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1.
Artigo em Inglês | MEDLINE | ID: mdl-39105835

RESUMO

BACKGROUND: The aim of this study was to evaluate the interobserver reliability of measurements of the Acromiohumeral Distance (AHD) first described by Golding et al., the Critical Shoulder Angle (CSA), the Acromion Index with Glenoid Humeral (GH) and Glenoid Acromial (GA) distances, following the measuring method by Nyffeler et al., the Lateral Acromion Angle (LAA), as well as the morphology of the acromion according to Bigliani and the humeral head position according to Maloney in X-rays and MRI. Furthermore, the study assessed the correlation of measurement results in X-ray with those in MRI for AHD, CSA, GA, GH, AI, and LAA. METHODS: A total of 187 patients who underwent shoulder joint X-ray and MRI examinations from 09/2016 to 05/2023 were included in the study. Patients with poor imaging quality, arthrosis or radical prior surgeries, like shoulder prosthetic surgery, status post humerus fractures, that have undergone surgery and therefore changed the anatomical features were excluded, what lead to a total study population of 78. X-ray measurements were performed by two observers in the true anteroposterior view, so that the humeral head and the glenoid are shown without overlap, providing a clear view into the joint space. MRI measurements were performed in oblique coronal MRI slices, using the most accurately depicted glenoid surface as a landmark. RESULTS: Interobserver measurement results showed a significance with p < 0.001 for the assessment of acromion type according to Bigliani, humeral head offset assessment according to Maloney, and AHD. No significance was found for interobserver reliability in measuring LAA. Additionally, there was a high correlation of measurement results in X-ray with measurements in MRI for, CSA, GH/GA, and consequently AI, a good correlation for AHD but no correlation could be shown for LAA. CONCLUSIONS: These findings provide valuable insights into the robustness of radiological parameters for evaluating shoulder pathology, offering promising prospects for clinical applications and further research. Nevertheless, the specific methodological considerations and patient characteristics should be taken into account when interpreting the results to ensure their accurate application in clinical practice.

2.
Materials (Basel) ; 17(13)2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38998245

RESUMO

Using waste materials as replacements for sand in building materials helps reduce waste and improve the properties and sustainability of the construction materials. Authors proved the possibility of using imperial smelting furnace (ISF) slag granules as a 100% substitute for natural sand in self-compacting (SCC) cement-based mortars of calcium sulfoaluminates (CSA). The study proved that ISF slag's radioactive properties meet this area's requirements. CSA cement eliminates the noted problem in the case of concrete with Portland cement, which is the extended setting of the cement binder. The research findings indicate that using slag to replace sand up to 100% in mortars without grains smaller than 0.125 mm allows high flowability, compaction, low porosity and mechanical parameters. The compressive strength of the CSA cement mortars was about 110 MPa, and more than 140 MPa for geopolymer mortar. Unfortunately, the alkaline pH of a geopolymer causes high leachability of barium and sodium. Thus, the CSA cement is in a more favourable binder to achieve high strength, is environmentally friendly, and is a self-compacting mortar or concrete.

3.
N Am Spine Soc J ; 18: 100326, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38947493

RESUMO

Background: Low back pain (LBP) is the most frequent indication to magnetic resonance imaging (MRI) examinations of the lumbosacral spine. The individual role of soft tissues, including muscles, on LBP is not fully understood and the contribution of each MRI-derived parameter of soft tissues status on the intensity of LBP has not been investigated in detail. Methods: The study design was observational retrospective, single center carried out at a University Hospital. Images were acquired using a using a 1.5 Tesla scanner. Patients completed a symptom questionnaire and rated their pain intensity using the Visual Analogue Scale (VAS). The VAS scores ​​were categorized as mild, moderate, and severe using cutoff values of 3.8 and 5.7, based on the literature. Biometric data, including weight and height, were also recorded to calculate the body mass index (BMI). The ratios between intramuscular fat infiltration and net muscle area were also calculated. Patient sample included 94 patients with LBP underwent MRI of the lumbosacral spine. Results: The stepwise analysis revealed that increasing psoas net area was associated with lower VAS levels (odds ratio [OR]: 0.94: 95% confidence interval [CI]: 0.90-0.98; p=.005), and an increase of one square centimeter of total psoas area resulted in a greater probability of reporting a mild (+1.21%; 95% CI: 0.37, 2.05%) or a moderate VAS (+0.40%; 95% CI: -0.02, 0.82%), Furthermore, a more severe VAS was associated with a higher BMI (OR: 1.13; 95% CI: 1.00-1.27). Conclusion: Our study demonstrates a relationship between LBP and MRI parameters of paravertebral and psoas muscles status. The psoas muscle is extremely important for spine stabilization and is linked to clinical symptoms of patients affected by LBP. These findings could contribute to future studies and improve treatment options in patients with LBP, possibly reducing the impact on disability, quality of life and socioeconomical burden.

4.
Front Med (Lausanne) ; 11: 1363844, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39045414

RESUMO

Background: In low- and middle-income nations, a significant proportion of maternal and infant deaths are caused by a short birth interval (SBI). In Ethiopia, it is the main factor contributing to maternal and infant mortality. Understanding the spatial distribution of SBIs, i.e., birth intervals of less than 33 months, and the factors that influence them is important for categorizing and promoting targeted interventions. This study used a geographically weighted regression model to evaluate the factors associated with SBIs in hot areas of Ethiopia. Methods: The 2019 Ethiopian Mini Demographic and Health Survey, which is nationally representative, provided the data for this study. The first step in the two-stage cluster design used to collect the data was enumeration areas, and the second stage was households. The survey was conducted between 21 March 2019 and 28 June 2019. A hot spot analysis (local Getis-Ord Gi* statistics) was initially used to investigate spatial variation in SBIs. Geographically weighted regression was used to examine the regional variation in the relationship between SBIs and the factors that cause them. Result: The study indicated that the overall proportion of SBIs among women in Ethiopia was 43.2%. The values for Global Moran's I (Moran's I = 0.773 and p < 0.001) showed the presence of significant SBIs clustering in Ethiopian administrative zones in Ethiopia. High-risk areas of the SBIs include Jarar, Doolo, Shabelle, Afder, Liben, Korahe, Nogob, West Harerge, Guji, Sidama, and Assosa zones. Conclusion: Living in a geographic region with a high proportion of uneducated women, women lacking breastfeeding practices, and followers of Orthodox religions increased the proportion of SBIs. Our full map of hot spots for short birth spacing and the factors that affect them helps in the implementation of precise public health measures for decision-makers.

5.
J Environ Manage ; 366: 121689, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38991340

RESUMO

In North Bihar (NB), the conventional rice-wheat cropping system has led to soil, water, and environmental degradation, alongside low profitability, threatening sustainability. To address these concerns, a thorough field research was conducted over the course of three years to assess different methods of tillage and crop establishment in a rice, wheat, and greengram cycle. The experiment involved five scenarios with different combinations of crop rotation, tillage techniques, seeding procedures, fertilizer use, and irrigation strategies. Uncertainty analysis showed no significant change in mean and variance estimation among seven scenario replications at 5% significance level. Compared to traditional farming (SN-1), managing DSR-rice (SN-5) increased profitability by 17.56%, improved energy use efficiency (EUE) by 32.16%, and reduced irrigation by 24.76% and global warming potential (GWP) by 23.46%. Similarly, substituting zero tillage wheat (ZTW) SN-5 resulted in comparable profitability gains (18.25%) and significant improvements in irrigation (10 %), EUE (+48.65%), and GWP (-20 %) compared to SN-1. Green gram ZT also showed increased profitability (17.35%), with notable improvements in EUE (+38.31%) and GWP (-12.92%) compared to SN-1. Principal component and correlation analyses revealed relationships between total energy inputs, yields, economic returns, and sustainability indices, highlighting the benefits of crop rotation and tillage practices in optimizing resource use. The study suggests that compared to conventional systems, significant improvements in productivity, profitability, energy-use efficiency, and environmental mitigation can be achieved with Crop Rotation and Tillage Operations techniques.


Assuntos
Agricultura , Produtos Agrícolas , Gases de Efeito Estufa/análise , Gases de Efeito Estufa/metabolismo , Índia , Produtos Agrícolas/crescimento & desenvolvimento , Produtos Agrícolas/metabolismo , Agricultura/economia , Agricultura/métodos , Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Triticum/crescimento & desenvolvimento , Triticum/metabolismo , Verduras/crescimento & desenvolvimento , Verduras/metabolismo , Incerteza , Energia Renovável/economia , Irrigação Agrícola/economia , Irrigação Agrícola/métodos
6.
Heliyon ; 10(11): e31616, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38828343

RESUMO

Developing countries with predominantly agricultural economies are particularly vulnerable to short-term climate variability and long-term climate change adversities. This provides the context for adopting climate-smart agricultural (CSA) practices to ensure consistent agricultural product supply and food security. Although concepts of CSA tools and strategies are well-established, their adoption trends in developing regions are still undesirable, with little to no empirical understanding of factors contributing to these trends. The current research aims to address this gap of knowledge by assessing the nature of climate change impacts, adaptation strategies, and socio-economic characteristics of the farmers influencing the adoption of CSA techniques in a rural cohort in Southwestern Bangladesh. Systematically designed interview schedules revealed that the most common and devastating consequences of climate change in the study area were increased infestation of pests and diseases. Other overlooked hazards including water-logging, cyclones and cold waves, are posing new threats to regional agriculture by changing conventional patterns. Contrary to the status quo, many CSA technologies, especially indigenous approaches, are widely and effectively adopted by farmers in the studied area to cope with climate change. These adoption tendencies and innovations in CSA were found to be significantly driven by factors such as extension and training programs, education of farmers, and dependence on on-farming income. The findings of the current study provide a preliminary analysis of the attitude, knowledge and trends of CSA technology adoption by farmers in a less-saline floodplain niche of a predominantly salinity-impacted coastal region. The study acts as a model for future relevant investigations and implementations for stakeholders with supply of inputs, technologies and expertise in finding sustainable solutions and appropriate extension for communities around the world confronted with similar challenges.

7.
J Biochem ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861406

RESUMO

Chondroitin sulfate (CS) is a linear polysaccharide chain of alternating residues of glucuronic acid (GlcA) and N-acetylgalactosamine (GalNAc), modified with sulfate groups. Based on the structure, CS chains bind to bioactive molecules specifically and regulate their functions. For example, CS whose GalNAc is sulfated at the C4 position, termed CSA, and CS whose GalNAc is sulfated at both C4 and C6 positions, termed CSE, bind to a malaria protein VAR2CSA and receptor type of protein tyrosine phosphatase sigma (RPTPσ), respectively in a specific manner. Here, we modified CSA and CSE chains with phosphatidylethanolamine (PE) at a reducing end, attached them to liposomes containing phospholipids, and generated CSA- and CSE-liposomes. The CS-PE was incorporated into the liposome particles efficiently. Inhibition ELISA revealed specific interaction of CSA and CSE with recombinant VAR2CSA and RPTPσ, respectively, more efficiently than CS chains alone. Furthermore, CSE-liposome was specifically incorporated into RPTPσ-expressing HEK293T cells. These results indicate CS-liposome as a novel and efficient drug delivery system, especially for CS-binding molecules.

8.
Sensors (Basel) ; 24(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38894135

RESUMO

To enhance fault detection in slewing bearing vibration signals, an advanced noise-reduction model, HRCSA-VMD-WT, is designed for effective signal noise elimination. This model innovates by refining the Chameleon Swarm Algorithm (CSA) into a more potent Hybrid Reinforcement CSA (HRCSA), incorporating strategies from Chaotic Reverse Learning (CRL), the Whale Optimization Algorithm's (WOA) bubble-net hunting, and the greedy strategy with the Cauchy mutation to diversify the initial population, accelerate convergence, and prevent local optimum entrapment. Furthermore, by optimizing Variate Mode Decomposition (VMD) input parameters with HRCSA, Intrinsic Mode Function (IMF) components are extracted and categorized into noisy and pure signals using cosine similarity. Subsequently, the Wavelet Threshold (WT) denoising targets the noisy IMFs before reconstructing the vibration signal from purified IMFs, achieving significant noise reduction. Comparative experiments demonstrate HRCSA's superiority over Particle Swarm Optimization (PSO), WOA, and Gray Wolf Optimization (GWO) regarding convergence speed and precision. Notably, HRCSA-VMD-WT increases the Signal-to-Noise Ratio (SNR) by a minimum of 74.9% and reduces the Root Mean Square Error (RMSE) by at least 41.2% when compared to both CSA-VMD-WT and Empirical Mode Decomposition with Wavelet Transform (EMD-WT). This study improves fault detection accuracy and efficiency in vibration signals and offers a dependable and effective diagnostic solution for slewing bearing maintenance.

9.
IEEE J Transl Eng Health Med ; 12: 457-467, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38899144

RESUMO

OBJECTIVE: Pulmonary cavity lesion is one of the commonly seen lesions in lung caused by a variety of malignant and non-malignant diseases. Diagnosis of a cavity lesion is commonly based on accurate recognition of the typical morphological characteristics. A deep learning-based model to automatically detect, segment, and quantify the region of cavity lesion on CT scans has potential in clinical diagnosis, monitoring, and treatment efficacy assessment. METHODS: A weakly-supervised deep learning-based method named CSA2-ResNet was proposed to quantitatively characterize cavity lesions in this paper. The lung parenchyma was firstly segmented using a pretrained 2D segmentation model, and then the output with or without cavity lesions was fed into the developed deep neural network containing hybrid attention modules. Next, the visualized lesion was generated from the activation region of the classification network using gradient-weighted class activation mapping, and image processing was applied for post-processing to obtain the expected segmentation results of cavity lesions. Finally, the automatic characteristic measurement of cavity lesions (e.g., area and thickness) was developed and verified. RESULTS: the proposed weakly-supervised segmentation method achieved an accuracy, precision, specificity, recall, and F1-score of 98.48%, 96.80%, 97.20%, 100%, and 98.36%, respectively. There is a significant improvement (P < 0.05) compared to other methods. Quantitative characterization of morphology also obtained good analysis effects. CONCLUSIONS: The proposed easily-trained and high-performance deep learning model provides a fast and effective way for the diagnosis and dynamic monitoring of pulmonary cavity lesions in clinic. Clinical and Translational Impact Statement: This model used artificial intelligence to achieve the detection and quantitative analysis of pulmonary cavity lesions in CT scans. The morphological features revealed in experiments can be utilized as potential indicators for diagnosis and dynamic monitoring of patients with cavity lesions.


Assuntos
Aprendizado Profundo , Pulmão , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Pulmão/diagnóstico por imagem , Pulmão/patologia , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Pneumopatias/diagnóstico por imagem , Pneumopatias/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Redes Neurais de Computação , Aprendizado de Máquina Supervisionado , Algoritmos
10.
Molecules ; 29(12)2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38930843

RESUMO

Cyclophilin A (CypA), the cellular receptor of the immunosuppressant cyclosporin A (CsA), is an abundant cytosolic protein and is involved in a variety of diseases. For example, CypA supports cancer proliferation and mediates viral infections, such as the human immunodeficiency virus 1 (HIV-1). Here, we present the design of PROTAC (proteolysis targeting chimera) compounds against CypA to induce its intracellular proteolysis and to investigate their effect on immune cells. Interestingly, upon connecting to E3 ligase ligands, both peptide-based low-affinity binders and CsA-based high-affinity binders can degrade CypA at nM concentration in HeLa cells and fibroblast cells. As the immunosuppressive effect of CsA is not directly associated with the binding of CsA to CypA but the inhibition of phosphatase calcineurin by the CypA:CsA complex, we investigated whether a CsA-based PROTAC compound could induce CypA degradation without affecting the activation of immune cells. P3, the most efficient PROTAC compound discovered from this study, could deplete CypA in lymphocytes without affecting cell proliferation and cytokine production. This work demonstrates the feasibility of the PROTAC approach in depleting the abundant cellular protein CypA at low drug dosage without affecting immune cells, allowing us to investigate the potential therapeutic effects associated with the endogenous protein in the future.


Assuntos
Ciclofilina A , Ciclosporina , Ativação Linfocitária , Proteólise , Linfócitos T , Humanos , Ciclofilina A/metabolismo , Ciclosporina/farmacologia , Proteólise/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Células HeLa , Proliferação de Células/efeitos dos fármacos , Imunossupressores/farmacologia , Imunossupressores/química , Quimera de Direcionamento de Proteólise
11.
J Child Sex Abus ; 33(4): 415-423, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38769896

RESUMO

Research suggests that individuals involved in the criminal justice system have higher rates of childhood trauma, including experiences of child sexual abuse (CSA). Studies also suggest that childhood victimization has an impact on the success of mental health treatment for offenders which may contribute to recidivism rates. Accordingly, policymakers and correctional staff can be better informed in choosing appropriate assessments and intervention approaches when they understand the ways in which prior experiences of CSA impact individuals in correctional settings. This special section highlights four novel studies that advance the research examining CSA in incarcerated populations.


Assuntos
Vítimas de Crime , Prisioneiros , Criança , Humanos , Sobreviventes Adultos de Maus-Tratos Infantis/psicologia , Abuso Sexual na Infância/psicologia , Vítimas de Crime/psicologia , Prisioneiros/psicologia , Adulto
12.
Quant Imaging Med Surg ; 14(5): 3593-3605, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38720864

RESUMO

Background: The degeneration and functional decline of paravertebral muscles (PVMs) are reported to be closely linked to the incidence of degenerative lumbar scoliosis (DLS), a spinal deformity of the mature skeleton. However, the functional role and degeneration of PVMs and their relationship to the development of spinal deformities remain controversial. Therefore, the present study analyzed the morphological changes in the PVMs of patients with DLS, and explored the relationship between PVM degeneration and spinal osseous parameters. Methods: In this retrospective case-control study, we evaluated the PVM parameters of patients with DLS (n=120) and compared them with patients free of DLS (control group, n=120). The cross-sectional area (CSA) and computed tomography (CT) values of the PVM at the lumbar vertebra 1-5 levels were measured. Further, the lumbar scoliosis Cobb, lumbar lordotic, and apical vertebral rotation angles were measured on CT and radiographs in the DLS group, and the relationship between PVM changes and these factors was analyzed. Results: In the control group, the PVM CSA and CT values differed insignificantly between the bilateral sides at all levels (P>0.05). In the DLS group, the CSAs of the multifidus (MF) and erector spinae (ES) were larger on the convex side than the concave side (P>0.05), whereas that of the psoas major (PM) was smaller on the convex side than the concave side (P<0.05). The CT value of the PVM was lower on the convex side at all levels (P<0.05). The CSA and CT values on both sides of the patients were lower in the DLS group than the control group at all levels (P<0.05). Further, the degree of PVM asymmetry at the apical vertebral level was positively correlated with the lumbar scoliosis (P<0.01) and apical vertebral rotation angles (P<0.05), but negatively correlated with the lumbar lordotic angle (P<0.05). Conclusions: Asymmetric degeneration of the PVM was observed bilaterally in DLS patients, and the degeneration was more pronounced on the concave side than the convex side. This asymmetrical degeneration was closely associated with the severity of lumbar scoliosis, vertebral rotation, and loss of lumbar lordosis, and a stronger correlation was observed with the MF and ES than with the PM.

13.
Behav Sci (Basel) ; 14(5)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38785910

RESUMO

Educational institutions and educators are significant in children's lives, and they have a crucial role in implementing policies, practices, and sexual education to enhance children's safety. Such policies and practices should be based on the voices of CSA survivors. This study explored child sexual abuse (CSA) survivors' viewpoints on their past experiences with educators and the educational system. A qualitative thematic approach was used to analyze 61 written testimonies collected in 2020-2021 by the Israeli Independent Public Inquiry on CSA. Two interrelated themes arose: (1) CSA survivors' retrospective perspectives of educators and the educational system's responses to signs of their CSA, described as ranging from abusive to life-saving. Specifically, they shared three types of responses: (a) harmful and hurtful; (b) dismissive and ignoring; and (c) accepting and attending. (2) The second theme described the survivors' messages to educators to promote constructive change. The survivors conveyed expectations that educators should play a central role in CSA prevention, detection, and intervention and, specifically, the need for educators to receive professional training, provide beneficial sexual education, and identify and respond to CSA. The findings promoted moving beyond individual-level interventions to focus on improving educational institutional and organizational cultures related to CSA in both national and international contexts.

14.
Behav Sci (Basel) ; 14(5)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38785915

RESUMO

School counselors play a crucial role in preventing, disclosing, and intervening in child sexual abuse cases (CSA) and in maintaining safe and protected school environments. However, research on their experiences coping with CSA remains limited. The purpose of the present study was to describe and analyze the coping experiences of Israeli Jewish and Arab school counselors with CSA disclosure, particularly the consequences for their processes of professional identity construction (the ongoing process through which they develop and refine their sense of self in their profession). Semi-structured interviews were conducted with 21 Israeli Jewish and Arab school counselors working in elementary schools (grades 1-6) with significant experience in coping with CSA. Two themes surfaced, reflecting the counselors' professional identity construction: (1) Counselors' professional identity transformation following encounters with CSA among their students; (2) Integrating professional knowledge, attitudes, and engagement behaviors into professional identity. The findings describe a trajectory of transformation and professional development among the counselors, beginning with defining and refining their professional roles and followed by the integration of professional knowledge, attitudes, and behaviors into their professional routines. Arab counselors also highlighted specific sociocultural challenges within this process, relating to the gap between cultural values and role expectations. Implications for future research, policy, and practice are discussed.

15.
Int J Mol Sci ; 25(10)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38791288

RESUMO

Sleep-disordered breathing (SDB), including obstructive and central sleep apnea, significantly exacerbates heart failure (HF) through adverse cardiovascular mechanisms. This review aims to synthesize existing literature to clarify the relationship between SDB and HF, focusing on the pathophysiological mechanisms, diagnostic challenges, and the effectiveness of treatment modalities like continuous positive airway pressure (CPAP) and adaptive servo-ventilation ASV. We analyzed peer-reviewed articles from 2003 to 2024 sourced from PubMed, EMBASE, Scopus, and Web of Science databases. The prevalence of SDB in HF patients is high, often underdiagnosed, and underappreciated. Management strategies, including CPAP and ASV, have been shown to mitigate symptoms and improve cardiac function. However, despite the availability of effective treatments, significant challenges in screening and diagnosis persist, affecting patient management and outcomes. DB significantly impacts HF prognosis. Enhanced screening strategies and broader utilization of therapeutic interventions like CPAP and ASV are essential to improve the management and outcomes of HF patients with concomitant SDB. Future research should focus on refining diagnostic and treatment protocols to optimize care for HF patients with SDB.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Insuficiência Cardíaca , Síndromes da Apneia do Sono , Humanos , Insuficiência Cardíaca/terapia , Síndromes da Apneia do Sono/terapia , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/diagnóstico , Prognóstico
16.
Clin Hematol Int ; 6(1): 88-95, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38817698

RESUMO

Cyclosporine A (CSA) is a commonly used immunosuppressive agent for the prophylaxis of graft-versus-host disease following allogeneic hematopoietic stem cell transplantation (alloHSCT). While tachycardia is a known adverse effect of CSA, bradycardia remains a phenomenon rarely described in the literature. We conducted a retrospective evaluation of the incidence of bradycardia in patients after alloHSCT treated with CSA between January 2020 and February 2023 at our center. Out of 206 patients, sinus bradycardia following the administration of CSA was observed in 6 (2.9%), comprising 3 women and 3 men, with the median age of 55 years (range: 20-65). The underlying diseases were myeloid malignancies in 4 and aggressive lymphoma in 2 patients. The patients received grafts from a matched unrelated (n=5) or a haploidentical family donor (n=1) following various conditioning regimens. Coexisting cardiovascular disorders were found in 5 of the 6 patients. All patients experienced symptomatic bradycardia within 1-4 days (median 2 days) after CSA introduction, which persisted until CSA withdrawal. One patient required treatment with atropine. All patients continued their immunosuppressive therapy with tacrolimus, which was well-tolerated Our study indicates CSA as a causative factor of sinus bradycardia in a small percentage of alloHSCT patients receiving CSA as graft-versus host disease (GvHD) prophylaxis. Importantly, these patients did not experience any cardiac complications when switched to tacrolimus. Although further research on the effects of CSA on heart automatation is needed, our single-center experience can help prompt diagnosis and therapeutic intervention in daily clinical practice.

17.
Eur J Immunol ; 54(7): e2350825, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38650034

RESUMO

Cyclosporin A is a well-established immunosuppressive drug used to treat or prevent graft-versus-host disease, the rejection of organ transplants, autoimmune disorders, and leukemia. It exerts its immunosuppressive effects by inhibiting calcineurin-mediated dephosphorylation of the nuclear factor of activated T cells (NFAT), thus preventing its nuclear entry and suppressing T cell activation. Here we report an unexpected immunostimulatory effect of cyclosporin A in activating the mammalian target of rapamycin complex 1 (mTORC1), a crucial metabolic hub required for T cell activation. Through screening a panel of tool compounds known to regulate mTORC1 activation, we found that cyclosporin A activated mTORC1 in CD8+ T cells in a 3-phosphoinositide-dependent protein kinase 1 (PDK1) and protein kinase B (PKB/AKT)-dependent manner. Mechanistically, cyclosporin A inhibited the calcineurin-mediated AKT dephosphorylation, thereby stabilizing mTORC1 signaling. Cyclosporin A synergized with mTORC1 pathway inhibitors, leading to potent suppression of proliferation and cytokine production in CD8+ T cells and an increase in the killing of acute T cell leukemia cells. Consequently, relying solely on CsA is insufficient to achieve optimal therapeutic outcomes. It is necessary to simultaneously target both the calcineurin-NFAT pathway and the mTORC1 pathway to maximize therapeutic efficacy.


Assuntos
Linfócitos T CD8-Positivos , Ciclosporina , Imunossupressores , Ativação Linfocitária , Alvo Mecanístico do Complexo 1 de Rapamicina , Transdução de Sinais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Ciclosporina/farmacologia , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Animais , Imunossupressores/farmacologia , Camundongos , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fatores de Transcrição NFATC/metabolismo , Humanos , Serina-Treonina Quinases TOR/metabolismo , Calcineurina/metabolismo , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Proliferação de Células/efeitos dos fármacos , Complexos Multiproteicos/metabolismo
18.
Environ Pollut ; 350: 123973, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38636841

RESUMO

We investigated methane (CH4) and nitrous oxide (N2O), two important greenhouse gases (GHGs) emissions using the closed chamber method from a flooded rice field in Brahmaputra valley of Assam, northeast part of India. We tried to understand the factors responsible for the emission and identify appropriate agro-technologies for their mitigation. Various factors like water level, drainage management, soil organic carbon management, crop management, fertilizer amendment, cultivar type etc. affect the GHG production and emission from the flooded rice soil. In this study, six treatments were employed, namely, farmer's practice (FP), recommended fertilizer dosage (RDF), direct seeded rice (DSR), intermittent wetting drying (IWD), use of efficient methanotrophs (MTH), and use of ammonium sulfate as a nitrogen source for real-time nitrogen management using leaf color chart, (AS). GHG flux was measured through the static closed chamber technique. Soil temperature, pH, and redox potential (Eh) and other soil physico-chemical and biological properties that have a potential role in GHG emission were also assessed. The lowest CH4 flux was observed in IWD treatment. The highest CH4 but lowest N2O flux was observed in RDF thus portraying a tradeoff relationship among these two GHGs. The highest N2O flux was observed in AS. Changes in Eh strongly altered CH4 and N2O emissions. The CH4 flux for the growing season varied from 62.5 to 86.3 kg ha-1 with an average of 72.4 kg ha-1. The average N2O flux was 0.89 kg ha-1 with values fluctuating between 0.72 - and 1.08 kg ha-1. The findings of this study could assist in understanding the factors affecting the source, production, and sink of these two important GHGs. IWD, along with judicious N-based fertilizer use, could provide significant respite from GHG emissions in rice-based agriculture. These climate-smart strategies not only reduce emissions but also have the potential to improve yield.


Assuntos
Agricultura , Fertilizantes , Gases de Efeito Estufa , Metano , Óxido Nitroso , Oryza , Gases de Efeito Estufa/análise , Oryza/crescimento & desenvolvimento , Agricultura/métodos , Óxido Nitroso/análise , Metano/análise , Índia , Fertilizantes/análise , Solo/química , Inundações , Poluentes Atmosféricos/análise , Monitoramento Ambiental/métodos , Clima
19.
Int J Ment Health Syst ; 18(1): 16, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637858

RESUMO

BACKGROUND: Research shows that only around half of all survivors of child sexual abuse (CSA) disclose the abuse during childhood and adolescence. This is worrying, as CSA is related to substantial suffering later in life. The proportion of children and adolescents who have been exposed to CSA is significantly higher in Child and Adolescent Psychiatry (CAP) than in the general population. Healthcare professionals report that uncovering CSA is a complex and challenging task. However, we know little about how they proceed when uncovering CSA. More knowledge of healthcare personnel's experience is therefore necessary to facilitate and increase CSA disclosure. The study aims to explore how CAP healthcare professionals in Norway proceed when assessing and detecting CSA, how they experience this work, and what hinders or facilitates their efforts. METHODS: The study employed a mixed method approach. Data was collected through an anonymous online survey, generating both quantitative and qualitative data. The sample consisted of 111 healthcare professionals in CAP, of whom 84% were women, with a mean age of 40.7 years (range 24-72; sd = 10.8). Mean years of CAP clinical experience were 8.3 years (range 0-41; sd = 7.5). The quantitative data was analysed using descriptive statistics, correlations, and independent sample t-tests, while the qualitative data was analysed using a team-based qualitative content analysis. RESULTS: The results showed that detection of CSA was viewed as an important, but complex task in CAP, and the existing procedures were deemed to be insufficient. The therapists mostly felt confident about how to proceed when they suspected or detected CSA, yet they seldom detected CSA. In their initial assessment they applied standardised procedures, but if their suspicion of possible CSA persisted, they seemed to rely more on clinical judgement. Specific challenges and facilitators for CSA detection were identified, both in the individual and in the organisation. CONCLUSIONS: The study highlights the challenges and complexities healthcare professionals and the CAP system face when assessing CSA, which may account for the low detection rate. The results show that healthcare professionals believe room for clinical autonomy and targeted competence development may improve CSA detection. Additionally, the findings suggest a need for CAP to define roles and responsibilities within and between agencies.

20.
Heliyon ; 10(5): e26777, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38495197

RESUMO

Fused Deposition Modeling (FDM) 3D printing creates components by layering extruded material. Printer parameters such as layer height and infill density can greatly impact the mechanical properties and quality of the printed parts. One critical factor to be considered in analysis is the anisotropy nature of printed components, considering all cross-sectional area (CSA) profiles for less than 100% infill density. This paper investigates the effect of the anisotropy nature of 3D printed CSA has on stress calculations and hence mechanical properties of the specimen through Design of Experiment (DOE). Analysis of variance (ANOVA) is utilised to evaluate the results. Printed specimens were tensile tested as per ASTM D638-14. Raw data was analysed using various CSA profiles, taking changes in infill density and layer height into account. Fixed parameter such as shell count, top and bottom layers, nozzle diameter, Hexagonal pattern were defined. Specimens Ultimate Tensile Strength (UTS) values increased on average by 30% using average profile CSA data compared to using external specimen dimensions. Further analysis assessing printer parameters affect on recycled Polyethylene Terephthalate (rPET) specimen's Young's Modulus (YM) and UTS was studied. One significant finding from this study suggests that the thickness of each layer has the most significant impact on the material properties of 3D printed rPET, as observed through the analysis of tensile test data obtained from 3D printed samples. A 3D printed rPET specimen with 30% infill density and 0.25 mm layer height has a higher YM (1175 MPa) and UTS (39 MPa) compared to a specimen with 75% infill density and 0.1 mm layer height (1159 MPa, 31 MPa). However careful interpretation of the results is required because for the same 30% infill parameter at 0.2 mm layer height the YM (936 MPa) and UTM (28 MPa) are significantly lower than at 0.25 mm layer height. If a higher value of YM and UTS is required an infill setting of 50% and layer height of 0.25 mm gave the highest values, YM (1330 MPa) and UTS (43 MPa).

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