Transitioning to home and beyond following stroke: a prospective cohort study of outcomes and needs.

INTRODUCTION: Understanding of the needs of people with stroke at hospital discharge and in the first six-months is limited. This study aim was to profile and document the needs of people with stroke at hospital discharge to home and thereafter. METHODS: A prospective cohort study recruiting individuals with stroke, from three hospitals, who transitioned home, either directly, through rehabilitation, or with early supported discharge teams. Their outcomes (global-health, cognition, function, quality of life, needs) were described using validated questionnaires and a needs survey, at 7-10 days, and at 3-, and 6-months, post-discharge. RESULTS: 72 patients were available at hospital discharge; mean age 70 (SD 13); 61% female; median NIHSS score of 4 (IQR 0-20). 62 (86%), 54 (75%), and 45 (63%) individuals were available respectively at each data collection time-point. Perceived disability was considerable at hospital discharge (51% with mRS ≥ 3), and while it improved at 3-months, it increased thereafter (35% with mRS ≥ 3 at 6-months). Mean physical health and social functioning were "fair" at hospital discharge and ongoing; while HR-QOL, although improved over time, remained impaired at 6-months (0.69+/-0.28). At 6-months cognitive impairment was present in 40%. Unmet needs included involvement in transition planning and care decisions, with ongoing rehabilitation, information, and support needs. The median number of unmet needs at discharge to home was four (range:1-9), and three (range:1-7) at 6-months. CONCLUSION: Stroke community reintegration is challenging for people with stroke and their families, with high levels of unmet need. Profiling outcomes and unmet needs for people with stroke at hospital-to-home transition and onwards are crucial for shaping the development of effective support interventions to be delivered at this juncture. ISRCTN REGISTRATION: 02/08/2022; ISRCTN44633579.

Adolescent Cancer Survivors and Their Parents' Experiences With the Transition Off Treatment to Survivorship: A Qualitative Interview Study.

Background: Transitioning from active cancer treatment to survivorship represents a vulnerable yet underresearched phase for adolescents and their families. Knowledge of their support needs, the challenges they experience, and how they manage them are useful to inform tailored follow-up care. Thus, we aimed to explore their transition experiences. Method: We interviewed 15 adolescents (12-19 years) who had transitioned off of treatment 1 to 47 months prior at Oslo University Hospital's Department of Paediatric Haematology and Oncology and their biological parents (n = 16). The interviews were analyzed using inductive, reflexive thematic analysis inspired by Braun and Clarke. NVivo-12 was used for data management. Results: Four main themes were identified: (a) consequences of cancer beyond transition, (b) transition back to normalcy, (c) survivorship competence, and (d) changes in roles and relationships. The families described happiness and relief but also said that the lingering effects of cancer treatment had a profound impact on day-to-day living. The adolescents expressed closeness with and dependency on their parents, and they perceived family and friends as essential for social readjustment. Discussion: Although adolescent survivors and their parents described a wide variety of strategies for returning to "normalcy," their perspectives also illustrate ongoing psychosocial and educational support needs that changed over time. Our findings indicate a need for improved preparation for and support through the transition. Nurses are well positioned to provide continuous and structured transition support tailored to the needs of the individual survivors and their families.

The axial skeleton of Tiktaalik roseae.

The axial columns of the earliest limbed vertebrates show distinct patterns of regionalization as compared to early tetrapodomorphs. Included among their novel features are sacral ribs, which provide linkage between the vertebral column and pelvis, contributing to body support and propulsion by the hindlimb. Data on the axial skeletons of the closest relatives of limbed vertebrates are sparce, with key features of specimens potentially covered by matrix. Therefore, it is unclear in what sequence and under what functional context specializations in the axial skeletons of tetrapods arose. Here, we describe the axial skeleton of the elpistostegalian Tiktaalik roseae and show that transformations to the axial column for head mobility, body support, and pelvic fin buttressing evolved in finned vertebrates prior to the origin of limbs. No atlas-axis complex is observed; however, an independent basioccipital-exoccipital complex suggests increased mobility at the occipital vertebral junction. While the construction of vertebrae in Tiktaalik is similar to early tetrapodomorphs, its ribs possess a specialized sacral domain. Sacral ribs are expanded and ventrally curved, indicating likely attachment to the expanded iliac blade of the pelvis by ligamentous connection. Thus, the origin of novel rib types preceded major alterations to trunk vertebrae, and linkage between pelvic fins and axial column preceded the origin of limbs. These data reveal an unexpected combination of post-cranial skeletal characters, informing hypotheses of body posture and movement in the closest relatives of limbed vertebrates.

Peer mentorship and academic supports build sense of community and improve outcomes for transfer students.

The experience of transferring to a 4-year college, especially in STEM programs, can be particularly challenging for students. While much of the onus for preparing students for transfer has been placed on community colleges, the 4-year institutions to which students transfer have critical roles to play. With this in mind, we established the Pre-transfer Interventions, Mentoring, and Experience in Research (PRIMER) program to support students transferring into the biology department at our university. The design of this program is based around the key elements of Schlossberg's Transition Theory, focusing on the support and strategies elements of the theory. Through a weekly academic skill course, peer mentoring, and informal academic and social supports, our goals were for students to increase their involvement in the campus community and to increase their use of academic support resources. We used qualitative and quantitative assessments to compare sense of community and use of campus resources between students who participated in our program and others. We found that students in our program strongly increased their sense of community during the semester compared to other students and used campus resources at a higher rate. Our insights from the PRIMER program can help others in developing programs to support transfer students in biology departments.

Epithelial-mesenchymal transition dysregulation in prostate cancer: Insights from molecular unraveling and epidemiological analyses in Tunisia, North Africa.

INTRODUCTION: The progression of prostate cancer (PCa) has been linked worldwide, including in African populations, to the dysregulation of the epithelial-mesenchymal transition (EMT). METHODS: To clarify the connection among EMT markers, clinicopathological parameters, and epidemiological factors, we analyzed 35 PCa specimens from patients in Tunisia, a country in North Africa, arranged by stages. We also carried out extensive molecular and epidemiological analyses. RESULTS: Significant dysregulation of EMT genes was found, with an overexpression of ZEB-1, Twist, Snail-1, and Vimentin (p < 0.05) and underexpression of E-cadherin and ß-catenin (p < 0.05). Positive correlations were observed between transcription factors and the mesenchymal marker Vimentin (p < 0.001, r = 0.574; p = 0.029, r = 0.411; and p < 0.001; r = 0.506) according to Spearman correlation analyses, whereas negative correlations were found between epithelial markers (E-cadherin, ß-catenin) and Vimentin (p < 0.05; r < 0). Higher PSA, Gleason scores, and metastasis were all correlated with the dysregulation of EMT (p < 0.05). Notably, there was a positive correlation between higher consumption of tobacco (≥20 Packets per year) and Vimentin expression (p < 0.001, r = 0.854), suggesting a relationship between smoking and EMT activation in the Tunisian population. Moreover, Twist showed a positive correlation with diabetes (p < 0.001, r = 0.385), whereas no significant correlations were found between EMT markers and comorbidities such as hypertension and coronary insufficiency. These results demonstrate the intricate connection between molecular changes, epidemiological factors, and disease progression, and they emphasize the crucial role that EMT plays in promoting PCa aggressiveness in African populations, particularly in Tunisia. CONCLUSION: In summary, understanding these correlations could help develop focused treatment plans and enhance patient outcomes for PCa management in African settings.

Polarization Saturation in Multi-layered Interfacial Ferroelectrics.

Van der Waals (vdW) polytypes of broken inversion and mirror symmetries were recently shown to exhibit switchable electric polarization even at the ultimate two-layer thin limit. Their out-of-plane polarization was found to accumulate in a ladder-like fashion with each successive layer, offering 2D building blocks for the bottom-up construction of 3D ferroelectrics. Here, we demonstrate experimentally that beyond a critical stack thickness, the accumulated polarization in rhombohedral polytypes of molybdenum disulfide (r-MoS2) saturates. The underlying saturation mechanism, deciphered via DFT and self-consistent Poisson-Schrödinger calculations, point to a purely electronic redistribution involving.(1) polarization-induced bandgap closure that allows for cross-stack charge transfer and the emergence of free surface charge,(2) reduction of the polarization saturation value, as well as the critical thickness at which it is obtained, by the presence of free carriers. The resilience of polar layered structures to atomic surface reconstruction, which is essentially unavoidable in polar 3D crystals, potentially allows for the design of new devices with mobile surface charges. Our findings, which are of general nature, should be accounted for when designing switching and/or conductive devices based on ferroelectric layered materials. This article is protected by copyright. All rights reserved.

Osteopontin-driven partial epithelial-mesenchymal transition governs the development of middle ear cholesteatoma.

Cholesteatoma is a common disease of the middle ear. Currently, surgical removal is the only treatment option and patients face a high risk of relapse. The molecular basis of cholesteatoma remains largely unknown. Here, we show that Osteopontin (OPN), a predominantly secreted protein, plays a crucial role in the development of middle ear cholesteatoma. Global transcriptome analysis revealed the loss of epithelial features and an enhanced immune response in human cholesteatoma tissues. Quantitative RT-PCR and immunohistochemical staining of middle ear cholesteatoma validated the reduced expression of epithelial markers, as well as the elevated expression of mesenchymal markers including Vimentin and Fibronectin, but not N-Cadherin, α-smooth muscle actin (α-SMA) or ferroptosis suppressor protein 1 (FSP1), indicating a partial epithelial-mesenchymal transition (EMT) state. Besides, the expression of OPN was significantly elevated in human cholesteatoma tissues. Treatment with OPN promoted cell proliferation, survival and migration and led to a partial EMT in immortalized human keratinocyte cells. Importantly, blockade of OPN signaling could remarkably improve the cholesteatoma-like symptoms in SD rats. Our mechanistic study demonstrated that the AKT-zinc finger E-box binding homeobox 2 (ZEB2) axis mediated the effects of OPN. Overall, these findings suggest that targeting the OPN signaling represents a promising strategy for the treatment of middle ear cholesteatoma.

Dynamics of Single-Cell Protein Covariation during Epithelial-Mesenchymal Transition.

Physiological processes, such as the epithelial-mesenchymal transition (EMT), are mediated by changes in protein interactions. These changes may be better reflected in protein covariation within a cellular cluster than in the temporal dynamics of cluster-average protein abundance. To explore this possibility, we quantified proteins in single human cells undergoing EMT. Covariation analysis of the data revealed that functionally coherent protein clusters dynamically changed their protein-protein correlations without concomitant changes in the cluster-average protein abundance. These dynamics of protein-protein correlations were monotonic in time and delineated protein modules functioning in actin cytoskeleton organization, energy metabolism, and protein transport. These protein modules are defined by protein covariation within the same time point and cluster and, thus, reflect biological regulation masked by the cluster-average protein dynamics. Thus, protein correlation dynamics across single cells offers a window into protein regulation during physiological transitions.

Navigating the path to dual carbon goals: Understanding the driving forces of energy transition welfare performance.

China's double carbon target aims to improve human well-being and sustainable development. Energy transformation welfare performance (ETWP) is the efficiency of energy transition (ET) in enhancing human well-being. ETWP considers both human well-being and sustainable development. Research on its driving force is helpful in achieving the double carbon goal. Thus, this paper used Logarithmic Mean Divisia Index Model, Fixed Panel Regression Model and Grey Relational Analysis Model to analyze China's ETWP from 2006 to 2022 and predicted ETWP of 31 provinces from 2023 to 2030. The results showed that: (1) ETWP had two rising periods in 2006-2014 and 2015-2022. (2) The government's rationalization policy on energy and environment and technological innovation ability were fundamental driving forces for improving ETWP. (3) There were obvious spatial and temporal distinctions in ETWP, and it would bring out different degrees in most areas. Thus, ET should be promoted by improving the ecological environment and resource utilization efficiency; The importance of the role of scientific and technological innovation and policies should be focused on in promoting ETWP; ET policies based on local developments should be formulated and the energy structure should be changed.

Altered spreading of fast aperiodic brain waves relates to disease duration in Amyotrophic Lateral Sclerosis.

OBJECTIVE: To test the hypothesis that patients affected by Amyotrophic Lateral Sclerosis (ALS) show an altered spatio-temporal spreading of neuronal avalanches in the brain, and that this may related to the clinical picture. METHODS: We obtained the source-reconstructed magnetoencephalography (MEG) signals from thirty-six ALS patients and forty-two healthy controls. Then, we used the construct of the avalanche transition matrix (ATM) and the corresponding network parameter nodal strength to quantify the changes in each region, since this parameter provides key information about which brain regions are mostly involved in the spreading avalanches. RESULTS: ALS patients presented higher values of the nodal strength in both cortical and sub-cortical brain areas. This parameter correlated directly with disease duration. CONCLUSIONS: In this work, we provide a deeper characterization of neuronal avalanches propagation in ALS, describing their spatio-temporal trajectories and identifying the brain regions most likely to be involved in the process. This makes it possible to recognize the brain areas that take part in the pathogenic mechanisms of ALS. Furthermore, the nodal strength of the involved regions correlates directly with disease duration. SIGNIFICANCE: Our results corroborate the clinical relevance of aperiodic, fast large-scale brain activity as a biomarker of microscopic changes induced by neurophysiological processes.

Impact of discharge criteria on the length of stay in preterm infants: A retrospective study in Japan and Finland.

BACKGROUND: To shorten the hospital stay in preterm infants, it is important to understand the factors extending the length of stay. AIMS: To understand how different discharge criteria affect the length of stay in preterm infants. STUDY DESIGN: A retrospective comparison study. SUBJECTS: Preterm infants born at 28 to 31 gestational weeks in 2020-2021 in a Level IV NICU in Japan (n = 22) and a Level III NICU in Finland (n = 49). OUTCOME MEASURES: We compared the most common last discharge criteria and the postmenstrual age (PMA) between the two NICUs. The potential extending effects of each discharge criterion on the length of stay were also evaluated. The discharge criteria were classified into six categories: temperature, respiration, feeding, examination, weight limit, and family readiness. RESULTS: The PMA at discharge was significantly higher in Japan than in Finland: median 40.7 (interquartile range 39.9-41.3) vs. 37.9 (36.9-39.0) weeks; r = 0.58; p < 0.001. The most common last discharge criterion was the family criterion in Japan (n = 19; 86 %) and the respiration criterion in Finland (n = 43; 88 %). In Japan, the length of stay was extended by 7.9 (standard deviation [SD] 7.0) days due to a lack of family readiness for discharge and 8.7 (SD 8.7) days due to not having discharged home with a feeding tube as a common practice. CONCLUSIONS: The length of stay of preterm infants in Japan could be notably reduced by supporting the parents' earlier readiness for discharge and allowing tube feeding at home.

Spin-disorder intervened avoidance of quantum criticality in B20 cubic Mn1-xVxSi.

The effect of negative chemical pressure with the substitution of transition metal V in an itinerant helimagnetically ordered MnSi, Mn1-xVxSi withx= 0-0.1, is explored using dc and ac-susceptibilities. With increasingx, the manifestations are unaffected crystal structure with increasing unit cell volume, suppression of long-range magnetic order, weakening of itinerant character and reduced spin-cooperative phenomenon. The emergence of spin-glass behaviour forx≥ 0.1 intervenes in the occurrence of quantum phase transition. The constructed concentration-temperaturex-Tphase diagram illustrates the substitution-driven changes in the magnetism of MnSi. Further, the study suggests that the presence of a precursor state can favour the formation of spin-textures in magnetically ordered compositions 0

PLAU promotes cell proliferation and migration of head and neck cancer via STAT3 signaling pathway.

It was reported that within the head and neck cancer (HNC) cell line CAL21 the epithelial-mesenchymal transition (EMT) and cell proliferation were promoted by Urokinase-Type Plasminogen Activator (PLAU) proteinase through TNFRSF12A. Additionally, in this paper HNC cell lines refer to Fadu and Tu686. A novel PLAU-STAT3 axis was found to be involved in HNC cell line proliferation and metastasis. PLAU expression in HNC samples was upregulated, besides, the elevated expression of PLAU was linked to the lower overall survival (OS) and disease-free survival (DFS). Ectopic PLAU expression promoted cell proliferation and migration, while PLAU knockdown exhibited opposite results. RNA-seq data identified the JAK-STAT signaling pathway, confirmed by western blotting. A recovery assay using S3I-201, a selective inhibitor of signal transducer and activator of transcription 3 (STAT3), indicated that PLAU promoted HNC cell line progression via STAT3 signaling in vitro. The oncogenic role of PLAU in HNC tumor growth in vivo was confirmed using xenograft models. In summary, we identified the tumorigenic PLAU function in the HNC progress. PLAU may represent a potential prognostic biomarker of HNC and the PLAU-STAT3 pathway might be considered a therapeutic target of HNC.

Eosinophil peroxidase promotes bronchial epithelial cells to secrete asthma-related factors and induces the early stage of airway remodeling.

Asthma is a heterogeneous disease characterized by chronic airway inflammation, reversible airflow limitation, and airway remodeling. Eosinophil peroxidase (EPX) is the most abundant secondary granule protein unique to activated eosinophils. In this study, we aimed to illustrate the effect of EPX on the epithelial-mesenchymal transition (EMT) in BEAS-2B cells. Our research found that both EPX and ADAM33 were negatively correlated with FEV1/FVC and FEV1%pred, and positively correlated with IL-5 levels. Asthma patients had relatively higher levels of ADAM33 and EPX compared to the healthy control group. The expression of TSLP, TGF-ß1 and ADAM33 in the EPX intervention group was significantly higher. Moreover, EPX could promote the proliferation, migration and EMT of BEAS-2B cells, and the effect of EPX on various factors was significantly improved by the PI3K inhibitor LY294002. The findings from this study could potentially offer a novel therapeutic target for addressing airway remodeling in bronchial asthma, particularly focusing on EMT.

siRNA treatment targeting integrin α11 overexpressed via EZH2-driven axis inhibits drug-resistant breast cancer progression.

BACKGROUND: Breast cancer, the most prevalent cancer in women worldwide, faces treatment challenges due to drug resistance, posing a serious threat to patient survival. The present study aimed to identify the key molecules that drive drug resistance and aggressiveness in breast cancer cells and validate them as therapeutic targets. METHODS: Transcriptome microarray and analysis using PANTHER pathway and StemChecker were performed to identify the most significantly expressed genes in tamoxifen-resistant and adriamycin-resistant MCF-7 breast cancer cells. Clinical relevance of the key genes was determined using Kaplan-Meier survival analyses on The Cancer Genome Atlas dataset of breast cancer patients. Gene overexpression/knockdown, spheroid formation, flow cytometric analysis, chromatin immunoprecipitation, immunocytochemistry, wound healing/transwell migration assays, and cancer stem cell transcription factor activation profiling array were used to elucidate the regulatory mechanism of integrin α11 expression. Tumour-bearing xenograft models were used to demonstrate integrin α11 is a potential therapeutic target. RESULTS: Integrin α11 was consistently upregulated in drug-resistant breast cancer cells, and its silencing inhibited cancer stem cells (CSCs) and epithelial-mesenchymal transition (EMT) while restoring sensitivity to anticancer drugs. HIF1α, GLI-1, and EZH2 contributed the most to the regulation of integrin α11 and EZH2 expression, with EZH2 being more necessary for EZH2 autoinduction than HIF1α and GLI-1. Additionally, unlike HIF1α or EZH2, GLI-1 was the sole transcription factor activated by integrin-linked focal adhesion kinase, indicating GLI-1 as a key driver of the EZH2-integrin α11 axis operating for cancer stem cell survival and EMT. Kaplan-Meier survival analysis using The Cancer Genome Atlas (TCGA) dataset also revealed both EZH2 and integrin α11 could be strong prognostic factors of relapse-free and overall survival in breast cancer patients. However, the superior efficacy of integrin α11 siRNA therapy over EZH2 siRNA treatment was demonstrated by enhanced inhibition of tumour growth and prolonged survival in murine models bearing tumours. CONCLUSION: Our findings elucidate that integrin α11 is upregulated by EZH2, forming a positive feedback circuit involving FAK-GLI-1 and contributing to drug resistance, cancer stem cell survival and EMT. Taken together, the results suggest integrin α11 as a promising prognostic marker and a powerful therapeutic target for drug-resistant breast cancer.

Transition from pediatrics to adult health care in girls with turner syndrome.

INTRODUCTION: Turner Syndrome is a rare condition secondary to a complete or partial loss of one X chromosome, leading to a wide spectrum of clinical manifestations. Short stature, gonadal dysgenesis, cardiovascular malformations, and dysmorphic features characterize its common clinical picture. AREAS COVERED: The main endocrine challenges in adolescent girls with Turner Syndrome are puberty induction (closely intertwined with growth) and fertility preservation. We discuss the most important clinical aspects that should be faced when planning an appropriate and seamless transition for girls with Turner Syndrome. EXPERT OPINION: Adolescence is a complex time for girls and boys: the passage to young adulthood is characterized by changes in the social, emotional, and educational environment. Adolescence is the ideal time to encourage the development of independent self-care behaviors and to make the growing girl aware of her health, thus promoting healthy lifestyle behaviors. During adulthood, diet and exercise are of utmost importance to manage some of the common complications that can emerge with aging. All clinicians involved in the multidisciplinary team must consider that transition is more than hormone replacement therapy: transition in a modern Healthcare Provider is a proactive process, shared between pediatric and adult endocrinologists.

Ferromagnetic Order in 2D Layers of Transition Metal Dichlorides.

Magnetism in two dimensions is traditionally considered an exotic phase mediated by spin fluctuations, but far from collinearly ordered in the ground state. Recently, two-dimensional magnetic states have been discovered in layered van der Waals compounds. Their robust and tunable magnetic state by material composition, combined with reduced dimensionality, foresee a strong potential as a key element in magnetic devices. Here, we present a class of two-dimensional magnets based on metallic chlorides. The magnetic order survives on top of a metallic substrate, even down to the monolayer limit, and can be switched from perpendicular to in-plane by substituting the metal ion from iron to nickel. Using functionalized STM tips as magnetic sensors, we have identified local exchange fields, even in the absence of an external magnetic field. Since the compounds are processable by molecular beam epitaxy techniques, they provide a platform with large potential for incorporation into current device technologies. This article is protected by copyright. All rights reserved.

Cancer spreading patterns based on epithelial-mesenchymal plasticity.

Introduction: Metastasis is a major cause of cancer-related deaths, underscoring the necessity to discern the rules and patterns of cancer cell spreading. Epithelial-mesenchymal plasticity contributes to cancer aggressiveness and metastasis. Despite establishing key determinants of cancer aggressiveness and metastatic ability, a comprehensive understanding of the underlying mechanism is unknown. We aimed to propose a classification system for cancer cells based on epithelial-mesenchymal plasticity, focusing on hysteresis of the epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype. Methods: We extensively reviewed the concept of epithelial-mesenchymal plasticity, specifically considering the hysteresis of the epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype. Results: In this review and hypothesis article, based on epithelial-mesenchymal plasticity, especially the hysteresis of epithelial-mesenchymal transition and the hybrid epithelial/mesenchymal phenotype, we proposed a classification of cancer cells, indicating that cancer cells with epithelial-mesenchymal plasticity potential could be classified into four types: irreversible hysteresis, weak hysteresis, strong hysteresis, and hybrid epithelial/mesenchymal phenotype. These four types of cancer cells had varied biology, spreading features, and prognoses. Discussion: Our results highlight that the proposed classification system offers insights into the diverse behaviors of cancer cells, providing implications for cancer aggressiveness and metastasis.

A key parametric study of ultrasonic exfoliation of 2D TiB2 using DI water as a unique medium.

Liquid Phase Exfoliation (LPE) is a very effective technique for the synthesis of few layered two dimensional (2D) nanosheets. There is a surge to find environment friendly solvents for efficient exfoliation of layered materials to produce 2D nanosheets. TiB2 is an important layered material with very little reported work on its 2D nanosheets. The present work is about successful LPE of TiB2 using deionized (DI) water as a clean, green and low cost dispersion medium to make TiB2 nanosheets. The impact of ultrasonication conditions i.e. input power and treatment duration for efficient synthesis of few layered 2D nanosheets in DI water is studied by Atomic Force Microscopy (AFM), X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM). It is found that by increasing input power, the layer thickness is reduced from bulk to 34 nm with lateral dimensions as huge as up to 5 µm. The increased treatment duration has further reduced the layer thickness to 21 nm associated with a decrease in lateral dimensions to about 1 µm. The mechanism of variation in the aspect ratio of the 2D nanosheets with ultrasonication power and treatment duration is explained. The optimum conditions for the fabrication of high aspect ratio 2D nanosheets of TiB2 owe to a greater acoustic cavitation intensity, an optimum treatment duration and a homogenous distribution of the cavitation events while using an appropriate size of the sonotrode in the sonicated volume during ultrasonication.

Periparturient blood T-lymphocyte PD-1 and CTLA-4 expression as potential predictors of new intramammary infections in dairy cows during early lactation (short communication).

BACKGROUND: The periparturient period in dairy cows is marked by immunosuppression which increases the likelihood of infectious disorders, particularly also mastitis. An in-depth understanding of peripartum leukocyte biology is vital for the implementation of highly successful post-partum disease prevention measures. Immune checkpoint molecules, such as programmed death 1 (PD-1) and cytotoxic T-lymphocyte antigen 4 (CTLA-4), are critical inhibitory receptors expressed on immune cells, particularly T cells, that drive immunosuppressive signaling pathways. However, the potential role of immune checkpoint molecules expression in T-cells on udder health has never been explored. Thus, the association between the occurrence of new postpartum intramammary infections (IMIs) and the expression of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) on blood T-cells during the peripartum period was investigated. RESULTS: In this study, the incidence of IMIs by any pathogen in early lactation was not associated with a higher expression of PD-1 and CTLA-4 in the periparturient period. However, the incidence of IMIs by major pathogens throughout the first month of lactation was significantly associated with higher expression of PD-1 at 14 days before calving (P = 0.03) and CTLA-4 at parturition (P = 0.03) by blood T-cells. Also, the expression of CTLA-4 at D0 (P = 0.012) by T-cells was associated with the occurrence of persistent IMIs during the first month of lactation. CONCLUSIONS: To our knowledge, this is the first report to investigate the expression of PD-1 and CTLA-4 by blood T-lymphocytes during the periparturient period in dairy cows and to explore their relationship with the incidence of new IMIs in the postpartum period. Thus, a comprehensive understanding of leukocyte biology during peripartum would appear to be a prerequisite for the identification of resilient dairy cows or targets innovative (immunological) non-antibiotic approaches in the transition period.