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Background and Aims: There is little evidence on the impact of current recommendations on the use of antiplatelet therapy during the perioperative and periprocedural period in our setting. The aim of this study was to analyze the incidence and clinical impact of inappropriate use of antiplatelet therapy in a population of patients undergoing surgery or a diagnostic or therapeutic procedure in "real life" in Spain., Methods: A prospective multicenter observational study of patients treated with antiplatelet agents requiring intervention was conducted. The incidence of thrombotic and hemorrhagic events at 30 days was analyzed according to peri-intervention management of antiplatelet therapy., Results: We included 643 patients (31.9% women, 39.0% over 75 years of age), most of them (87.7%) receiving aspirin as antiplatelet therapy at a dose of 100mg/day. Indications for antiplatelet therapy were ischemic heart disease (44.9%), cerebrovascular disease (21.7%), and peripheral vascular disease (23.0%). Ischemic risk was low in 74.3%, while 51.6% had a low bleeding risk of the intervention. Periprocedural management was considered appropriate in 61.7% of cases. 30-day incidence of the combined primary endpoint of thrombotic events and major bleeding (12.1% versus 5.0%; p=0.002) and 30-day mortality (5.2% versus 1.5%; p=0.008) were significantly higher in patients with inappropriate periprocedural management of antiplatelet agents., Conclusions: Despite current recommendations for the use of antiplatelet drugs in the perioperative/periprocedural period, their implementation in the "real world" remains low. Inappropriate use is associated with an increased incidence of adverse events, both thrombotic and hemorrhagic., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

The crystal structure of the salt calcium (2R,3R)-tartrate tetrahydrate {systematic name: poly[[diaqua[μ 4 -(2R,3R)-2,3-dihydroxybutanedioato]calcium(II)] dihydrate]}, {[Ca(C 4 H 8 O 8 )(H 2 O) 2 ]·2H 2 O} n , is reported. The absolute configuration of the crystal was established unambiguously using anomalous dispersion effects in the diffraction patterns. High-quality data also allowed the location and free refinement of all the H atoms, and therefore to a careful analysis of the hydrogen-bond interactions., (open access.)

Hepatic bile acid regulation is a multifaceted process modulated by several hepatic transporters and enzymes. Drug-induced cholestasis (DIC), a main type of drug-induced liver injury (DILI), denotes any drug-mediated condition in which hepatic bile flow is impaired. Our ability in translating preclinical toxicological findings to human DIC risk is currently very limited, mainly due to important interspecies differences. Accordingly, the anticipation of clinical DIC with available in vitro or in silico models is also challenging, due to the complexity of the bile acid homeostasis. Herein, we assessed the in vitro inhibition potential of 47 marketed drugs with various degrees of reported DILI severity towards all metabolic and transport mechanisms currently known to be involved in the hepatic regulation of bile acids. The reported DILI concern and/or cholestatic annotation correlated with the number of investigated processes being inhibited. Furthermore, we employed univariate and multivariate statistical methods to determine the important processes for DILI discrimination. We identified time-dependent inhibition (TDI) of cytochrome P450 (CYP) 3A4 and reversible inhibition of the organic anion transporting polypeptide (OATP) 1B1 as the major risk factors for DIC among the tested mechanisms related to bile acid transport and metabolism. These results were consistent across multiple statistical methods and DILI classification systems applied in our dataset. We anticipate that our assessment of the two most important processes in the development of cholestasis will enable a risk assessment for DIC to be efficiently integrated into the preclinical development process., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Staphylococcus aureus prosthetic valve endocarditis (SAPVE) is a serious infection with high mortality. The main objective of this study was to identify factors associated with in-hospital mortality., Methods: From January 2008 to December 2021, consecutive patients from a Spanish cohort of infective endocarditis with a definitive diagnosis of SAPVE were analyzed., Results: During the study period, 219 cases of definitive SAPVE were diagnosed, which accounted for 16.7% of a total of 1309 cases of definitive prosthetic valve endocarditis (PVE). Patients presented advanced age and marked comorbidity. There was a higher incidence of persistent bacteremia, septic shock, stroke, and acute kidney injury than in cases of PVE caused by other microorganisms. Methicillin resistance was not associated with differences in clinical presentation, echocardiographic findings, or mortality. Only 50.6% of the patients with surgical indications (88 patients) underwent surgery. Overall, in-hospital mortality was 47.9%. The variables associated with in-hospital mortality were age (OR:1.03, 95% CI: 1.00-1.05; p = 0.016), heart failure (OR:2.86, 95% CI: 1.53-5.32; p = 0.001), acute kidney injury (OR:2.42, 95%CI:1.28-4.58; p = 0.006), stroke (OR:3.53, 95%CI:1.79-6.96; p < 0.001) and surgery indicated but not performed (OR:2.01, 95%CI:1.06-3.8; p = 0.030). On the other hand, the performance of surgery per se in patients with SAPVE, regardless of whether there was a surgical indication according to the guidelines, was not associated with a reduction in in-hospital mortality., Conclusions: SAPVE is characterized by high mortality, which is more marked in patients who present a surgical indication but do not undergo surgery., (© 2024. The Author(s).)

One hundred and forty bitches and their offspring (689 puppies) were involved in this study. The influence of different maternal features such as age, breed (brachycephalic/non-brachycephalic), previous births (primiparous/multiparous), health status (complete/incomplete) and litter size over the type of cesarean sections (scheduled/emergency), the neonatal survival, and the incidence of congenital malformations were also examined. Scheduled cesareans were predominant (104/140), of which 90 % were brachycephalic breeds and females were mostly between 2 and 4 years old (54.8 %), multiparous (88.4 %) and with a correct health status (67.3 %). Emergency cesarean sections mainly involved non-brachycephalic breeds (80 %) and were carried out mostly in females under 4 years of age (72.2 %), primiparous (77.7 %), with incomplete health status and a large litter size (47.2 %). Perinatal mortality was notably higher in emergency C-sections (3.25 % and 13.3 %, scheduled and emergency C-sections, respectively); the highest incidence of neonatal mortality was recorded in young females (<2, 2-4 years old), primiparous and with incomplete health status. Congenital anomalies were observed in 4.50 % (31/689) of the puppies, with anasarca (38.71 %) and cleft palate (29.03 %) being the most frequently observed malformations. A higher incidence of congenital malformations was detected in puppies from dams with incomplete sanitary health and from inbreeding cross. Overall, the study provides valuable insights into the complex interplay between maternal characteristics and cesarean outcomes. Appropriate genetic selection, good sanitary health conditions, and the age of the reproducers, are pivotal factors in planning for gestation and improving the survival of neonates., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: This study assessed quit attempts among adults who use cigarettes either exclusively or with e-cigarettes in Mexico, where non-daily smoking predominates., Methods: An open cohort of Mexican adults who smoke was surveyed every four months from November 2018 to March 2021. Participants followed to the next survey were analyzed (n = 2220 individuals, 4560 observations). Multinomial logistic models regressed smoking quit attempts reported at the followup survey (ref = no attempt; tried to quit; sustained attempt of ≥30 days) on e-cigarette use frequency (none = ref; 1-2 days/week; ≥3 days/week), adjusting for sociodemographics and smoking-related variables. Additional models subdivided e-cigarette users by intentions to quit smoking in the next six months (i.e., yes/no), use of nicotine (i.e., yes/no), and vaping device used (i.e., open/closed)., Results: At 4-month follow-up, 32.7 % had tried to quit, and 2.9 % had quit for 30 days or more. Compared to those who smoke exclusively, occasional, and frequent e-cigarette users were more likely to try to quit (Adjusted Relative Risk Ratio or ARRR = 1.26 and 1.66, respectively) but no more likely to sustain their quit attempt. Among those who intended to quit smoking, e-cigarette users were no more likely to either try or sustain quit attempts. Furthermore, use of e-cigarettes with nicotine (59.6 %) was unassociated with cessation except that those who frequently used e-cigarettes with nicotine were more likely to try to quit than those who smoke exclusively (ARRR = 1.88). Device type used was not differentially associated with outcomes., Conclusions: Mexicans who smoke and use e-cigarettes appear more likely than those who smoke exclusively to try to quit but not to sustain abstinence., 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 Ltd.)

Parasites, including pathogens, can adapt to better exploit their hosts on many scales, ranging from within an infection of a single individual to series of infections spanning multiple host species. However, little is known about how the genomes of parasites in natural communities evolve when they face diverse hosts. We investigated how Bartonella bacteria that circulate in rodent communities in the dunes of the Negev Desert in Israel adapt to different species of rodent hosts. We propagated 15 Bartonella populations through infections of either a single host species (Gerbillus andersoni or Gerbillus pyramidum) or alternating between the two. After 20 rodent passages, strains with de novo mutations replaced the ancestor in most populations. Mutations in two mononucleotide simple sequence repeats (SSRs) that caused frameshifts in the same adhesin gene dominated the evolutionary dynamics. They appeared exclusively in populations that encountered G. andersoni and altered the dynamics of infections of this host. Similar SSRs in other genes are conserved and exhibit ON/OFF variation in Bartonella isolates from the Negev Desert dunes. Our results suggest that SSR-based contingency loci could be important not only for rapidly and reversibly generating antigenic variation to escape immune responses but that they may also mediate the evolution of host specificity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Rodríguez-Pastor et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Importance: Drug-resistant temporal lobe epilepsy (TLE) has been associated with hippocampal pathology. Most surgical treatment strategies, including resection and responsive neurostimulation (RNS), focus on this disease epicenter; however, imaging alterations distant from the hippocampus, as well as emerging data from responsive neurostimulation trials, suggest conceptualizing TLE as a network disorder., Objective: To assess whether brain networks connected to areas of atrophy in the hippocampus align with the topography of distant neuroimaging alterations and RNS response., Design, Setting, and Participants: This retrospective case-control study was conducted between July 2009 and June 2022. Data collection for this multicenter, population-based study took place across 4 tertiary referral centers in Montréal, Canada; Querétaro, México; Nanjing, China; and Salt Lake City, Utah. Eligible patients were diagnosed with TLE according to International League Against Epilepsy criteria and received either neuroimaging or neuroimaging and RNS to the hippocampus. Patients with encephalitis, traumatic brain injury, or bilateral TLE were excluded., Main Outcomes and Measures: Spatial alignment between brain network topographies., Results: Of the 110 eligible patients, 94 individuals diagnosed with TLE were analyzed (51 [54%] female; mean [SD] age, 31.3 [10.9] years). Hippocampal thickness maps in TLE were compared to 120 healthy control individuals (66 [55%] female; mean [SD] age, 29.8 [9.5] years), and areas of atrophy were identified. Using an atlas of normative connectivity (n = 1000), 2 brain networks were identified that were functionally connected to areas of hippocampal atrophy. The first network was defined by positive correlations to temporolimbic, medial prefrontal, and parietal regions, whereas the second network by negative correlations to frontoparietal regions. White matter changes colocalized to the positive network (t93 = -3.82; P = 2.44 × 10-4). In contrast, cortical atrophy localized to the negative network (t93 = 3.54; P = 6.29 × 10-3). In an additional 38 patients (20 [53%] female; mean [SD] age, 35.8 [11.3] years) treated with RNS, connectivity between the stimulation site and atrophied regions within the negative network was associated with seizure reduction (t212 = -2.74; P = .007)., Conclusions and Relevance: The findings in this study indicate that distributed pathology in TLE may occur in brain networks connected to the hippocampal epicenter. Connectivity to these same networks was associated with improvement following RNS. A network approach to TLE may reveal therapeutic targets outside the traditional target in the hippocampus.

Introduction: Patients with sickle cell disease exhibit different patterns in pulmonary function tests. In particular, there is little evidence on the fractional exhaled nitric oxide (FeNO) test, and its value ranges and its interpretation in these patients have been under debate in recent years., Methods: We conduced a cross-sectional, observational and descriptive study between November 2021 and January 2023 including patients aged 6-18 years with sickle cell disease able to perform the FeNO test. We applied the GLI-2012 reference values and the ERS/ATS standards. We defined statistical significance as P < 0.05., Results: The sample included 43 patients with a median age of 12 years (IQR, 10-15). We did not find an association between significantly elevated FeNO (≥25 ppb) and the diagnosis of asthma (P = 0.37), an obstructive pattern in spirometry (P = 0.67), a positive bronchodilator test (P = 0.53), clinical bronchial hyperreactivity in the context of cold or flu-like symptoms (P = 0.48), cough with exercise (P = 0.42) or nocturnal cough (P = 1.0), but found an association with peripheral eosinophilia (P < 0.01)., Conclusions: We found no association between FeNO values and the classic features of asthma (clinical or spirometric) in patients with sickle cell disease. Therefore, airway inflammation mechanisms are probably different in these patients., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Limited data exist on educational programs for people using insulin pump (IP) therapy or those considering its initiation, and the influence of individual characteristics on their educational pathway remains unclear. Our aim was to analyze the characteristics of people with type 1 diabetes (T1D) referred for IP therapy and how these characteristics may influence their educational process. A retrospective descriptive observational study was carried out on people with T1D referred for participation in a structured pre-IP educational program in a hospital setting. Educational, sociodemographic and clinical variables were collected and analyzed. Participants were followed up 5 years after IP placement. Seventy-one people finalized the educational program, of whom 10 experienced major barriers to completing it. People with lower educational level required more sessions and weeks to complete it compared to those with higher educational levels. People referred due to suboptimal metabolic control and hypoglycemia also required more time to complete the process. It is essential for diabetes educators to recognize the diversity of characteristics, needs and challenges among the participants in an educational program. Based on this, they must adapt strategies to provide more effective, person-centered diabetes education and support, fostering positive and sustained outcomes and engagement for participants., (© The Author(s) 2024. Published by Oxford University Press.)

Background: There are numerous mobile health (mHealth) interventions for treatment adherence and self-management; yet, little is known about user engagement or interaction with these technologies., Objective: This systematic review aimed to answer the following questions: (1) How is user engagement defined and measured in studies of mHealth interventions to promote adherence to prescribed medical or health regimens or self-management among people living with a health condition? (2) To what degree are patients engaging with these mHealth interventions? (3) What is the association between user engagement with mHealth interventions and adherence or self-management outcomes? (4) How often is user engagement a research end point?, Methods: Scientific database (Ovid MEDLINE, Embase, Web of Science, PsycINFO, and CINAHL) search results (2016-2021) were screened for inclusion and exclusion criteria. Data were extracted in a standardized electronic form. No risk-of-bias assessment was conducted because this review aimed to characterize user engagement measurement rather than certainty in primary study results. The results were synthesized descriptively and thematically., Results: A total of 292 studies were included for data extraction. The median number of participants per study was 77 (IQR 34-164). Most of the mHealth interventions were evaluated in nonrandomized studies (157/292, 53.8%), involved people with diabetes (51/292, 17.5%), targeted medication adherence (98/292, 33.6%), and comprised apps (220/292, 75.3%). The principal findings were as follows: (1) >60 unique terms were used to define user engagement; "use" (102/292, 34.9%) and "engagement" (94/292, 32.2%) were the most common; (2) a total of 11 distinct user engagement measurement approaches were identified; the use of objective user log-in data from an app or web portal (160/292, 54.8%) was the most common; (3) although engagement was inconsistently evaluated, most of the studies (99/195, 50.8%) reported >1 level of engagement due to the use of multiple measurement methods or analyses, decreased engagement across time (76/99, 77%), and results and conclusions suggesting that higher engagement was associated with positive adherence or self-management (60/103, 58.3%); and (4) user engagement was a research end point in only 19.2% (56/292) of the studies., Conclusions: The results revealed major limitations in the literature reviewed, including significant variability in how user engagement is defined, a tendency to rely on user log-in data over other measurements, and critical gaps in how user engagement is evaluated (infrequently evaluated over time or in relation to adherence or self-management outcomes and rarely considered a research end point). Recommendations are outlined in response to our findings with the goal of improving research rigor in this area., Trial Registration: PROSPERO International Prospective Register of Systematic Reviews CRD42022289693; https://www.crd.york.ac.uk/prospero/display&#95;record.php?ID=CRD42022289693., (©Cyd Eaton, Natalie Vallejo, Xiomara McDonald, Jasmine Wu, Rosa Rodríguez, Nishanth Muthusamy, Nestoras Mathioudakis, Kristin A Riekert. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 24.09.2024.)

Objective: Respiratory syncytial virus (RSV) bronchiolitis is the leading cause of hospitalization in infants. This season, a long half-life monoclonal antibody (Nirsevimab) is available to prevent this disease for all infants born from 1 April-30 September to 2023 and all those born during RSV season (October2023- March 2024). The aim of this study was to evaluate the impact of the implementation of this antibody on RSV admissions in a tertiary hospital., Methods: Observational, retrospective and analytical study. All patients <6 months in October admitted for bronchiolitis at 2 time points were included: T1 or Pre-nirsevimab time: 1 September 2015-30 September 2023 and T2 or Nirsevimab time: 1 October-31 December 2023. Total admissions due to any cause of infants <6 months in the same period were used as the reference population. To assess the impact of the implementation of nirsevimab, we calculated the reduction in the percentage of admissions due to RSV with respect to total admissions in both periods, and also in the 2023-2024 season we calculated the double negative test to calculate the effectiveness of the intervention (1-Odds ratio) x 100., Results: In infants under 6 months of age, we found significant differences in the number of admissions for RSV bronchiolitis between the last season and the previous 7 seasons [574/1195 (48%) vs 6/138 (4.3%); p<0.01, RPI: 91%). In the 2023/2024 season, the effectiveness of nirsevimab in preventing admission for RSV bronchiolitis in children under 6 months of age was 85% (CI 95%: 32-97%)., Conclusions: The implementation of nirsevimab has had an important impact on the number of hospital admissions for RSV bronchiolitis. There were no differences in the severity of bronchiolitis., (©The Author 2024. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Oropharyngeal Dysphagia (OD) increases the risk of hospitalization and the use of health services; however, it is often detected and studied in institutionalized patients with limited attention given to the community. The aim of this study was to determine the prevalence of OD and its associated factors after conducting a program consisting of a systematic assessment of OD for in patients living independently in their dwellings and requiring home-based care. We conducted a cross-sectional study involving a systematic assessment of disabled and elderly patients enrolled in a home-based primary care program at three urban centers (Barcelona, Spain). OD was assessed using the Volume-Viscosity Swallow Test. Data on morbidity, incontinence, functional independence, pressure sore risk, brain deficit, social risk, nutritional status, and healthcare utilization were collected. Prevalence was determined, and differences between OD and non-OD patients were analysed using independent tests. Associations between OD and hospital admissions, emergency department visits, emergency home ambulance use, and consultations with family physicians or primary care nurses were examined using logistic regression models adjusted for covariates. We included 1,002 patients with a mean age of 88.75 years old (SD = 8.19), 73.05% of whom were female. The prevalence of OD was 25.95% (95% CI 23.26%-28.78%). OD was associated with past pneumonia episodes (adjusted OR: 5.09, 95% CI: 2.2-11.79), increased frequency of cough and common cold (adjusted OR: 1.11, 95% CI: 1.05-1.18), and more family physician consultations (adjusted OR: 1.07, 95% CI: 1.03-1.10). These findings highlight that OD remains an underdiagnosed geriatric syndrome in the community setting. Implementing systematic OD diagnoses assessments, especially among home care-based patients could reduce the incidence of secondary pneumonia, decrease cough episodes, and lower the frequency of clinician consultations., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Smilax genus possesses bioactive properties attributed to phenolic compounds, which may exhibit antioxidant effects and inhibit the advanced glycation end products (AGEs). However, identifying these phenolic compounds and AGEs has become increasingly relevant to understanding such activities. This study aimed to identify phenolic compounds in extracts of Smilax spp. and evaluate their antioxidant and AGEs inhibitory activities. To achieve this, the Smilax genus was identified via PCR, and phenolic compounds including chlorogenic acid, naringenin-6-C-glucoside, quercetin, quercetin-3-O-glucoside, and myricetin were identified using HPLC-MS/MS. Antioxidant activity was assessed by ferric reducing antioxidant power (FRAP), and radicals such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2'-azino-bis-[3-ethyl-benzothiazoline]-6-sulfonic acid (ABTS), while AGEs inhibition was evaluated using a model system formed by bovine serum albumin-glucose. The highest antioxidant activity was 3612.18 mM TE/g, and the inhibition of AGEs was 52.44 %. These results demonstrate that Smilax spp. can inhibit AGEs, neutralize free radicals, and reduce compounds associated with antioxidant capacity., Competing Interests: Declaration of competing interest There are no activities that may have any conflict of interest 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. The group of authors declares no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: The aim of this study was to assess the accuracy of a surface-guided radiotherapy (SGRT) system for setup and intra-fraction motion control in frameless non-coplanar stereotactic radiosurgery (fSRS) using actual patient data immobilized with two different types of open-faced masks and employing a novel SGRT systems settings., Methods and Materials: Forty-four SRS patients were immobilized with two types of open-faced masks. Sixty lesions were treated, involving the analysis of 68 cone-beam scans (CBCT), 157 megavoltage (MV) images, and 521 SGRT monitoring sessions. The average SGRT translations/rotations and 3D vectors (MAG-Trasl and MAG-Rot) were compared with CBCT or antero-posterior MV images for 0° table or non-coplanar beams, respectively. The intrafraction control was evaluated based on the average shifts obtained from each monitoring session. To assess the association between the SGRT system and the CBCT, the two types of masks and the 3D vectors, a generalized estimating equations (GEE) regression analysis was performed. The Wilcoxon singed-rank test for paired samples was performed to detect differences in couch rotation with longitudinal (LNG) and lateral (LAT) translations and/or yaw., Results: The average SGRT corrections were smaller than those detected by CBCT (≤0.5 mm and 0.1°), with largest differences in LNG and yaw. The GEE analysis indicated that the average MAG-Trasl, obtained by the SGRT system, was not statistically different (p = 0.09) for both mask types, while, the MAG-Rot was different (p = 0.01). For non-coplanar beams, the Wilcoxon singed-rank test demonstrated no significantly differences for the corrections (LNG, LAT, and yaw) for any table rotation except for LNG corrections at 65° (p = 0.04) and 75° (p = 0.03) table angle position; LAT shifts at 65° (p = 0.03) and 270° (p < 0.001) table angle position, and yaw rotation at 30° (p = 0.02) table angle position. The average intrafraction motion was < 0.1 mm and 0.1° for any table angle., Conclusion: The SGRT system used, along with the novel workflow performed, can achieve the setup and intra-fraction motion control accuracy required to perform non-coplanar fSRS treatments. Both masks ensure the accuracy required for fSRS while providing a suitable surface for monitoring., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics is published by Wiley Periodicals, Inc. on behalf of The American Association of Physicists in Medicine.)

Background: Health systems are fundamental to the promotion and protection of breastfeeding. Health professionals have a pivotal influence on families' infant feeding decisions and may act as facilitators or barriers to adequate breastfeeding practices., Research Aim: To explore factors influencing health professionals' decisions regarding the indication of infant formula in Montevideo, the capital of Uruguay, an emerging Latin American country., Method: This was a qualitative study based on semi-structured interviews with 30 health professionals (neonatologists, pediatricians, family doctors, and nurses) working in primary and secondary care in both private and public health institutions. The interviews were audio-recorded, transcribed, and analyzed using content analysis based on deductive-inductive coding., Results: The narratives of the participants identified maternity wards as the healthcare sites where the indication of infant formula occurs most frequently. Motives underlying the indication of infant formula by health professionals were diverse. The type of birth and the conditions of the child and the mother were the most relevant in secondary care, whereas maternal work was the main determining factor in primary care. A wide range of factors encouraging and discouraging the indication of infant formula were identified by health professionals in primary and secondary healthcare locations, which were related to all the levels of influence of the socioecological model., Conclusions: Strategies to reduce the use of infant formula in Uruguay should include improving the support and guidance provided to families in the maternity ward, strengthening the implementation and monitoring of the Baby-Friendly Hospital Initiative, and improving the current maternity leave regulations., Competing Interests: Disclosures and Conflicts of InterestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aim: To determine the proportion of people who undergo discharge follow-up when indicated., Design: Retrospective longitudinal observational study, with an analytical approach., Population: persons discharged from the Hospital Universitario de la Princesa of any age and sex, with any reason for admission and with an indication for discharge follow-up in Primary Care. Users who did not have an assigned Autonomous Personal Identification Code (CIPA) were excluded. Random sample (n=289)., Variables: Discharge follow-up and readmissions (<30 days). Sociodemographic, clinical and discharge follow-up variables were included from the electronic medical records of Primary and Hospital Care. A descriptive analysis of the sociodemographic and clinical characteristics of the study population was conducted. To analyze the association between discharge follow-up and readmissions, a logistic regression model was used., Results: Age 72.4 years (RIQ 60-87). 55.2% of the population were women. Follow-up was conducted in 61.2% of those indicated. According to the logistic regression model performed between early readmission and discharge follow-up, adjusted for all other factors, the group with discharge follow-up had a 66% lower likelihood of hospital readmission (OR 0.34, 95% CI (0.18-0.67))., Conclusions: These findings suggest that nursing discharge follow-up conducted in primary care reduces the risk of early readmission., (Copyright © 2024 The Author(s). Publicado por Elsevier España S.L.U. All rights reserved.)

Background: Obesity increases reactive oxygen species production and alters adipokines levels, resulting in a low-grade chronic inflammation state, which contributes to tissue metabolic dysfunction. 10-gingerol, a phenol present in ginger, has shown potential anti-obesogenic effects in vitro. However, the antioxidant and anti-inflammatory properties of 10-gingerol have not been approached. The aim of this study was to investigate the effects of 10-gingerol on antioxidant enzymes' expression and adipokine production in 3T3-L1 adipocytes in response to lipopolysaccharide (LPS)-induced inflammation., Methods: 10-gingerol antioxidant capacity was assessed through Oxygen Radical Absorbance Capacity (ORAC) , Ferric Reducing Antioxidant Power (FRAP), and radical scavenging activity of 2,2-diphenyl-2-picrylhydrazyl (DPPH) assays. 3T3-L1 cells were differentiated and stimulated with 100 ng/mL LPSs. Then, 15 µg/mL 10-gingerol was added for 48 h. The mRNA expression and protein abundance of antioxidant enzymes were evaluated by qPCR and Western blot, respectively. Adipokine levels were determined by ELISA., Results: 10-gingerol showed low FRAP and DPPH values but a moderate ORAC value. Moreover, 10-gingerol increased Gpx1 and Sod1 but downregulated Cat expression. Additionally, 10-gingerol significantly increased CAT and GPx1 levels but not SOD-1. Finally, adiponectin and leptin concentrations were increased while resistin and tumor necrosis factor alpha (TNFα) were decreased by 10-gingerol., Conclusions: 10-gingerol presented antioxidant potential by increasing antioxidant enzymes and attenuated LPS-induced inflammation by modulating adipokines in 3T3-L1 adipocytes.

Objectives: Host responses to infection are a major determinant of outcome. However, the existence of different response profiles in patients with endocarditis has not been addressed. Our objective was to apply transcriptomics to identify endotypes in patients with infective endocarditis., Methods: A total of 32 patients with infective endocarditis were studied. Clinical data and blood samples were collected at diagnosis and RNA sequenced. Gene expression was used to identify two clusters (endocarditis endotype 1 [EE1] and endocarditis endotype 2 [EE2]). RNA sequencing was repeated after surgery. Transcriptionally active cell populations were identified by deconvolution. Differences between endotypes in clinical data, survival, gene expression, and molecular pathways involved were assessed. The identified endotypes were recapitulated in a cohort of COVID-19 patients., Results: A total of 18 and 14 patients were assigned to EE1 and EE2, respectively, with no differences in clinical data. Patients assigned to EE2 showed an enrichment in genes related to T-cell maturation and a decrease in the activation of the signal transducer and activator of transcription protein family pathway, with higher counts of active T cells and lower counts of neutrophils. A total of 14 patients (nine in EE1 and five in EE2) were submitted to surgery. Surgery in EE2 patients shifted gene expression toward a EE1-like profile. In-hospital mortality was higher in EE1 (56% vs 14%, P = 0.027), with an adjusted hazard ratio of 12.987 (95% confidence interval 3.356-50). Translation of these endotypes to COVID-19 and non-COVID-19 septic patients yielded similar results in cell populations and outcome., Conclusions: Gene expression reveals two endotypes in patients with acute endocarditis, with different underlying pathogenetic mechanisms, responses to surgery, and outcomes., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To describe the proportion of patients with liver fibrosis in at-risk populations in primary care (PC). To know the agreement between FIB-4 and transitional elastography (TE), interobserver agreement between PC and hospital care (HC) in TE, and associated risk Factors (RF)., Methods: Observational, descriptive, cross-sectional study in ≥16 years of age with RF for chronic liver disease. Sex and age, RF (alteration of liver tests [LT], metabolic syndrome, diabetes, obesity, alcohol consumption, hepatic steatosis), and FIB-4, controlled attenuation parameter and TE in PC and in HC, were collected. According to a consensus algorithm, vibration-controlled TE was performed in PC in patients with FIB-4≥1,3, and those with measurement ≥8kPa were referred to HC., Results: 326 patients were studied. 71% were not referred to HC, due to liver stiffness <8kPa. 83 of the 95 derivations did TE in HC. 45 (54%) had TE ≥8, and 25 (30%) ≥12. The proportion of patients with stiffness ≥8kPa was 13,8% (45/326) and ≥12kPa, 7,6% (25/326). The predictive values of the FIB-4 were low. The interobserver correlation coefficient between TE in PC and HC was 0,433. Variables associated with TE ≥8 in PC: LT alteration, diabetes and steatosis. With TE ≥12: LT alteration, diabetes and obesity., Predictor Variables: LT alteration and obesity., Conclusions: The study supports the sequential performance of serum indices and TE as a screening for fibrosis in the at-risk population in PC, which allows a reduction in the percentage of patients referred to AH, and a better stratification of risk patients., (Copyright © 2024 Elsevier España, S.L.U. All rights reserved.)

Chirality at the metal center is a well-established concept, exemplified by numerous four- and six-coordinated complexes. Here, a pioneering example of linear chirality-at-metal is described: L-2-[Ag(NHC)2]+ (NHC = N-heterocyclic carbene). In solution, stabilizing π-π interactions preserve the chiral information of the solid state. Consequently, a novel class of atropisomers is identified, whose stereogenicity arises from hindered rotation about a C-Ag-C axis, instead of a typical C-C bond., (© 2024 Wiley‐VCH GmbH.)

Lasso peptides, ribosomally synthesized and post-translationally modified peptides, are primarily produced by bacteria and some archaea. Streptomyces lasso peptides have been known for their antimicrobial, anticancer, and antiviral properties. However, understanding their role in the morphology and production of secondary metabolites remains limited. We identified a previously unknown lasso peptide gene cluster in the genome of Streptomyces sp. L06. This gene cluster (LASS) produces two distinct lasso peptides, morphosin-1 and - 2. Notably, morphosin-2 is a member of a new subfamily of lasso peptides, with BGCs exhibiting a similar structure. When LASS was expressed in different Streptomyces hosts, it led to exciting phenotypic changes, including the absence of spores and damage in aerial mycelium development. In one of the hosts, LASS even triggered antibiotic formation. These findings open up a world of possibilities, suggesting the potential role of morphosins in shaping Streptomyces' morphological and biochemical development., (© 2024. The Author(s).)

In this paper, we analyze the influence of the perceived level of economic inequality in daily life on people's recognition of the perceived humanity gap between low- and high-socioeconomic groups within society. To achieve this purpose, in Studies 1A-B, we analyzed the relationship between economic inequality and the humanity gap. In Studies 2A-B, we manipulated the level of inequality (low vs. high) to identify differences in the humanity gap. Results indicated that higher perceptions of economic inequality lead individuals to recognize a wider humanity gap between low- and high-socioeconomic groups in society. Implications are discussed.

Purpose: We report the 5-year study closeout results for the ROBUST I trial evaluating the safety and efficacy of the Optilume drug-coated balloon (DCB) for men with short, recurrent bulbar urethral strictures., Materials and Methods: Adult men with recurrent bulbar urethral strictures ≤ 2 cm long and lumen < 12F were included in the study and treated with the Optilume DCB. Outcome measures included symptom questionnaires, maximum urinary flow rate, postvoid residual, and freedom from repeat intervention. Functional success was defined as improvement in International Prostate Symptom Score ≥ 50% without re-treatment., Results: Fifty-three men were enrolled and treated, and 31 subjects completed all follow-up. Functional success was achieved in 58% (25/43) patients at 5 years. Average International Prostate Symptom Score improved from a mean of 25.2 at baseline to 7.2 at 5 years ( P < .001). Freedom from repeat intervention was maintained through 5 years at 71.7% estimated by Kaplan-Meier. Maximum urinary flow rate improved from 5.0 mL/s at baseline to 19.9 ( P < .01), and average postvoid residual was reduced from 141.4 mL to 59.5 mL ( P < .01) at 5 years of follow-up. Erectile function remained unaffected. There were no serious treatment-related adverse events., Conclusions: In this challenging cohort of men with failed prior endoscopic treatment, the Optilume DCB shows sustained improvement in subjective and objective voiding parameters at 5 years. Optilume is a safe and effective treatment option for appropriately selected men with recurrent bulbar urethral stricture who wish to avoid urethroplasty. Results are in line with the ROBUST III randomized controlled trial that will continue follow-up through 5 years., Clinical Trial No.: : NCT03014726.

Between the 8th and 11th centuries CE, the Iberian Peninsula underwent profound upheaval due to the Umayyad invasion against the Visigoths, resulting in population shifts and lasting demographic impacts. Our understanding of this period is hindered by limited written sources and few archaeogenetic studies. We analyzed 33 individuals from Las Gobas, a necropolis in northern Spain, spanning the 7th to 11th centuries. By combining archaeological and osteological data with kinship, metagenomics, and ancestry analyses, we investigate conflicts, health, and demography of these individuals. We reveal intricate family relationships and genetic continuity within a consanguineous population while also identifying several zoonoses indicative of close interactions with animals. Notably, one individual was infected with a variola virus phylogenetically clustering with the northern European variola complex between ~885 and 1000 CE. Last, we did not detect a significant increase of North African or Middle East ancestries over time since the Islamic conquest of Iberia, possibly because this community remained relatively isolated.

Tuberculosis (TB) is an important infectious disease in relation to global public health and is caused species of the Mycobacterium tuberculosis complex (MTBC). In this study, we used whole-genome sequencing (WGS) and comparative genomics to investigate the genetic diversity of M. tuberculosis ( Mtb ) isolates circulating in North Santander (NS), Colombia. WGS was used for the phylogenetic and lineage characterization of 18 isolates of Mtb typed with orphan genotypes from 11 municipalities of NS between 2015 and 2018. The isolates studied were included in six sublineages from L4; the most frequent were 4.1.2.1, 4.3.3, and 4.3.4.2, corresponding to a proportion of 22.2%. The genome analysis conducted allowed the identification of a set of genetic variants mainly associated with determinants of virulence and evasion of the immune system ( PPE34 and PE&#95;PGRS2 ); adaptation and survival ( PGL/p-HBAD ); stress response ( sigJ and sigM ); geographic variability ( PPE34 ); and carbohydrate and lipid metabolism ( aldA , rocA , and cyp144 ). This is the first description of the molecular epidemiology of Mtb isolates circulating in NS achieved through WGS. It was possible to perform comparative genomics analyses between Mtb isolates against the universal reference H37Rv and Colombian UT205 genome, which can help us to understand the local genetic diversity and is relevant for epidemiological studies, providing insight into TB transmission dynamics in NS.

The shiitake mushroom has gained popularity in the last decade, ranking second in the world for mushrooms consumed, providing consumers with a wide variety of nutritional and healthy benefits. It is often not clear the origin of these mushrooms, so it becomes of great importance to the consumers. In this research, different machine learning algorithms were developed to determine the geographical origin of shiitake mushrooms ( Lentinula edodes ) consumed in Korea, based on experimental data reported in the literature (δ 13 C, δ 15 N, δ 18 O, δ 34 S, and origin). Regarding the origin of shiitake in three categories (Korean, Chinese, and mushrooms from Chinese inoculated sawdust blocks), the random forest model presents the highest accuracy value (0.940) and the highest kappa value (0.908) for the validation phase. To determine the origin of shiitake mushrooms in two categories (Korean and Chinese, including mushrooms from Chinese inoculated sawdust blocks in the latter ones), the support vector machine model is chosen as the best model due to the high accuracy (0.988) and kappa (0.975) values for the validation phase. Finally, to determine the origin in two categories (Korean and Chinese, but this time including the mushrooms from Chinese inoculated sawdust blocks in the Korean ones), the best model is the random forest due to its higher accuracy value (0.952) in the validation phase (kappa value of 0.869). The accuracy values in the testing phase for the best selected models are acceptable (between 0.839 and 0.964); therefore, the predictive capacity of the models could be acceptable for their use in real applications. This allows us to affirm that machine learning algorithms would be suitable modeling instruments to determine the geographical origin of shiitake.

Deviation of the nail plate in the transverse plane has traditionally been regarded as a postoperative complication following the definitive surgical treatment of ingrown toenails, particularly when only a single nail fold is addressed. The quantification and longitudinal comparison of the operated versus non-operated nail folds could elucidate potential transverse deviations of the nail plate. The objective of this study was to assess the presence or absence of transverse nail plate deviation following ingrown toenail surgery on a single nail fold., Methods: A cohort of 11 patients (three males, eight females) with recurrent ingrown toenails undergoing unilateral partial matricectomy were included in this study. Preoperative measurements were compared to those taken at 7, 14, 21, 28, and 35 days postoperatively., Results: The analysis revealed no statistically significant differences in measurements between the operated and non-operated nail folds, nor were there significant changes in the measurements over time within each group ( p > 0.05)., Conclusions: Despite the absence of visible deviations in the orientation of the nail plate, the angular measurements post-surgery at 35 days showed no statistically significant alterations. The angular values observed across all time points appeared to be influenced by the intrinsic morphological characteristics of each nail plate.

Acute myeloid leukemia (AML) is an aggressive hematological disease that mainly affects elderly patients. Following the randomized VIALE-A trial, current standard treatment in patients who are not candidates for intensive chemotherapy consists of the combination of venetoclax (VEN), a selective inhibitor of the anti-apoptotic protein BCL-2, with azacitidine (AZA) or decitabine (DEC). We performed a systematic review to critically assess the growing existing evidence regarding the effectiveness of the VEN-based combinations in unfit adult patients with newly diagnosed AML in the real-world setting. Following PRISMA guidelines, a systematic search of published manuscripts and conference abstracts (European Hematology Association and American Society of Hematology) was conducted (updated March 2024). Primary outcomes were composite complete remission (CRc) and median overall survival (mOS). A total of 73 studies fulfilled inclusion criteria, with a median age of 73 years old. The weighted mean mOS was 10.3 months among 7 138 patients, significantly lower than expected according to the VIALE-A trial (14.7 months), while the weighted mean CRc rate was 58.2% among 5 831 patients, slightly lower to that reported in the VIALE-A (66.4%). Early death rates at 30 and 60 days were 5% and 13%, respectively. The weighted mean percentage of subsequent allogeneic transplant was 15.4%. In conclusion, breakthrough mOS reported in the VIALE-A trial using VEN-AZA was not well reproduced in real world for unfit newly diagnosed AML patients, while CRc rates were more consistent. Strategies to optimize patient selection, dosing regimens, and supportive care are crucial to improve outcomes in real-world., (© 2024. The Author(s).)

Objective: To determine the pharmaceutical interventions in patients eligible for phase I cancer clinical trials, focusing specifically on exclusion criteria related to medication or relevant interactions., Method: Descriptive, observational study conducted at a comprehensive cancer centre. Patients undergoing screening for phase I clinical trials (March 2019-December 2022) were included. The pharmacist reviewed concomitant medication and provided a recommendation., Results: The concomitant medication of 512 patients eligible to participate in 84 phase I clinical trials was analysed. In 230 (44.9%) patients, the clinical trial treatment included oral medication. The median number of concomitant medications was 5 (IQR 3-8) per patient.A total of 280 pharmaceutical interventions were performed in 140 (27.3%) patients: 240 (85.7%) were due to interactions in 124 (24.2%) patients, and 40 (14.3%) were due to exclusion criteria in 34 (6.6%) patients. Interactions and exclusion criteria were detected in 18 (3.5%) patients. The main groups of drugs involved were 68 (24.3%) antacids and antiulcer drugs, 28 (10.0%) antidepressants and 26 (9.3%) opioids. Acceptance analysis of the recommendation was applicable in 215 cases; in 208 (96.7%), the pharmaceutical intervention was accepted.Differences were identified for exclusion criteria (7 vs 27) and interactions (37 vs 87) between parenteral and oral clinical trial medication (p<0.001)., Conclusion: The pharmacist's review of concomitant medication during the screening period in phase I clinical trials enables the detection of prohibited medication or relevant interactions, potentially avoiding screening failures and increasing the efficacy and safety of treatments., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

The effects of global warming are numerous and recent studies reveal that they can affect the timing of pollination. Temperature is the meteorological variable that presents a clearer relationship with the start of the pollination season of most of the observed airborne pollen taxa. In Catalonia, in the last fifty years, the average annual air temperature has increased by +0.23 °C/decade, and the local warming has been slightly higher than the one on a global scale. Projections point to an increase in temperature in the coming decades, which would be more marked towards the middle of the century. To analyse the effect of the increase in temperature due to global warming on the starting date of pollen season in Barcelona, a forecasting model has been applied to a set of projected future temperatures estimated by the European RESCCUE project. This model, largely used in the literature, is based on determining the thermal needs of the plant for the pollen season to begin. The model calibration to obtain the initial parameters has been made by using 20 years of pollen data (2000-2019), and the model effectiveness has subsequently been tested through an internal evaluation over the period of the calibration and an external evaluation on 4 years not included in the calibration (2020-2023). The mean bias error in the internal calibration ranged between -0.4 and - 0.6 days, and between +0.5 and - 8.3 in the external one, depending on the taxon. The results of the application of the model to the temperature projections over the 21st century point to a progressive advancement in the pollination dates of several pollen types abundant in the city, allergenic most of them. These advances ranged, at the end of the century, between 15 and 27 days, depending on the climate model, for the scenario of the highest concentrations (RCP8.5) and between 7 and 12 days for the emissions stabilization scenario (RCP4.5)., 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 B.V. All rights reserved.)

Silica-based scaffolds are promising in Tissue Engineering by enabling personalized scaffolds, boosting exceptional bioactivity and osteogenic characteristics. Moreover, silica materials are highly tunable, allowing for controlled drug release to enhance tissue regeneration. In this study, we developed a 3D printable silica material with controlled mesoporosity, achieved through the sol-gel reaction of tetraethyl orthosilicate (TEOS) at mild temperatures with the addition of different calcium concentrations. The resultant silica inks exhibited high printability and shape fidelity, while maintaining bioactivity and biocompatibility. Notably, the increased mesopore size enhanced the incorporation and release of large molecules, using cytochrome C as a drug model. Due to the varying surface charge of silica depending on the pH, a pH-dependent control release was obtained between pH 2.5 and 7.5, with maximum release in acidic conditions. Therefore, silica with controlled mesoporosity could be 3D printed, acting as a pH stimuli responsive platform with therapeutic potential., Competing Interests: 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., (© 2024 The Authors.)

Flourensia cernua DC, commonly known as hojasen or tarbush, is a medicinal plant used in arid regions due to its therapeutic properties, especially in the treatment of gastrointestinal disorders. This study aimed to assess the toxicity of a polyphenolic extract obtained from F. cernua . This research involved both in vitro (hemolytic and brine shrimp assay) and in vivo tests (acute oral toxicity) to determine the safety profile of this extract. The extract was obtained through a novel ultrasound-microwave extraction and purified by ion-exchange chromatography. Analysis of the polyphenolic extract revealed a rich composition of flavonoids and hydroxycinnamic acids, mainly apigenin glycosides. In toxicity tests, the polyphenols did not exhibit toxicity towards Artemia salina at a concentration of 1 mg/ml. Furthermore, incubation at 500  μ g/ml for 4 hours showed a slight toxic effect on erythrocytes. In the acute oral toxicity test in mice, doses of 300 mg/kg and 2000 mg/kg did not result in animal mortality, indicating that the LD 50 exceeds 2000 mg/kg. However, the higher dose induced signs of toxicity, including lethargy, drowsiness, piloerection, and a significant decrease in weight during the initial two days postadministration of the polyphenolic extract. In addition, histological analysis suggested potential kidney damage at the 2000 mg/kg dose. According to OECD guidelines, while the extract can be classified as category 5 (low acute toxicity) due to the absence of mortality at 2000 mg/kg, the observed signs of toxicity should be considered in the overall risk assessment. These findings highlight the potential of F. cernua in pharmaceutical and nutraceutical applications due to its high polyphenolic content. However, further investigations are necessary to explore the specific effects of the compounds present in the extract. In addition, continuous evaluation of its long-term toxicity is essential to fully understand the extract's safety profile and efficacy., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2024 Yulma Lizbeth Aguirre-García et al.)

Pneumonia continues to be one of the most frequent infectious syndromes and a relevant cause of death and health resources utilization. The OPENIN ("Optimización de procesos clínicos para el diagnóstico y tratamiento de infecciones") Group is composed of Infectious Diseases specialists and Microbiologists and aims at generating recommendations that can contribute to improve the approach to processes with high impact on the health system. Such task relies on a critical review of the available scientific evidence. The first Group meeting (held in October 2023) aimed at answering the following questions: Can we optimize the syndromic and microbiological diagnosis of pneumonia? Is it feasible to safely shorten the length of antibiotic therapy? And, is there any role for the immunomodulatory strategies based on the adjuvant use of steroids, macrolides or immunoglobulins? The present review summarizes the literature reviewed for that meeting and offers a series of expert recommendations., (Copyright © 2024 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Understanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions. This evaluation should be compared to established probes like lactulose, a non-digestible disaccharide indicative of paracellular permeability, and mannitol, reflecting transcellular permeability., Methods: Fifteen participants underwent simultaneous ingestion of standardized doses of gluten (10 g), lactulose (10 g), and mannitol (1 g) under fasting conditions for at least 8 hours pre-ingestion and during 6 hours post-ingestion period. Urine samples were collected over specified time intervals. Excretion patterns were analyzed, and correlations between the lactulose-to-mannitol ratio (LMR) and u-GIP parameters were assessed., Results: The majority of u-GIP were detected within the first 12 hours post-ingestion. Analysis of the variability in cumulative excretion across two sample collection ranges demonstrated that lactulose and u-GIP exhibited similar onset and excretion dynamics, although GIP reached its maximum peak earlier than either lactulose or mannitol. Additionally, a moderate correlation was observed between the LMR and u-GIP parameters within the longest urine collection interval, indicating potential shared characteristics among permeability pathways. These findings suggest that extending urine collection beyond 6 hours may enhance data reliability., Discussion: This study sheds light on the temporal dynamics of u-GIP in comparison to lactulose and mannitol, established probes for assessing intestinal permeability. The resemblance between u-GIP and lactulose excretion patterns aligns with the anticipated paracellular permeability pathway. The capacity to detect antigenic food protein fragments in urine opens novel avenues for studying protein metabolism and monitoring pathologies related to the digestive and intestinal systems., Competing Interests: ÁC is the founder and current CEO of Biomedal S.L. Seville, Spain; RR-R, MF, IM, and JL are employees at Biomedal S.L. The remaining author declares 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 © 2024 Rodríguez-Ramírez, Fernández Peralbo, Mendía, Long, Sousa and Cebolla.)

Cytomegalovirus (CMV) infection remains a significant challenge in solid organ transplantation (SOT). The last international consensus guidelines on the management of CMV in SOT were published in 2018, highlighting the need for revision to incorporate recent advances, notably in cell-mediated immunity monitoring, which could alter the current standard of care. A working group including members from the Group for the Study of Infection in Transplantation and the Immunocompromised Host (GESITRA-IC) of the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC) and the Spanish Society of Transplantation (SET), developed consensus-based recommendations for managing CMV infection in SOT recipients. Recommendations were classified based on evidence strength and quality using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The final recommendations were endorsed through a consensus meeting and approved by the expert panel., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Julian Torre-Cisneros reports administrative support, article publishing charges, travel, and writing assistance were provided by Spanish Society of Infectious Diseases and Clinical Microbiology. Julian Torre-Cisneros reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: consulting or advisory and speaking and lecture fees. Julian Torre-Cisneros reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory. Julian Torre-Cisneros reports a relationship with Biotest AG that includes: consulting or advisory and speaking and lecture fees. Julian Torre-Cisneros reports a relationship with QIAGEN GmbH that includes: consulting or advisory, funding grants, and speaking and lecture fees. Jose Maria Aguado reports a relationship with Mundipharma International Limited that includes: consulting or advisory and speaking and lecture fees. Jose Maria Aguado reports a relationship with Pfizer that includes: consulting or advisory and speaking and lecture fees. Jose Maria Aguado reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: consulting or advisory and speaking and lecture fees. Jose Maria Aguado reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory and speaking and lecture fees. Sara Cantisan reports a relationship with QIAGEN GmbH that includes: funding grants and speaking and lecture fees. Juan Jose Caston reports a relationship with Pfizer Inc. that includes: funding grants and speaking and lecture fees. Juan Jose Caston reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: speaking and lecture fees. Juan Jose Caston reports a relationship with A Menarini International Pharmaceutics that includes: speaking and lecture fees. Juan Jose Caston reports a relationship with Novartis Pharmaceuticals Corporation that includes: speaking and lecture fees. Juan Jose Caston reports a relationship with QIAGEN GmbH that includes: funding grants and speaking and lecture fees. Carme Facundo reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: consulting or advisory. Mirian Fernandez-Alonso reports a relationship with Roche Diagnostics Corporation that includes: travel reimbursement. Mirian Fernandez-Alonso reports a relationship with Werfen that includes: travel reimbursement. Mirian Fernandez-Alonso reports a relationship with QIAGEN GmbH that includes: non-financial support. Mario Fernandez-Ruiz reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: consulting or advisory. Mario Fernandez-Ruiz reports a relationship with Biotech that includes: consulting or advisory. Sabina Herrera reports a relationship with Pfizer Inc. that includes: speaking and lecture fees and travel reimbursement. Sabina Herrera reports a relationship with Shionogi Inc. that includes: speaking and lecture fees. Sabina Herrera reports a relationship with Shire that includes: travel reimbursement. Sabina Herrera reports a relationship with A Menarini International Pharmaceutics that includes: travel reimbursement. Oscar Len reports a relationship with Pfizer that includes: funding grants and speaking and lecture fees. Oscar Len reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: funding grants and speaking and lecture fees. Oscar Len reports a relationship with Astellas Pharma Inc. that includes: speaking and lecture fees. Oscar Len reports a relationship with Novartis Pharmaceuticals Corporation that includes: speaking and lecture fees. Ibai Los-Arcos reports a relationship with Pfizer Inc. that includes: speaking and lecture fees and travel reimbursement. Ibai Los-Arcos reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: speaking and lecture fees and travel reimbursement. Ibai Los-Arcos reports a relationship with Gilead Sciences Inc. that includes: travel reimbursement. Ibai Los-Arcos reports a relationship with A Menarini International Pharmaceutics that includes: travel reimbursement. David Navarro reports a relationship with Roche Diagnostics Corporation that includes: consulting or advisory and speaking and lecture fees. David Navarro reports a relationship with Abbott that includes: consulting or advisory and speaking and lecture fees. David Navarro reports a relationship with bioMérieux SA that includes: consulting or advisory and speaking and lecture fees. David Navarro reports a relationship with Beckton Dickinson that includes: consulting or advisory and speaking and lecture fees. David Navarro reports a relationship with Gilead Sciences Inc. that includes: consulting or advisory and speaking and lecture fees. David Navarro reports a relationship with Takeda Pharmaceutical Company Limited that includes: consulting or advisory and speaking and lecture fees. David Navarro reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: consulting or advisory and speaking and lecture fees. David Navarro reports a relationship with Pfizer Inc. that includes: consulting or advisory and speaking and lecture fees. Maricela Valerio reports a relationship with Pfizer Inc. that includes: speaking and lecture fees and travel reimbursement. Maricela Valerio reports a relationship with Merck Sharp & Dohme UK Ltd. that includes: speaking and lecture fees and travel reimbursement. Maricela Valerio reports a relationship with Shionogi and Co Ltd. that includes: speaking and lecture fees and travel reimbursement. Maricela Valerio reports a relationship with GSK that includes: speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Since the last century, it has been shown that dedifferentiated cells of Camellia sinensis can produce catechins and other secondary metabolites under in vitro conditions, with potential applications in the cosmetic, pharmaceutical and food industries. In this work, cell suspension cultures of a C. sinensis cell line (LSC-5Y) were established in a liquid medium in order to optimize the biomass productivity, catechin monomer (GC, EGC, C, EC, CG, and ECG) and alkaloid (TB and CAF) productivity. The following factors were evaluated: concentration of growth regulators (BA and IBA), inoculum size, age of the cell line, light exposure, and effect of biotic elicitors (MeJA and extracts of Ciborinia camelliae ). GC, EGC, and ECG increased approximately 1.80-fold when the auxin IBA concentration was increased from 0.1 to 2.0 mg/L. In addition, better productivity of EGC, C, EC, and CAF was achieved by using inoculum densities between 50 and 100 g/L. Although lower inoculum densities (25 g/L) showed a higher growth rate (0.20 d -1 ), the use of inoculum densities higher than 25 g/L favors a 2-4-fold increase in total catechin (TC) productivity, with maximum productivity being reached after 21 days of culture. However, the cell line showed instability in TC productivity: in the short term (in three successive subcultures), the coefficient of variation was 32.80%, and catechin production capacity was 2.5 years with maximum productivity at 0.5 years. Finally, it was observed that ethanol, used as an elicitor solvent, has a strong elicitor effect capable of increasing the accumulation of catechins up to 5.24 times compared to the treatment without an elicitor.

Origami biosensors leverage paper foldability to develop total analysis systems integrated in a single piece of paper. This capability can also be utilized to incorporate additional features that would be difficult to achieve with rigid substrates. In this article, we report a new design for 3D origami biosensors called OriPlex, which leverages the foldability of filter paper for the multiplexed detection of bacterial pathogens. OriPlex immunosensors detect pathogens by folding nanoparticle reservoirs containing different types of nanoprobes. This releases antibody-coated nanoparticles in a central channel where targets are captured through physical interactions. The OriPlex concept was demonstrated by detecting the respiratory pathogens Pseudomonas aeruginosa (PA) and Klebsiella pneumoniae (KP) with a limit of detection of 3.4·10 3  cfu mL -1 and 1.4·10 2  cfu mL -1 , respectively, and with a turn-around time of 25 min. Remarkably, the OriPlex biosensors allowed the multiplexed detection of both pathogens spiked into real bronchial aspirate (BAS) samples at a concentration of 10 5  cfu mL -1 (clinical infection threshold), thus demonstrating their suitability for diagnosing lower tract respiratory infections. The results shown here pave the way for implementing OriPlex biosensors as a screening test for detecting superbugs requiring personalized antibiotics in suspected cases of nosocomial pneumonia., Competing Interests: Declaration of competing interest The authors declare the following competing financial interest(s): Roberto de la Rica, Antonio Clemente, Cristina Adrover-Jaume, Estrella Rojo and Antonio Oliver have filed a patent application describing the method for sample liquefaction (P202030403). Roberto de la Rica, and Cristina Adrover-Jaume, have filed a patent application describing the method for storing nanoparticles in paper reservoirs (PCT/EP 2020/075,013). Andreu Vaquer, Roberto de la Rica, Cristina Adrover-Jaume, and Antonio Clemente are founders of Nanodecaldx S.L. and have a financial interest in the company., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The system of fertilizing agricultural soils with sludge or compost from wastewater treatment processes, as one of the principles of the circular economy, can lead to microplastic (MP) contamination. The existing technical standards for fertilization are very recent and do not consider this problem, although there is scientific evidence of their existence. Therefore, this study, on the one hand, evaluates the presence of MPs in agricultural soils, previously treated with sludge or compost from wastewater treatment plants for fertilization, and on the second hand, it studies the effect of these MPs on earthworms in three different locations in the south of Spain. For the study, selected composts deriving from the different stages of the composting process and three fertilized soils with increasing MP doses were followed. Samples were taken from different sections in depth (0-5, 5-10, and 10-20 cm) to study the shape, size, type, and abundance of MPs using infrared spectroscopy (FTIR). The results showed that the most abundant shape was fiber, followed by fragment and finally bulk, for both composts and soils. Regarding size distribution, 100 µm was the predominant size in composts (64.3% ± 9.8), while in the case of soils, the predominant range was from 100 to 500 µm. The prevalent polymers in both, composts and soils, were PTFE, TPE, PP, and PET, with four times higher amounts in composts than in soils. Ingestion of common MPs were also verified in two earthworm species, which ingested concentrations higher than 2.1% w/w. PP was the most ingested MP and Eisenia fetida was more voracious compared with Lumbricus terrestris. Therefore, it can be considered a suitable bioindicator for monitoring microplastic contamination in agricultural soil., (© 2024. The Author(s).)

Cardiogenic shock is characterized by tissue hypoperfusion due to the inadequate cardiac output to maintain the tissue oxygen demand. Despite some advances in cardiogenic shock management, extremely high mortality is still associated with this clinical syndrome. Its management is based on the immediate stabilization of hemodynamic parameters through medical care and the use of mechanical circulatory supports in specialized centers. This review aims to understand the cardiogenic shock current medical treatment, consisting mainly of inotropic drugs, vasopressors and coronary revascularization. In addition, we highlight the relevance of applying measures to other organ levels based on the optimization of mechanical ventilation and the appropriate initiation of renal replacement therapy., (Copyright © 2024 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.)

Experimental and clinical studies have indicated a potential role of the protein S100β in the pathogenesis and phenotype of neurodegenerative diseases. However, its impact on spinocerebellar ataxia type 2 (SCA2) remains to be elucidated. The objective of the study is to determine the serum levels of S100β in SCA2 and its relationship with molecular, clinical, cognitive, and peripheral inflammatory markers of the disease. Serum concentrations of S100β were measured by enzyme-linked immunosorbent assay in 39 SCA2 subjects and 36 age- and gender-matched controls. Clinical scores of ataxia, non-ataxia symptoms, cognitive dysfunction, and some blood cell count-derived inflammatory indices were assessed. The SCA2 individuals manifested S100β levels similar to the control group, at low nanomolar concentrations. However, the S100β levels were directly associated with a better performance of cognitive evaluation within the SCA2 cohort. Moreover, the S100β levels were inversely correlated with most peripheral inflammatory indices. Indeed, the neutrophil-to-lymphocyte ratio significantly mediated the effect of serum S100β on cognitive performance, even after controlling for the ataxia severity in the causal mediation analysis. Our findings suggested that, within physiologic concentrations, the protein S100β exerts a neuroprotective role against cognitive dysfunction in SCA2, likely via the suppression of pro-inflammatory mechanisms., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Neuroendocrine neoplasms (NENs) encompass tumors arising from neuroendocrine cells in various organs, including the gastrointestinal tract, pancreas, adrenal gland, and paraganglia. Despite advancements, accurately predicting the aggressiveness of gastroenteropancreatic (GEP) NENs based solely on pathological data remains challenging, thereby limiting optimal clinical management. Our previous research unveiled a crucial link between hypermethylation of the protocadherin PCDHGC3 gene and neuroendocrine tumors originating from the paraganglia and adrenal medulla. This epigenetic alteration was associated with increased metastatic potential and succinate dehydrogenase complex (SDH) dysfunction. Expanding upon this discovery, the current study explored PCDHGC3 gene methylation within the context of GEP-NENs in a cohort comprising 34 cases. We uncovered promoter hypermethylation of PCDHGC3 in 29% of GEP-NENs, with a significantly higher prevalence in gastrointestinal (GI) neuroendocrine carcinomas (NECs) compared with both pancreatic (Pan) NECs and neuroendocrine tumors (NETs) of GI and Pan origin. Importantly, these findings were validated in one of the largest multi-center GEP-NEN cohorts. Mechanistic analysis revealed that PCDHGC3 hypermethylation was not associated with SDH mutations or protein loss, indicating an SDH-independent epigenetic mechanism. Clinically, PCDHGC3 hypermethylation emerged as a significant prognostic factor, correlating with reduced overall survival rates in both patient cohorts. Significantly, whereas PCDHGC3 hypermethylation exhibited a strong correlation with TP53 somatic mutations, a hallmark of NEC, its predictive value surpassed that of TP53 mutations, with an area under the curve (AUC) of 0.95 (95% CI 0.83-1.0) for discriminating GI-NECs from GI-NETs, highlighting its superior predictive performance. In conclusion, our findings position PCDHGC3 methylation status as a promising molecular biomarker for effectively stratifying patients with GI-NENs. This discovery has the potential to advance patient care by enabling more precise risk assessments and tailored treatment strategies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland., (© 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.)

Introduction: Asthma is a common chronic disease in the paediatric age group that requires close follow-up. Clinical practice guidelines offer evidence-based recommendations to achieve adequate control of the disease., Objective: To assess the management of childhood asthma in the primary care setting in the Community of Madrid, and the adherence of health care professionals to guideline recommendations. To analyse the association of asthma management with age, the socioeconomic level of the catchment population and the workload of primary care centres., Methods: retrospective longitudinal study in patients aged 6-14 years newly diagnosed with asthma in primary care centres of the Community of Madrid in 2021. We analysed sociodemographic and clinical variables and the compliance with recommendations at the time of diagnosis and over 1 year of follow-up. The source of data was the electronic health record database of the primary care system., Results: We found a proportion of compliance with the recommendations upon diagnosis of the disease of 5.84%, with differences associated to the socioeconomic level of the catchment population (P = .033), and the pressure of care (P = .006). The proportion of compliance with recommendations during follow-up was 12.73%, with differences based on age (P = .01), socioeconomic level (P = 0.006) and centre workloads (P = .002)., Conclusions: Compliance with the recommendations of the main childhood asthma management guidelines in the primary care setting was low in the Community of Madrid. Strategies need to be implemented to improve the management of this disease and the adherence of professionals to the protocols developed for this purpose., (Copyright © 2024 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Background and Objectives: Interactive multimedia systems are widely used to enhance participation in meaningful activities for older people living with dementia. This review aims to analyze and synthesize current evidence regarding personalization of these systems, by considering the type of content included, the selection process and the experience of people living with dementia when interacting with the content., Materials and Methods: In accordance with PRISMA guidelines (PROSPERO registration number blinded for review), a systematic search was undertaken across 4 databases. Meta-aggregation pooled data for synthesis., Results: A total of 520 articles were identified from searches in four databases, and 15 were included in this review. Two classes of content were identified: personal, often autobiographical; and curated, carefully chosen generic content appropriate for a wider group of people in the demographic. Variety of content can act as a trigger for autobiographical memories. Personalized music enhanced a desire to engage and prompted meaningful interactions among participants., Discussion and Implications: Despite some differences in the selected studies, the findings enabled us outline key points to consider when personalizing interactive multimedia systems for people living with dementia. Further research should focus on studying the social condition of the target users during the personalization process and on the benefits for caregivers., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest regarding the research, authorship and/or publication of this article., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction: In recent decades, Caribbean coral reefs have lost many vital marine species due to diseases. The well-documented mass mortality event of the long-spined black sea urchin Diadema antillarum in the early 1980s stands out among these collapses. This die-off killed over 90% of D. antillarum changing the reefscape from coral to algal-dominated. Nearly 40 years later, D. antillarum populations have yet to recover. In early 2022, a new mortality event of D. antillarum was reported along the Caribbean, including Puerto Rico., Methods: This study identifies the gut microbiota changes associated with the D. antillarum during this mortality event. It contrasts them with the bacterial composition of gut samples from healthy individuals collected in 2019 by using 16S rRNA sequencing analyses., Results: Notably, the die-off group's core microbiome resembled bacteria commonly found in the human skin and gut, suggesting potential anthropogenic contamination and wastewater pollution as contributing factors to the 2022 dysbiosis. The animals collected in 2022, especially those with signs of disease, lacked keystone taxa normally found in Diadema including Photobacterium and Propionigenium ., Discussion: The association between human microbes and disease stages in the long-spined urchin D. antillarum , especially in relation to anthropogenic contamination, highlights a complex interplay between environmental stressors and marine health. While these microbes might not be the direct cause of death in this species of sea urchins, their presence and proliferation can indicate underlying issues, such as immune depletion due to pollution, habitat destruction, or climate change, that ultimately compromise the health of these marine organisms., 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., (Copyright © 2024 Ruiz-Barrionuevo, Kardas, Rodríguez-Barreras, Quiñones-Otero, Ruiz-Diaz, Toledo-Hernández and Godoy-Vitorino.)

PM742 ( 1 ), a new chemical entity, has been isolated from the sponge Discodermia du Bocage collected in the Pacific Ocean. This compound showed strong in vitro cytotoxicity against several human tumor cell lines as well as a tubulin depolymerization mechanism of action, which led us to conduct an extensive Structure-Activity-Relationship study through the synthesis of different analogs. As a result, a derivatively named PM534 ( 2 ) is currently in its first human Phase I clinical trial. Herein, we present a comprehensive review of the isolation, structural elucidation, and antitumor activities of the parent compound PM742.

Declarative memory encompasses episodic and semantic divisions. Episodic memory captures singular events with specific spatiotemporal relationships, while semantic memory houses context-independent knowledge. Behavioural and functional neuroimaging studies have revealed common and distinct neural substrates of both memory systems, implicating mesiotemporal lobe (MTL) regions such as the hippocampus and distributed neocortices. Here, we explored declarative memory system reorganization in patients with unilateral temporal lobe epilepsy (TLE) as a human disease model to test the impact of variable degrees of MTL pathology on memory function. Our cohort included 31 patients with TLE as well as 60 age and sex-matched healthy controls, and all participants underwent episodic and semantic retrieval tasks during a multimodal MRI session. The functional MRI tasks were closely matched in terms of stimuli and trial design. Capitalizing on non-linear connectome gradient mapping techniques, we derived task-based functional topographies during episodic and semantic memory states, both in the MTL and in neocortical networks. Comparing neocortical and hippocampal functional gradients between TLE patients and healthy controls, we observed a marked topographic reorganization of both neocortical and MTL systems during episodic memory states. Neocortical alterations were characterized by reduced functional differentiation in TLE across lateral temporal and midline parietal cortices in both hemispheres. In the MTL, on the other hand, patients presented with a more marked functional differentiation of posterior and anterior hippocampal segments ipsilateral to the seizure focus and pathological core, indicating perturbed intrahippocampal connectivity. Semantic memory reorganization was also found in bilateral lateral temporal and ipsilateral angular regions, while hippocampal functional topographies were unaffected. Leveraging MRI proxies of MTL pathology, we furthermore observed alterations in hippocampal microstructure and morphology that were associated with TLE-related functional reorganization during episodic memory. Moreover, correlation analysis and statistical mediation models revealed that these functional alterations contributed to behavioural deficits in episodic, but again not semantic memory in patients. Altogether, our findings suggest that semantic processes rely on distributed neocortical networks, while episodic processes are supported by a network involving both the hippocampus and neocortex. Alterations of such networks can provide a compact signature of state-dependent reorganization in conditions associated with MTL damage, such as TLE., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients., Methods: Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases., Results: In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died., Conclusions: NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)