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Background: Underdiagnosis or undertreatment of osteoporosis consequently impacts individual morbidity and mortality, as well as on healthcare systems and communities as a whole. Dual-energy x-ray absorptiometry (DXA) is the gold standard method for identifying osteoporosis, however, opportunistic CT screening is capable of precisely estimating bone mineral density (BMD) in abdominopelvic imaging with no additional cost, radiation exposure or inconvenience to patients. This study uses opportunistic CT screening to determine the prevalence of osteoporosis and anatomic distribution patterns in patients presenting with lower extremity fractures at our institution., Hypothesis: Trauma patients with low bone mineral density (BMD) are more likely to present with peri-articular versus shaft fractures., Patients and Methods: We conducted a retrospective review of 721 patients presenting as trauma activations to the emergency department (ED) of a Level 1 Trauma Center with lower extremity fractures. Patients were excluded if under the age of 18 or lacking a CT scan upon arrival in the ED. Hounsfield Units (HU) were measured at the L1 vertebral level on CT scans to determine bone mineral density. Values of ≤100 HU were consistent with osteoporosis, whereas 101-150 HU were consistent with osteopenia., Results: The final cohort included 416 patients, with mean age of 49 ± 21 years. Average bone density was 203.9 ± 73.4 HU. 15.9% of patients were diagnosed as osteopenic and 9.9% as osteoporotic. 64.2% of fractures were peri-articular, 25.7% were shaft, and 10.1% were a combination. Peri-articular fractures were significantly more likely to have lower average BMD than shaft fractures (189 ± 74.7 HU vs. 230.6 ± 66.1 HU, p < 0.001)., Discussion: Our study demonstrates a significant relationship between low bone mineral density and lower extremity fracture pattern, however, likely influenced by other factors such as sex. Opportunistic CT screening for osteoporosis in trauma settings provides ample opportunity for early detection of low BMD and implementation of highly effective lifestyle modification and pharmacotherapy intervention. Reduction in the overall incidence of peri-articular fracture with widespread adoption of opportunistic CT screening may lessen the morbidity, mortality, and total cost currently afflicting patients, healthcare systems, and communities., Level of Evidence: III, therapeutic., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objectives: Skateboarding and motorized boards are popular as a recreational activity and mode of transportation. Prior studies have investigated injury patterns from these activities in the pediatric population, but there is little data in the adult population. This study aims to investigate and compare the type and severity of injuries associated with skateboarding and motorized boards., Methods: Retrospective analysis of injury data collected from the NIESS (National Electronic Injury Surveillance system) database, including cases of fractures involving skateboards or motorized boards from 2018 to 2022. Data collected was demographic information, injury characteristics (e.g., body region affected, injury type), environmental factors, mechanism of injury, and hospital treatment and disposition. Statistical analysis including chi-square and independent t-test were employed to determine significant differences in injury pattern., Results: A total of 104,301 cases were included for analysis. 73.0 % of patients were male. 61.8 % of injuries were to the upper extremity. The most common fractures were of the wrist (20.2 %) and ankle (12.4 %). Patients injured on motorized boards were more likely to be older (40.0 ± 15.4 years) than those injured on skateboards (27.8 ± 9.8 years; p < 0.001). 13.9 % of fractures required hospital admission. Skateboard accidents were more likely to present with lower extremity fractures (p < 0.001), despite upper extremity injuries being the majority in both groups. There was a significant association between motorized board injuries and multiple fractures (p < 0.001, OR = 1.2), and hospital admission (p < 0.001, OR = 1.7)., Discussion: Our study shows a high prevalence of upper extremity injuries, regardless of board type. Motorized boards are associated with a higher risk of multiple fractures and hospital admission. Motorized boards likely have increased risk due to their ability to sustain elevated speeds., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this study., (Copyright © 2024. Published by Elsevier Inc.)

Background and Objective: Serological screening for Chagas disease (CD) in Latin American adults living in Europe is a cost-effective strategy for transmission prevention. The World Health Organization recommends two different serological tests including native and recombinant antigens for IgG detection. In Spain, most commercialized native tests require manual processing. We aimed to evaluate the sensitivity and specificity of the automated Vitros® Anti-T. cruzi native antigen-based test., Methods: A total of 556 serum samples were tested using two different tests: 1) our reference assay, a chemiluminescence immunoassay employing a recombinant multi-antigen protein (Liaison® XL Murex Chagas); 2) a chemiluminescence immunoassay with native antigen (Vitros® Anti-T. cruzi assay). Additionally, 180 samples were also processed by a manual indirect immunofluorescent assay (Chagas IFA). Sensibility, specificity and kappa index were calculated., Results: Vitros® showed a kappa index of 0.94 (IC 95 %: 0.86-1.03) compared to Liaison® XL with a sensitivity of 93.6 % and specificity of 99.5 %. Compared to IFA, Vitros® showed a kappa index of 0.61 (IC 95 %: 0.47-0.76), sensitivity of 97.5 % and specificity of 70.37 %. Discrepant results were obtained mainly in treated patients., Conclusions: The Vitros® Anti-T. cruzi assay showed potential for implementation as an automated serological screening test, enhancing the diagnostic process in high-throughput microbiology laboratories., 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.)

Introduction: Evidence on the association of biomarkers of host response to infection with COVID-19 clinical outcomes has focused mainly on hospitalized patients. We investigated the prognostic performance of 39 immune and endothelial activation markers measured early in the course of disease to predict the development of severe COVID-19 and hospitalization., Methods: We conducted a nested case-control study from a randomized clinical trial evaluating the efficacy of COVID-19 convalescent plasma in outpatients aged 50 years or older presenting with mild-to-moderate COVID-19. We selected participants who were hospitalized within 28 days (cases) and who were not (controls) to compare their biomarker levels in plasma samples collected at enrolment., Results: A total of 42 cases and 42 controls were included in this study. The levels of CRP, IL6, IP10, ferritin, IFNα, IL8, IL1RA, MCP1, and RANTES, determined within 7 days of symptoms onset, showed good individual prognostic performance for COVID-19 associated hospitalization by day 28. The biomarkers CRP, IL6, IP10, IL8, IL1RA, and suPAR showed good individual prognostic performance for severe COVID-19. CRP, IL6 and IP10 had the most robust association with both hospitalization and severe COVID-19, with CRP having the highest discriminatory capacity with hospitalization, and IL6 for severe COVID-19., Discussion: Our study shows good prognostic performance of CRP and IL6 for 28-day hospitalization in patients with mild-to-moderate COVID-19, in the absence of clinical criteria for admission upon enrolment. These findings confirm the value of these biomarkers at early stages of COVID-19 disease in the outpatient setting to support management decisions., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Alemany, Balanza, Millat-Martinez, Ouchi, Corbacho-Monné, Morales-Indiano, Fernández Rivas, Blanco, Mitjà, Aguilar, Dobaño, Bassat, Moncunill, Baro and COnV-ert BMK STUDY GROUP.)

A large fraction of soluble protein within the interior of living cells may reversibly associate with structural elements, including proteinaceous fibers and phospholipid membranes. In this opinion, we present theoretical and experimental evidence that many of these associations are due to nonspecific attraction between the protein and the surface of the fiber or membrane, and that such associations may lead to substantial changes in the association state of the adsorbed proteins, the biological function of the adsorbed proteins, and the distribution of these proteins between the many microenvironments existing within the cell., Competing Interests: Declaration of interests None declared by authors., (Published by Elsevier Ltd.)

Study Design: Retrospective review., Objective: To use opportunistic computed tomography (CT) screening to determine the prevalence of osteoporosis (OP) in patients presenting with spinal fractures and the rate of identification and treatment at our institution., Background: OP remains a highly underdiagnosed and undertreated disease. Opportunistic abdominopelvic CT scans offer a feasible, accessible, and cost-effective screening tool for OP., Methods: Retrospective review of 519 patients presenting as trauma activation to the emergency department of a Level 1 Trauma Center after a spinal fracture. Patients were excluded if under the age of 18 or lacking a CT scan upon arrival in the emergency department. Hounsfield Units (HU) were measured at the L1 vertebral level on CT scans to determine bone density levels. Values of ≤100 HU were considered osteoporotic, whereas 101-150 HU were osteopenic., Results: A total of 424 patients were included. The average HU was 204.8 ± 74.3 HU. Of the patients, 16.7% were diagnosed as osteopenic and 9.9% as osteoporotic. The mean age was 65 ± 14 years for osteopenic patients and 77 ± 11 years for osteoporotic. A statistically significant inverse relationship was found between age and bone density. Of the patients, 42.5% with low bone density HU measurements had a previously documented history of OP/osteopenia. There was a statistically significant association between females and low bone density. Patients injured in a fall were statistically significantly more likely to have lower bone densities than those in motor vehicle accidents. Of the osteoporotic patients, 9.5% were treated by our institution's fragility fracture team., Conclusions: Our study shows that among a cohort of patients with spinal fractures, 58% of patients with radiographic signs of OP are currently undiagnosed, resulting in a low treatment rate of OP. Increasing and standardizing the use of opportunistic CT scans would allow an increase in the diagnosis and treatment of OP in patients with spinal fractures. Further, opportunistic CT scans could also be useful for a broader orthopedic population at high risk of fragility fractures., Level of Evidence: Level II-therapeutic., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This study conducted in Madrid (Spain) between 2018 and 2023 shows a significant decrease in the pediatric bacterial community-acquired pneumonia cases during the COVID-19 pandemic, followed by a notable postpandemic increase surpassing prepandemic incidence. Streptococcus pneumoniae remains predominant, with an increasing prevalence of serotype 3, while Streptococcus pyogenes was the second most common pathogen., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

An increasing number of proteins involved in bacterial cell cycle events have been recently shown to undergo phase separation. The resulting biomolecular condensates play an important role in cell cycle protein function and may be involved in development of persister cells tolerant to antibiotics. Here we report that the E. coli chromosomal Ter macrodomain organizer MatP, a division site selection protein implicated in the coordination of chromosome segregation with cell division, forms biomolecular condensates in cytomimetic systems. These condensates are favored by crowding and preferentially localize at the membrane of microfluidics droplets, a behavior probably mediated by MatP-lipid binding. Condensates are negatively regulated and partially dislodged from the membrane by DNA sequences recognized by MatP ( matS ), which partition into them. Unexpectedly, MatP condensation is enhanced by FtsZ, a core component of the division machinery previously described to undergo phase separation. Our biophysical analyses uncover a direct interaction between the two proteins, disrupted by matS sequences. This binding might have implications for FtsZ ring positioning at mid-cell by the Ter linkage, which comprises MatP and two other proteins that bridge the canonical MatP/FtsZ interaction. FtsZ/MatP condensates interconvert with bundles in response to GTP addition, providing additional levels of regulation. Consistent with discrete foci reported in cells, MatP biomolecular condensates may facilitate MatP's role in chromosome organization and spatiotemporal regulation of cytokinesis and DNA segregation. Moreover, sequestration of MatP in these membraneless compartments, with or without FtsZ, could promote cell entry into dormant states that are able to survive antibiotic treatments.

Background: Past exposure to schistosomiasis is frequent among migrants from endemic countries, and chronic untreated infection may lead to long-term morbidities., Methods: We carried out a prospective population-based cross-sectional study among migrants from endemic Sub-Saharan countries living in Barcelona, Spain. Participants had not been previously diagnosed or treated for schistosomiasis. Clinical signs and symptoms were scrutinised through a systematic revision of electronic medical records and an on-site standardised questionnaire, and blood and urine samples were screened for Schistosoma., Findings: We recruited 522 eligible participants, 74.3% males, mean age 42.7 years (SD=11.5, range 18-76), Overall, 46.4% were from Senegal and 23.6% from Gambia. They had lived in the European Union for a median of 16 years (IQR 10-21). The prevalence of a Schistosoma-positive serology was 35.8%. S. haematobium eggs were observed in urine samples in 6 (1.2%) participants. The most prevalent symptoms among Schistosoma-positive participants were chronic abdominal pain (68.8%, OR=1.79; 95%CI 1.2-2.6), eosinophilia (44.9%, OR=2.69; 95%CI 1.8-4.0) and specific symptoms associated with urinary schistosomiasis, like self-reported episodes of haematuria (37.2%; OR=2.47; 95%CI 1.6-3.8), dysuria (47.9%, OR=1.84; 95%CI=1.3-2.7) and current renal insufficiency (13.4%; OR=2.35; 95%CI=1.3-4.3). We found a significant prevalence of gender-specific genital signs and symptoms among females (mainly menstrual disorders) and males (erectile dysfunction and pelvic pain). Individuals typically presented with a multitude of interconnected symptoms, most commonly chronic abdominal pain, which are often disregarded., Conclusions: Despite the lack of urine parasite identification, the high incidence of clinical signs and symptoms strongly correlated with a positive schistosomiasis serology suggests the existence of a heavy clinical burden among long-term West African migrants living for years/decades in the study region. More research is urgently required to determine whether these symptoms are the result of long-term sequelae or a persistent active Schistosoma infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Cell and gene therapy (CGT) is a field of therapeutic medicine that aims to treat, prevent, and cure diseases using engineered cells (stem cells, immune cells, and differentiated adult or fetal cells), vectors [Adeno Associated Virus (AAV), Adeno Virus (AV), Herpes Simplex Virus (HSV), Baculo Virus (BV), Lenti Virus (LV), Retro Virus (RV), etc.], and other carriers [non-viral vectors, virus-like particles (VLP), Lipid Nano-Particles (LNP), etc.]. Among viral CGT vectors, adeno-associated viruses and lentiviruses (AAV and LV) are the most widely applied vector platforms. The presence of non-functional (empty or non-infectious) vectors that carry null or partial genes in the final drug product is classified as an impurity by the FDA. These impurities impair dosage accuracy and induce non-specific immunogenicity and variability in drug efficacy. These non-functional viral vectors in the drug product need to be elucidated following International Conference on Harmonization (ICH) guidelines for clinical manufacturing of the final drug product. This article showcases an ion-exchange chromatography (IEX) high-resolution method supporting ICH guidelines using commercially available AAV8 filled and empty capsids as reference standards. Our method successfully separated empty to full capsids with a resolution of 15 and sustained a linearity greater than 0.98 even under a wide range of empty or full viral particle concentrations (E+9 to E+13 vp/mL), which is an upgrade to other IEX capsid separation methods. The medium-throughput capacity and shorter sample processing time improve testing efficiency and save costs while delivering quality as value. The discussed method is a reliable and reproducible platform to precisely evaluate the presence of non-functional viral particles in AAV8 samples. Aligned with other orthogonal results, the method is a powerful tool to improve the quality of rAAV analytics., Competing Interests: Authors SS, KM, CM, JS, UN, GR, IM, and DM were employed by Matica Biotechnology, Inc., (Copyright © 2024 Schrecke, McManus, Moshfegh, Stone, Nguyen, Rivas, Muhamed and Mitchell.)

Introduction: Estimated blood loss (EBL) is an important part of the perioperative process. This project aims to determine the accuracy of perioperative team members to estimate blood volume on drapes and the operating room floor., Methods: Aliquots of unused human blood were used to create surgical scenarios, and standardized pictures and videos were taken. Physicians, residents, nurses, medical students, and surgical technicians were surveyed and asked to estimate the blood volume for each series. Accuracy and consistency of responses was analyzed., Results: One hundred and forty five responses were recorded: 57 attending physicians, 36 residents, 27 registered nurses, 17 medical students, and seven circulating surgical techs. Median percent error (PE) for all cases was 211.11%, demonstrating a global overestimation of blood volume. PE for the 150 mL images was statistically significantly lower than that of the 50 and 100 mL images. Circulating Surgical Technicians were the most accurate group, with a median PE of 125%, followed closely by Medical Students (PE = 158.33%). The most accurate specialty was Orthopedics (PE = 168.06%). The least accurate groups were Attending Physicians (PE = 286.11%) and General surgery (GSGY) (PE = 327.78%). The most accurate orthopedic surgery and GSGY subspecialties were Hand (PE = 237.64%) and Vascular (PE = 108.33%), respectively. Statistical analyses showed no significant differences by clinical role, surgical specialty, or subspecialty., Conclusion: This study demonstrates a global overestimation of blood volume when using the visual method, with improved accuracy at higher volumes. Our findings highlight the limitations of visual estimation methods for EBL., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Interleukin-2 (IL-2) has been used in cancer treatment for over 30 years. However, due to its high toxicity, new mutant variants have been developed. These variants retain some of the biological properties of the original molecule but offer other therapeutic advantages. At the Center of Molecular Immunology, the IL-2 no-alpha mutein, an IL-2 agonist with lower toxicity than wtIL-2, has been designed, produced, and is currently being evaluated in a Phase I/II clinical trial. The mutein is produced in E. coli as an insoluble material that must be refolded in vitro to yield a fully active protein. Controlled oxidation steps are essential in the purification process of recombinant proteins produced in E. coli to ensure the proper formation of the disulfide bonds in the molecules. In this case, the new purification process includes a copper-catalyzed air oxidation step to induce disulfide bond establishment. The optimal conditions of pH, copper, protein and detergent concentration for this step were determined through screening. The produced protein demonstrated a conserved 3D structure, higher purity, and greater biological activity than the obtained by established process without the oxidation step. Four batches were produced and evaluated, demonstrating the consistency of the new process., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Infectious Bronchitis Virus (IBV) is a major threat to the poultry industry worldwide, causing significant economic losses. While the virus's genetic structure is well understood, the specific strains circulating in Bolivia have remained uncharacterized until now. This study aimed to identify and characterize new IBV strains in Bolivia. Tissue samples from broilers exhibiting clinical signs of Infectious Bronchitis were screened to detect IBV using real-time RT-PCR (RT-qPCR). Positive samples with low cycle threshold (Ct) values were selected for sequencing the full S1 gene. Of the 12 samples analyzed, 10 were determined to be positive for IBV. However, only four samples yielded sufficient genetic material for sequencing and subsequent phylogenetic analysis. The results revealed the presence of GI-1 and GI-23 lineages, both belonging to genotype I (GI). The GI-1 lineage showed >99% sequence identity to the H120 and Massachusetts vaccine strains, suggesting a close relationship. In contrast, the GI-23 lineage clustered with other IBV strains, showing a distinct subclade that is genetically distant from Brazilian strains. No evidence of recombination was found. Furthermore, amino acid substitution analysis identified specific mutations in the S1 subunit, particularly in the hypervariable regions 1, 2, and 3. These mutations could potentially alter the virus's antigenicity, leading to reduced vaccine efficacy. The findings of this study highlight the importance of continued and broad genomic surveillance of circulating IBV strains and the need to improve vaccination strategies in Bolivia.

An innovative supramolecular architecture is reported for bienzymatic glucose biosensing based on the use of a nanohybrid made of multi-walled carbon nanotubes (MWCNTs) non-covalently functionalized with a Schiff base modified with two phenylboronic acid residues (SB-dBA) as platform for the site-specific immobilization of the glycoproteins glucose oxidase (GOx) and horseradish peroxidase (HRP). The analytical signal was obtained from amperometric experiments at - 0.050 V in the presence of 5.0 × 10 -4  M hydroquinone as redox mediator. The concentration of GOx and HRP and the interaction time between the enzymes and the nanohybrid MWCNT-SB-dBA deposited at glassy carbon electrodes (GCEs) were optimized through a central composite design (CCD)/response surface methodology (RSM). The optimal concentrations of GOx and HRP were 3.0 mg mL -1 and 1.50 mg mL -1 , respectively, while the optimum interaction time was 3.0 min. The bienzymatic biosensor presented a sensitivity of (24 ± 2) × 10 2 µA dL mg -1 ((44 ± 4) × 10 2 µA M -1 ), a linear range between 0.06 mg dL -1 and 21.6 mg dL -1 (3.1 µM-1.2 mM) (R 2  = 0.9991), and detection and quantification limits of 0.02 mg dL -1 (1.0 µM) and 0.06 mg dL -1 (3.1 µM), respectively. The reproducibility for five sensors prepared with the same MWCNT-SB-dBA nanohybrid was 6.3%, while the reproducibility for sensors prepared with five different nanohybrids and five electrodes each was 7.9%. The GCE/MWCNT-SB-dBA/GOx-HRP was successfully used for the quantification of glucose in artificial human urine and commercial human serum samples., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Introduction: Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study., Research Design and Methods: We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations., Results: Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation., Conclusions: HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The placenta plays an essential role in pregnancy, leading to proper fetal development and growth. As an organ with multiple physiological functions for both mother and fetus, it is a highly energetic and metabolically demanding tissue. Mitochondrial physiology plays a crucial role in the metabolism of this organ and thus any alteration leading to mitochondrial dysfunction has a severe outcome in the development of the fetus. Pregnancy-related pathological states with a mitochondrial dysfunction outcome include preeclampsia and gestational diabetes mellitus. In this review, we address the role of mitochondrial morphology, metabolism and physiology of the placenta during pregnancy, highlighting the roles of the cytotrophoblast and syncytiotrophoblast. We also describe the relationship between preeclampsia, gestational diabetes, gestational diabesity and pre-pregnancy maternal obesity with mitochondrial dysfunction., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

Heart failure (HF) is a heterogeneous condition that can be categorized according to the left ventricular ejection fraction (EF) into HF with reduced (HFrEF) or preserved (HFpEF) EF. Although HFrEF and HFpEF share some common clinical manifestations, the mechanisms underlying each phenotype are often found to be distinct. Identifying shared and divergent pathophysiological features might expand our insights on HF pathophysiology and assist the search for therapies for each HF subtype. In this study, we evaluated and contrasted two new murine models of non-ischaemic HFrEF and cardiometabolic HFpEF in terms of myocardial structure, left ventricular function, gene expression, cardiomyocyte calcium handling, mitochondrial polarization and protein acetylation in a head-to-head fashion. We found that in conditions of similar haemodynamic stress, the HFrEF myocardium underwent a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation was greater in the HFpEF myocardium. We observed opposing features on calcium release, which was diminished in the HFrEF cardiomyocyte but enhanced in the HFpEF cardiomyocyte. Mitochondria were less polarized in both HFrEF and HFpEF cardiomyocytes, reflecting similarly impaired metabolic capacity. Hyperacetylation of cardiac proteins was observed in both models, but it was more accentuated in the HFpEF heart. Despite shared features, unique triggering mechanisms (neurohormonal overactivation in HFrEF vs. inflammation in HFpEF) appear to determine the distinct phenotypes of HF. The findings of the present research stress the need for further exploration of the differential mechanisms underlying each HF subtype, because they might require specific therapeutic interventions. KEY POINTS: The mechanisms underlying heart failure with either reduced (HFrEF) or preserved (HFpEF) ejection fraction are often found to be different. Previous studies comparing pathophysiological traits between HFrEF and HFpEF have been conducted on animals of different ages and strains. The present research contrasted two age-matched mouse models of non-ischaemic HFrEF and cardiometabolic HFpEF to uncover divergent and shared features. We found that upon similar haemodynamic stress, the HFrEF heart experienced a more pronounced hypertrophic and fibrotic remodelling, whereas inflammation appeared to be greater in the HFpEF myocardium. Calcium release was diminished in the HFrEF cardiomyocyte and enhanced in the HFpEF cardiomyocyte. Mitochondria were comparably less polarized in both HFrEF and HFpEF myocytes. Hyperacetylation of proteins was common to both models, but stronger in the HFpEF heart. Casting light on common and distinguishing features might ease the quest for phenotype-specific therapies for heart failure patients., (© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.)

The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)-induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B-dependent hypertrophic and proinflammatory signaling. Moreover, we identified a calcium/calmodulin-independent protein kinase II/cyclic adenosine monophosphate response element-binding protein signaling modulating MCU upregulation by ANGII. Additionally, we found upregulation of MCU in ANGII-induced left ventricular HF in mice, and in the LV of HF patients, which was correlated with pathological remodeling. Following left ventricular assist device implantation, MCU expression decreased, suggesting tissue plasticity to modulate MCU expression., Competing Interests: This work was partially supported by the CONACYT Grants 256577, 258197, Fronteras de la Ciencia Grant (0682). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

L-Lactate is an important bioanalyte in the food industry, biotechnology, and human healthcare. In this work, we report the development of a new L-lactate electrochemical biosensor based on the use of multiwalled carbon nanotubes non-covalently functionalized with avidin (MWCNT-Av) deposited at glassy carbon electrodes (GCEs) as anchoring sites for the bioaffinity-based immobilization of a new recombinant biotinylated lactate oxidase (bLOx) produced in Escherichia coli through in vivo biotinylation. The specific binding of MWCNT-Av to bLOx was characterized by amperometry, surface plasmon resonance (SPR), and electrochemical impedance spectroscopy (EIS). The amperometric detection of L-lactate was performed at -0.100 V, with a linear range between 100 and 700 µM, a detection limit of 33 µM, and a quantification limit of 100 µM. The proposed biosensor (GCE/MWCNT-Av/bLOx) showed a reproducibility of 6.0% and it was successfully used for determining L-lactate in food and enriched serum samples.

Epithelial intercellular adhesion molecule (ICAM)-1 is apically polarized, interacts with, and guides leukocytes across epithelial barriers. Polarized hepatic epithelia organize their apical membrane domain into bile canaliculi and ducts, which are not accessible to circulating immune cells but that nevertheless confine most of ICAM-1. Here, by analyzing ICAM-1&#95;KO human hepatic cells, liver organoids from ICAM-1&#95;KO mice and rescue-of-function experiments, we show that ICAM-1 regulates epithelial apicobasal polarity in a leukocyte adhesion-independent manner. ICAM-1 signals to an actomyosin network at the base of canalicular microvilli, thereby controlling the dynamics and size of bile canalicular-like structures. We identified the scaffolding protein EBP50/NHERF1/SLC9A3R1, which connects membrane proteins with the underlying actin cytoskeleton, in the proximity interactome of ICAM-1. EBP50 and ICAM-1 form nano-scale domains that overlap in microvilli, from which ICAM-1 regulates EBP50 nano-organization. Indeed, EBP50 expression is required for ICAM-1-mediated control of BC morphogenesis and actomyosin. Our findings indicate that ICAM-1 regulates the dynamics of epithelial apical membrane domains beyond its role as a heterotypic cell-cell adhesion molecule and reveal potential therapeutic strategies for preserving epithelial architecture during inflammatory stress., Competing Interests: CC, CL, NR, NC, AC, JC, SB, Gd, SC, AP, GD, CM, JF, GA, FM, PM, IC, JC, SN, MH, JM No competing interests declared, (© 2023, Cacho-Navas et al.)

We report a nanohybrid material obtained by non-covalent functionalization of multi-walled carbon nanotubes (MWCNTs) with the new ligand (((1E,1'E)-(naphthalene-2,3-diylbis(azaneylylidene))bis(methaneylylidenedene)) bis(4-hydroxy-3,1-phenylene))diboronic acid (SB-dBA), rationally designed to mimic some recognition properties of biomolecules like concanavalin A, for the development of electrochemical biosensors based on the use of glycobiomolecules as biorecognition element. We present, as a proof-of-concept, a hydrogen peroxide biosensor obtained by anchoring horseradish peroxidase (HRP) at a glassy carbon electrode (GCE) modified with the nanohybrid prepared by sonication of 2.0 mg mL -1 MWCNTs and 0.50 mg mL -1 SB-dBA in N,N-dimethyl formamide (DMF) for 30 min. The hydrogen peroxide biosensing was performed at -0.050 V in the presence of 5.0 × 10 -4  M hydroquinone. The analytical characteristics of the resulting biosensor are the following: linear range between 0.175 μM and 6.12 μM, detection limit of 58 nM, and reproducibility of 2.0 % using the same nanohybrid (6 biosensors), and 9.0 % using three different nanohybrids. The sensor was successfully used to quantify hydrogen peroxide in enriched milk and human blood serum samples and in a commercial disinfector., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Aims: Immune checkpoint inhibitors (ICIs) are antineoplastic drugs designed to activate the immune system's response against cancer cells. Evidence suggests that they may lead to immune-related adverse events, particularly when combined (e.g., anti-CTLA-4 plus anti-PD-1), sometimes resulting in severe conditions such as myocarditis. We aimed to investigate whether a previously sustained cardiac injury, such as pathological remodelling due to hypertension, is a prerequisite for ICI therapy-induced myocarditis., Methods: We evaluated the cardiotoxicity of ICIs in a hypertension (HTN) mouse model (C57BL/6). Weekly doses were administered up to day 21 after the first administration. Our analysis encompassed the following parameters: (i) survival and cardiac pathological remodelling, (ii) cardiac function assessed using pressure-volume (PV)-loops, with brain natriuretic peptide (BNP) serving as a marker of haemodynamic dysfunction and (iii) cardiac inflammation (cytokine levels, infiltration, and cardiac antigen autoantibodies)., Results: After the first administration of ICI combined therapy, the treated HTN group showed a 30% increased mortality (P = 0.0002) and earlier signs of hypertrophy and pathological remodelling compared with the untreated HTN group. BNP (P = 0.01) and TNF-α (<0.0001) increased 2.5- and 1.7-fold, respectively, in the treated group, while IL-6 (P = 0.8336) remained unchanged. Myocarditis only developed in the HTN group treated with ICIs on day 21 (score >3), characterised by T cell infiltration and increased cardiac antigen antibodies (86% showed a titre of 1:160). The control group treated with ICI was unaffected in any evaluated feature., Conclusions: Our findings indicate that pre-existing sustained cardiac damage is a necessary condition for ICI-induced myocarditis., (© 2023 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Schistosomiasis is highly endemic in sub-Saharan Africa and frequently imported to Europe. Male urogenital manifestations are often neglected. We aimed to ascertain the prevalence of genitourinary clinical signs and symptoms among long-term African migrants in a non-endemic European country using a serology test., Methods: We carried out a prospective, community-based cross-sectional study of adult male migrants from sub-Saharan Africa living in Spain. Schistosoma serology tests and microscopic urine examinations were carried out, and clinical data were obtained from an electronic medical record search and a structured questionnaire., Results: We included 388 adult males, mean age 43.5 years [Standard Deviation (SD) = 12.0, range: 18-76]. The median time since migration to the European Union was 17 [Interquartile range (IQR): 11-21] years. The most frequent country of origin was Senegal (N = 179, 46.1%). Of the 338, 147 (37.6%) tested positive for Schistosoma. Parasite eggs were present in the urine of only 1.3%. Nine genitourinary clinical items were significantly associated with positive Schistosoma serology results: pelvic pain (45.2%; OR = 1.57, 95% CI: 1.0-2.4), pain on ejaculation (14.5%; OR = 1.85, 95% CI: 1.0-3.5), dyspareunia (12.4%; OR = 2.45, 95% CI: 1.2-5.2), erectile dysfunction (9.5%; OR = 3.10, 95% CI: 1.3-7.6), self-reported episodes of infertility (32.1%; OR = 1.69, 95% CI: 1.0-2.8), haematuria (55.2%; OR = 2.37, 95% CI: 1.5-3.6), dysuria (52.1%; OR = 2.01, 95% CI: 1.3-3.1), undiagnosed syndromic STIs (5.4%), and orchitis (20.7%; OR = 1.81, 95% CI: 1.0-3.1). Clinical signs tended to cluster., Conclusions: Urogenital clinical signs and symptoms are prevalent among male African long-term migrants with a positive Schistosoma serology results. Genital involvement can be frequent even among those with long periods of non-residence in their sub-Saharan African countries of origin. Further research is needed to develop diagnostic tools and validate therapeutic approaches to chronic schistosomiasis., (© 2024. The Author(s).)

Major extremity fractures are serious limb injuries often including notable soft-tissue injury with possible injuries to the head, chest, or abdomen. High-energy traumatic fractures carry a high risk of surgical site infections even with use of systemic antibiotics and techniques in risk reduction. The American Academy of Orthopaedic Surgeons released a clinical practice guideline in 2023 based on current literature on the prevention of surgical site infections after major extremity trauma. The case presented in this article is an example to demonstrate the clinical application of these guidelines., (Copyright © 2023 by the American Academy of Orthopaedic Surgeons.)

Macromolecular crowding affects the activity of proteins and functional macromolecular complexes in all cells, including bacteria. Crowding, together with physicochemical parameters such as pH, ionic strength, and the energy status, influences the structure of the cytoplasm and thereby indirectly macromolecular function. Notably, crowding also promotes the formation of biomolecular condensates by phase separation, initially identified in eukaryotic cells but more recently discovered to play key functions in bacteria. Bacterial cells require a variety of mechanisms to maintain physicochemical homeostasis, in particular in environments with fluctuating conditions, and the formation of biomolecular condensates is emerging as one such mechanism. In this work, we connect physicochemical homeostasis and macromolecular crowding with the formation and function of biomolecular condensates in the bacterial cell and compare the supramolecular structures found in bacteria with those of eukaryotic cells. We focus on the effects of crowding and phase separation on the control of bacterial chromosome replication, segregation, and cell division, and we discuss the contribution of biomolecular condensates to bacterial cell fitness and adaptation to environmental stress.

The genome-organizing protein p6 of Bacillus subtilis bacteriophage φ29 plays an essential role in viral development by activating the initiation of DNA replication and participating in the early-to-late transcriptional switch. These activities require the formation of a nucleoprotein complex in which the DNA adopts a right-handed superhelix wrapping around a multimeric p6 scaffold, restraining positive supercoiling and compacting the viral genome. Due to the absence of homologous structures, prior attempts to unveil p6's structural architecture failed. Here, we employed AlphaFold2 to engineer rational p6 constructs yielding crystals for three-dimensional structure determination. Our findings reveal a novel fold adopted by p6 that sheds light on its self-association mechanism and its interaction with DNA. By means of protein-DNA docking and molecular dynamic simulations, we have generated a comprehensive structural model for the nucleoprotein complex that consistently aligns with its established biochemical and thermodynamic parameters. Besides, through analytical ultracentrifugation, we have confirmed the hydrodynamic properties of the nucleocomplex, further validating in solution our proposed model. Importantly, the disclosed structure not only provides a highly accurate explanation for previously experimental data accumulated over decades, but also enhances our holistic understanding of the structural and functional attributes of protein p6 during φ29 infection., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

PaaX is a transcriptional repressor of the phenylacetic acid (PAA) catabolic pathway, a central route for bacterial aerobic degradation of aromatic compounds. Induction of the route is achieved through the release of PaaX from its promoter sequences by the first compound of the pathway, phenylacetyl-coenzyme A (PA-CoA). We report the crystal structure of PaaX from Escherichia coli W. PaaX displays a novel type of fold for transcription regulators, showing a dimeric conformation where the monomers present a three-domain structure: an N-terminal winged helix-turn-helix domain, a dimerization domain similar to the Cas2 protein and a C-terminal domain without structural homologs. The domains are separated by a crevice amenable to harbour a PA-CoA molecule. The biophysical characterization of the protein in solution confirmed several hints predicted from the structure, i.e. its dimeric conformation, a modest importance of cysteines and a high dependence of solubility and thermostability on ionic strength. At a moderately acidic pH, the protein formed a stable folding intermediate with remaining α-helical structure, a disrupted tertiary structure and exposed hydrophobic patches. Our results provide valuable information to understand the stability and mechanism of PaaX and pave the way for further analysis of other regulators with similar structural configurations., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Cellular machines formed by the interaction and assembly of macromolecules are essential in many processes of the living cell. These assemblies involve homo- and hetero-associations, including protein-protein, protein-DNA, protein-RNA, and protein-polysaccharide associations, most of which are reversible. This chapter describes the use of analytical ultracentrifugation, light scattering, and fluorescence-based methods, well-established biophysical techniques, to characterize interactions leading to the formation of macromolecular complexes and their modulation in response to specific or unspecific factors. We also illustrate, with several examples taken from studies on bacterial processes, the advantages of the combined use of subsets of these techniques as orthogonal analytical methods to analyze protein oligomerization and polymerization, interactions with ligands, hetero-associations involving membrane proteins, and protein-nucleic acid complexes., (© 2024. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The conserved process of cell division in bacteria has been a long-standing target for antimicrobials, although there are few examples of potent broad-spectrum compounds that inhibit this process. Most currently available compounds acting on division are directed towards the FtsZ protein, a self-assembling GTPase that is a central element of the division machinery in most bacteria. Benzodioxane-benzamides are promising candidates, but poorly explored in Gram-negatives. We have tested a number of these compounds on E. coli FtsZ and found that many of them significantly stabilized the polymers against disassembly and reduced the GTPase activity. Reconstitution in crowded cell-like conditions showed that FtsZ bundles were also susceptible to these compounds, including some compounds that were inactive on protofilaments in dilute conditions. They efficiently killed E. coli cells defective in the AcrAB efflux pump. The activity of the compounds on cell growth and division generally showed a good correlation with their effect in vitro, and our experiments are consistent with FtsZ being the target in vivo. Our results uncover the detrimental effects of benzodioxane-benzamides on permeable E. coli cells via its central division protein, implying that lead compounds may be found within this class for the development of antibiotics against Gram-negative bacteria., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Silvia Zorrilla reports financial support was provided by Spanish Ministerio de Ciencia e Innovación. Marta Sobrinos-Sanguino reports financial support was provided by Agencia Estatal de Investigación and the European Social Fund. William Margolin reports financial support was provided by National Institutes of Health., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Microfluidically fabricated polymer microgels are used as an experimental platform to analyze protein-DNA interactions regulating bacterial cell division. In particular, we focused on the nucleoid-associated protein SlmA, which forms a nucleoprotein complex with short DNA binding sequences (SBS) that acts as a negative regulator of the division ring stability in Escherichia coli . To mimic the bacterial nucleoid as a dense DNA region of a bacterial cell and investigate the influence of charge and permeability on protein binding and diffusion in there, we have chosen nonionic polyethylene glycol and anionic hyaluronic acid as precursor materials for hydrogel formation, previously functionalized with SBS. SlmA binds specifically to the coupled SBS for both types of microgels while preferentially accumulating at the microgels' surface. We could control the binding specificity by adjusting the buffer composition of the DNA-functionalized microgels. The microgel charge did not impact protein binding; however, hyaluronic acid-based microgels exhibit a higher permeability, promoting protein diffusion; thus, they were the preferred choice for preparing nucleoid mimics. The approaches described here provide attractive tools for bottom-up reconstitution of essential cellular processes in media that more faithfully reproduce intracellular environments.

The bottom-up reconstitution of proteins for their modular engineering into synthetic cellular systems can reveal hidden protein functions in vitro. This is particularly evident for the bacterial Min proteins, a paradigm for self-organizing reaction-diffusion systems that displays an unexpected functionality of potential interest for bioengineering: the directional active transport of any diffusible cargo molecule on membranes. Here, the MinDE protein system is reported as a versatile surface patterning tool for the rational design of synthetically assembled 3D systems. Employing two-photon lithography, microswimmer-like structures coated with tailored lipid bilayers are fabricated and demonstrate that Min proteins can uniformly pattern bioactive molecules on their surface. Moreover, it is shown that the MinDE system can form stationary patterns inside lipid vesicles, which allow the targeting and distinctive clustering of higher-order protein structures on their inner leaflet. Given their facile use and robust function, Min proteins thus constitute a valuable molecular toolkit for spatially patterned functionalization of artificial biosystems like cell mimics and microcarriers., (© 2023 The Authors. Small Methods published by Wiley-VCH GmbH.)

Currently, the majority of the population has been vaccinated against COVID-19 and/or has experienced SARS-CoV-2 infection either before or after vaccination. The immunological response to repeated episodes of infections is not completely clear. We measured SARS-CoV-2 specific neutralization titers by a pseudovirus assay after BA.1 infection and RBD-specific immunoglobulin G (IgG), immunoglobulin A (IgA), and immunoglobulin M (IgM) in a cohort of COVID-19 uninfected and triple vaccinated individuals (breakthrough infection group, BTI) as compared with those previously infected by SARS-CoV-2 (reinfection group, REI) who underwent identical vaccination schedule. SARS-CoV-2 specific neutralizing response after BA.1 infection was significantly higher in the BTI group as compared with the REI. Furthermore, neutralization titers in REI were not significant different from convalescent non reinfected controls. RBD-specific IgG and IgA, but not IgM, were also significantly higher in BTI as compared with REI. Our results show that the first episode of SARS-CoV-2 infection induces a significant increase in neutralizing titers in triple vaccinated individuals and that previous SARS-CoV-2 infection compromise significantly the neutralization response induced by reinfection, even by divergent SARS-CoV-2 variants and at least up to 2 years postinfection, suggesting a fundamental limitation in inducing effective booster through the intranasal route in previously infected individuals., (© 2023 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Systemic inflammatory diseases, such as sepsis and severe COVID-19, provoke acute respiratory distress syndrome in which the pathological hyperpermeability of the microvasculature, induced by uncontrolled inflammatory stimulation, causes pulmonary edema. Identifying the inflammatory mediators that induce human lung microvascular endothelial cell barrier dysfunction is essential to find the best anti-inflammatory treatments for critically ill acute respiratory distress syndrome patients., Methods: We have compared the responses of primary human lung microvascular endothelial cells to the main inflammatory mediators involved in cytokine storms induced by sepsis and SARS-CoV2 pulmonary infection and to sera from healthy donors and severely ill patients with sepsis. Endothelial barrier function was measured by electric cell-substrate impedance sensing, quantitative confocal microscopy, and Western blot., Results: The human lung microvascular endothelial cell barrier was completely disrupted by IL (interleukin)-6 conjugated with soluble IL-6R (IL-6 receptor) and by IL-1β (interleukin-1beta), moderately affected by TNF (tumor necrosis factor)-α and IFN (interferon)-γ and unaffected by other cytokines and chemokines, such as IL-6, IL-8, MCP (monocyte chemoattractant protein)-1 and MCP-3. The inhibition of IL-1 and IL-6R simultaneously, but not separately, significantly reduced endothelial hyperpermeability on exposing human lung microvascular endothelial cells to a cytokine storm consisting of 8 inflammatory mediators or to sera from patients with sepsis. Simultaneous inhibition of IL-1 and JAK (Janus kinase)-STAT (signal transducer and activator of transcription protein), a signaling node downstream IL-6 and IFN-γ, also prevented septic serum-induced endothelial barrier disruption., Conclusions: These findings strongly suggest a major role for both IL-6 trans-signaling and IL-1β signaling in the pathological increase in permeability of the human lung microvasculature and reveal combinatorial strategies that enable the gradual control of pulmonary endothelial barrier function in response to a cytokine storm., Competing Interests: Disclosures None.

Heart failure with reduced ejection fraction (HFrEF) is accompanied by disregulation of cardiovascular function. Heart rate variability (HRV) is commonly used to assess autonomic dysfunction in HFrEF. However, analysis of stroke volume variability (SVV) may provide additional insights. We examined HRV and SVV in a mouse model of HFrEF. HFrEF mice exhibited reduced stroke volume and ejection fraction versus controls, confirming cardiac contractile dysfunction. HRV was preserved in HFrEF mice. However, SVV was markedly diminished, indicating dissociation between HRV and SVV regulation. Using a mathematical model, we propose that Frank-Starling mechanism abnormalities in HFrEF disrupt SVV independent of HRV. Assessing SVV could thus provide unique insights beyond HRV into cardiovascular control deficits in HFrEF., Competing Interests: All authors declare no conflicts of interest in this paper., (Copyright: © 2023 Fernández-Mendoza 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.)

In veterinary field, drug exposure during milk production in dairy cattle is considered a major health problem which concerns dairy consumers. The induced expression of the ABC transporter G2 (ABCG2) in the mammary gland during lactation plays a significant role in the active secretion of many compounds into milk. The main objective of this study was to determine the involvement of ABCG2 in the secretion into milk of the antiparasitic clorsulon in sheep as well as the possible effect of the coadministration of model ABCG2 inhibitors such as macrocyclic lactones on this process. Cells transduced with the ovine variant of ABCG2 were used to carry out in vitro transepithelial transport assays in which we showed that clorsulon is a substrate of the ovine transporter. In addition, ivermectin and abamectin significantly inhibited clorsulon transport mediated by ovine ABCG2. In vivo interactions were studied in Assaf sheep after coadministration of clorsulon (in DMSO, 2 mg/kg, s.c.) with ivermectin (Ivomec ® , 0.2 mg/kg, s.c.) or abamectin (in DMSO, 0.2 mg/kg, s.c.). After ivermectin and abamectin treatment, no relevant statistically significant differences in plasma levels of clorsulon were reported between the experimental groups since there were no differences in the area under the plasma concentration-curve (AUC) between clorsulon treatment alone and coadministration with macrocyclic lactones. With regard to milk, total amount of clorsulon, as percentage of dose excreted, did not show statistically significant differences when macrocyclic lactones were coadministered. However, the AUC for clorsulon significantly decreased ( p < 0.05) after coadministration with ivermectin (15.15 ± 3.17 μg h/mL) and abamectin (15.30 ± 3.25 μg h/mL) compared to control group (20.73 ± 4.97 μg h/mL). Moreover, milk parameters such as half-life ( T 1/2 ) and mean residence time (MRT) were significantly lower ( p < 0.05) after coadministration of macrocyclic lactones. This research shows that the milk pharmacokinetics of clorsulon is affected by the coadministration of ABCG2 inhibitors, reducing drug persistence in milk., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2023 Blanco-Paniagua, Álvarez-Fernández, Millán-García, Rivas, Álvarez and Merino.)

Objective: To evaluate a Zika virus screening program applied to asymptomatic exposed pregnant women., Methodology: Analysis of data generated during the roll out of a Zika screening program. We included socio-demographic data, ultrasounds, and serological results (IgM, IgG, and Plaque Reduction Neutralization Test; PRNT) from asymptomatic pregnant women exposed to Zika virus enrolled in the screening program between 2016 to 2019., Results: We included 406 asymptomatic ZIKV-exposed pregnant women who gave 400 full-term new-borns. The median age was 30 years (IQR = 25-34), which was lower (29 years; IQR = 24-34) among women of non-EU migrant origin (76.4% of the sample). Migrant women tended to delay the first pre-natal consultation compared to EU origin women (p = .003). Overall, 83.2% (N = 328) of participants had ZIKV low risk serological profile (IgM-/IgG- or IgM-/IgG+ and PRNT-), 3.0% (N = 12) showed high risk of recent ZIKV infection (IgM+ or PRNT+) and 13.7% (N = 54) had indeterminate results. A fetal malformation was identified in 29 children (9.3%). Fetal malformation was associated with a ZIKV high risk serological profile [24 out of the 246 (1.6%) with low risk profile and 3 out of the 12 with at high risk profile (25.0%; p = .02)]. Four newborns with high risk profile had a positive ZIKV-PCR test, which included two cases with microcephaly. No association was observed between maternal exposure to ZIKV infection and developmental abnormalities during the post-natal period follow-up., Conclusions: The ZIKV-screening program had considerable costs and yielded a high rate of indeterminate results among asymptomatic pregnant women. Considering the poor value for decision-making of the results, efforts should focus on providing early access to routine maternity care, especially to migrant women. A simpler screening protocol might consider an initial ZIKV-PCR or IgM determination and subsequent referral to a fetal medicine specialist in those women with a positive result and/or whom ultrasound examination has revealed fetal abnormalities (10% of total women in our study sample)., (© 2023 Wiley Periodicals LLC.)

The COVID-19 pandemic disrupted healthcare for patients with chronic diseases, including cancer. Barriers to healthcare increased, especially for racial and ethnic minorities. While many institutions developed webinars to educate community members, few webinars used a community-based participatory approach, employed a theory-based engagement design, and were evaluated. This manuscript reports the outcomes of "Vamos a educarnos contra el cáncer," a 2021 webinar series. Monthly educational webinars were conducted in Spanish on cancer-related topics. The presentations were delivered by Spanish-speaking content experts from different organizations. Webinars were conducted using the video conferencing platform Zoom. Polls were launched during the webinar to collect data and evaluate each webinar. The RE-AIM model of reach, effectiveness, adoption, implementation, and maintenance was used to evaluate the series. The SAS Analytics Software was used for analysis and data management. Two hundred ninety-seven people participated with over 3000 views of the webinar recordings (Reach); 90% rated the sessions as good or excellent (Effectiveness); 86% agreed to adopt or improve a cancer-related behavior, and 90% reported willingness to adopt or improve a cancer-related action for someone else (Adoption); 92% reported feeling engaged (Implementation). The series has produced a resource library, manual of operations, and agreement of the Hispanic/Latino Cancer Community Advisory Board (CAB) to continue the webinar series in the future (Maintenance). Overall, these results highlight the impact of this webinar series and provide a standard approach to planning, delivering, and evaluating webinars as a strategy for cancer prevention and control in a culturally appropriate manner., (© 2023. The Author(s) under exclusive licence to American Association for Cancer Education.)

Noise is present in cell biology. The capability of cells to respond to noisy environment have become essential. This study aimed to investigate whether noise can enhance the contractile response and Ca 2+ handling in cardiomyocytes from a cardiomyopathy model. Experiments were conducted in an experimental setup with Gaussian white noise, frequency, and amplitude control to stimulate myocytes. Cell shortening, maximal shortening velocity, time to peak shortening, and time to half relaxation variables were recorded to cell shortening. Ca 2+ transient amplitude and raise rate variables were registered to measure Ca 2+ transients. Our results for cell shortening, Ca 2+ transient amplitude, and raise rate suggest that cell response improve when myocytes are noise stimulated. Also, cell shortening, maximal shortening velocity, Ca 2+ transient amplitude, and raise improves in control cells. Altogether, these findings suggest novel characteristics in how cells improve their response in a noisy environment., (© 2023. Springer Nature Limited.)

Background: Inflammation affecting the heart and surrounding tissues is a clinical condition recently reported following COVID-19 mRNA vaccination. Assessing trends of these events related to immunization will improve vaccine safety surveillance and best practices for forthcoming vaccine campaigns. However, the causality is unknown, and the mechanisms associated with cardiac myocarditis are not understood., Case Presentation: After the first dose, we reported an mRNA vaccine-induced perimyocarditis in a young patient with a history of recurrent myocardial inflammation episodes and progressive loss of cardiac performance. We tested this possible inflammatory cytokine-mediated cardiotoxicity after vaccination in the acute phase (ten days), and we found a significant elevation of MCP-1, IL-18, and IL-8 inflammatory mediators. Still, these cytokines decreased considerably at the recovery phase (42 days later). We used the cardiomyoblasts cell line to test the effect of serum on cell viability, observing that serum from the acute phase reduced the cell viability to 75%. We did not detect this toxicity in cells when we tested serum from the patient in the recovery phase. We also tested serum-induced hypertrophy, a phenomenon in myocarditis and heart failure. We found that acute phase-serum has hypertrophy effects, increasing 25% of the treated cardiac cells' surface and significantly increasing B-type natriuretic peptide. However, we did not observe the hypertrophic effect in the recovery phase or sera from healthy controls., Conclusion: Our results opened the possibility of the inflammatory cytokines or serum soluble mediators as key factors for vaccine-associated myocarditis. In this regard, identifying anti-inflammatory molecules that reduce inflammatory cytokines could help avoid vaccine-induced myocardial inflammation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

The COVID-19 pandemic had devastating effects throughout the world, producing a severe crisis in the health systems and in the economy of a long list of countries, even developed ones. Therefore, highly sensitive and selective analytical bioplatforms that allow the descentralized and fast detection of the severe acute respiratory síndrome coronavirus 2 (SARS-CoV-2), are extremely necessary. Since 2020, several reviews have been published, most of them focused on the different strategies to detect the SARS-CoV-2, either from RNA, viral proteins or host antibodies produced due to the presence of the virus. In this review, the most relevant biosensors for the detection of SARS-CoV-2 RNA are particularly addressed, with special emphasis on the discussion of the biorecognition layers and the different schemes for transducing the hybridization event., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The H9c2 myoblast cell line, isolated from the left ventricular tissue of rat, is currently used in vitro as a mimetic for skeletal and cardiac muscle due to its biochemical, morphological, and electrical/hormonal signaling properties. During culture, H9c2 cells acquire a myotube phenotype, where a critical component is the inclusion of retinoic acid (RA). The results from some authors on H9c2 suggested that thousands of genes respond to RA stimuli, while others report hundreds of genes responding to RA over different cell types. In this article, using a more appropriate experimental design, we first confirm the H9c2 cardiac phenotype with and without RA and report transcriptomic and physiological changes regarding calcium handling, bioenergetics, and other biological concepts. Interestingly, of the 2360 genes showing a transcriptional change, 622 genes were statistically associated with the RA response. Of these genes, only 305 were RA-specific, and the rest also showed a culture-time component. Thus, the major expression changes (from 74 to 87%) were indeed due to culture conditions over time. Unexpectedly, only a few components of the retinol pathway in KEGG responded to RA. Our results show the role of RA in the H9c2 cultures impacting the interpretation using H9c2 as an in vitro model., (© 2023. The Author(s).)