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Veterinary Sciences Jun 2024Traditionally, non- staphylococci and mammaliicocci (NASM) were not considered significant players in bovine mastitis. This study investigated the involvement of NASM (...
Traditionally, non- staphylococci and mammaliicocci (NASM) were not considered significant players in bovine mastitis. This study investigated the involvement of NASM ( and ) and lactic acid bacteria (LAB) strains () through bovine neutrophil responses. Bovine neutrophils displayed minimal apoptosis upon NASM and LAB challenge. Neutrophils expressed high TLR2 after challenge, but TLR6 expression varied and remained low in NASM pathogen recognition. Bovine neutrophils effectively engulfed and killed LAB, but their activity was significantly impaired against NASM. This was evident in , where reduced TLR6 recognition and a weakened phagocytic response likely contributed to a lower bactericidal effect. Regardless of the bacteria encountered, intracellular ROS production remained high. -challenged neutrophils displayed upregulation in genes for pathogen recognition (TLRs), ROS production, and both pro- and anti-apoptotic pathways. This response mirrored that of . except for and , suggesting these bacteria have divergent roles in triggering cell death. Our findings suggest that manipulates bovine neutrophil defenses through coordinated changes in functional responses and gene expression, while LAB strains have a weaker influence on apoptosis.
PubMed: 38922009
DOI: 10.3390/vetsci11060262 -
Cancer Research Communications Jun 2024Evaluate the efficacy of WEE1 inhibitor adavosertib in patients (pts) with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B).
PURPOSE
Evaluate the efficacy of WEE1 inhibitor adavosertib in patients (pts) with solid tumor malignancies (cohort A) and clear cell renal cell carcinoma (ccRCC; cohort B).
PATIENTS AND METHODS
NCT03284385 was a parallel cohort, Simon two-stage, phase II study of adavosertib (300 mg QDAY by mouth on days 1-5 and 8-12 of each 21-day cycle) in pts with solid tumor malignancies harboring a pathogenic SETD2 mutation. The primary endpoint was objective response rate (ORR). Correlative assays evaluated loss of H3K36me3 by immunohistochemistry (IHC), a downstream consequence of SETD2 loss, in archival tumor tissue.
RESULTS
Eighteen pts were enrolled (9/cohort). Median age was 60 years (range 45 - 74). The median duration of treatment was 1.28 months (range 0 - 24+). No objective responses were observed in either cohort; accrual was halted following stage 1. Minor tumor regressions were observed in 4/18 (22%) evaluable pts. Stable disease (SD) was the best overall response in 10/18 (56%) pts, including three pts with SD >4 months. One pt with ccRCC remains on treatment for >24 months. The most common adverse events (AE) of any grade were nausea (59%), anemia (41%), diarrhea (41%), and neutropenia (41%). Nine pts (50%) experienced a Grade ≥ 3 AE. Of 8 evaluable archival tissue samples, 6 (75%) had loss of H3K36me3 by IHC.
CONCLUSIONS
Adavosertib failed to exhibit objective responses in SETD2-altered ccRCC and other solid tumor malignancies though prolonged stable disease was observed in a subset of pts. Combination approaches may yield greater depth of tumor response.
PubMed: 38920407
DOI: 10.1158/2767-9764.CRC-24-0213 -
Housing Policy Debate 2024Sexual and gender minority (SGM) individuals experience high rates of homelessness and criminal justice system involvement, underscoring the need for supportive housing...
Sexual and gender minority (SGM) individuals experience high rates of homelessness and criminal justice system involvement, underscoring the need for supportive housing services. To explore the service needs of this population, we interviewed providers (n = 11) and clients (n = 10) from eight supportive housing organizations working with SGM populations in Los Angeles County, USA. We used the Consolidated Framework for Implementation Research to synthesize interview responses into themes (by domain and cross-cutting). Take-aways included the need for investment in systems of care for vulnerable SGM populations; the particular marginalization of Trans individuals and providers that serve them; the roles of supportive housing staff, residents, and leadership in cultivating an affirming environment; prevalence of discrimination and stigma within supportive housing programs and broader society; and the complex interrelationships among SGM identity, homelessness, and criminal justice system involvement. These findings have important implications for supportive housing services and related policy.
PubMed: 38919911
DOI: 10.1080/10511482.2022.2055615 -
International Journal of Circumpolar... Dec 2024The COVID-19 pandemic posed a grave threat not only to Indigenous people's health and well-being, but also to Indigenous communities and societies. This applies also to... (Review)
Review
The COVID-19 pandemic posed a grave threat not only to Indigenous people's health and well-being, but also to Indigenous communities and societies. This applies also to the Indigenous peoples of the Arctic, where unintentional effects of public health actions to mitigate the spread of virus may have long-lasting effects on vulnerable communities. This study aim was to identify and describe Sámi perspectives on how the Sámi society in Sweden was specifically affected by the pandemic and associated public health actions during 2020-2021. A mixed-method qualitative case study approach was employed, including a media scoping review and stakeholder interviews. The media scoping review included 93 articles, published online or in print, from January 2020 to 1 September 2021, in Swedish or Norwegian, regarding the pandemic-related impacts on Sámi society in Sweden. The review informed a purposeful selection of 15 stakeholder qualitative interviews. Thematic analysis of the articles and interview transcripts generated five subthemes and two main themes: "weathering the storm" and "stressing Sámi culture and society". These reflect social dynamics which highlight stressors towards, and resilience within, the Sámi society during the pandemic. The results may be useful when evaluating and developing public health crisis response plans concerning or affecting the Sámi society in Sweden.
Topics: Humans; COVID-19; Arctic Regions; Sweden; SARS-CoV-2; Qualitative Research; Indigenous Peoples; Pandemics; Public Health
PubMed: 38917207
DOI: 10.1080/22423982.2024.2372123 -
Molecular Biology and Evolution Jun 2024Nest building is a vital behavior exhibited during breeding in birds, and is possibly induced by environmental and social cues. Although such behavioral plasticity has...
Nest building is a vital behavior exhibited during breeding in birds, and is possibly induced by environmental and social cues. Although such behavioral plasticity has been hypothesized to be controlled by adult neuronal plasticity, empirical evidence, especially at the neurogenomic level, remains limited. Here, we aim to uncover the gene regulatory networks that govern avian nest construction and examine whether they are associated with circuit rewiring. We designed an experiment to dissect this complex behavior into components in response to pair bonding and nest material acquisition by manipulating the presence of mates and nest materials in 30 pairs of zebra finches. Whole-transcriptome analysis of 300 samples from five brain regions linked to avian nesting behaviors revealed nesting-associated gene expression enriched with neural rewiring functions, including neurogenesis and neuron projection. The enriched expression was observed in the motor/sensorimotor and social behavior networks of female finches, while in the dopaminergic reward system of males. Female birds exhibited predominant neurotranscriptomic changes to initiate the nesting stage, while males showed major changes after entering this stage, underscoring sex-specific roles in nesting behavior. Notably, major neurotranscriptomic changes occurred during pair bonding, with minor changes during nest material acquisition, emphasizing social interactions in nest construction. We also revealed gene expression associated with reproductive behaviors and tactile sensing for nesting behavior. This study presents novel neurogenomic evidence supporting the hypothesis of adult neural plasticity underlying avian nest-construction. By uncovering the genetic toolkits involved, we offer novel insights to the evolution of animals' innate ability to construct nests.
PubMed: 38916488
DOI: 10.1093/molbev/msae125 -
Frontiers in Bioengineering and... 2024Intervertebral Disc (IVD) Degeneration (IDD) is a significant health concern, potentially influenced by mechanotransduction. However, the relationship between the IVD...
Intervertebral Disc (IVD) Degeneration (IDD) is a significant health concern, potentially influenced by mechanotransduction. However, the relationship between the IVD phenotypes and mechanical behavior has not been thoroughly explored in local morphologies where IDD originates. This work unveils the interplays among morphological and mechanical features potentially relevant to IDD through Abaqus UMAT simulations. A groundbreaking automated method is introduced to transform a calibrated, structured IVD finite element (FE) model into 169 patient-personalized (PP) models through a mesh morphing process. Our approach accurately replicates the real shapes of the patient's Annulus Fibrosus (AF) and Nucleus Pulposus (NP) while maintaining the same topology for all models. Using segmented magnetic resonance images from the former project , 169 models with structured hexahedral meshes were created employing the Bayesian Coherent Point Drift++ technique, generating a unique cohort of PP FE models under the initiative. Machine learning methods, including Linear Regression, Support Vector Regression, and eXtreme Gradient Boosting Regression, were used to explore correlations between IVD morphology and mechanics. We achieved PP models with AF and NP similarity scores of 92.06\% and 92.10\% compared to the segmented images. The models maintained good quality and integrity of the mesh. The cartilage endplate (CEP) shape was represented at the IVD-vertebra interfaces, ensuring personalized meshes. Validation of the constitutive model against literature data showed a minor relative error of 5.20%. Analysis revealed the influential impact of local morphologies on indirect mechanotransduction responses, highlighting the roles of heights, sagittal areas, and volumes. While the maximum principal stress was influenced by morphologies such as heights, the disc's ellipticity influenced the minimum principal stress. Results suggest the CEPs are not influenced by their local morphologies but by those of the AF and NP. The generated free-access repository of individual disc characteristics is anticipated to be a valuable resource for the scientific community with a broad application spectrum.
PubMed: 38915337
DOI: 10.3389/fbioe.2024.1384599 -
BMC Public Health Jun 2024Physical activity is essential for physical, mental, and cognitive health. Providing evidence to develop better public health policies to encourage increased physical...
BACKGROUND
Physical activity is essential for physical, mental, and cognitive health. Providing evidence to develop better public health policies to encourage increased physical activity is crucial. Therefore, we developed an in-depth survey as part of the Korea Youth Risk Behavior Survey to assess the current status and determinants of physical activity among Korean adolescents.
METHODS
We developed an initial version of the questionnaire based on a review of validated questionnaires, recent trends and emerging issues related to adolescent physical activity, and the national public health agenda pertaining to health promotion. Content validity was confirmed by a panel of 10 experts. Face validity was confirmed through focus group interviews with 12 first-year middle school students. The test-retest reliability of the questionnaire was evaluated by administering it twice, approximately two weeks apart, to a sample of 360 middle and high school students. Additionally, the frequency or average number of responses was analyzed in a sample of 600 students who participated in the initial test-retest reliability evaluation of the questionnaire developed in this study.
RESULTS
Through item pool generation and content and face validity test, the final 15 questionnaire items were developed across five themes: levels of physical activity, school sports club activities, transportation-related physical activity, physical activity-promoting environments, and factors mediating physical activity. The test-retest reliability ranged from fair to substantial. Results from the newly developed survey reveal that only a minority of adolescents engage in sufficient physical activity, with only 17.2% and 21.5% participating in vigorous and moderate-intensity activities, respectively, for at least five days per week. Among school-based activities, 44.3% of students do not participate in school sports clubs due to reasons including absence of clubs and disinterest in exercise. The major motivators for physical activity are personal enjoyment and health benefits, whereas preferences for other leisure activities and academic pressures are the predominant barriers.
CONCLUSIONS
This study developed valid and reliable in-depth survey items to assess physical activity among Korean youths. It will hopefully enhance our understanding of adolescent physical activity, offering essential preliminary evidence to inform the development of public health strategies aimed at promoting adolescent health.
Topics: Humans; Adolescent; Surveys and Questionnaires; Republic of Korea; Male; Female; Psychometrics; Reproducibility of Results; Risk-Taking; Exercise; Focus Groups; Adolescent Behavior; Motor Activity
PubMed: 38914967
DOI: 10.1186/s12889-024-19216-z -
Journal of Visualized Experiments : JoVE Jun 2024Fundamental cancer research and the development of effective counterattack therapies both rely on experimental studies detailing the interactions between cancer and...
Fundamental cancer research and the development of effective counterattack therapies both rely on experimental studies detailing the interactions between cancer and immune cells, the so-called cancer-immunity cycle. In vitro co-culture systems combined with multiparametric flow cytometry (mFC) and tumor-on-a-chip microfluidic devices (ToCs) enable simple, fast, and reliable monitoring and characterization of each step of the cancer-immunity cycle and lead to the identification of the mechanisms responsible for tipping the balance between cancer immunosurveillance and immunoevasion. A thorough understanding of the dynamic interplays between cancer and immune cells provides critical insights to outsmart tumors and will accelerate the pace of therapeutic personalization and optimization in patients. Specifically, here we detail a straightforward mFC- and ToC-assisted protocol for unraveling the dynamic complexities of each step of the cancer-immunity cycle in murine cancer cell lines and mouse-derived immune cells and focus on immunosurveillance. Considering the time- and cost-related features of this protocol, it is certainly feasible on a large scale. Moreover, with minor variations, this protocol can be both adapted to human cancer cell lines and human peripheral-blood-derived immune cells and combined with genetic and/or pharmacologic inhibition of specific pathways in order to identify biomarkers of immune response.
Topics: Coculture Techniques; Mice; Animals; Flow Cytometry; Cell Line, Tumor; Lab-On-A-Chip Devices; Neoplasms; Microfluidic Analytical Techniques; Humans
PubMed: 38912773
DOI: 10.3791/66729 -
Psychology Research and Behavior... 2024Dissociation is a necessary part of our threat response system, common to all animal species, normally temporarily activated under conditions of extreme or inescapable... (Review)
Review
PURPOSE
Dissociation is a necessary part of our threat response system, common to all animal species, normally temporarily activated under conditions of extreme or inescapable threat. Pathological dissociation, however, continues to occur after the initial threat has passed, in response to reminders or inaccessibility of safety and security. Present across the spectrum of psychiatric diagnoses, recurrent dissociative symptoms are linked to severe trauma exposure, insecure attachment, treatment non-response, and maladaptive coping behaviors such as substance use, suicidality, and self-harm. However, empirical studies testing treatments specific to dissociative processes remain scarce. This narrative review summarizes existing studies and provides theoretical, neurobiological, and evolutionary perspectives on dissociative processes and treatments for pathological dissociation.
METHODS
A systematic search of five databases (MEDLINE, EMBASE, APA PsycINFO, CINAHL plus, Scopus) was conducted on April 13, 2023. Peer-reviewed clinical studies with adult participants, assessing intervention effects on dissociative symptoms, were included. Results were thematically analyzed and summarized.
RESULTS
Sixty-nine studies were identified, mainly focused on posttraumatic stress disorder, trauma-exposed populations, and borderline personality disorder. Psychotherapy was studied in 72.5% of studies; other interventions included medications and neurostimulation. The majority reported positive outcomes, despite the heterogeneous spectrum of interventions. However, treatment of dissociative symptoms was the primary objective in only a minority.
CONCLUSION
Pathological dissociation is a complex phenomenon involving brain and body systems designed for perceiving and responding to severe threats, requiring an individualized approach. A literature is emerging regarding potentially evidence-based treatments to help those impacted by recurrent dissociative symptoms. When contextualized within a neurobiological and evolutionary perspective, these treatments can be understood as facilitating an internal and/or relational sense of safety, resulting in symptom reduction. Further studies are needed to explore effective treatments for dissociative symptoms.
PubMed: 38912158
DOI: 10.2147/PRBM.S402456 -
Frontiers in Immunology 2024Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy....
BACKGROUND
Immune checkpoint inhibitors (ICIs) have reshaped the treatment landscape of small cell lung cancer (SCLC), but only a minority of patients benefit from this therapy. Therefore, it is critical to identify potential risk factors that could predict the efficacy of ICI treatment in SCLC patients and identify patient subgroups who may benefit the most from ICI therapy.
METHODS
Our study included a total of 183 SCLC patients who had received at least one dose of ICI treatment. We utilized both logistic regression and Cox proportional hazard regression to evaluate whether various patient clinical factors and serum biomarkers could serve as predictors of patient response to treatment and overall survival (OS) during ICI therapy.
RESULTS
Logistic regression showed that patients with a history of surgery (p=0.003, OR 9.06, 95% CI: (2.17, 37.9)) and no metastasis (p=0.008, OR 7.82, 95% CI: (1.73, 35.4)) exhibited a higher odds of response to ICI treatment. Cox regression analyses demonstrated that pretreatment blood albumin (p=0.003, HR 1.72, 95% CI: (1.21, 2.45)) and derived neutrophil to lymphocyte ratio (dNLR) (p=0.003, HR 1.71, 95% CI: (1.20-2.44)) were independent predictors for OS in SCLC patients. By establishing a pre-treatment prognostic scoring system based on baseline albumin and dNLR, we found that patients with high albumin and low dNLR exhibited a significantly better prognosis than those with low albumin and high dNLR in both the full (P<.0001, HR 0.33, 95% CI: 0.20-0.55) and the metastatic cohort (P<.0001, HR 0.28, 95% CI: 0.15-0.51). The better prognostic group also had younger age, higher BMI and lower systemic inflammatory biomarker values than the unfavorable group (P<.0001).
CONCLUSION
Our data reveals the significant role of metastasis status and treatment history in predicting the initial response of SCLC patients to ICI treatment. However, baseline serum albumin and dNLR provide a more precise prognostic prediction for patient OS. The scoring system based on albumin and dNLR enhances the ability to stratify patient prognosis and holds the potential to guide clinical decision-making for SCLC patients undergoing ICI therapy.
Topics: Humans; Small Cell Lung Carcinoma; Neutrophils; Male; Female; Immune Checkpoint Inhibitors; Lung Neoplasms; Aged; Middle Aged; Lymphocytes; Biomarkers, Tumor; Prognosis; Serum Albumin, Human; Serum Albumin; Aged, 80 and over; Retrospective Studies; Adult; Lymphocyte Count
PubMed: 38911864
DOI: 10.3389/fimmu.2024.1327449