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1.
Artigo em Inglês | MEDLINE | ID: mdl-38837803

RESUMO

BACKGROUND: Selection of central venous catheter (CVC) lock solution impacts catheter mechanical complications and central line-associated bloodstream infections (CLABSIs) in pediatric patients with intestinal failure. Disadvantages of the current clinical standards, heparin and ethanol lock therapy (ELT), led to the discovery of new lock solutions. High-risk pediatric patients with intestinal failure who lost access to ELT during a recent shortage were offered enrollment in a compassionate use trial with 4% tetrasodium EDTA (T-EDTA), a lock solution with antimicrobial, antibiofilm, and antithrombotic properties. METHODS: We performed a descriptive cohort study including 14 high-risk pediatric patients with intestinal failure receiving 4% T-EDTA as a daily catheter lock solution. CVC complications were documented (repairs, occlusions, replacements, and CLABSIs). Complication rates on 4% T-EDTA were compared with baseline rates, during which patients were receiving either heparin or ELT (designated as heparin/ELT). RESULTS: Patients initiated 4% T-EDTA at the time they were enrolled in the compassionate use protocol. Use of 4% T-EDTA resulted in a 50% reduction in CVC complications, compared with baseline rates on heparin/ELT (incidence rate ratio: 0.50; 95% CI, 0.25-1.004; P = 0.051). CONCLUSION: In a compassionate use protocol for high-risk pediatric patients with intestinal failure, the use of 4% T-EDTA reduced composite catheter complications, including those leading to emergency department visits, hospital admissions, additional procedures, and mortality. This outcome suggests 4% T-EDTA has benefits over currently available lock solutions.

2.
BMC Cardiovasc Disord ; 24(1): 288, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816791

RESUMO

Clinical risk factors associated obesity and smoking, as well as their combined effect, are not fully understood. This study aims to determine sex differences in risk factors in a population of acute ischemic stroke (AIS) patients who are obese and with a history of previous or current smoking. METHODS: A retrospective analysis of risk factors in male and female AIS patients with baseline data of obesity and current or previous history of smoking, smoking, and obesity alone was determined. The primary predictor and outcome are risk factors associated with male and female AIS patients. Baseline risk factors were analyzed using a multivariate regression analysis to determine specific risk factors linked with the combined effect of obesity and current or previous history of smoking''. RESULTS: Male obese AIS patients who are current or previous smokers were more likely to be older patients(OR = 1.024, 95% CI, 1.022-1.047, P = 0.033) that present with coronary artery disease (OR = 1.806, 95% CI, 1.028-3.174, P = 0.040), a history of alcohol use (OR = 2.873, 95% CI, 1.349-6.166, P = 0.006), elevated serum creatinine (OR = 4.724, 95% CI, 2.171-10.281, P < 0.001) and systolic blood pressure (OR = 1.029, 95% CI, 1.011-1.047, P < 0.002). Females were more associated with depression (OR = 0.432, 95% CI, 0.244-0.764, P = 0.004), previous TIA (OR = 0.319, 95% CI, 0.142-0.714, P < 0.005), and higher levels of HDL (OR = 0.938, 95% CI, 0.915-0.962, P < 0.001). CONCLUSION: Our results reveal sex differences in risk factors in obese AIS patients with a current or past history of smoking. This finding emphasizes the need to develop management strategies to improve the care of obese AIS patients who are either current or former smokers.


Assuntos
AVC Isquêmico , Obesidade , Fumar , Humanos , Masculino , Feminino , Fatores de Risco , Obesidade/epidemiologia , Obesidade/diagnóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologia , AVC Isquêmico/epidemiologia , AVC Isquêmico/diagnóstico , AVC Isquêmico/etiologia , Medição de Risco , Disparidades nos Níveis de Saúde , Ex-Fumantes , Idoso de 80 Anos ou mais , Prognóstico
3.
J Am Heart Assoc ; 13(10): e034552, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38726901

RESUMO

BACKGROUND: Fractional flow reserve (FFR) is the ratio of blood pressure measured distal to a stenosis and pressure proximal to a stenosis. FFR can be estimated noninvasively using computed tomography (CT) although the usefulness of this technique remains controversial. This meta-analysis evaluated the agreement of FFR estimated by CT (FFR-CT) with invasively measured FFR. The study also evaluated the diagnostic accuracy of FFR-CT, defined as the ability of FFR-CT to classify lesions as hemodynamically significant (invasive FFR ≤0.8) or insignificant (invasive FFR >0.8). METHODS AND RESULTS: Forty-three studies reporting on 7291 blood vessels from 5236 patients were included. A moderate positive linear relationship between FFR-CT and invasively measured FFR was observed (Spearman correlation coefficient: 0.67). Agreement between the 2 measures increased as invasively measured FFR values approached 1. The overall diagnostic accuracy, sensitivity and specificity of FFR-CT were 82.2%, 80.9%, and 83.1%, respectively. Diagnostic accuracy of 90% could be demonstrated for FFR-CT values >0.90 and <0.49. The diagnostic accuracy of off-site tools was 79.4% and the diagnostic accuracy of on-site tools was 84.1%. CONCLUSIONS: The agreement between FFR-CT and invasive FFR is moderate although agreement is highest in vessels with FFR-CT >0.9. Diagnostic accuracy varies widely with FFR-CT value but is above 90% for FFR-CT values >0.90 and <0.49. Furthermore, on-site and off-site tools have similar performance. Ultimately, FFR-CT may be a useful adjunct to CT coronary angiography as a gatekeeper for invasive coronary angiogram.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Humanos , Estenose Coronária/fisiopatologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/diagnóstico , Angiografia Coronária/métodos , Angiografia por Tomografia Computadorizada/métodos , Valor Preditivo dos Testes , Cateterismo Cardíaco , Reprodutibilidade dos Testes , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X/métodos
4.
Geriatr Nurs ; 57: 217-223, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38696879

RESUMO

INTRODUCTION: This study aimed to examine baseline risk factors in Alzheimer's Disease (AD) and Vascular dementia (VaD) patients with neuropsychiatry symptoms (NPS), and determine whether specific risk factors differ by subtypes of dementia for AD and VaD patients with NPS. METHODS: A retrospective data analysis was conducted to evaluate similarities and differences in the risk factors for AD and VaD with NPS. The analysis included 2949 patients with VaD and 6341 patients with clinical confirmation of AD and VaD with or without NPS collected between February 2016 and August 2021. The multivariate logistic regression analysis was used to determine the risk factors associated with AD and VaD with NPS, by predicting the increasing odds (odds ratios (ORs) of an association of a specific baseline risk factor with AD or VaD with NPS. The validity of the regression models was tested using a Hosmer-Lemeshow test, while the Receiver Operating Curve (ROC) was used to test the sensitivity of the models. RESULTS: In the adjusted analysis TSH (OR = 1.781, 95 % CI, p = 0.0025) and CHF (OR = 1.620, 95 %, p = 0.016) were associated with VaD with NPS, while a history of emergency department(ED) admission (OR = 0.277, 95 % CI, p = 0.003) likely to be associated with VaD patients without NPS. For AD patients, a history of CVA (OR = 1.395, 95 % CI, p = 0.032) and cancer (OR = 1.485, 95 % CI, p = 0.013) were associated with AD patients with NPS. DISCUSSION: The findings of this study indicate that an abnormal thyroid gland and CHF were linked to VaD patients with behavioral disturbances, while CVA and cancer were linked to AD patients with behavioral disturbances. These findings suggest the need to develop management strategies for the care of patients with AD and VaD with NPS.


Assuntos
Doença de Alzheimer , Comorbidade , Demência Vascular , Humanos , Doença de Alzheimer/complicações , Masculino , Feminino , Estudos Retrospectivos , Idoso , Fatores de Risco , Idoso de 80 Anos ou mais
5.
Front Oncol ; 14: 1264611, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38751808

RESUMO

Cervical cancer is a significant concern for women, necessitating early detection and precise treatment. Conventional cytological methods often fall short in early diagnosis. The proposed innovative Heap Optimizer-based Self-Systematized Neural Fuzzy (HO-SsNF) method offers a viable solution. It utilizes HO-based segmentation, extracting features via Gray-Level Co-Occurrence Matrix (GLCM) and Local Binary Pattern (LBP). The proposed SsNF-based classifier achieves an impressive 99.6% accuracy in classifying cervical cancer cells, using the Herlev Pap Smear database. Comparative analyses underscore its superiority, establishing it as a valuable tool for precise cervical cancer detection. This algorithm has been seamlessly integrated into cervical cancer diagnosis centers, accessible through smartphone applications, with minimal resource demands. The resulting insights provide a foundation for advancing cancer prevention methods.

6.
Neurosci Insights ; 19: 26331055241246745, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38706531

RESUMO

Objective: This study aims to determine sex differences in poststroke hypertriglyceridemia (serum triglyceride levels ⩾ 200 mg/dl) and high stroke severity in ischemic stroke patients. Method: Our study analyzed data from 392 males and 373 females with hypertriglyceridemia. Stroke severity on admission was measured using the National Institute of Health Stroke Scale (NIHSS) with a value ⩽7 indicating a more favorable post-stroke prognosis while a score of >7 indicates poorer post-stroke outcomes. Logistic regression models adjusted for demographic and risk factors. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each clinical risk factor were used to predict the increasing odds of an association of a specific clinical baseline risk factor with the male or female AIS with hypertriglyceridemia. Results: In the adjusted analysis, male patients with hypertriglyceridemia, diastolic blood pressure (OR = 1.100, 95% CI, 1.034-1.171, P = .002), and Ischemic stroke mortality (OR = 6.474, 95% CI, 3.262-12.847, P < .001) were significantly associated with increased stroke severity. In female patients with hypertriglyceridemia, age (OR = 0.920, 95% CI, 0.866-0.978, P = .008) was associated with reduced stroke severity, while ischemic stroke mortality score (OR = 37.477, 95% CI, 9.636-145.756, P < .001) was associated with increased stroke severity. Conclusion: Increased ischemic stroke mortality risk score was associated with increased severity in both male and female AIS patients with hypertriglyceridemia. Our findings provide information about sex differences in specific risk factors that can be managed to improve the care of male and female ischemic stroke patients with hypertriglyceridemia.

7.
Eur Radiol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637427

RESUMO

OBJECTIVE: To assess the clinical impact of regular whole-body magnetic resonance imaging (WBMRI) surveillance in myxoid liposarcoma patients. METHODS: This was a retrospective cohort study of myxoid liposarcoma patients who underwent at least one WBMRI at our institution between October 2006 and December 2020. The effect of WBMRI on clinical management, namely treatment modification or additional diagnostic investigations was studied. A standardised WBMRI surveillance protocol was instituted in 2015. We compared patient outcomes for the metastatic patients who had and had not received regular WBMRI surveillance and performed survival analysis for both subgroups. RESULTS: Of the 56 patients (60.7% male, median age: 48.1 years) who underwent 345 WBMRI, 17 (30.3%) had metastases, and 168 WBMRI were performed in this group. The median imaging follow-up for the entire cohort was 35 months; the metastatic group had a median follow-up of 42 months. WBMRI changed the clinical management in 13 (76.5%) metastatic patients, with 33 instances of treatment modification. Thirty-five lesions were labelled 'indeterminate,' 16 (45.7%) had additional investigations/interventions, and 4 (11.4%) were confirmed to be metastatic. Twenty-one metastatic lesions were missed initially on WBMRI and confirmed on subsequent WBMRI, of which 5 (23.8%) were clinically significant. The 5-year survival since the detection of metastasis was better in the regular surveillance subgroup (85.7% vs. 45%), but this was not statistically significant (p = 0.068). Five patients (8.9%) developed their first metastasis more than 5 years after diagnosing the primary lesion. CONCLUSION: Regular WBMRI surveillance of myxoid liposarcoma patients considerably impacts clinical management by frequently influencing treatment decisions. CLINICAL RELEVANCE STATEMENT: WBMRI has been recently recommended as an imaging option for the staging and surveillance of myxoid liposarcoma patients. Our study highlights the impact of regular WBMRI surveillance on the clinical management of these patients and how it affects their survival.

8.
Clin Appl Thromb Hemost ; 30: 10760296241246264, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38600881

RESUMO

The objective of this study is to determine risk factors that may contribute to exclusion decision from recombinant tissue plasminogen activator (rtPA) in patients with acute ischemic stroke (AIS) with a combined current or history of smoking and obesity. This study was conducted on data from 5469 patients with AIS collected from a regional stroke registry. Risk factors associated with inclusion or exclusion from rtPA were determined using multivariate logistic regression analysis. The adjusted odds ratios and 95% confidence interval for each risk factor were used to predict the increasing odds of an association of a specific risk factor with exclusion from rtPA. In the adjusted analysis, obese patients with AIS with a history of smoking (current and previous) excluded from rtPA were more likely to present with carotid artery stenosis (OR = 0.069, 95% CI 0.011-0.442), diabetes (OR = 0.604, 95% CI 0.366-0.997), higher total cholesterol (OR = 0.975, 95% CI 0.956-0.995), and history of alcohol use (OR = 0.438, 95% CI 0.232-0.828). Higher NIHSS score (OR = 1.051, 95% CI 1.017-1.086), higher triglycerides (OR = 1.004, 95% CI 1.001-1.006), and higher high-density lipoprotein (OR = 1.028, 95% CI 1.000-1.057) were associated with the inclusion for rtPA. Our findings reveal specific risk factors that contribute to the exclusion of patients with AIS with a combined effect of smoking and obesity from rtPA. These findings suggest the need to develop management strategies to improve the use of rtPA for obese patients with AIS with a history of smoking.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Ativador de Plasminogênio Tecidual/uso terapêutico , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/etiologia , Fibrinolíticos/uso terapêutico , Fumar/efeitos adversos , Isquemia Encefálica/etiologia , Isquemia Encefálica/tratamento farmacológico , Terapia Trombolítica/efeitos adversos , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/complicações , Fatores de Risco , Obesidade/complicações , Obesidade/tratamento farmacológico , Resultado do Tratamento
9.
Nutrients ; 16(7)2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38613083

RESUMO

The aim of this systematic review is to comprehensively assess the weight loss (WL) practices in different combat sports (CS). The review protocol was preregistered with PROSPERO [CRD42023487196]. Three databases were searched (Web of Science, EBSCOhost, and PubMed) until 8 December 2023. Eligible studies had to meet five criteria: they must have been (a) written in English, (b) published in a peer-reviewed journal, (c) used a survey design to investigate the WL practices of CS athletes, and (d) reported the WL methods used by athletes using a five-point scale. Twenty-six studies (3994 participants from 14 CS) were included. This review found that (1) WL is highly prevalent in CS athletes; (2) many CS athletes started losing weight for competition as teenagers two to three times a year; (3) CS athletes usually lose <5% body weight in 7-14 days before competition; (4) increasing exercise and gradually dieting are the most commonly used WL methods; and (5) the influence of scientific practitioners on athletes is negligible. The habitual practices of CS athletes may be relatively harmless, but in some special cases, CS athletes also perform extreme WL practices. Scientific practitioners have little influence on their WL practices, which may form a vicious cycle of non-qualified influence.


Assuntos
Atletas , Esportes , Adolescente , Humanos , Triptofano Oxigenase , Bases de Dados Factuais , Redução de Peso
11.
Nutr Clin Pract ; 39 Suppl 1: S17-S28, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38429962

RESUMO

Fat malabsorption is central to the pathophysiology of short bowel syndrome (SBS). It occurs in patients with insufficient intestinal surface area and/or function to maintain metabolic and growth demands. Rapid intestinal transit and impaired bile acid recycling further contribute to fat malabsorption. A significant portion of patients require parenteral nutrition (PN) for their survival but may develop sepsis and liver dysfunction as a result. Despite advancements in the treatment of SBS, fat malabsorption remains a chronic issue for this vulnerable patient population. Peer-reviewed literature was assessed on the topic of fat malabsorption in SBS. Current management of patients with SBS involves dietary considerations, PN management, antidiarrheals, glucagon-like peptide 2 agonists, and multidisciplinary teams. Clinical trials have focused on improving intestinal fat absorption by facilitating fat digestion with pancreatic enzymes. Targeting fat malabsorption in SBS is a potential pathway to improving lifestyle and reducing morbidity and mortality in this rare disease.


Assuntos
Síndrome do Intestino Curto , Humanos , Síndrome do Intestino Curto/complicações , Síndrome do Intestino Curto/terapia , Intestinos , Nutrição Parenteral , Absorção Intestinal , Dieta
12.
Arthroscopy ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38395269

RESUMO

Evidence-based medicine is the commanding philosophy of patient care in the field of orthopaedic surgery, and analysis of clinical research is facilitated by instruments and scales developed for assessing methodologic quality and validity of conclusions. In contrast, little consideration has been given to developing metrics to assess the quality and validity of orthopaedic ex vivo and laboratory research. This is easier said than done because these studies may be heterogeneous and complex in design, and methodologic details may not be intuitive to (non-engineer) readers. The recently described Biomechanics Objective Basic Science Quality Assessment Tool (BOBQAT) represents a reliable means to assess cadaveric biomechanical studies. The BOBQAT emphasizes essential study elements including a clinically relevant, answerable purpose; detailed description of the specimens studied; thorough description of surgical technique; and careful consideration of loading conditions including clinically relevant cyclic loading. The BOBQAT provides a logical recipe for the design of future studies, a mechanism of quality assessment for systematic reviews, and a framework for readers to assess biomechanical research consistent with the ethos of evidence-based medicine.

13.
Int J Lab Hematol ; 46(3): 495-502, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38379463

RESUMO

BACKGROUND: Detection of del(17p) in myeloma is generally performed by fluorescence in situ hybridization (FISH) on a slide with analysis of up to 200 nuclei. The small cell sample analyzed makes this a low precision test. We report the utility of an automated FISH method, called "immuno-flowFISH", to detect plasma cells with adverse prognostic risk del(17p) in bone marrow and blood samples of patients with myeloma. METHODS: Bone marrow (n = 31) and blood (n = 19) samples from 35 patients with myeloma were analyzed using immuno-flowFISH. Plasma cells were identified by CD38/CD138-immunophenotypic gating and assessed for the 17p locus and centromere of chromosome 17. Cells were acquired on an AMNIS ImageStreamX MkII imaging flow cytometer using INSPIRE software. RESULTS: Chromosome 17 abnormalities were identified in CD38/CD138-positive cells in bone marrow (6/31) and blood (4/19) samples when the percent plasma cell burden ranged from 0.03% to 100% of cells. Abnormalities could be identified in 14.5%-100% of plasma cells. CONCLUSIONS: The "immuno-flowFISH" imaging flow cytometric method could detect del(17p) in plasma cells in both bone marrow and blood samples of myeloma patients. This method was also able to detect gains and losses of chromosome 17, which are also of prognostic significance. The lowest levels of 0.009% (bone marrow) and 0.001% (blood) for chromosome 17 abnormalities was below the detection limit of current FISH method. This method offers potential as a new means of identifying these prognostically important chromosomal defects, even when only rare cells are present and for serial disease monitoring.


Assuntos
Cromossomos Humanos Par 17 , Citometria de Fluxo , Hibridização in Situ Fluorescente , Mieloma Múltiplo , Plasmócitos , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Plasmócitos/patologia , Citometria de Fluxo/métodos , Cromossomos Humanos Par 17/genética , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Medula Óssea/patologia , Deleção Cromossômica , Idoso de 80 Anos ou mais , Imunofenotipagem , Adulto
14.
Immunology ; 172(1): 144-162, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38361249

RESUMO

Macrophages expressing group V phospholipase A2 (Pla2g5) release the free fatty acid (FFA) linoleic acid (LA), potentiating lung type 2 inflammation. Although Pla2g5 and LA increase in viral infections, their role remains obscure. We generated Pla2g5flox/flox mice, deleted Pla2g5 by using the Cx3cr1cre transgene, and activated bone marrow-derived macrophages (BM-Macs) with poly:IC, a synthetic double-stranded RNA that triggers a viral-like immune response, known Pla2g5-dependent stimuli (IL-4, LPS + IFNγ, IL-33 + IL-4 + GM-CSF) and poly:IC + LA followed by lipidomic and transcriptomic analysis. Poly:IC-activated Pla2g5flox/flox;Cx3cr1cre/+ BM-Macs had downregulation of major bioactive lipids and critical enzymes producing those bioactive lipids. In addition, AKT phosphorylation was lower in poly:IC-stimulated Pla2g5flox/flox;Cx3cr1cre/+ BM-Macs, which was not restored by adding LA to poly:IC-stimulated BM-Macs. Consistently, Pla2g5flox/flox;Cx3cr1cre/+ mice had diminished poly:IC-induced lung inflammation, including inflammatory macrophage proliferation, while challenging Pla2g5flox/flox;Cx3cr1cre/+ mice with poly:IC + LA partially restored lung inflammation and inflammatory macrophage proliferation. Finally, mice lacking FFA receptor-1 (Ffar1)-null mice had reduced poly:IC-induced lung cell recruitment and tissue macrophage proliferation, not corrected by LA. Thus, Pla2g5 contributes to poly:IC-induced lung inflammation by regulating inflammatory macrophage proliferation and LA/Ffar1-mediated lung cell recruitment and tissue macrophage proliferation.


Assuntos
Ácido Linoleico , Pneumonia , Animais , Camundongos , Proliferação de Células , Interleucina-4/metabolismo , Ácido Linoleico/metabolismo , Pulmão , Macrófagos
15.
Access Microbiol ; 6(1)2024.
Artigo em Inglês | MEDLINE | ID: mdl-38361647

RESUMO

Arbuscular mycorrhizal (AM) fungi have been shown to be associated with an estimated 70 % of vascular terrestrial plants. Such relationships have been shown to be sensitive to soil disturbance, for example, tillage in the preparation of a seed bed. From the application of arable soil management, AM fungal populations have been shown to be negatively impacted in abundance and diversity, reducing plant growth and development. The present study aims to utilise two sources (multipurpose compost and a commercial inocula) of mycorrhizal fungi for the amendment of arable soils supporting Zulu winter wheat under controlled conditions and quantify plant growth responses. A total of nine fields across three participating farms were sampled, each farm practicing either conventional, reduced, or zero tillage soil management exclusively. Soil textures were assessed for each sampled soil. Via the employment of AM fungal symbiosis quantification methods, AM fungi were compared between soil amendments and their effects on crop growth and development. The present study was able to quantify a mean 6 cm increase to crop height (P<0.001), 10 cm reduction to root length corresponding with a 2.45-fold increase in AM fungal arbuscular structures (P<0.001), a 1.15-fold increase in soil glomalin concentration corresponding to a 1.26-fold increase in soil carbon, and a 1.32-fold increase in the relative abundance of molecular identified AM fungal sequences for compost amended soils compared to control samples. Mycorrhizal inocula, however, saw no change to crop height or root length, AM fungal arbuscules were reduced by 1.43-fold, soil glomalin was additionally reduced by 1.55-fold corresponding to a reduction in soil carbon by 1.31-fold, and a reduction to relative AM fungal species abundance by 1.26-fold. The present study can conclude the addition of compost as an arable soil amendment is more beneficial for the restoration of AM fungi beneficial to wheat production and soil carbon compared to the addition of a commercial mycorrhizal inocula.

16.
Sci Rep ; 14(1): 4240, 2024 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378873

RESUMO

Patients with intestinal failure who receive long-term parenteral nutrition (PN) often develop intestinal failure-associated liver disease (IFALD). Although there are identified risk factors, the early pathogenesis is poorly understood and treatment options are limited. Here, we perform a transcriptomic analysis of liver tissue in a large animal IFALD model to generate mechanistic insights and identify therapeutic targets. Preterm Yorkshire piglets were provided PN or bottle-fed with sow-milk replacer for 14 days. Compared to bottle-fed controls, piglets receiving PN developed biochemical cholestasis by day of life 15 (total bilirubin 0.2 vs. 2.9 mg/dL, P = 0.01). RNA-Seq of liver tissue was performed. Ingenuity Pathway Analysis identified 747 differentially expressed genes (343 upregulated and 404 downregulated) with an adjusted P < 0.05 and a fold-change of > |1|. Enriched canonical pathways were identified, demonstrating broad activation of inflammatory pathways and inhibition of cell cycle progression. Potential therapeutics including infliximab, glucocorticoids, statins, and obeticholic acid were identified as predicted upstream master regulators that may reverse the PN-induced gene dysregulation. The early driver of IFALD in neonates may be inflammation with an immature liver; identified therapeutics that target the inflammatory response in the liver should be investigated as potential treatments.


Assuntos
Enteropatias , Insuficiência Intestinal , Hepatopatias , Falência Hepática , Animais , Humanos , Feminino , Suínos , Hepatopatias/genética , Hepatopatias/complicações , Enteropatias/genética , Enteropatias/complicações , Falência Hepática/complicações , Inflamação/genética , Inflamação/complicações
17.
Cell Commun Signal ; 22(1): 30, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212807

RESUMO

Glioblastoma is the most common and aggressive primary brain tumour in adults. The development of anti-brain cancer agents are challenged by the blood-brain barrier and the resistance conferred by the local tumour microenvironment. Heptamethine cyanine dyes (HMCDs) are a class of near-infrared fluorescence compounds that have recently emerged as promising agents for drug delivery. We conjugated palbociclib, a cyclin-dependent kinase (CDK) 4/6 inhibitor, to an HMCD, MHI-148, and conducted drug activity analysis on primary patient-derived glioblastoma cell lines. In addition to the expected cytostatic activity, our in vitro studies revealed that palbociclib-MHI-148 conjugate resulted in an almost 100-fold increase in cytotoxicity compared to palbociclib alone. This shift of palbociclib from cytostatic to cytotoxic when conjugated to MHI-148 was due to increased DNA damage, as indicated by an increase in γH2AX foci, followed by an increased expression of key extrinsic apoptosis genes, including TP53, TNFR1, TRAIL, FADD and caspase 8. In addition, we observed a time-dependent increase in the cell surface expression of TNFR1, consistent with an observed increase in the secretion TNFα, followed by TNFR1 endocytosis at 48 h. The treatment of patient GBM cells with the palbociclib-MHI-148 conjugate prevented TNFα-induced NFκB translocation, suggesting conjugate-induced TNFR1 signalling favoured the TNFR1-mediated apoptotic response rather than the pro-inflammatory response pathway. Notably, pharmacological inhibition of endocytosis of TNFR1, and siRNA-knockdown of TNFR1 reversed the palbociclib-MHI-148-induced cell death. These results show a novel susceptibility of glioblastoma cells to TNFR1-dependent apoptosis, dependent on inhibition of canonical NFκB signalling using our previously reported palbociclib-HMCD conjugate. Video Abstract.


Assuntos
Antineoplásicos , Carbocianinas , Citostáticos , Glioblastoma , Indóis , Piperazinas , Piridinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Apoptose , Linhagem Celular Tumoral , Citostáticos/farmacologia , Citostáticos/uso terapêutico , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Receptores do Fator de Necrose Tumoral/fisiologia , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Microambiente Tumoral , Fator de Necrose Tumoral alfa/metabolismo
18.
Arthroscopy ; 40(3): 919-921, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38219104

RESUMO

Osteochondral lesions of the ankle are common, but only a small proportion of these lesions are found on the tibial plafond (osteochondral lesions of the tibial plafond, ie, OLTP). By and large, surgical treatment strategies for OLTP have been derived from techniques employed for those of the talus (ie, osteochondral lesion of the talus). Despite the clinical success of surgical treatments for osteochondral lesion of the talus, namely bone marrow stimulation, it is quite possible that OLTP may not respond similarly, given the unique anatomy and biomechanical properties of the tibia. To this end, the literature surrounding OLTP is relatively sparse, and studies evaluating the clinical and radiographic outcomes of treatments specific to OLTP are necessary. Still, if it works for the talus, it seems sensible that it could work for the plafond. Pending future research, there is no need to reinvent the wheel.


Assuntos
Tálus , Tíbia , Humanos , Tíbia/cirurgia , Medula Óssea , Tálus/cirurgia , Tálus/patologia , Transplante Autólogo , Articulação do Tornozelo/cirurgia , Articulação do Tornozelo/patologia
19.
Matern Child Health J ; 28(2): 274-286, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37943397

RESUMO

OBJECTIVES: The COVID-19 pandemic has had significant impacts on maternal mental health. We explored the lived experiences of women with perinatal depression and anxiety to elucidate their perceptions of how the pandemic influenced their mental health and access to care. METHODS: We conducted a qualitative descriptive study using semi-structured interviews. From March to October 2021, purposive sampling was used to recruit a socio-demographically diverse sample of women with self-reported perinatal depression or anxiety who were pregnant or within one year postpartum between March 2020 and October 2021. Interviews were conducted remotely and thematically analyzed. RESULTS: Fourteen women were interviewed. Three major themes arose. Theme 1, Negative impacts of COVID-19 on symptoms of depression and anxiety, described how the pandemic magnified underlying symptoms of depression and anxiety, increased social isolation, generated anxiety due to fears of COVID-19 infection, and caused economic stress. In theme 2, Negative impacts of COVID-19 on access to and quality of health care, women described stressful and isolating delivery experiences, negative psychological impact of partners not being able to participate in their perinatal health care, interruptions and barriers to mental health treatment, and challenges in using telehealth services for mental health care. Theme 3, Positive impacts of COVID-19 on mental health, identified advantages of increased telehealth access and ability to work and study from home. CONCLUSIONS FOR PRACTICE: The COVID-19 pandemic negatively affected women with perinatal depression and anxiety by magnifying underlying symptoms, increasing stress and social isolation, and disrupting access to mental health care. Findings provide support for policies and interventions to prevent and address social isolation, as well as optimization of telehealth services to prevent and address gaps in perinatal mental health treatment.


Assuntos
COVID-19 , Gravidez , Feminino , Humanos , COVID-19/epidemiologia , Pandemias , Depressão/epidemiologia , Depressão/etiologia , Ansiedade/epidemiologia , Transtornos de Ansiedade
20.
Med Teach ; 46(3): 399-405, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37722805

RESUMO

BACKGROUND: Clinicians encounter patients under legal guardianship. We aimed to assess the knowledge, attitudes and practices (KAP) on legal guardianship in residents. METHODS: A KAP pilot survey about legal guardianship was developed by an interdisciplinary medicine-law-public health team and was distributed via institutional email to internal medicine, psychiatry, and neurology residents in a single academic institution. RESULTS: Of the 172 invited residents, 105 (61%) responded and 102 surveys were included in the final analysis. Most respondents (58% women; internal medicine 73%, neurology 15%, psychiatry 12%) had attended 42 medical schools from 16 countries and had heard about guardianship (88%), but only 23% reported having received training on guardianship during medical school or residency. The vast majority (97%) understood the intended benefit of guardianship, but only 22.5% reported knowing that guardianship removed an individual's decision-making rights. Nearly half (47%) of respondents reported never having asked for documentation to prove that an individual was a patient's guardian, and only 15% expected to see a court order as proof of guardianship status. CONCLUSIONS: Although most residents intuitively understood the intended benefit of guardianship, they did not understand its full implications for clinical practice. Training interventions are warranted.


Assuntos
Médicos , Psiquiatria , Humanos , Feminino , Masculino , Conhecimentos, Atitudes e Prática em Saúde , Tutores Legais , Saúde Pública
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