidation is associated with increased whole-body energy expenditure. In the present study, increased fatty acid oxidation was associated with slower disease progression. However, within the patient cohort, there was considerable heterogeneity in whole-body metabolism and fuel oxidation profiles. Thus, future studies that decipher specific metabolic changes at an individual patient level are essential for the development of treatments that aim to target metabolic pathways in amyotrophic lateral sclerosis., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objective: The frequency of enostosis incidentally found on CT and CT attenuation value to distinguish them from untreated osteoblastic metastases (UOM)., Methods: Enostosis group: 46 polytrauma patients underwent thoracoabdominal CT. Inclusion criteria: age range 14-35 years. Exclusion criteria: cancer, previous fractures. UOM group: 20 patients with radiological diagnosis of UOM. Analyzed data: number, size, location and density of enostoses and metastases. The density was measured with the broadest possible region of interest at the center of the lesion by two radiologists independently. Receiver operatingcharacteristic analysis to determine the sensitivity and specificity, area under the curve 95% confidence intervals and cutoff values of CT density to differentiate metastases from enostoses., Results: Patients were 28 ± 7 years old (72% males). 41 (89%) patients had 124 enostoses (2-15 mm) with an average density of 1007 ± 122 Hounsfiled unit (HU, observer1) and 1052 ± 107 (observer2). The most common sites of occurrence were the proximal femur (34%), the pelvis (22%), the acetabulum (20%), the proximal humerus (11%), the vertebrae (11%) and the rib (2%). 13 patients had 1 bone island, 8 patients had 2, 9 cases had 3 and 11 cases had more than 3 enostoses. Overall, 114 UOM were evaluated, their average density was 728 ± 163 HU (observer1) and 712 ± 178 HU (observer2). The area under the curve value of mean density to distinguish enostoses from UOM was 0,982. Using a cut-off of 881 HU for mean density, sensitivity was 98% and specificity 95%., Conclusion: The frequency of enostosis in this study is 89%. The average density identified can help to distinguish enostoses from UOM., Advances in Knowledge: We report the exact frequency of enostosis.

This work aimed at characterizing the role of peroxisome proliferator-activated receptors (PPAR)alpha in human white adipocyte metabolism and at comparing PPAR alpha and PPAR gamma actions in these cells. Primary cultures of human fat cells were treated with the PPAR alpha agonist GW7647 or the PPAR gamma agonist rosiglitazone. Changes in gene expression were determined using DNA microarrays and quantitative RT-PCR. Western blot and metabolic studies were performed to identify the biological effects elicited by PPAR agonist treatments. GW7647 induced an up-regulation of beta-oxidation gene expression and increased palmitate oxidation. Unexpectedly, glycolysis was strongly reduced at transcriptional and functional levels by GW7647 leading to a decrease in pyruvate and lactate production. Glucose oxidation was decreased. Triglyceride esterification and de novo lipogenesis were inhibited by the PPAR alpha agonist. GW7647-induced alterations were abolished by a treatment with a PPAR alpha antagonist. Small interfering RNA-mediated extinction of PPAR alpha gene expression in hMADS adipocytes attenuated GW7647 induction of palmitate oxidation. Rosiglitazone had no major impact on glycolysis and beta-oxidation. Altogether these results show that PPAR alpha can selectively up-regulate beta-oxidation and decrease glucose utilization in human white adipocytes.

Context: Retinol-binding protein 4 (RBP4) may play a role in the development of insulin resistance., Objective: We investigated whether RBP4 adipose tissue mRNA expression and plasma level are related to insulin sensitivity during a diet-induced weight loss., Design, Setting, Patients, and Intervention: Obese women followed a dietary intervention composed of a 4-wk very low-calorie diet (VLCD), a 2-month low-calorie diet, and 3-4 months of a weight maintenance (WM) phase., Main Outcome Measures: Clinical investigation was performed before and at the end of each phase. Insulin sensitivity was assessed with the euglycemic hyperinsulinemic clamp. Adipose tissue mRNA and plasma levels of RBP4 were determined using reverse transcription-quantitative PCR and ELISA, respectively., Results: Weight and fat mass decreased during VLCD and were stabilized during WM. Glucose disposal rate increased during VLCD and remained elevated thereafter. Plasma levels of RBP4 decreased after VLCD and, although increasing at subsequent phases, remained lower than prediet values. Adipose tissue mRNA levels were diminished after VLCD, and increased during low-calorie diet and WM to reach basal values. Basal RBP4 levels or diet-induced variations of RBP4 were not different in lean women and two groups of obese women with high- and low-insulin sensitivity., Conclusions: Severe calorie restriction promotes a reduction in adipose tissue and plasma levels of RBP4. The study does not bring evidence for a role for RBP4 in the regulation of diet-induced changes in insulin sensitivity.

Aim/hypothesis: Obesity is associated with increased triacylglycerol (TAG) storage in adipose tissue and insulin resistance. The mobilization of stored TAG is mediated by hormone-sensitive lipase (HSL) and the recently discovered adipose triglyceride lipase (ATGL). The aim of the present study was to examine whether ATGL and HSL mRNA and protein expression are altered in insulin-resistant conditions. In addition, we investigated whether a possible impaired expression could be reversed by a period of weight reduction., Methods: Adipose tissue biopsies were taken from obese subjects (n = 44) with a wide range of insulin resistance, before and just after a 10-wk hypocaloric diet. ATGL and HSL protein and mRNA expression was determined by Western blot and quantitative RT-PCR, respectively., Results: Fasting insulin levels and the degree of insulin resistance (using the homeostasis model assessment index for insulin resistance) were negatively correlated with ATGL and HSL protein expression, independent of age, gender, fat cell size, and body composition. Both mRNA and protein levels of ATGL and HSL were reduced in insulin-resistant compared with insulin-sensitive subjects (P < 0.05). Weight reduction significantly decreased ATGL and HSL mRNA and protein expression. A positive correlation between the decrease in leptin and the decrease in ATGL protein level after weight reduction was observed. Finally, ATGL and HSL mRNA and protein levels seem to be highly correlated, indicating a tight coregulation and transcriptional control., Conclusions: In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass. Data on weight reduction indicated that also other factors (e.g. leptin) relate to ATGL and HSL protein expression.

Streptococcus pneumoniae resistance to penicillin and erythromycin in relation to beta-lactam and macrolide consumption in Spain over 19 years (1979-1997) was studied from resistance data collected by a search of the literature. Antibiotic consumption was expressed in defined daily dosage (DDD)/1000 inhabitants/day. A significant relationship (P: < 0.001) between erythromycin resistance (MIC >/= 1 mg/L) and global macrolide consumption (r = 0.942), as well as between high-level penicillin resistance (MIC >/= 2 mg/L) and global beta-lactam consumption (r = 0.948) was observed. The relationship between erythromycin resistance and macrolide consumption was due mainly to consumption of macrolides taken twice a day (adjusted r(2) = 0.886). Prevalence of high-level penicillin resistance correlated with consumption of oral cephalosporins (adjusted r(2) = 0.877); however, there appeared to be no correlation of consumption of oral or parenteral aminopenicillins, narrow-spectrum penicillins or cephalosporins with intermediate-level penicillin resistance (MIC 0. 12-1 mg/L). The prevalence of high-level penicillin and of erythromycin resistance were also strongly correlated with each other (r = 0.903, P: < 0.001). In addition to global consumption, different categories of resistance (high or intermediate), and the differential capability of antibiotics to select resistance, must be taken into account when studying antibiotic impact on bacterial populations. Although this ecological analysis is not able to demonstrate a causal relationship between antibiotic consumption and development of resistance, it suggests that overuse of certain specific antibiotics is more likely to be related to the increase in drug-resistant strains of S. pneumoniae.