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Abstract Monoclonal antibody (mAb) glycoengineering has the potential to improve the efficacy of biopharmaceuticals by fine-tuning specific biological properties. Glycosylation analysis is key to monitoring the glycoengineering process. Various mass spectrometry (MS)-based methods are available to characterize mAb glycosylation at different structural levels, but comprehensive analysis is typically time-consuming and costly. Here, we present an approach that combines conventional intact mass measurement of glycoforms by direct infusion ESI-MS with an advanced MALDI-in-source decay FT-ICR MS method for direct analysis of glycans in intact mAbs, without the need for enzymatic release and separation. Using a sodium-doped MALDI matrix, glycans were directly released as ISD fragment ions from the intact mAbs during the ionization process. Measurement of 0,2A fragment signals yielded reproducible glycan profiles that were consistent with conventional methods, yet was achieved with unprecedented speed, providing complementary information to that obtained through intact mass measurement. The methods were applied to standard and glycoengineered trastuzumab and rituximab, allowing rapid glycosylation profiling and structural analysis of glycans by tandem MS of selected ISD fragment ions. This fast approach can facilitate the early-phase development of glycoengineering processes by constraining further in-depth analyses. We envision a broader applicability in studies focused on glycosylation changes in mAbs.

Abstract Dimethylsulfoxide (DMSO) has conventionally been used for cell cryopreservation both in research and in clinical applications, but has long-term cytotoxic effects. Trehalose, a natural disaccharide, has been proposed as a non-toxic cryoprotectant. However, the lack of specific cell membrane transporter receptors inhibits transmembrane transport and severely limits its cryoprotective capability. This research presents a method to successfully deliver trehalose into mesenchymal stem cells (MSCs) using ultrasound in the presence of microbubbles. The optimised trehalose concentration was shown to be able to not only preserve membrane integrity and cell viability but also the multipotency of MSCs, which are essential for stem cell therapy. Confocal imaging revealed that rhodamine-labelled trehalose was transported into cells rather than simply attached to the membrane. Additionally, the membranes were successfully preserved in lyophilised cells. This study demonstrates that ultrasonication with microbubbles facilitated trehalose delivery, offering promising cryoprotective capability without the cytotoxicity associated with DMSO-based methods.

Abstract Hepatocellular carcinoma (HCC) associated with viral or metabolic liver diseases is a growing cancer without effective therapy. AMPK is downregulated in HCC and its activation diminishes tumor growth. Alpha lipoic acid (ALA), an indirect AMPK activator that inhibits hepatic steatosis, shows antitumor effects in different cancers. We aimed to study its putative action in liver-cancer derived cell lines through AMPK signaling. We performed cytometric studies for apoptosis and cell cycle, and 2D and 3D migration analysis in HepG2/C3A and Hep3B cells. ALA led to significant inhibition of cell migration/invasion only in HepG2/C3A cells. We showed that these effects depended on AMPK, and ALA also increased the levels and nuclear compartmentalization of the AMPK target p53. The anti-invasive effect of ALA was abrogated in stable-silenced (shTP53) versus isogenic-TP53 HepG2/C3A cells. Furthermore, ALA inhibited epithelial-mesenchymal transition (EMT) in control HepG2/C3A but not in shTP53 nor in Hep3B cells. Besides, we spotted that in patients from the HCC-TCGA dataset some EMT genes showed different expression patterns or survival depending on TP53. ALA emerges as a potent activator of AMPK-p53 axis in HCC cells, and it decreases migration/invasion by reducing EMT which could mitigate the disease in wild-type TP53 patients.

Abstract Background Erosive tooth wear is an increasingly common pathology in the youth population. It refers to the chronic, localized, painless loss of dental hard tissues caused by non-bacterial acids, often originating from external sources like acidic beverages. Energy drink consumption is on the rise, frequently preceding physical exercise to enhance perceived energy levels. However, there are other types of beverages that also provide energy, such as pre-workout drinks, classified as sports drinks. The main objective of this research study has been conducted with the purpose of analyzing the pH of energy drinks and pre-workout beverages, and studying the frequency of consumption of such beverages in amateur athletes who practice sports. Methods A total of 67 beverages were examined, comprising 43 energy drinks and 24 sports supplementation beverages, also known as pre-workout or pre-training beverages. The participants were given a survey to complete. They were asked to respond whether they consumed any type of pre-workout or energy drink, and they were also asked about the timing of consumption. Results The findings indicated an average pH of 3.3 among the studied beverages, indicating a pH below the critical threshold. Out of the 113 participants, 51% reported taking some form of supplementation. Conclusions Consequently, it was concluded that most of the analyzed beverages recorded pH values low enough to classify them as erosive, posing a threat to enamel surface. When analyzing the frequency of consumption of energy drinks and pre-workout beverages in amateur athletes, we observed that most participants aged 29 years or younger took supplements 3 to 5 times a week, while the older age groups more frequently took supplements 1 to 2 times a week.

Abstract Objectives To evaluate the tuberculin skin test (TST) conversion in chronic inflammatory arthropathies (CIA) patients on TNFα inhibitors (TNFi) and without previous latent tuberculosis infection (LTBI) treatment. Methods Patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) with negative LTBI were retrospectively evaluated for TST conversion and active tuberculosis (TB) after six months of exposition to TNFi. Two groups were compared: patients who repeated TST (TST-repetition) during the follow-up and patients who did not (non-TST-repetition). Results A total of 355 CIA patients on TNFi were screened and 138 (38.9%) did not fulfill the inclusion criteria. Of the remaining 217 CIA patients, 81 (37.3%) repeated TST during TNFi treatment. TST conversion rate was observed in 18 (22.2%) patients without significant differences among CIA (p = 0.578). The number of TB cases was low (n = 10; 4.6%) and was similar in TST-repetition and non-TST-repetition groups [2 (2.5%) vs. 8 (5.9%), p = 0.328]. Of note, 30% of active TB occurred early (6–12 months of TNFi exposure) and the median (full range) time to incident TB was 1.3 (0.6–10.6) years, whereas the median (full range) time to TST repetition was later [3.3 (0.5–13.4) years]. The incidence of active TB was lower among RA patients than AS patients [342 (95% CI 41 − 1446) vs. 1.454 (95% CI 594-2993)/100,000 patient-years, p = 0.049]. Conclusion These results indicate that TST repetition is associated with a high conversion rate, suggesting the need for recommended treatment. The delayed repetition of TST and low number of active TB cases hampered the evaluation of this strategy effectiveness to prevent active infection. Larger studies with systematic repetition patterns are necessary. In addition, the study highlights the need for a greater surveillance for TB in AS patients.

Abstract Homologous recombination (HR) and mismatch repair (MMR) defects are driver mutational imprints and actionable biomarkers in DNA repair-defective tumors. Although usually thought as mutually exclusive pathways, recent preclinical and clinical research provide preliminary evidence of a functional crosslink and crosstalk between HRR and MMR. Shared core proteins are identified as key players in both pathways, broadening the concept of DNA repair mechanism exclusivity in specific tumor types. These observations may result in unexplored forms of synthetic lethality or hypermutable tumor phenotypes, potentially impacting the cancer risk management, and considerably expanding in the future the therapeutic window for DNA repair-defective tumors.

Abstract During their development, amphibians undergo various physiological processes that may affect their susceptibility to environmental pollutants. Naturally occurring fluctuations caused by developmental events are often overlooked in ecotoxicological studies. Our aim is to investigate how biomarkers of oxidative stress are modulated at different stages of larval development in the Amazonian amphibian species, Physalaemus ephippifer. The premetamorphosis, prometamorphosis and metamorphic climax stages were used to analyze total antioxidant capacity (ACAP), glutathione S-transferase (GST) activity, lipid peroxidation (LPO) levels and the expression of genes nrf2, gst, gsr (glutathione reductase) and gclc (glycine-cysteine ligase, catalytic subunit). Although there was no difference in ACAP and the genes expression among the studied stages, individuals from the premetamorphosis and prometamorphosis showed higher GST activity than ones under the climax. LPO levels were highest in individuals from the metamorphic climax. The present study suggests that the oxidative status changes during ontogeny of P. ephippifer tadpoles, especially during the metamorphic climax, the most demanding developmental phase. Variations in the redox balance at different developmental stages may lead to a divergent response to pollution. Therefore, we recommend that studies using anuran larvae as biomonitors consider possible physiological differences during ontogeny in their respective analyses.

Abstract Long COVID has been linked to a decline in physical activity and functional capacity. However, it remains unclear which physical symptoms are associated with specific aspects of movement behaviors and functional capacity. We aimed to investigate the associations of fatigue, dyspnea, post-exertional malaise, myalgia, and the co-occurrence of symptoms with movement behaviors and functional capacity in individuals with Long COVID. A cross-sectional multicenter study was conducted. Questionnaires were used to assess fatigue, dyspnea, post-exertional malaise, and myalgia. Accelerometry was employed to assess sedentary time, steps per day, light physical activity, and moderate-to-vigorous physical activity. The six-minute walk test, 30-s chair stand test, and timed up and go were used to assess functional capacity. One hundred and two community-dwelling individuals who had been living with Long COVID for 15 ± 10 months participated in the study. Fatigue, post-exertional malaise, and the co-occurrence of physical symptoms showed a negative association with step count, while post-exertional malaise was also negatively associated with moderate-to-vigorous physical activity. Dyspnea showed a negative association with the functional score, including all tests. Our findings suggest that fatigue, post-exertional malaise, and the co-occurrence of physical symptoms are negatively associated with physical activity, while dyspnea is negatively associated with functional capacity in individuals with Long COVID.

Abstract The mosquito microbiome significantly influences vector competence, including in Aedes albopictus, a globally invasive vector. Describing the microbiome and Wolbachia strains of Ae. albopictus from different regions can guide area-specific control strategies. Mosquito samples from Spain and São Tomé were analyzed using 16S rRNA gene sequencing and metagenomic sequencing. Wolbachia infection patterns were observed by sex and population. Female mosquitoes were blood-fed, a factor considered in analyzing their microbiota. Results revealed a dominance of dual Wolbachia infections, strains A and B, in the microbiome of both populations of Ae. albopictus, especially among females. Both populations shared a core microbiome, although 5 and 9 other genera were only present in Spain and São Tomé populations, respectively. Genera like Pelomonas and Nevskia were identified for the first time in Aedes mosquitoes. This study is the first to describe the Ae. albopictus bacteriome in Spain and São Tomé, offering insights for the development of targeted mosquito control strategies. Understanding the specific microbiome composition can help in designing more effective interventions, such as microbiome manipulation and Wolbachia-based approaches, to reduce vector competence and transmission potential of these mosquitoes.

Abstract The Gram-negative bacterium Klebsiella pneumoniae is an important human pathogen. Its treatment has been complicated by the emergence of multi-drug resistant strains. The human complement system is an important part of our innate immune response that can directly kill Gram-negative bacteria by assembling membrane attack complex (MAC) pores into the bacterial outer membrane. To resist this attack, Gram-negative bacteria can modify their lipopolysaccharide (LPS). Especially the decoration of the LPS outer core with the O-antigen polysaccharide has been linked to increased bacterial survival in serum, but not studied in detail. In this study, we characterized various clinical Klebsiella pneumoniae isolates and show that expression of the LPS O1-antigen correlates with resistance to complement-mediated killing. Mechanistic data reveal that the O1-antigen does not inhibit C3b deposition and C5 conversion. In contrast, we see more efficient formation of C5a, and deposition of C6 and C9 when an O-antigen is present. Further downstream analyses revealed that the O1-antigen prevents correct insertion and polymerization of the final MAC component C9 into the bacterial membrane. Altogether, we show that the LPS O1-antigen is a key determining factor for complement resistance by K. pneumoniae and provide insights into the molecular basis of O1-mediated MAC evasion.

Abstract Background Neurofibromatosis type 1 (NF1), an autosomal dominant disorder, characterized by a spectrum of diverse neurocutaneous manifestations, is caused by heterozygous pathogenic variants in NF1 gene. While patients with NF1 often exhibit characteristic features, atypical phenotypes can arise, necessitating consideration of differential diagnoses or concurrent pathologies. Case presentation A seven-year-old boy with suspected NF1 underwent clinical evaluation. He presented hallmark café-au-lait spots, axillary freckling, and neurofibromas. Neuroimaging revealed a cranial plexiform neurofibroma. Additionally, he exhibited attention-deficit hyperactivity disorder and developmental delay. Genetic testing identified an Alu insertion variant within the NF1 gene, and subsequent array comparative genomic hybridization detected a 16p13.11 duplication. Conclusions This case underscores the intricate molecular bases of NF1 by identifying a rare Alu insertion variant. The patient's neurocognitive challenges and dysmorphic features prompted exploration of a potential overlapping genetic condition. Coexisting genetic disorders have been documented in NF1 patients, emphasizing the necessity of discerning atypical manifestations. The observed 16p13.11 duplication likely contributes to the patient's phenotype, enhancing the precision of diagnosis, prognosis, and genetic counseling.

Abstract Culturing and genomic sequencing of Mycobacterium tuberculosis (MTB) from tuberculosis (TB) cases is the basis for many research and clinical applications. The alternative, culture-free sequencing from diagnostic samples, is promising but poses challenges to obtain and analyse the MTB genome. Paradoxically, culture is assumed to impose a diversity bottleneck, which, if true, would entail unexplored consequences. To unravel this paradox we generate high-quality genomes of sputum-culture pairs from two different settings after developing a workflow for sequencing from sputum and a tailored bioinformatics analysis. Careful downstream comparisons reveal sources of sputum-culture incongruences due to false positive/negative variation associated with factors like low input MTB DNA or variable genomic depths. After accounting for these factors, contrary to the bottleneck dogma, we identify a 97% variant agreement within sputum-culture pairs, with a high correlation also in the variants’ frequency (0.98). The combined analysis from five different settings and more than 100 available samples shows that our results can be extrapolated to different TB epidemic scenarios, demonstrating that for the cases tested culture accurately mirrors clinical samples.

Abstract Background Epidemiological and toxicological studies indicate that increased exposure to air pollutants can lead to neurodegenerative diseases. To further confirm this relationship, we evaluated the association between exposure to ambient air pollutants and corneal nerve measures as a surrogate for neurodegeneration, using corneal confocal microscopy. Methods We used population-based observational cross-sectional data from The Maastricht Study including N = 3635 participants (mean age 59.3 years, 51.6% were women, and 19.9% had type 2 diabetes) living in the Maastricht area. Using the Geoscience and hEalth Cohort COnsortium (GECCO) data we linked the yearly average exposure levels of ambient air pollutants at home address-level [particulate matter with diameters of ≤ 2.5 µm (PM2.5), and ≤ 10.0 µm (PM10), nitrogen dioxide (NO2), and elemental carbon (EC)]. We used linear regression analysis to study the associations between Z-score for ambient air pollutants concentrations (PM2.5, PM10, NO2, and EC) and Z-score for individual corneal nerve measures (corneal nerve bifurcation density, corneal nerve density, corneal nerve length, and fractal dimension). Results After adjustment for potential confounders (age, sex, level of education, glucose metabolism status, corneal confocal microscopy lag time, inclusion year of participants, smoking status, and alcohol consumption), higher Z-scores for PM2.5 and PM10 were associated with lower Z-scores for corneal nerve bifurcation density, nerve density, nerve length, and nerve fractal dimension [stβ (95% CI): PM2.5 -0.10 (-0.14; -0.05), -0.04 (-0.09; 0.01), -0.11 (-0.16; -0.06), -0.20 (-0.24; -0.15); and PM10 -0.08 (-0.13; -0.03), -0.04 (-0.09; 0.01), -0.08 (-0.13; -0.04), -0.17 (-0.21; -0.12)], respectively. No associations were found between NO2 and EC and corneal nerve measures. Conclusions Our population-based study demonstrated that exposure to higher levels of PM2.5 and PM10 are associated with higher levels of corneal neurodegeneration, estimated from lower corneal nerve measures. Our results suggest that air pollution may be a determinant for neurodegeneration assessed in the cornea and may impact the ocular surface health as well.

Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equine cases caused by a novel WEEV lineage identified through a nearly complete coding sequence analysis, which we propose as lineage C. Our findings highlight the importance of continued surveillance and equine vaccination to control future WEEV outbreaks in South America.

Abstract The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC–MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system’s activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR.

Tuberculosis (TB) remains a significant global health challenge, particularly within pediatric populations. This article reports the case of a 7-year-old female patient admitted with massive fibrinous pleural effusion secondary to TB, highlighting the key role of ultrasound in disease monitoring and therapeutic guidance. The patient presented with fever, cough, and abdominal pain. Imaging confirmed the presence of pleural effusion and lymphadenopathy. Serial ultrasound assessments demonstrated superior sensitivity compared to CT in characterizing the pleural effusion, leading to the initiation of intrapleural urokinase therapy under ultrasound guidance. The treatment resulted in the successful dissolution of fibrin septations and marked clinical improvement. The discussion explores the diagnostic advantages of ultrasound in pediatric TB, its effectiveness in monitoring therapeutic response, and the utility of localized fibrinolytic therapy. This case highlights the value of ultrasound as a cost-effective, noninvasive, radiation-free tool in the management of pediatric TB, advocating for its increased integration into routine pediatric care.

Anatomical variations in hepatic arteries are both common and diverse. According to the classic classification systems, a replaced right hepatic artery typically originates from the superior mesenteric artery, supplying blood to the right liver lobe in the absence of the right branch of the proper hepatic artery. This article reports 2 cases of a rare variation, a replaced right hepatic artery arising directly from the celiac trunk. In these cases, the artery courses posterior to the common hepatic artery and then behind the portal vein within the hepatoduodenal ligament. The first case, involving a 62-year-old male with intraductal papillary mucinous neoplasm (IPMN) of the pancreas, was identified intraoperatively during a pancreaticoduodenectomy. The second case, involving a 58-year-old female with chronic sclerosing cholangitis, was detected through contrast-enhanced computed tomography angiography. Identification of such variations is critical in hepatobiliary and pancreatic surgeries to prevent serious postoperative complications. Injury to a replaced right hepatic artery can lead to biliary-enteric anastomosis dehiscence after pancreaticoduodenectomy or ischemic liver complications. While hepatic arteries display numerous anatomical variations, classic classification systems fail to encompass all these anomalies. A more comprehensive classification system, such as CRL and ex-CRL classification, is necessary to ensure safer surgical outcomes.

Objectives: The United States Centers for Disease Control and Prevention (CDC) conducts active surveillance for typhoid fever cases caused by Salmonella enterica serovar Typhi (Typhi). Here we describe the characteristics of the first two cases of mph(A)-positive azithromycin-resistant Typhi identified through US surveillance. Methods: Isolates were submitted to public health laboratories, sequenced, and screened for antimicrobial resistance determinants and plasmids, as part of CDC PulseNet's routine genomic surveillance. Antimicrobial susceptibility testing and long-read sequencing were also performed. Basic case information (age, sex, travel, outcome) was collected through routine questionnaires; additional epidemiological data was requested through follow-up patient interviews. Results: The patients are related and both reported travel to India (overlapping travel dates) before illness onset. Both Typhi genomes belong to the GenoTyphi lineage 4.3.1.1 and carry the azithromycin-resistance gene mph(A) on a PTU-FE (IncFIA/FIB/FII) plasmid. These strains differ genetically from mph(A)-positive Typhi genomes recently reported from Pakistan, suggesting independent emergence of azithromycin resistance in India. Conclusions: Cases of typhoid fever caused by Typhi strains resistant to all available oral treatment options are cause for concern and support the need for vaccination of travellers to Typhi endemic regions. US genomic surveillance serves as an important global sentinel for detection of strains with known and emerging antimicrobial resistance profiles, including strains from areas where routine surveillance is not conducted.

Transforming growth factor-β (TGFβ) and FoxP3 regulatory T cells (Treg) are involved in human breast carcinogenesis. This topic is not well documented in canine mammary tumors (CMT). In this work, the tumoral TGFβ expression was assessed by immunohistochemistry in 67 malignant CMT and its correlation to previously determined FoxP3, VEGF, and CD31 markers and other clinicopathologic parameters was evaluated. The high levels of TGFβ were statistically significantly associated with skin ulceration, tumor necrosis, high histological grade of malignancy (HGM), presence of neoplastic intravascular emboli and presence of lymph node metastases. The observed levels of TGFβ were positively correlated with intratumoral FoxP3 (strong correlation), VEGF (weak correlation) and CD31 (moderate correlation). Tumors that presented a concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31 markers were statistically significantly associated with parameters of tumor malignancy (high HGM, presence of vascular emboli and nodal metastasis). Additionally, shorter overall survival (OS) time was statistically significantly associated with tumors with an abundant TGFβ expression and with concurrent high expression of TGFβ/FoxP3, TGFβ/VEGF, and TGFβ/CD31. The presence of lymph node metastasis increased 11 times the risk of disease-related death, arising as an independent predictor of poor prognosis in the multivariable analysis. In conclusion, TGFβ and Treg cells seem involved in tumor progression emerging as potential therapeutic targets for future immunotherapy studies.

In a recent study, we have identified BPH03 as a promising scaffold for the development of compounds aimed at modulating the interaction between PED/PEA15 (Phosphoprotein Enriched in Diabetes/Phosphoprotein Enriched in Astrocytes 15) and PLD1 (phospholipase D1), with potential applications in type II diabetes therapy. PED/PEA15 is known to be overexpressed in certain forms of diabetes, where it binds to PLD1, thereby reducing insulin-stimulated glucose transport. The inhibition of this interaction reestablishes basal glucose transport, indicating PED as a potential target of ligands capable to recover glucose tolerance and insulin sensitivity. In this study, we employ computational methods to provide a detailed description of BPH03 interaction with PED, evidencing the presence of a hidden druggable pocket within its PLD1 binding surface. We also elucidate the conformational changes that occur during PED interaction with BPH03. Moreover, we report new NMR data supporting the in-silico findings and indicating that BPH03 disrupts the PED/PLD1 interface displacing PLD1 from its interaction with PED. Our study represents a significant advancement toward the development of potential therapeutics for the treatment of type II diabetes.

Abstract Platelet rich plasma and ozone therapy have been suggested in the clinical setting as promising and adjuvant therapies for managing the symptoms related to the facial aging. However, there is a lack of evidence about the effects of combining both therapies on rejuvenation. Thus, the aim of the present study was to evaluate and to compare the safety and efficacy of both therapies in facial aging. A single-center prospective pilot study was conducted. Female participants, aged 40 to 60 years, were randomized into 2 groups: participants received the platelet rich plasma treatment (PRP); participants received the therapy with platelet rich plasma associated with ozone therapy (PRPOT). Interventions were performed using the facial intradermal technique in 42 pre-established points, for 4 sessions with an interval of 15 days between them. After analyses performed using photographic records, assessment of frontal, periorbital, nasolabial and marionette wrinkles (Wrinkle Assessment Scale), self-esteem assessment (Brazilian Version of Rosenberg’s Self-Esteem Scale) and assessment of patient satisfaction (FACE-Q) can be suggested that the platelet rich plasma protocol performed in the present study, as well as its association with volume-controlled ozone therapy, proved to be safe and potentially promising modalities in the treatment of facial aging.

Introdução: O tratamento de quimioterapia pode provocar um conjunto de sintomas adversos, com implicações no bem-estar e qualidade de vida dos doentes oncológicos, pelo que se justificam intervenções de enfermagem destinadas a promover a sua autogestão. Objetivo: Avaliar a perceção de autoeficácia e qualidade de vida em doentes oncológicos a realizar quimioterapia, acompanhados presencialmente e via telefone na autogestão dos sintomas da quimioterapia. Método: Estudo descritivo-correlacional e longitudinal, com 51 doentes oncológicos, acompanhados ao longo do primeiro mês de tratamento de quimioterapia e avaliados em três momentos. Apresentação dos resultados e discussão: Os resultados indicam uma boa perceção de autoeficácia e de qualidade de vida ao longo do primeiro mês de quimioterapia. As náuseas e vómitos foram os sintomas mais lesivos, em especial na primeira fase. Os resultados sugerem ainda que as orientações para monitorização e autogestão dos sintomas ministradas pelos enfermeiros possam ter sido positivas para a adaptação à quimioterapia.

BackgroundPoint of care hemoglobin meters play key roles in increasing access to anemia screening in antenatal care especially in settings with limited access to laboratories. We aimed to determine the diagnostic accuracy of a non-invasive spot-check hemoglobin (SpHb) meter, Masimo Rad-67® Pulse CO-Oximeter®, in the diagnosis of anemia in pregnant women attending antenatal care clinics in Kilifi, Kenya.MethodsThis was a diagnostic accuracy study that retrospectively evaluated SpHb against a validated reference standard of laboratory assessed hemoglobin (Lab Hb) by a SYSMEX XN-330 automated hematology analyzer. The study was nested within a prospective pregnancy cohort study that recruited unselected pregnant women from antenatal care clinics in two public hospitals in Kilifi County, coastal Kenya. Records with both SpHb and Lab Hb were selected from pregnancy visits between May 2021 and December 2022. Linear regression and Bland-Altman analysis were performed to compare the two tests and diagnostic accuracy parameters obtained for the diagnosis of anemia.ResultsA total of 2,975 records (from 2,203 unique participants), with paired SpHb and Lab Hb were analyzed. Linear regression showed a significant but weak positive correlation, a proportional bias of 0.44 (95% CI 0.41–0.47) and a constant of 7.59 (95% CI 7.30–7.87, p

Summary: CombiVacS study has demonstrated a strong immune response of the heterologous ChAdOx1-S/BNT162b2 vaccine combination. The primary outcomes of the study were to assess the humoral immune response against SARS-CoV-2, 28 days after a third dose of a mRNA vaccine, in subjects that received a previous prime-boost scheme with ChAdOx1-S/BNT162b2. Secondary outcomes extended the study to 3 and 6 months. The third vaccine dose of mRNA-1273 in naive participants previously vaccinated with ChAdOx1-S/BNT162b2 regimen reached higher neutralizing antibodies titers against the variants of concern Delta and BA.1 lineage of Omicron compared with those receiving a third dose of BNT162b2 at day 28. These differences between BNT162b2 and mRNA-1273 arms were observed against the ancestral variant G614 at day 90. Suboptimal neutralizing response was observed against BQ.1.1, XBB.1.5/XBB.1.9, and JN.1 in a relevant proportion of individuals 180 days after the third dose, even after asymptomatic Omicron breakthrough infections. EudraCT (2021-001978-37); ClinicalTrials.gov (NCT04860739).

KneeBones3Dify is a Python software tool that supports detailed analysis of knee pathologies and preoperative planning for knee replacement surgery based on patient-specific 3D models. It produces printable 3D bones in a stereolithography file format by automatically segmenting the femur, patella, and tibia from high-resolution Magnetic Resonance (MR) images with nearly isotropic voxel dimensions. Our software avoids time-consuming and subjective manual segmentation by specialists, offering an accurate and efficient alternative employing GPU acceleration. We validated the results by computing objective metrics against the ground truth voxel-wise segmentation produced for a 3D MR image by specialists, who also confirmed the reconstruction accuracy qualitatively. KneeBones3Dify and annotated data are publicly available, enabling broader research and clinical practice use.

Controlled study designs usually report that physical exercise improves the health of women living with breast cancer. However, many of these women are not sufficiently active to experience the benefits of exercise. The main objective was to analyze the effect of a physical exercise program on quality of life, self-esteem, and depression in breast cancer survivors. Thirteen participants (46.54 ± 6.31 years old) completed the exercise intervention. Three patient-reported questionnaires were used: Supplementary Questionnaire Breast Cancer Module (QLQ-BR23), Beck Depression Inventory (BDI), and Rosenberg Self-Esteem Scale (RSES). All participants had significantly improved self-esteem (p = 0.004). Although there were no statistically significant changes in depression, there was a notable decrease in scores (6.39 ± 4.75 vs. 5.00 ± 4.75; p = 0.080). Regarding quality of life, significant improvements were observed in “future perspectives” (p = 0.047) and “arm symptoms” (p = 0.015). No significant changes were noted in the other variables. Our results suggest that physical exercise is an effective strategy that positively affects breast cancer survivors’ quality of life and self-esteem. The results reinforce the need for community-based exercise programs for breast cancer survivors. Healthcare professionals should promote physical exercise to improve health outcomes before, during, and after treatment.

Nitrogen is a very important nutrient in grass maintenance fertilization and therefore must be applied at the appropriate moment. The objective of this study was to identify the most responsive moment to nitrogen fertilization and to verify if root mass and the content of carbohydrates and nitrogen in roots influence the moment of fertilization in cultivars of Megathyrsus maximus (syn. Panicum maximum). This study was carried out simultaneously in a greenhouse using a completely randomized design, with sixteen treatments and five replications, in a 4×4 factorial design. The treatments consisted of four intervals between cultivar defoliation and nitrogen fertilization (0, 3, 6 and 9 days) and four Megathyrsus maximus cultivars, Mombasa, BRS Zuri, BRS Quenia and BRS Tamani, which were evaluated in five regrowth cycles. No difference in forage mass was observed among cultivars when fertilization was performed on days zero, three and nine after harvesting. On day nine, Mombasa showed a higher forage mass compared to BRS Tamani. Nitrogen content in the roots of Zuri decreased when fertilization was performed on the third day after defoliation, remaining constant in the other fertilization intervals. A linear reduction in root starch in BRS Zuri was observed, while in Mombasa cultivars, a linear increase was observed when fertilization was performed nine days after harvesting. Thus, nitrogen fertilization of BRS Tamani should be carried out closer to defoliation, while Mombasa, BRS Zuri and BRS Quenia can be fertilized up to nine days after harvesting, which results in greater flexibility regarding the moment of nitrogen fertilization.

The design of an antimicrobial coating material has become important in the prevention of infections caused by the transmission of pathogens coming from human contact with contaminated surfaces. With that aim, layered single hydroxides (LSHs) and layered double hydroxides (LDHs) containing Zn and Cu intercalated with antimicrobial molecules were synthesized and characterized. Cinnamate and salicylate anions were chosen because of their well-known antimicrobial activity. Several coatings based on polyvinyl alcohol (PVA) and LDHs or LSHs with increasing amounts of filler were prepared and filmed on a polyethylene terephthalate (PET) substrate. The coatings were characterized, and their antimicrobial activity was evaluated against several pathogens that are critical in nosocomial infections, showing a synergistic effect between metal ions and active molecules and the ability to inhibit their growth.

A 98-year-old patient with cognitive impairment and a history of squamous cell carcinoma of the nasal pyramid was referred to the radiation oncology department of our institution’s hospital given that surgery was not recommended. The lesion was sized 6 × 6 cm, ulcerated, and bleeding; was significantly impairing the patient’s health-related quality of life, causing pain; and was not responsive to analgesics, including opioids. The patient experienced deterioration of her general conditions, with a Karnofsky performance status of 40. A single radiotherapy (RT) fraction was delivered on a weekly basis for 3 weeks, up to a total dose of 21 Gy, using a VMAT technique (7 Gy/fraction). The patient was given three fractions of radiotherapy, during which she received continuous assistance due to episodes of mental disorientation and an altered sense of consciousness. One month after the conclusion of the treatment, the patient exhibited a nearly complete clinical response, with full pain relief and an improved health-related quality of life. This favourable clinical outcome was maintained for a period of four months following the conclusion of RT. A brief review was performed on the role of hypofractionated radiation therapy in elderly patients with locally advanced skin cancer of the head and neck region.

Despite the well-documented detrimental health effects of prolonged engagement in sedentary behaviors, children and adolescents spent a large amount of time with seated activities. The present study examined the association between participation in club sports and various sedentary behaviors during weekdays and the weekend in youth between 11 and 17 years of age. A total of 1225 (50.1% male) adolescents completed a validated questionnaire that examined sitting time in activities related to work as well as during leisure time such as screen use, reading, and listening to music in addition to sleep time. Participants spent an average of 12.7 ± 1.7 and 9.9 ± 2.0 h/day during weekdays and the weekend, respectively, in seated behaviors while they were awake. Club sports participants reported less time spent sitting (p < 0.01), which was mainly attributed to recreational activities (e.g., screen use, reading, listening to music). Sleep time during weekdays, on the other hand, was higher in club sports participants. Sex-specific results further showed that differences by club sports participation were more pronounced in girls compared to boys. Despite the potential beneficial effects of club sports participation, additional efforts are needed to reduce sitting time in adolescents as either group spent the majority of their time awake with sedentary behaviors.

The ever-growing knowledge regarding NSCLC molecular biology has brought innovative therapies into clinical practice; however, the treatment situation in the non-metastatic setting is rapidly evolving. Indeed, immunotherapy-based perioperative treatments are currently considered the standard of care for patients with resectable NSCLC in the absence of EGFR mutations or ALK gene rearrangements. Recently, data have been presented on the use of tyrosine kinase inhibitors (TKIs) in the adjuvant and locally advanced setting for patients with NSCLC harboring such driver gene alterations. The aim of the current work is to review the available evidence on the use of targeted treatments in the non-metastatic setting, together with a summary of the ongoing trials designed for actionable gene alterations other than EGFR and ALK. To date, 3-year adjuvant osimertinib treatment has been demonstrated to improve DFS and OS and to reduce CNS recurrence in resected EGFR-mutated NSCLC in stage IB–IIIA (TNM 7th edition). The use of osimertinib after chemo-radiation in stage III unresectable EGFR-mutated NSCLC showed the relevant PFS improvement. In the ALK-positive setting, 2-year alectinib treatment was shown to clearly improve DFS compared to adjuvant standard chemotherapy in resected NSCLC with stage IB (≥4 cm)–IIIA (TNM 7th edition). Several trials are ongoing to establish the optimal adjuvant TKI treatment duration, as well as neoadjuvant TKI strategies in EGFR- and ALK-positive disease, and (neo)adjuvant targeted treatments in patients with actionable gene alterations other than EGFR or ALK. In conclusion, our review depicts how the current treatment scenario is expected to rapidly change in the context of non-metastatic NSCLC with actionable gene alterations, hence appropriate molecular testing from the early stages has become crucial to establish the most adequate approaches both in the perioperative and the locally advanced disease.

Fungal infections are a significant threat to human health and the environment. The emergence of multidrug-resistant strains of fungi and the growing prevalence of azole resistance in invasive fungal infections exacerbate the problem, with efflux pumps being a major cause of antifungal resistance and a prime target for several counteractive strategies. In Candida albicans, the ATP-binding cassette superfamily transporter CaCdr1p is the predominant efflux pump involved in azole resistance. Marine organisms have unique phenotypic characteristics to survive in challenging environments, resulting in biologically active compounds. The cyclodepsipeptides unnarmicin A and C have shown promising results as inhibitors of rhodamine 6G efflux in cells expressing CaCdr1p. Herein, a series of unnarmicin analogues were designed and docked against a CaCdr1p efflux pump based on the cryogenic electron microscopy structure available to select the most promising compounds. Analogue 33 was predicted to be the best considering its high affinity for the efflux pump and pharmacokinetic profile. These results pave the way for further synthesis and in vitro biological studies of novel unnarmicins seeking a synergistic effect with fluconazole.

Abstract Introduction Multiple sclerosis (MS) is a chronic neurodegenerative disease that leads to impaired cognitive function and accumulation of disability, with significant socioeconomic burden. Serious unmet need in the context of managing MS has given rise to ongoing research efforts, leading to the launch of new drugs planned for the near future, and subsequent concerns about the sustainability of healthcare systems. This study assessed the changes in the Italian MS market and their impact on the expenditures of the Italian National Healthcare Service between 2023 and 2028. Methods A horizon-scanning model was developed to estimate annual expenditure from 2023 to 2028. Annual expenditure for MS was calculated by combining the number of patients treated with each product (clinical inputs) and the yearly costs of therapy (economic inputs). Baseline inputs (2020–2022) were collected from IQVIA® real-world data, while input estimation for the 5-year forecast was integrated with analog analyses and the insights of clinicians and former payers. Results The number of equivalent patients treated in 2028 in Italy was estimated at around 67,000, with an increase of 10% versus 2022. In terms of treatment pattern evolution, first-line treatments are expected to reduce their shares from 47% in 2022 to 27% in 2028, and Bruton tyrosine kinase inhibitors are expected to reach 23% of patient shares. Overall, expenditure for MS is estimated to decrease from €721 million in 2022 to €551 million in 2028, mainly due to losses of exclusivity and renegotiation of drug prices. Conclusion Despite the increase in the number of patients treated for MS and the launch of new molecules that will reach high market penetration, the model confirmed sustainability for the Italian National Healthcare Service.

This study aims to explore how elementary school teachers’ beliefs about the nature of history and pedagogical beliefs about teaching history developed over the course of a two-year professional development (PD) program and which elements of the program stimulated this development. This PD program aimed to develop participants’ skills in historical reasoning and in designing inquiry-based history lessons that encourage students to reason historically. Teachers engaged in historical reasoning and developed and implemented activities for inquiry-based learning in their history lessons. In this qualitative study, we interviewed nine teachers before and after the program, and they completed the Beliefs about Learning and Teaching History questionnaire before, during and after the program. Thematic analysis of the data shows that elementary teachers participating in our PD program developed more nuanced beliefs about history. Both epistemic and pedagogical beliefs became more crystallized and more criterialist in nature, but it is especially participants’ pedagogical beliefs that became more oriented toward inquiry into historical sources and the importance of developing historical reasoning skills in students. Our findings also indicate that more naïve ideas remained in addition to more nuanced beliefs. Participants indicated that their pedagogical beliefs about teaching history and conducting historical inquiry changed because of the program. Based on the final interviews, we identified five elements that enhanced participants’ professional development toward teaching inquiry-based history lessons and influenced their epistemic beliefs. It was the combination of engaging in historical inquiry, modeling by the facilitator, participating in group discussions about historical inquiry, searching for historical sources themselves and developing and discussing their own lesson designs and putting them into practice that made participants see the possibilities of inquiry-based history learning and stimulated the development of their beliefs. The findings of this study imply that to prepare elementary teachers to teach history in a way that fosters inquiry into historical sources and historical reasoning, PD programs and teacher education should pay attention to the epistemology of history as a discipline and provide teachers with tools to do inquiry.

Abstract Background Despite being one of the most popular measures of borderline pathology in adolescents, only one study has evaluated clinical cut-off scores for the Borderline Personality Features Scale for Children (BPFS-C) using a small sample without a healthy comparison group (Chang B, Sharp C, Ha C. The Criterion Validity of the Borderline Personality Features Scale for Children in an Adolescent Inpatient Setting. J Personal Disord. 2011;25(4):492–503. https://doi.org/10.1521/pedi.2011.25.4.492 .). The purpose of the current study was to replicate and improve on the limitations of the prior study conducted by Chang et al. to more definitively establish clinical cut-off scores for the self- and parent-report versions of the BPFS-C to detect clinical and sub-clinical borderline personality disorder (BPD) in a large sample of adolescents with BPD, other psychopathology, and no psychopathology. Methods A total of 900 adolescents ranging from ages 12–17 participated in this study. The clinical sample consisted of 622 adolescents recruited from an inpatient psychiatric facility, and the healthy control sample consisted of 278 adolescents recruited from the community. All participants completed the BPFS-C and were administered the Child Interview for DSM-IV Borderline Personality Disorder (CI-BPD). Results Using three-way ROC analyses, cut-off scores on the self- and parent-report versions of the BPFS-C distinguishing adolescents with BPD from those with subclinical BPD, and those with subclinical BPD from healthy adolescents were established. Conclusions These findings support the use of both versions of the BPFS-C to detect adolescents with BPD and sub-clinical BPD.

Abstract This commentary outlines the development of an Inclusion Collaborative in a large health district in Sydney, New South Wales Australia. The Collaborative grew out of ongoing efforts to reduce stigma associated with blood borne viruses while recognising that there are many health conditions and situations where people feel judged when attending services for health care. The formation of the Collaborative drew in health workers in other sectors to create a critical mass of voices calling for stigma reduction, move beyond siloed responses to stigma and to reframe conversations about stigma to a more positive description of “inclusion”. The involvement of consumer representatives (paid for their time) was a key principle of the Collaborative. The members of the Collaborative identified the common experience of their clients being ‘othered’ by the mainstream services and that services can be unwelcoming or not supportive of difference, and therefore create a significant barrier to accessing healthcare. The group considered ways to highlight these issues among colleagues from mainstream services and community members who were not ‘othered’. The Collaborative designed and carried out a range of activities including a Festival of Inclusion, a series of seeding grants for staff and consumer-focused initiatives, promotion of diversity days and an audit of compliance with strategic priorities. The Inclusion Collaborative is an example of a structured approach for efforts to reducing stigma that draws on the ambitions of many parts of a large, complex public health service to deliver better outcomes for its staff and consumers.

Abstract Background Multiple clinician adjustable parameters impact upon glycemia in people with type 1 diabetes (T1D) using Medtronic Mini Med 780G (MM780G) AHCL. These include glucose targets, carbohydrate ratios (CR), and active insulin time (AIT). Algorithm-based decision support advising upon potential settings adjustments may enhance clinical decision-making. Methods Single-arm, two-phase exploratory study developing decision support to commence and sustain AHCL. Participants commenced investigational MM780G, then 8 weeks Phase 1-initial optimization tool evaluation, involving algorithm-based decision support with weekly AIT and CR recommendations. Clinicians approved or rejected CR and AIT recommendations based on perceived safety per protocol. Co-design resulted in a refined algorithm evaluated in a further identically configured Phase 2. Phase 2 participants also transitioned to commercial MM780G following “Quick Start” (algorithm-derived tool determining initial AHCL settings using daily insulin dose and weight). We assessed efficacy, safety, and acceptability of decision support using glycemic metrics, and the proportion of accepted CR and AIT settings per phase. Results Fifty three participants commenced Phase 1 (mean age 24.4; Hba1c 61.5mmol/7.7%). The proportion of CR and AIT accepted by clinicians increased between Phases 1 and 2 respectively: CR 89.2% vs. 98.6%, p

The retinacula of the ankle are specialized anatomical structures characterized by localized thickenings of the crural fascia that envelop the deep components of the lower leg, ankle and foot. The ankle retinacula include the extensor retinacula, the peroneal retinacula and flexor retinaculum. Despite their potential to explain persistent and unexplained pain following an injury, these structures are often overlooked or incorrectly diagnosed. Hence, this comprehensive review was performed aiming to investigate the use and the methodology of US imaging to assess ankle retinacula. The search was performed on PubMed and Web of Science databases from inception to May 2024. The MeSH keywords used were as follows: “Ankle Retinacula”, “Foot Retinacula”, “Superior extensor retinaculum”, “Inferior extensor retinaculum”, “peroneal retinaculum”, “superior peroneal retinaculum”, “inferior peroneal retinaculum”, “flexor retinaculum”, “Ultrasound Imaging”, “Ultrasound”, “Ultrasonography” and “Ultrasound examination”. In total, 257 records underwent screening, resulting in 22 studies meeting the criteria for inclusion after the process of revision. Data heterogeneity prevents synthesis and consistent conclusions. The results showed that advanced US imaging holds promise as a crucial tool to perform an US examination of ankle retinacula, offering static and dynamic insights into ankle retinacula pathology. Understanding normal anatomy and US imaging is essential for accurately identifying injuries. Future research should focus on clinical trials to validate parameters and ensure their reliability in clinical practice.

Abstract Background Diabetic kidney disease (DKD) is associated with a higher risk of cardiovascular disease (CVD). Pentoxifylline (PTF), a nonselective phosphodiesterase inhibitor with anti-inflammatory, antiproliferative, and antifibrotic actions, has demonstrated renal benefits in both clinical trials and meta-analyses. The present work aimed to study the effects of PTF on the progression of subclinical atherosclerosis (SA) in a population of patients with diabetes and moderate to severe chronic kidney disease (CKD). Methods In this open-label, randomized controlled, prospective single-center pilot study the evolution of carotid intima-media thickness (CIMT) and ankle-brachial index (ABI) were determined in 102 patients with type 2 diabetes mellitus and CKD assigned to PTF, aspirin or control groups during 18 months. We also determined the variations in the levels of inflammatory markers and Klotho (KL), a protein involved in maintaining cardiovascular health, and their relationship with the progression of SA. Results Patients treated with PTF presented a better evolution of CIMT, increased KL mRNA levels in peripheral blood cells (PBCs) and reduced the inflammatory state. The progression of CIMT values was inversely related to variations in KL both in serum and mRNA expression levels in PBCs. Multiple regression analysis demonstrated that PTF treatment and variations in mRNA KL expression in PBCs, together with changes in HDL, were significant determinants for the progression of CIMT (adjusted R2 = 0.24, P

Abstract The implementation of the noninvasive prenatal test has shown the importance of involving future care providers in healthcare innovations at an early stage. Therefore, in this explorative study in-depth interviews were performed with Dutch midwife counselors who explicitly identify as religious, to explore how they currently deal with their worldview during counseling for prenatal anomaly screening and regarding their perspectives on heritable genome editing (HGE). HGE is a potentially disruptive technology in which a pregnancy is initiated with a modified embryo or gamete, thus passing on modified genes to a future child and the following generations. Currently, a significant majority of countries prohibit HGE. However, implications for healthcare policy and practice are discussed in an ongoing scientific and societal dialogue. Eleven counselors participated: eight Christians and three Muslims. Two main themes were identified: ‘a search for role identity as a healthcare counselor’ and ‘concerns about the application of HGE’. Our findings showed that both values and underlying worldview-based beliefs influence perspectives on current and emerging reproductive techniques. Healthcare counselors search for ways to harmonize their professional role with contrasting values based on worldview-based beliefs. Moreover, for HGE, counselors fear ‘slippery slopes’ regarding the boundaries between treatment and enhancement, the severity assessment of certain conditions, and society’s appreciation for the quality of life of people with disabilities. Regarding future implementation, counselors’ medical education might benefit from a focus not only on qualification (acquiring knowledge) but also on balancing between socialization (e.g., adhering the norm of nondirective counseling) and subjectification (being a ‘self’ in relation to everything learned). In the global call for broad public and stakeholder engagement to explore the acceptability of HGE, the influence of both values and beliefs should be deliberated.

Abstract Background Previne Brasil is a new way of financing Primary Health Care (PHC) in Brazil that places users of public health services at the center of the system’s analysis and attention through the use of seven performance indicators. This study aims to analyze the performance of Primary Health Care in Brazil under the new financing model (Previne Brasil) in the period from the first four months of 2022 to the first four months of 2023. Methods This is a territorial ecological study using secondary data from the Primary Care Health Information System (SISAB). Seven performance indicators were included and analyzed according to Brazil, its regions, states and capitals. A comparative descriptive analysis was carried out between the spatial units. Results Of the seven indicators analyzed, only one (Proportion of pregnant women tested for syphilis and HIV) reached the proposed target considering the average of the four-month periods evaluated (target: 60%; Observed: 62.5%). The Northeast was the region with the best performance, surpassing the target in three of the seven indicators (prenatal consultations, tests for syphilis and HIV in pregnant women and dental care for pregnant women). The states and capitals showed progressive improvement in the performance indicators over the four quarters analyzed, although unevenly between the indicators. The indicators related to hypertension and diabetes were the worst. The Final Synthetic Indicator (FSI) showed an increase in the median over the four quarters (4.78; 5.65; 6.02 6.29), which represents an increase of 1.51 in the indicator between the first four months of 2022 and the first four months of 2023. Conclusion Although there have been improvements in the performance of Primary Health Care in Brazil, the achievement of the agreed targets for the indicators seems a long way off. The socio-spatial inequalities in the indicators reflect the country’s health complexity and reinforce the need for policies that take into account the local-regional context.

Abstract The high salt-fed stroke-prone spontaneously hypertensive rat (SHRSP) is a suitable tool to study the mechanisms underlying stroke pathogenesis. Salt intake modifies the gut microbiota (GM) in rats and humans and alterations of the GM have previously been associated with increased stroke occurrence. We aimed to characterize the GM profile in SHRSPs fed a high-salt stroke-permissive diet (Japanese diet, JD), compared to the closely related stroke-resistant control (SHRSR), to identify possible changes associated with stroke occurrence. SHRSPs and SHRSRs were fed a regular diet or JD for 4 weeks (short-term, ST) or a maximum of 10 weeks (long-term, LT). Stroke occurred in SHRSPs on JD-LT, preceded by proteinuria and diarrhoea. The GM of JD-fed SHRSPs underwent early and late compositional changes compared to SHRSRs. An overrepresentation of Streptococcaceae and an underrepresentation of Lachnospiraceae were observed in SHRSPs JD-ST, while in SHRSPs JD-LT short-chain fatty acid producers, e.g. Lachnobacterium and Faecalibacterium, decreased and pathobionts such as Coriobacteriaceae and Desulfovibrio increased. Occludin gene expression behaved differently in SHRSPs and SHRSRs. Calprotectin levels were unchanged. In conclusion, the altered GM in JD-fed SHRSPs may be detrimental to gut homeostasis and contribute to stroke occurrence.

Abstract To compare the magnetic resonance imaging (MRI) features of different immunophenotypes of breast carcinoma of no special type (NST), with special attention to estrogen receptor (ER)-low-positive breast cancer. This retrospective, single-centre, Institutional Review Board (IRB)-approved study included 398 patients with invasive breast carcinoma. Breast carcinomas were classified as ER-low-positive when there was ER staining in 1–10% of tumour cells. Pretreatment MRI was reviewed to assess the tumour imaging features according to the 5th edition of the Breast Imaging Reporting and Data System (BI-RADS) lexicon. Of the 398 cases, 50 (12.6%) were luminal A, 191 (48.0%) were luminal B, 26 (6.5%) were luminal ER-low positive, 64 (16.1%) were HER2-overexpressing, and 67 (16.8%) were triple negative. Correlation analysis between MRI features and tumour immunophenotype showed statistically significant differences in mass shape, margins, internal enhancement and the delayed phase of the kinetic curve. An oval or round shape and rim enhancement were most frequently observed in triple-negative and luminal ER-low-positive tumours. Spiculated margins were most common in luminal A and luminal B tumours. A persistent kinetic curve was more frequent in luminal A tumours, while a washout curve was more common in the triple-negative, HER2-overexpressing and luminal ER-low-positive immunophenotypes. Multinomial regression analysis showed that luminal ER-low-positive tumours had similar results to triple-negative tumours for almost all variables. Luminal ER-low-positive tumours present with similar MRI findings to triple-negative tumours, which suggests that MRI can play a fundamental role in adequate radiopathological correlation and therapeutic planning in these patients.

Abstract The emerging world of 3D food printing is reviewed. Its role in food manufacturing, including benefits and impacts, underemphasized gastrophysical aspects, and limitations are discussed. Foods can be digitally designed and physically prepared using the layer-by-layer deposition of food components, unleashing opportunities to deliver nutritionally personalized food and new food-human interactions. Existing bottlenecks, under-researched gastropsychophysical aspects, and the lack of harmonized standards hindering its use for mass production are mentioned.

Abstract Objectives Neurogenic muscle hypertrophy (NMH) is a rare condition characterized by focal muscle hypertrophy caused by chronic partial nervous injury. Given its infrequency, underlying mechanisms remain poorly understood. Inspired by two clinical cases, we conducted a systematic review to gain insights into the different aspects of NMH. Methods We systematically searched online databases up until May 30, 2023, for reports of muscle hypertrophy attributed to acquired neurogenic factors. We conducted an exploratory analysis to identify commonly associated features. We also report two representative clinical cases. Results Our search identified 63 reports, describing 93 NMH cases, to which we added our two cases. NMH predominantly affects patients with compressive radiculopathy (68.4%), negligible muscular weakness (93.3%), and a chronic increase in muscle bulk. A striking finding in most neurophysiological studies (60.0%) is profuse spontaneous discharges, often hindering the analysis of voluntary traces. Some patients exhibited features consistent with more significant muscle damage, including higher creatine phosphokinase levels, muscle pain, and inflammatory muscle infiltration. These patients are sometimes referred to in literature as “focal myositis.” Treatment encompassed corticosteroid, Botulinum Toxin A, decompressive surgery, antiepileptic medications, and nerve blocks, demonstrating varying degrees of efficacy. Botulinum Toxin A yielded the most favorable response in terms of reducing spontaneous discharges. Interpretation This systematic review aims to provide a clear description and categorization of this uncommon presentation of an often‐overlooked neurological disorder. Though questions remain about the underlying mechanism, evidence suggests that aberrant fiber overstimulation along with increased workload that promotes focal damage may result in muscle hypertrophy. This may serve as a guide for therapeutic interventions.