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1.
Geroscience ; 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38733547

RESUMO

Traumatic brain injury (TBI) is one of the foremost causes of disability and mortality globally. While the scientific and medical emphasis is to save lives and avoid disability during acute period of injury, a severe health problem can manifest years after injury. For instance, TBI increases the risk of cognitive impairment in the elderly. Remote TBI history was reported to be a cause of the accelerated clinical trajectory of Alzheimer's disease-related dementia (ADRD) resulting in earlier onset of cognitive impairment and increased AD-associated pathological markers like greater amyloid deposition and cortical thinning. It is not well understood whether a single TBI event may increase the risk of dementia. Moreover, the cellular signaling pathways remain elusive for the chronic effects of TBI on cognition. We have hypothesized that a single TBI induces sustained neuroinflammation and disrupts cellular communication in a way that results later in ADRD pathology. To test this, we induced TBI in young adult CD1 mice and assessed the behavioral outcomes after 11 months followed by pathological, histological, transcriptomic, and MRI assessment. On MRI scans, these mice showed significant loss of tissue, reduced CBF, and higher white matter injury compared to sham mice. We found these brains showed progressive atrophy, markers of ADRD, sustained astrogliosis, loss of neuronal plasticity, and growth factors even after 1-year post-TBI. Because of progressive neurodegeneration, these mice had motor deficits, showed cognitive impairments, and wandered randomly in open field. We, therefore, conclude that progressive pathology after adulthood TBI leads to neurodegenerative conditions such as ADRD and impairs neuronal functions.

2.
Am J Emerg Med ; 81: 111-115, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38733663

RESUMO

BACKGROUND AND OBJECTIVES: Patient monitoring systems provide critical information but often produce loud, frequent alarms that worsen patient agitation and stress. This may increase the use of physical and chemical restraints with implications for patient morbidity and autonomy. This study analyzes how augmenting alarm thresholds affects the proportion of alarm-free time and the frequency of medications administered to treat acute agitation. METHODS: Our emergency department's patient monitoring system was modified on June 28, 2022 to increase the tachycardia alarm threshold from 130 to 150 and to remove alarm sounds for several arrhythmias, including bigeminy and premature ventricular beats. A pre-post study was performed lasting 55 days before and 55 days after this intervention. The primary outcome was change in number of daily patient alarms. The secondary outcomes were alarm-free time per day and median number of antipsychotic and benzodiazepine medications administered per day. The safety outcome was the median number of patients transferred daily to the resuscitation area. We used quantile regression to compare outcomes between the pre- and post-intervention period and linear regression to correlate alarm-free time with the number of sedating medications administered. RESULTS: Between the pre- and post-intervention period, the median number of alarms per day decreased from 1332 to 845 (-37%). This was primarily driven by reduced low-priority arrhythmia alarms from 262 to 21 (-92%), while the median daily census was unchanged (33 vs 32). Median hours per day free from alarms increased from 1.0 to 2.4 (difference 1.4, 95% CI 0.8-2.1). The median number of sedating medications administered per day decreased from 14 to 10 (difference - 4, 95% CI -1 to -7) while the number of escalations in level of care to our resuscitation care area did not change significantly. Multivariable linear regression showed a 60-min increase of alarm-free time per day was associated with 0.8 (95% CI 0.1-1.4) fewer administrations of sedating medication while an additional patient on the behavioral health census was associated with 0.5 (95% CI 0.0-1.1) more administrations of sedating medication. CONCLUSION: A reasonable change in alarm parameter settings may increase the time patients and healthcare workers spend in the emergency department without alarm noise, which in this study was associated with fewer doses of sedating medications administered.

4.
J Endocr Soc ; 8(6): bvae085, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38745824

RESUMO

Context: Data on germline genetics of pituitary adenomas (PAs) using whole-exome sequencing (WES) are limited. Objective: This study investigated the germline genetic variants in patients with PAs using WES. Methods: We studied 134 consecutive functioning (80.6%) and nonfunctioning (19.4%) PAs in 61 female (45.5%) and 73 male patients (54.5%). Their median age was 34 years (range, 11-85 years) and 31 patients had microadenomas (23.0%) and 103 macroadenomas (77%). None of these patients had family history of PA or a known PA-associated syndrome. Peripheral blood DNA was isolated and whole-exome sequenced. We used American College of Medical Genetics and Genomics (ACMG) criteria and a number of in silico analysis tools to characterize genetic variant pathogenicity levels and focused on previously reported PA-associated genes. Results: We identified 35 variants of unknown significance (VUS) in 17 PA-associated genes occurring in 40 patients (29.8%). Although designated VUS by the strict ACGM criteria, they are predicted to be pathogenic by in silico analyses and their extremely low frequencies in 1000 genome, gnomAD, and the Saudi Genome Project databases. Further analysis of these variants by the Alpha Missense analysis tool yielded 8 likely pathogenic variants in 9 patients in the following genes: AIP:c.767C>T (p.S256F), CDH23:c.906G>C (p.E302D), CDH23:c.1096G>A (p.A366T), DICER1:c.620C>T (p.A207V), MLH1:c.955G>A (p.E319K), MSH2:c.148G>A (p.A50T), SDHA:c.869T>C (p.L290P) and USP48 (2 patients): c.2233G>A (p.V745M). Conclusion: This study suggests that about 6.7% of patients with apparently sporadic PAs carry likely pathogenic variants in PA-associated genes. These findings need further studies to confirm them.

5.
Med Oncol ; 41(6): 140, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38713310

RESUMO

Glioblastoma (GBM) is an extremely aggressive primary brain tumor with poor prognosis, short survival time post-diagnosis and high recurrence. Currently, no cure for GBM exists. The identification of an effective therapeutic modality for GBM remains a high priority amongst medical professionals and researches. In recent studies, inhalant cannabidiol (CBD) has demonstrated promise in effectively inhibiting GBM tumor growth. However, exactly how CBD treatment affects the physiology of these tumor cells remains unclear. Stress granules (SG) (a sub-class of biomolecular condensates (BMC)) are dynamic, membrane-less intracellular microstructures which contain proteins and nucleic acids. The formation and signaling of SGs and BMCs plays a significant role in regulating malignancies. This study investigates whether inhaled CBD may play an intervening role towards SGs in GBM tumor cells. Integrated bioinformatics approaches were preformed to gain further insights. This includes use of Immunohistochemistry and flow cytometry to measure SGs, as well as expression and phosphorylation of eukaryotic initiation factor-2α (eIF2α). The findings of this study reveal that CBD receptors (and co-regulated genes) have the potential to play an important biological role in the formation of BMCs within GBM. In this experiment, CBD treatment significantly increased the volume of TIAR-1. This increase directly correlated with elevation in both eIF2α expression and p-eIF2α in CBD treated tissues in comparison to the placebo group (p < 0.05). These results suggest that inhalant CBD significantly up-regulated SGs in GBM, and thus support a theory of targeting BMCs as a potential therapeutic substrate for treating GBM.


Assuntos
Neoplasias Encefálicas , Canabidiol , Glioblastoma , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Glioblastoma/patologia , Canabidiol/farmacologia , Humanos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Grânulos de Estresse/metabolismo , Grânulos de Estresse/efeitos dos fármacos , Linhagem Celular Tumoral , Fator de Iniciação 2 em Eucariotos/metabolismo
6.
Nat Commun ; 15(1): 3728, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38697991

RESUMO

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.


Assuntos
Neoplasias Encefálicas , Imageamento por Ressonância Magnética , Radiocirurgia , Radiocirurgia/métodos , Humanos , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Melanoma/patologia , Adulto , Resultado do Tratamento , Carga Tumoral , Idoso de 80 Anos ou mais , Falha de Tratamento , Estudos Retrospectivos
7.
Antibiotics (Basel) ; 13(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38666996

RESUMO

Antimicrobial resistance is a global healthcare threat with significant clinical and economic consequences peaking at secondary and tertiary care hospitals where multidrug-resistant Gram-negative bacteria (MDR GNB) lead to poor outcomes. A prospective study was conducted between January and December 2019 for all invasive bloodstream infections (BSIs) secondary to MDR GNB in Qatar identified during routine microbiological service to examine their clinical, microbiological, and genomic characteristics. Out of 3238 episodes of GNB BSIs, the prevalence of MDR GNB was 13% (429/3238). The predominant MDR pathogens were Escherichia coli (62.7%), Klebsiella pneumoniae (20.4%), Salmonella species (6.6%), and Pseudomonas aeruginosa (5.3%), while out of 245 clinically evaluated patients, the majority were adult males, with the elderly constituting almost one-third of the cohort and with highest observed risk for prolonged hospital stays. The risk factors identified included multiple comorbidities, recent healthcare contact, previous antimicrobial therapy, and admission to critical care. The in-hospital mortality rate was recorded at 25.7%, associated with multiple comorbidities, admission to critical care, and the acquisition of MDR Pseudomonas aeruginosa. Resistant pathogens demonstrated high levels of antimicrobial resistance but noticeable susceptibility to amikacin and carbapenems. Genomic analysis revealed that Escherichia coli ST131 and Salmonella enterica ST1 were the predominant clones not observed with other pathogens.

8.
Helminthologia ; 61(1): 11-19, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38659469

RESUMO

This study investigates the presence of Trichuris trichiura eggs in soil samples collected from urban areas in Lahore, Pakistan. A total of 3600 soil samples were collected over two years from Lahore's urban regions. The detection of helminth eggs in these samples was performed using sodium hypochlorite (NaOCl) as a diagnostic technique. The study reveals an overall prevalence rate of T. trichiura at 0.97 % (35 out of 3600) in the contaminated soil samples from Lahore's slum areas. When analyzing the data by geographical areas, the study found the highest prevalence of T. trichiura in Allama Iqbal Town (1.83 %, 11 out of 600), followed by Samanabad (1.16 %, 7 out of 600), Wapda Town (1.00 %, 6 out of 600), Gulberg (1.00 %, 6 out of 600), and Cantt (0.50 %, 3 out of 600). Conversely, Valencia Town had the lowest prevalence rate at 0.33 % (2 out of 600). However, these variations in prevalence rates were not statistically significant (p = 0.117). Prevalence rates of T. trichiura's eggs varied significantly across different sampling seasons (p>0.001). In autumn, a total of 900 soil samples were collected, with 19 samples (2.11 %) testing positive for T. trichiura. This rate was notably higher compared to the prevalence rates observed in winter, spring, and summer, which were 0.66 %, 0.22 %, and 0.88 %, respectively. Regarding the sampling months, the study observed a significantly higher prevalence during September (3.33 %, 10 out of 300), followed by October (2.33 %, 7 out of 300), and August (1.33 %, 4 out of 300). Prevalence rates gradually decreased in other months, ranging from 1 % to 0.33 % (3 to 1 out of 300), with no parasite detection in March (0 %, 0 out of 300) (p < 0.001). This research underscores soil contamination due to fecal waste and highlights public unawareness of parasite biology, driven by open defecation practices.

9.
Sci Rep ; 14(1): 8979, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637638

RESUMO

Losses from catastrophic floods are driving intense efforts to increase preparedness and improve response to disastrous flood events by providing early warnings. Yet accurate flood forecasting remains a challenge due to uncertainty in modeling, calibrating, and validating a useful early warning system. This paper presents the Requisitely Simple (ReqSim) flood forecasting system that includes key variables and processes of basin hydrology and atmospheric forcing in a data-driven modeling framework. The simplicity of the modeling structure and data requirements of the system allows for customization and implementation in any medium to large rain-fed river basin globally, provided there are water level or discharge measurements at the forecast locations. The proposed system's efficacy is demonstrated in this paper through providing useful forecasts for various river basins around the world. This include 3-10-day forecasts for the Ganges and Brahmaputra rivers in South Asia, 2-3-day forecast for the Amur and Yangtze rivers in East Asia, 5-10-day forecasts for the Niger, Congo and Zambezi rivers in West and Central Africa, 6-8-day forecasts for the Danube River in Europe, 2-5-day forecasts for the Parana River in South America, and 2-7-day forecasts for the Mississippi, Missouri, Ohio, and Arkansas rivers in the USA. The study also quantifies the effect of basin size, topography, hydrometeorology, and river flow controls on forecast accuracy and lead times. Results indicate that ReqSim's forecasts perform better in river systems with moderate slopes, high flow persistence, and less flow controls. The simple structure, minimal data requirements, ease of operation, and useful operational accuracy make ReqSim an attractive option for effective real-time flood forecasting in medium and large river basins worldwide.

10.
Radiographics ; 44(5): e230067, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38635456

RESUMO

Artificial intelligence (AI) algorithms are prone to bias at multiple stages of model development, with potential for exacerbating health disparities. However, bias in imaging AI is a complex topic that encompasses multiple coexisting definitions. Bias may refer to unequal preference to a person or group owing to preexisting attitudes or beliefs, either intentional or unintentional. However, cognitive bias refers to systematic deviation from objective judgment due to reliance on heuristics, and statistical bias refers to differences between true and expected values, commonly manifesting as systematic error in model prediction (ie, a model with output unrepresentative of real-world conditions). Clinical decisions informed by biased models may lead to patient harm due to action on inaccurate AI results or exacerbate health inequities due to differing performance among patient populations. However, while inequitable bias can harm patients in this context, a mindful approach leveraging equitable bias can address underrepresentation of minority groups or rare diseases. Radiologists should also be aware of bias after AI deployment such as automation bias, or a tendency to agree with automated decisions despite contrary evidence. Understanding common sources of imaging AI bias and the consequences of using biased models can guide preventive measures to mitigate its impact. Accordingly, the authors focus on sources of bias at stages along the imaging machine learning life cycle, attempting to simplify potentially intimidating technical terminology for general radiologists using AI tools in practice or collaborating with data scientists and engineers for AI tool development. The authors review definitions of bias in AI, describe common sources of bias, and present recommendations to guide quality control measures to mitigate the impact of bias in imaging AI. Understanding the terms featured in this article will enable a proactive approach to identifying and mitigating bias in imaging AI. Published under a CC BY 4.0 license. Test Your Knowledge questions for this article are available in the supplemental material. See the invited commentary by Rouzrokh and Erickson in this issue.


Assuntos
Algoritmos , Inteligência Artificial , Humanos , Automação , Aprendizado de Máquina , Viés
11.
Res Sq ; 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38559131

RESUMO

Schizophrenia is characterized by substantial alterations in brain function, and previous studies suggest insulin signaling pathways, particularly involving AKT, are implicated in the pathophysiology of the disorder. This study demonstrates elevated mRNA expression of AKT1-3 in neurons from schizophrenia subjects, contrary to unchanged or diminished total AKT protein expression reported in previous postmortem studies, suggesting a potential decoupling of transcript and protein levels. Sex-specific differential AKT activity was observed, indicating divergent roles in males and females with schizophrenia. Alongside AKT, upregulation of PDPK1, a critical component of the insulin signaling pathway, and several protein phosphatases known to regulate AKT were detected. Moreover, enhanced expression of the transcription factor FOXO1, a regulator of glucose metabolism, hints at possible compensatory mechanisms related to insulin signaling dysregulation. Findings were largely independent of antipsychotic medication use, suggesting inherent alterations in schizophrenia. These results highlight the significance of AKT and related signaling pathways in schizophrenia, proposing that these changes might represent a compensatory response to a primary defect of conical insulin signaling pathways. This research underscores the need for a detailed understanding of these signaling pathways for the development of effective therapeutic strategies.

12.
ASAIO J ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38569184

RESUMO

Severe right heart failure, often overlooked and challenging to manage, has prompted a growing interest in innovative approaches to provide functional support. This study uses experimentation in large porcine models to introduce a novel prototype of a pulsatile mechanical circulatory support device and document its effects when deployed as a right ventricular assist device (RVAD). The pulsatile ventricular assist platform (pVAP), featuring a membrane pump driven by an intra-aortic balloon pump console, actively generates pulsatile flow to propel right ventricular blood into the pulmonary artery. This novel prototype demonstrates promising potential in addressing the challenges of right heart failure management. After preliminary in vitro assessments, the pVAP was tested on seven porcine models in a healthy state and after the induction of right ventricular failure. During the procedure, a set of standard (ie, standard-of-care) hemodynamic measurements was obtained. Additionally, invasive pressure-volume loop analysis was employed to examine left ventricular hemodynamics. Results indicated that activation of the pVAP during right ventricular failure significantly improved systemic hemodynamics and enhanced left ventricular function. This study sheds light on the potential of the pVAP in managing right heart failure.

13.
Am J Clin Nutr ; 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38685382

RESUMO

BACKGROUND: Environmental enteric dysfunction (EED), a chronic inflammatory condition of the small intestine, is an important driver of childhood malnutrition globally. Quantifying intestinal morphology in EED allows for exploration of its association with functional and disease outcomes. OBJECTIVE: We sought to define morphometric characteristics of childhood EED and determine whether morphology features were associated with disease pathophysiology. METHODS: Morphometric measurements and histology were assessed on duodenal biopsy slides for this cross-sectional study from children with EED in Bangladesh, Pakistan, and Zambia (n=69), and those with no pathologic abnormality (NPA; n=8) or celiac disease (n=18) in North America. Immunohistochemistry was also conducted on 46, 8, and 18 biopsy slides, respectively. Linear mixed-effects regression models were used to reveal morphometric differences between EED compared to NPA or celiac disease, and identify associations between morphometry and histology or immunohistochemistry amongst children with EED. RESULTS: In duodenal biopsies, median EED villus height (248 µm), crypt depth (299 µm), and villus:crypt (V:C) ratio (0.9) values ranged between those of NPA (396 µm villus height; 246 µm crypt depth; 1.6 V:C ratio) and celiac disease (208 µm villus height; 365 µm crypt depth; 0.5 V:C ratio). Among EED biopsy slides, morphometric assessments were not associated with histologic parameters or immunohistochemical markers, other than pathologist determined subjective semi-quantitative villus architecture. CONCLUSIONS: Morphometric analysis of duodenal biopsy slides across geographies identified morphologic features of EED, specifically short villi, elongated crypts, and a smaller V:C ratio relative to NPA slides; although not as severe as in celiac slides. Morphometry did not explain other EED features, suggesting that EED histopathologic processes may be operating independently of morphology. While acknowledging the challenges with obtaining relevant tissue, these data form the basis for further assessments of the role of morphometry in EED.

14.
Endocrine ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38580894

RESUMO

PURPOSE: Long noncoding RNAs (lncRNAs) play an essential role in the epigenetic regulation of various key genes involved in vital cellular functions. A somatic dinucleotide mutation in the lncRNA GAS8-AS1 was reported in Chinese papillary thyroid cancer. However, GAS8-AS1 dinucleotide alteration and its impact have never been explored in differentiated thyroid cancers and other populations. METHODS: We extracted genomic DNA from 265 DTCs and 97 normal healthy subjects, PCR amplified and Sanger sequenced to examine the GAS8-AS1 dinucleotide alteration. Calculated genotype/allele frequency to test Hardy-Weinberg Equilibrium (HWE) and performed a genetic model of inheritance to determine its association with DTC risk. Correlated the GAS8-AS1 dinucleotide variant distribution with clinical characteristics to find the association. Predicted GAS8-AS1 RNA secondary structure for wild type and variant using RemuRNA and RNAfold to assess the conformational changes. RESULTS: GAS8-AS1 dinucleotide alteration (n.713A > G, rs55742939; n.714T > C, rs61118444) identified in DTCs is a germline variant not somatic. The GAS8-AS1 genotype and allele frequency significantly deviated for HWE in DTCs (χ2 = 37.954; p = 0.0001) though not associated with its risk. Dinucleotide variant distribution was remarkably associated with early-stage disease (p = 0.002), lymph node (p = 0.01), and distant metastasis (p = 0.01) in DTCs. The GAS8-AS1 bearing dinucleotide variant markedly showed conformational change compared to that of its wild type. CONCLUSIONS: These findings indicate that GAS8-AS1 is genetically deregulated and implicated in several stages of DTC tumorigenesis suggesting it could be a promising prognostic biomarker in DTCs.

15.
Artigo em Inglês | MEDLINE | ID: mdl-38563578

RESUMO

BACKGROUND: As already proven in the literature, exercise positively affects mental health. However, the question regarding which type of exercise and what limit and time are sufficient to gain the maximum benefit still exists. The current study attempts to answer this question by comparing aerobic and anaerobic exercise in terms of the prevalence of depressive symptoms and their relationship with two different exercise categories. METHODS: Walking, running, and cycling represent forms of aerobic exercise, while resistance training represents anaerobic sport. A total of 680 participants, 428 males and 252 females, met the inclusion criteria. Of those, 368 stated that walking and running was their main form of exercise, while 174 preferred cycling and 138 took part in resistance training. RESULTS: The P value between the aerobic and anaerobic exercise groups in terms of the prevalence of depressive symptoms was 0.8, which is insignificant. This study also found that compliance, number of sessions, and time per session directly affected the prevalence of depressive symptoms. CONCLUSIONS: The results show that all exercise may lead to individuals becoming less prone to depression; there is no advantage to undertaking aerobic exercise over anaerobic exercise. As long as there is good adherence and the appropriate number of sessions and amount of time, individuals should be encouraged to choose their type of exercise according to their needs and preferences.

16.
Nat Commun ; 15(1): 2975, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582938

RESUMO

Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

17.
PLoS Comput Biol ; 20(4): e1011800, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38656994

RESUMO

Biochemical signaling pathways in living cells are often highly organized into spatially segregated volumes, membranes, scaffolds, subcellular compartments, and organelles comprising small numbers of interacting molecules. At this level of granularity stochastic behavior dominates, well-mixed continuum approximations based on concentrations break down and a particle-based approach is more accurate and more efficient. We describe and validate a new version of the open-source MCell simulation program (MCell4), which supports generalized 3D Monte Carlo modeling of diffusion and chemical reaction of discrete molecules and macromolecular complexes in solution, on surfaces representing membranes, and combinations thereof. The main improvements in MCell4 compared to the previous versions, MCell3 and MCell3-R, include a Python interface and native BioNetGen reaction language (BNGL) support. MCell4's Python interface opens up completely new possibilities for interfacing with external simulators to allow creation of sophisticated event-driven multiscale/multiphysics simulations. The native BNGL support, implemented through a new open-source library libBNG (also introduced in this paper), provides the capability to run a given BNGL model spatially resolved in MCell4 and, with appropriate simplifying assumptions, also in the BioNetGen simulation environment, greatly accelerating and simplifying model validation and comparison.


Assuntos
Método de Monte Carlo , Software , Difusão , Simulação por Computador , Modelos Biológicos , Linguagens de Programação , Biologia Computacional/métodos , Transdução de Sinais/fisiologia
18.
World Neurosurg ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38608813

RESUMO

OBJECTIVE: We conducted a systematic review on pediatric intraventricular gliomas to survey the patient population, tumor characteristics, management, and outcomes. METHODS: PubMed, Scopus, Web-of-Science, and Cochrane were searched using PRISMA guidelines to include studies reporting pediatric patients with intraventricular gliomas. RESULTS: A total of 30 studies with 317 patients were included. Most patients were male (54%), diagnosed at a mean age of 8 years (0.2-19), and frequently exhibited headache (24%), nausea and vomiting (21%), and seizures (15%). Tumors were predominantly located in the fourth (48%) or lateral ventricle (44%). Most tumors were WHO grade 1 (68%). Glioblastomas were rarely reported (2%). Management included surgical resection (97%), radiotherapy (27%), chemotherapy (8%), and cerebrospinal fluid diversion for hydrocephalus (38%). Gross total resection was achieved in 59% of cases. Cranial nerve deficit was the most common postsurgical complication (28%) but most were reported in articles published prior to the year 2000 (89%). Newer cases published during or after the year 2000 exhibited significantly higher rates of gross total resection (78% vs. 39%, P < 0.01), lower rates of recurrence (26% vs. 47%, P < 0.01), longer average overall survival time (42 vs. 21 months, P = 0.02), and a higher proportion of patients alive (83% vs. 70%, P = 0.03) than in older cases. CONCLUSIONS: Pediatric intraventricular gliomas correlate with parenchymal pediatric gliomas in terms of age at diagnosis and general outcomes. The mainstay of management is complete surgical excision and more recent studies report longer overall survival rates and less cranial nerve complications.

19.
Neotrop Entomol ; 53(3): 461-468, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38656593

RESUMO

We report the first record of the occurrence of the banana weevil, Cosmopolites sordidus (Germar, 1823) (Coleoptera: Curculionidae), an economically important pest of bananas (Musa spp.), from Fifa Mountains in Saudi Arabia. Moreover, we recorded the first observation of damage caused to bananas by C. sordidus in a banana farm in Jazan Province, southwestern Saudi Arabia, in March 2022. Molecular characterization using DNA sequences of the mitochondrial COI gene confirmed the morphological identification of C. sordidus. This discovery is considered a warning notice to prevent the potential establishment and spread of this dangerous pest in the banana cultivation regions in Saudi Arabia. Therefore, it is recommended that detection and monitoring of banana weevil should be undertaken in Saudi banana farms in order to restrict the dissemination of this weevil to other banana cultivation areas.


Assuntos
Musa , Gorgulhos , Animais , Gorgulhos/classificação , Arábia Saudita , Musa/parasitologia , Feminino , Masculino
20.
Artigo em Inglês | MEDLINE | ID: mdl-38688701

RESUMO

BACKGROUND: Poverty is associated with poor outcomes, yet exposure to distinct poverty trajectories in early childhood is not well understood. OBJECTIVE: To understand the prevalence of different trajectories of household poverty and their association with mid-childhood and mother indicators of physical health and psychopathology in Ireland. METHODS: We used a nationally representative, prospective cohort (Growing Up in Ireland-Infant Cohort). Household poverty included lowest third income decile, subjective poverty and material deprivation when children were aged 9 months, and 3, 5, 9 years. We used group-based multitrajectory cluster modelling to classify trajectories of poverty. Using multivariable logistic regression, adjusted with separate child and mother confounders, we assessed the association of poverty trajectories from 9 months to 9 years with child outcomes (overweight, any longstanding illness and psychopathology) at age 9 years and the same poverty trajectories over the same 9-year period with mother outcomes (overweight, any longstanding illness and depression). RESULTS: Of 11 134 participants, 4 trajectories were identified: never in poverty (43.1%), material/subjective>monetary poverty (16.1%), monetary>material poverty (25.6%) and persistent poverty (15.2%). Children in persistent poverty compared with those in never in poverty experienced higher odds of being overweight at 9 years (adjusted OR (aOR) 1.70, 95% CI 1.34, 2.16), having a longstanding illness (aOR 1.51, 95% CI 1.20, 1.91), and psychopathology (aOR 2.06, 95% CI 1.42, 2.99). The outcomes for primary parents (99.7% were mothers) were as follows: having higher odds of being overweight (aOR 1.49, 95% CI 1.16, 1.92), having a longstanding illness (aOR 2.13, 95% CI 1.63, 2.79), and depression (aOR 3.54, 95% CI 2.54, 4.94). CONCLUSIONS: Any poverty trajectory was associated with poorer psychopathology and physical well-being in late childhood for children and their mothers in Ireland.

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