Determinants of intended prevention behaviour against mosquitoes and mosquito-borne viruses in the Netherlands and Spain using the MosquitoWise survey: cross-sectional study.

BACKGROUND: Recently, Europe has seen an emergence of mosquito-borne viruses (MBVs). Understanding citizens' perceptions of and behaviours towards mosquitoes and MBVs is crucial to reduce disease risk. We investigated and compared perceptions, knowledge, and determinants of citizens' behavioural intentions related to mosquitoes and MBVs in the Netherlands and Spain, to help improve public health interventions. METHODS: Using the validated MosquitoWise survey, data was collected through participant panels in Spain (N = 475) and the Netherlands (N = 438). Health Belief Model scores measuring behavioural intent, knowledge, and information scores were calculated. Confidence Interval-Based Estimation of Relevance was used, together with potential for change indexes, to identify promising determinants for improving prevention measure use. RESULTS: Spanish participants' responses showed slightly higher intent to use prevention measures compared to those of Dutch participants (29.1 and 28.2, respectively, p 0.03). Most participants in Spain (92.2%) and the Netherlands (91.8%) indicated they used at least one prevention measure, but differences were observed in which types they used. More Spanish participants indicated to have received information on mosquitoes and MBVs compared to Dutch participants. Spanish participants preferred health professional information sources, while Dutch participants favoured government websites. Determinants for intent to use prevention measures included "Knowledge", "Reminders to Use Prevention Measures", and "Information" in the Netherlands and Spain. Determinants for repellent use included "Perceived Benefits" and "Cues to Action", with "Perceived Benefits" having a high potential for behavioural change in both countries. "Self-Efficacy" and "Knowledge" were determinants in both countries for breeding site removal. CONCLUSION: This study found differences in knowledge between the Netherlands and Spain but similarities in determinants for intent to use prevention measures, intent to use repellents and intent to remove mosquito breeding sites. Identified determinants can be the focus for future public health interventions to reduce MBV risks.

Survival after resection of malignant peripheral nerve sheath tumors: Introducing and validating a novel type-specific prognostic model.

Background: This study aimed to assess the performance of currently available risk calculators in a cohort of patients with malignant peripheral nerve sheath tumors (MPNST) and to create an MPNST-specific prognostic model including type-specific predictors for overall survival (OS). Methods: This is a retrospective multicenter cohort study of patients with MPNST from 11 secondary or tertiary centers in The Netherlands, Italy and the United States of America. All patients diagnosed with primary MPNST who underwent macroscopically complete surgical resection from 2000 to 2019 were included in this study. A multivariable Cox proportional hazard model for OS was estimated with prespecified predictors (age, grade, size, NF-1 status, triton status, depth, tumor location, and surgical margin). Model performance was assessed for the Sarculator and PERSARC calculators by examining discrimination (C-index) and calibration (calibration plots and observed-expected statistic; O/E-statistic). Internal-external cross-validation by different regions was performed to evaluate the generalizability of the model. Results: A total of 507 patients with primary MPNSTs were included from 11 centers in 7 regions. During follow-up (median 8.7 years), 211 patients died. The C-index was 0.60 (95% CI 0.53-0.67) for both Sarculator and PERSARC. The MPNST-specific model had a pooled C-index of 0.69 (95%CI 0.65-0.73) at validation, with adequate discrimination and calibration across regions. Conclusions: The MPNST-specific MONACO model can be used to predict 3-, 5-, and 10-year OS in patients with primary MPNST who underwent macroscopically complete surgical resection. Further validation may refine the model to inform patients and physicians on prognosis and support them in shared decision-making.

Prognostic relevance of high expression of kynurenine pathway markers in glioblastoma.

Glioblastoma (GBM) continues to exhibit a discouraging survival rate despite extensive research into new treatments. One factor contributing to its poor prognosis is the tumor's immunosuppressive microenvironment, in which the kynurenine pathway (KP) plays a significant role. This study aimed to explore how KP impacts the survival of newly diagnosed GBM patients. We examined tissue samples from 108 GBM patients to assess the expression levels of key KP markers-tryptophan 2,3-dioxygenase (TDO2), indoleamine 2,3-dioxygenase (IDO1/2), and the aryl hydrocarbon receptor (AhR). Using immunohistochemistry and QuPath software, three tumor cores were analyzed per patient to evaluate KP marker expression. Kaplan-Meier survival analysis and stepwise multivariate Cox regression were used to determine the effect of these markers on patient survival. Results showed that patients with high expression of TDO2, IDO1/2, and AhR had significantly shorter survival times. This finding held true even when controlling for other known prognostic variables, with a hazard ratio of 3.393 for IDO1, 2.775 for IDO2, 1.891 for TDO2, and 1.902 for AhR. We suggest that KP markers could serve as useful tools for patient stratification, potentially guiding future immunomodulating trials and personalized treatment approaches for GBM patients.

TB-related catastrophic costs in Ethiopia.

OBJECTIVES: To measure the progress towards reducing TB-related catastrophic costs in 19 zones of Amhara, Oromia, SNNP (Southern Nations and Nationalities, and Peoples) and Sidama Regions of Ethiopia. METHODS: A baseline survey was conducted in randomly selected health facilities from all districts within the 19 zones from November 2020 to February 2021. Interventions targeting the major drivers of catastrophic costs identified in the baseline survey, such as installation of 126 GeneXpert and 13 Truenat machines, securing connectivity of 372 GeneXpert, establishing alternative specimen referral systems, and capacity-building of health workers, were implemented. A follow-up survey was conducted from October to December 2022. The WHO generic tool was used to collect data based on probability proportional to size. Data were entered into STATA software, and the proportion of catastrophic costs was calculated and compared between the two surveys. RESULTS: A total of 433 and 397 patients participated in the baseline and follow-up surveys, respectively. The proportion of catastrophic costs reduced from 64.7% to 43.8% (P < 0.0001). The share of direct non-medical costs decreased from 76.2% to 19.2%, while medical and indirect costs increased from 11.6% and 12.3% to 30.4% and 52.4 %. CONCLUSION: The proportion of households facing TB-related catastrophic costs has significantly reduced over the 2-year period. However, it remains unacceptably high and varies among regions. Further reducing the catastrophic costs requires multisectoral response, reviewing the TB service exemption policy, further decentralisation and improving the quality of TB services.

OBJECTIFS: Mesurer les progrès accomplis dans la réduction des coûts catastrophiques liés à la TB dans 19 zones des régions d'Amhara, d'Oromia, de SNNP (Région des nations, nationalités et peuples du Sud) et de Sidama en Éthiopie. MÉTHODES: Une enquête de base a été menée dans des établissements de santé sélectionnés au hasard dans tous les districts des 19 zones de novembre 2020 à février 2021. Des interventions ciblant les principaux facteurs de coûts catastrophiques identifiés dans l'enquête de référence, telles que l'installation de 126 machines GeneXpert et 13 Truenat, la sécurisation de la connectivité de 372 GeneXpert, la mise en place de systèmes alternatifs d'orientation des échantillons et le renforcement des capacités des agents de santé, ont été mises en œuvre. Une enquête de suivi a été menée d'octobre à décembre 2022. L'outil générique de l'OMS a été utilisé pour recueillir des données fondées sur une probabilité proportionnelle à la taille. Les données ont été saisies dans le logiciel STATA, et la proportion des coûts catastrophiques a été calculée et comparée entre les deux enquêtes. RÉSULTATS: Au total, 433 et 397 patients ont participé respectivement à l'enquête de base et à l'enquête de suivi. La proportion des coûts catastrophiques est passée de 64,7% à 43,8% (P < 0,0001). La part des coûts non médicaux directs a diminué, passant de 76,2% à 19,2%, tandis que les coûts médicaux et indirects sont passés de 11,6% et 12,3% à 30,4% et 52,4%. CONCLUSION: La proportion de ménages confrontés à des coûts catastrophiques liés à la tuberculose a considérablement diminué au cours de la période de 2 ans. Cependant, il reste inacceptable et varie selon les régions. Pour réduire davantage les coûts catastrophiques, il faut une réponse multisectorielle, une révision de la politique d'exemption des services de lutte contre la TB, une décentralisation plus poussée et une amélioration de la qualité des services de lutte contre la TB.

Feasibility, reliability and satisfaction of (automated) capillary carcinoembryonic antigen measurements for future home-based blood sampling: the prospective CASA-I study.

AIM: Follow-up for colorectal cancer (CRC) necessitates regular monitoring of carcinoembryonic antigen (CEA) at the hospital. Capillary home-based blood collection, including minimally invasive techniques such as lancet sampling or an automated upper arm device (TAP-II), has the potential to replace a significant portion of hospital-based blood sampling, thereby enhancing self-reliance and quality of life. The objectives of this study were to assess the feasibility, reliability and preference for CEA blood collection. METHODS: Baseline venous and capillary (by lancet and TAP-II) blood samples were collected from 102 participants, including 20 CRC patients with elevated CEA levels, 60 CRC patients undergoing postoperative outpatient monitoring and 20 healthy volunteers. The second group performed capillary blood collections at home on two consecutive follow-up appointments and subsequently sent them to the hospital. Satisfaction was assessed via patient reported outcome measures on pain, burden, ease of use and preference. RESULTS: The Pearson's correlation test of all usable samples resulted in a linear coefficient of 0.998 (95% CI 0.997-0.998) for the TAP-II method and 0.997 (95% CI 0.996-0.998) for the lancet method, both compared to venipuncture. Following the initial blood collection, 86% of the participants (n = 102) favoured the TAP-II, rating it as the least painful and burdensome option. After two home-based blood samples, the preference for the TAP-II method persisted, with 64% of the patients endorsing its use. CONCLUSION: This study demonstrated the feasibility of home-based capillary sampling of CEA. The TAP-II blood collection is the most reliable method and is preferred by patients over venipuncture and lancet sampling.

Inhibition of Enzyme and Bacteria Activities in Diabetic Ulcer-like Scenarios via WAAPV-Loaded Electrospun Fibers.

In diabetic ulcers, an increased secretion of human neutrophil elastase (HNE) and bacterial infections play crucial roles in hindering healing. Considering that, the present study proposed the development of multi-action polycaprolactone (PCL)/polyethylene glycol (PEG) electrospun fibers incorporating elastase-targeting peptides, AAPV and WAAPV, via blending. Characterization confirmed WAAPV's efficacy in regulating proteolytic enzymes by inhibiting HNE. The engineered fibers, particularly those containing PEG, exhibited optimal wettability but an accelerated degradation that was mitigated with the peptide's inclusion, thus promoting a sustained peptide release over 24 h. Peptide loading was verified indirectly through thermal stability and hydration capacity studies (hydrophobic bonding between PCL and WAAPV and hydrophilic affinities between PCL/PEG and AAPV) and determined at ≈51.1 µg/cm2 and ≈46.0 µg/cm2 for AAPV and ≈48.5 µg/cm2 and ≈51.3 µg/cm2 for WAAPV, respectively, for PCL and PCL/PEG. Both AAPV and WAAPV effectively inhibited HNE, with PEG potentially enhancing this effect by interacting with the peptides and generating detectable peptide-PEG complexes (≈10% inhibition with PCL + peptide fibers after 6 h of incubation, and ≈20% with PCL/PEG + peptide fibers after 4 h incubation). Peptide-loaded fibers demonstrated antibacterial efficacy against Staphylococcus aureus (up to ≈78% inhibition) and Escherichia coli (up to ≈66% inhibition), with peak effectiveness observed after 4 and 2 h of incubation, respectively. This study provides initial insights into the WAAPV's potential for inhibiting HNE and bacteria activities, showing promise for applications in diabetic ulcer management.

Ixodes ricinus as potential vector for Usutu virus.

Usutu virus (USUV) is an emerging flavivirus that is maintained in an enzootic cycle with mosquitoes as vectors and birds as amplifying hosts. In Europe, the virus has caused mass mortality of wild birds, mainly among Common Blackbird (Turdus merula) populations. While mosquitoes are the primary vectors for USUV, Common Blackbirds and other avian species are exposed to other arthropod ectoparasites, such as ticks. It is unknown, however, if ticks can maintain and transmit USUV. We addressed this question using in vitro and in vivo experiments and field collected data. USUV replicated in IRE/CTVM19 Ixodes ricinus tick cells and in injected ticks. Moreover, I. ricinus nymphs acquired the virus via artificial membrane blood-feeding and maintained the virus for at least 70 days. Transstadial transmission of USUV from nymphs to adults was confirmed in 4.9% of the ticks. USUV disseminated from the midgut to the haemocoel, and was transmitted via the saliva of the tick during artificial membrane blood-feeding. We further explored the role of ticks by monitoring USUV in questing ticks and in ticks feeding on wild birds in the Netherlands between 2016 and 2019. In total, 622 wild birds and the Ixodes ticks they carried were tested for USUV RNA. Of these birds, 48 (7.7%) carried USUV-positive ticks. The presence of negative-sense USUV RNA in ticks, as confirmed via small RNA-sequencing, showed active virus replication. In contrast, we did not detect USUV in 15,381 questing ticks collected in 2017 and 2019. We conclude that I. ricinus can be infected with USUV and can transstadially and horizontally transmit USUV. However, in comparison to mosquito-borne transmission, the role of I. ricinus ticks in the epidemiology of USUV is expected to be minor.

Predominance of CD137+ And TNF-α Expressing CD8+ Central Memory T Cells in Mild COVID-19 Recovered Patients Upon SARS-CoV-2 Re-Exposure.

INTRODUCTION: Memory CD8+ T cells are essential for long-term immune protection in viral infections, including COVID-19. METHODS: This study examined the responses of CD8+ TEM, TEMRA, and TCM subsets from unvaccinated individuals who had recovered from mild and severe COVID-19 by flow cytometry. RESULTS AND DISCUSSION: The peptides triggered a higher frequency of CD8+ TCM cells in the recovered mild group. CD8+ TCM and TEM cells showed heterogeneity in CD137 expression between evaluated groups. In addition, a predominance of CD137 expression in naïve CD8+ T cells, TCM, and TEM was observed in the mild recovered group when stimulated with peptides. Furthermore, CD8+ TCM and TEM cell subsets from mild recovered volunteers had higher TNF-α expression. In contrast, the expression partner of IFN-γ, IL-10, and IL-17 indicated an antiviral signature by CD8+ TEMRA cells. These findings underscore the distinct functional capabilities of each memory T cell subset in individuals who have recovered from COVID-19 upon re-exposure to SARS-CoV-2 antigens.

Microplastic pollution status in the coral reef ecosystems on the Southern and Western coasts of Sri Lanka during the Southwest monsoon.

We investigated the microplastics (MP) abundance, characteristics and pollution severity in the six coral reef ecosystems along the southern and western coasts of Sri Lanka during the southwest monsoon. The small blue-coloured fibres dominated within coral reefs and reef environments. The average coral, surface water and surface sediment MP concentration were 806.64 ± 93.72 particles kg-1ww, 23.42 ± 5.01 particles m-3, and 54.11 ± 8.04 particles kg-1dw, respectively. Coral MP concentration was significantly correlated with surface water (r = 0.65) and surface sediments (r = 0.59) indicating that the reef environment was the source of coral MP enrichment. Coral MP concentration was spatially different (p < 0.05) which may likely be due to the changes in winds, waves, coral biology and plastic sources. MP Pollution Load Index indicated that low MP contamination hazard. Since the presence of MP often deteriorates coral's health, further investigations are necessary to understand the MP's effects on the health of coral reef ecosystems.

Genomic characterization of the bacterial phylum Candidatus Effluviviacota, a cosmopolitan member of the global seep microbiome.

The microbial communities of marine seep sediments contain unexplored physiological and phylogenetic diversity. Here, we examined 30 bacterial metagenome-assembled genomes (MAGs) from cold seeps in the South China Sea, the Indian Ocean, the Scotian Basin, and the Gulf of Mexico, as well as from deep-sea hydrothermal sediments in the Guaymas Basin, Gulf of California. Phylogenetic analyses of these MAGs indicate that they form a distinct phylum-level bacterial lineage, which we propose as a new phylum, Candidatus Effluviviacota, in reference to its preferential occurrence at diverse seep areas. Based on tightly clustered high-quality MAGs, we propose two new genus-level candidatus taxa, Candidatus Effluvivivax and Candidatus Effluvibates. Genomic content analyses indicate that Candidatus Effluviviacota are chemoheterotrophs that harbor the Embden-Meyerhof-Parnas glycolysis pathway. They gain energy by fermenting organic substrates. Additionally, they display potential capabilities for the degradation of cellulose, hemicellulose, starch, xylan, and various peptides. Extracellular anaerobic respiration appears to rely on metals as electron acceptors, with electron transfer primarily mediated by multiheme cytochromes and by a flavin-based extracellular electron transfer (EET) mechanism that involves NADH-quinone oxidoreductase-demethylmenaquinone-synthesizing enzymes, uncharacterized membrane proteins, and flavin-binding proteins, also known as the NUO-DMK-EET-FMN complex. The heterogeneity within the Ca. Effluviviacota phylum suggests varying roles in energy metabolism among different genera. While NUO-DMK-EET-FMN electron transfer has been reported predominantly in Gram-positive bacteria, it is now identified in Ca. Effluviviacota as well. We detected the presence of genes associated with bacterial microcompartments in Ca. Effluviviacota, which can promote specific metabolic processes and protect the cytosol from toxic intermediates. IMPORTANCE: The newly discovered bacterial phylum Candidatus Effluviviacota is widespread across diverse seepage ecosystems, marine environments, and freshwater environments, with a notable preference for cold seeps. While maintaining an average abundance of approximately 1% in the global gene catalog of cold seep habitats, it has not hitherto been characterized. The metabolic versatility of Ca. Effluviviacota in anaerobic carbon, hydrogen, and metal cycling aligns with its prevalence in anoxic niches, with a preference for cold seep environments. Variations in metabolic potential between Ca. Effluvivivax and Ca. Effluvibates may contribute to shaping their respective habitat distributions.

Double lesion MRgFUS thalamotomy for essential tremor: 4.5-year outcomes and framework for assessing loss of efficacy and tremor progression.

BACKGROUND: The essential tremor (ET) course to 54 months post-unilateral VIM/PSA magnetic resonance-guided focused ultrasound (MRgFUS) in the treated arm (TA) and non-treated arm (NTA) of 12 patients is reported. METHODS: Tremor severity was rated using Bain Findley spirography (BFS) scores in the TA and NTA. We divided follow-up into 'Early' (0-6 months) and 'Late' (6-54 months) phases, to minimise the effect of peri-lesion oedema resolution on the latter. RESULTS: The mean baseline BFS score was 6.2 in TA and 5.7 in the NTA. After unilateral VIM/PSA MRgFUS, mean BFS improved in TA at all subsequent time points (p < 0.001), with no significant differences between BFS scores at consecutive assessments or between 1 and 54 months, while the NTA BFS scores worsened between 12 and 24 months (p < 0.003). Three patients showed worsening of their TA BFS scores and an increasing NTA-TA BFS difference, indicating slower tremor worsening in TA compared to NTA, whilst one patient showed a greater rate of worsening in the TA compared to NTA BFS. CONCLUSION: After 54 months, the beneficial effect of MRgFUS is usually maintained with any worsening of BFS scores in TA slower than in NTA. Loss of treatment benefit is rare.

Production and characterization of the lipopeptide with anti-adhesion for oral biofilm on the surface of titanium for dental implants.

Titanium implants are subject to bacterial adhesion and peri-implantitis induction, and biosurfactants bring a new alternative to the fight against infections. This work aimed to produce and characterize the biosurfactant from Bacillus subtilis ATCC 19,659, its anti-adhesion and antimicrobial activity, and cell viability. Anti-adhesion studies were carried out against Streptococcus sanguinis, Staphylococcus aureus, Fusobacterium nucleatum, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Proteus mirabilis as the minimum inhibitory concentration and the minimum bactericidal concentration. Cell viability was measured against osteoblast and fibroblast cells. The biosurfactant was classified as lipopeptide, with critical micelle concentration at 40 µg mL- 1, and made the titanium surface less hydrophobic. The anti-adhesion effect was observed for Staphylococcus aureus and Streptococcus sanguinis with 54% growth inhibition and presented a minimum inhibitory concentration of 15.7 µg mL- 1 for Streptococcus sanguinis and Aggregatibacter actinomycetemcomitans. The lipopeptide had no cytotoxic effect and demonstrated high potential application against bacterial biofilms.

Horismenus saturnus n. sp. (Hymenoptera, Eulophidae) a New Parasitoid Wasp from Eggs of Saturniidae (Lepidoptera) from the Atlantic Forest, Minas Gerais, Brazil.

A new species of Horismenus Walker, H. saturnus Schoeninger & Hansson (Hymenoptera: Eulophidae), is described from material reared from eggs of an unidentified species of Saturniidae (Lepidoptera). The new species is compared to H. cupreus (Ashmead, 1894), a species it is very similar to, and to H. ancillus (Brèthes), a species with the same type of host as H. saturnus. A total of 30 adult specimens developed from the eggs of Saturniidae. This is the second record of a Horismenus species parasitizing eggs of Saturniidae and the first record of this host from Brazil. Here, we provide a diagnosis and description of the new species including morphological and molecular characters, and multiple illustrations.

The influence of sex on left ventricular remodeling in patients with aortic dissection.

AIMS: Patients with aortic dissection have a high prevalence of left ventricular structural alterations, including left ventricular hypertrophy (LVH), but little is known about the impact of sex on this regard. This study compared clinical, cardiac, and prognostic characteristics between men and women with aortic dissection. METHODS: We retrospectively assessed clinical and echocardiographic characteristics, and 1-year mortality in 367 aortic dissection patients (30% women; 66% with Stanford-A) who underwent echocardiography 60 days before or after the diagnosis of aortic dissection from three Brazilian centers. RESULTS: Men and women had similar clinical characteristics, except for higher age (59.4 ±â€Š13.4 vs. 55.9 ±â€Š11.6 years; P = 0.013) and use of antihypertensive classes (1.4 ±â€Š1.3 vs. 1.1 ±â€Š1.2; P = 0.024) and diuretics (32 vs. 19%; P = 0.004) in women compared with men. Women had a higher prevalence of LVH (78 vs. 65%; P = 0.010) and lower prevalence of normal left ventricular geometry (20 vs. 10%; P = 0.015) than men. Logistic regression analysis adjusted for confounding factors showed that women were less likely to have normal left ventricular geometry (odds ratio, 95% confidence interval = 0.42, 0.20-0.87; P = 0.019) and were more likely to have LVH (odds ratio, 95% confidence interval = 1.91, 1.11-3.27; P = 0.019). Conversely, multivariable Cox-regression analysis showed that women had a similar risk of death compared to men 1 year after aortic dissection diagnosis (hazard ratio, 95% confidence interval = 1.16, 0.77-1.75; P = 0.49). CONCLUSION: In aortic dissection patients, women were typically older, had higher use of antihypertensive medications, and exhibited a greater prevalence of LVH compared with men. However, 1-year mortality after aortic dissection diagnosis did not differ between men and women.

Pilot Experiment on Non-Invasive Non-Thermal Disintegration of Human Mucinous Breast Carcinoma Ex Vivo Using Boiling Histotripsy.

We present the results of a pilot study demonstrating the feasibility of non-invasive non-thermal disintegration of human mucinous carcinoma of the breast ex vivo using sequences of high-intensity focused ultrasound pulses in boiling histotripsy regimen. The target volume was sonicated by focusing ultrasound pulses (n=20) of 1.5 MHz frequency, 10-msec duration and 1-sec pulse repetition period, 517 W acoustic power within the pulse, and 103 MPa shock front amplitude at the focus into each node of a volumetric grid 4×4×1 mm. Sonication was visualized and controlled using B-mode ultrasound imaging, total time of the treatment was 21 min. Histological hematoxylin and eosin and Masson's trichrome staining revealed the absence of tumor elements in the treated region confirming destruction of cancer cells and their nuclei after boiling histotripsy procedure.

Characteristics of the Antitumor Effect of Doxorubicin and Pegylated Hyaluronidase on Models of Rat Brain Tumors.

Hyaluronidase increases tissue permeability and diffusion of the extracellular fluid by cleaving hyaluronan, the primary component of the extracellular matrix. Hyaluronidase pegylation (Hyal-PEG) decreases its clearance and enhances biodistribution. The pro- and anticancer activity of Hyal-PEG and a combination of Hyal-PEG with doxorubicin were studied in vitro (morphological analysis of rat glioblastoma 101.8 spheroids) and in vivo (by the survival time of rats after intracerebral transplantation of the tumor and morphological analysis). In the presence of doxorubicin and Hyal-PEG in the culture medium in vitro, spheroids lost their ability to adhere to the substrate and disintegrate into individual cells. Intracerebral transplantation of the tumor tissue with Hyal-PEG did not accelerate glioblastoma growth. The mean survival time for animals receiving transplantation of the tumor alone and in combination with Hyal-PEG was 13 and 20 days, respectively. In one rat with transplanted tumor and Hyal-PEG, this parameter increased by 53%. The survival time of rats receiving systemic therapy with doxorubicin and Hyal-PEG significantly increased (p=0.003). Antitumor effect of therapeutic doses of doxorubicin combined with Hyal-PEG was demonstrated on the model of rat glioblastoma 101.8 in vitro. Hyal-PEG inhibited adhesion of tumor cells, but did not cause their death. Transplantation of Hyal-PEG-treated tumor did not reduce animal survival time. Systemic administration of therapeutic doses of doxorubicin with Hyal-PEG increased survival time of rats with glioblastoma 101.8.

Comparison of "IN-REC-SUR-E" and LISA in preterm neonates with respiratory distress syndrome: a randomized controlled trial (IN-REC-LISA trial).

BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.

Generation of human induced pluripotent stem cell (hiPSC) lines derived from three patients carrying the pathogenic CRYAB (A527G) mutation and one non-carrier family member.

A newly identified pathogenic variant (A527G) in alpha B-crystallin (αB-crystallin) has been linked to congenital cataract and young-onset dilated cardiomyopathy (DCM) within a Dutch family, although the disease mechanism remains unclear. Four human induced pluripotent stem cell (hiPSC) clones were generated from three symptomatic patients carrying the A527G variant, and one healthy proband. Peripheral blood mononuclear cells (PBMCs) were reprogrammed using integration-free Sendai viral pluripotency vectors. The established hiPSCs clones exhibited regular ESC-like morphology, expression of pluripotency markers, and normal karyotyping. These hiPSC lines can facilitate future studies to understand the chaperone function and its role in DCM disease progression.

How to get your work published.

The pressure on academics to publish is greater than ever. Sharing knew knowledge has always been satisfying and is necessary for career development. There are also ethical imperatives to avoid withholding knowledge and to prevent colleagues duplicating research unnecessarily, which would waste their time and burden participants. On top of these long-standing drivers, academic institutions must now manage their resources carefully and want to see a return on their investment in you, which will be measured in terms of quality and quantity of research outputs. As the need for publications has increased, so has the number of submissions and consequently, the competition to publish in the best-known journals. In some years CDH receives ten times more manuscripts than we can fit in the journal. Academics must publish more often, and their submissions must be of the highest quality to stand a chance of publication.