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1.
Can J Urol ; 31(2): 11840-11846, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38642462

RESUMO

INTRODUCTION: There are multiple historic reports linking lower urinary tract symptoms (LUTS) in children with food allergies (FA), but contemporary studies are sparse. The objective of this study was to evaluate a potential link between FA and LUTS in the pediatric population. We hypothesized that children with FAs are more likely to have LUTS. MATERIALS AND METHODS: After local IRB approval, pediatric patients (6-17 years [y]) with FAs proven by positive skin prick and/or serum IgE testing were invited to participate. A control group of pediatric patients without FAs was also recruited. All families/legal guardians signed informed consent, and all children signed written assent. Each participant filled out the Vancouver Symptom Score (VSS), a validated questionnaire for dysfunctional elimination syndrome, and the Pediatric Incontinence Questionnaire (PinQ), a validated quality of life assessment for children with bladder dysfunction. Demographic and clinical information were obtained retrospectively. RESULTS: From 2019-2020, 26 children with FAs and 57 without agreed to participate. Mean age was 9.3 y (IQR 7.9 y-13.5 y). There were no differences in gender, age, or race between the two cohorts. There were no significant differences between the two groups in mean VSS score or mean PinQ score. Four children with FAs (15%) and 15 children without (26%) had VSS score ≥ 11 (p = 0.339), indicating dysfunctional elimination. The median PinQ score was 0 (IQR 0-2) in both cohorts. CONCLUSIONS: This study did not identify an association between FAs and LUTS in a population of pediatric patients with laboratory proven FAs.


Assuntos
Hipersensibilidade Alimentar , Sintomas do Trato Urinário Inferior , Incontinência Urinária , Humanos , Criança , Estudos de Casos e Controles , Qualidade de Vida , Estudos Retrospectivos , Sintomas do Trato Urinário Inferior/diagnóstico , Incontinência Urinária/complicações , Inquéritos e Questionários , Hipersensibilidade Alimentar/complicações
2.
Med Teach ; : 1-2, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564808

RESUMO

Generation Z students can be challenging. The Internet, the Covid-19 epidemic, its political aftermath, and the substantial online educational content they have been required to endure, has left them with a perspective towards a work-life balance to which we older, more experienced faculty are not accustomed. Here, I give caution and guidance to my colleagues regarding their interactions with this cohort through my reading of the Hippocratic corpus.

3.
Res Sq ; 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38559235

RESUMO

BACKGROUND: The global setback in tuberculosis (TB) prevalence and mortality in the post-COVID-19 era have been partially attributed to pandemic-related disruptions in healthcare systems. The additional biological contribution of COVID-19 to TB is less clear. The goal of this study was to determine if there is an association between COVID-19 in the past 18 months and a new TB episode, and the role played by type 2 diabetes mellitus (DM) comorbidity in this relationship. METHODS: A cross-sectional study was conducted among 112 new active TB patients and 373 non-TB controls, identified between June 2020 and November 2021 in communities along the Mexican border with Texas. Past COVID-19 was based on self-report or positive serology. Bivariable/multivariable analysis were used to evaluate the odds of new TB in hosts with past COVID-19 and/or DM status. RESULTS: The odds of new TB were higher among past COVID-19 cases vs. controls, but only significant among DM patients (aOR 2.3). The odds of TB given DM was 2.7-fold among participants without past COVID-19 and increased to 7.9-fold among those with past COVID-19. CONCLUSION: DM interacts with past COVID-19 synergistically to magnify the risk of TB. Latent TB screening and prophylactic treatment, if positive, is recommended in this COVID-19/DM/latent TB high-risk group.

4.
J R Soc Interface ; 21(213): 20230659, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38565158

RESUMO

The flow of cerebrospinal fluid (CSF) along perivascular spaces (PVSs) is an important part of the brain's system for clearing metabolic waste. Astrocyte endfeet bound the PVSs of penetrating arteries, separating them from brain extracellular space. Gaps between astrocyte endfeet might provide a low-resistance pathway for fluid transport across the wall. Recent studies suggest that the astrocyte endfeet function as valves that rectify the CSF flow, producing the net flow observed in pial PVSs by changing the size of the gaps in response to pressure changes. In this study, we quantify this rectification based on three features of the PVSs: the quasi-circular geometry, the deformable endfoot wall, and the pressure oscillation inside. We provide an analytical model, based on the thin-shell hoop-stress approximation, and predict a pumping efficiency of about 0.4, which would contribute significantly to the observed flow. When we add the flow resistance of the extracellular space (ECS) to the model, we find an increased net flow during sleep, due to the known increase in ECS porosity (decreased flow resistance) compared to that in the awake state. We corroborate our analytical model with three-dimensional fluid-solid interaction simulations.


Assuntos
Sistema Glinfático , Sistema Glinfático/fisiologia , Encéfalo/irrigação sanguínea , Artérias/fisiologia , Pressão , Transporte Biológico , Líquido Cefalorraquidiano/metabolismo
5.
J Orthop ; 52: 129-132, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38596621

RESUMO

Objectives: The purpose of this study is to evaluate the outcomes of operatively treated Mason Type III radial head fractures. Additionally, this project seeks to assess efficacy of PROMIS in evaluating post-operative outcomes for this patient population. Methods: A total of 143 patients who underwent operative treated Mason Type III radial head fractures were analyzed retrospectively. PROMIS physical function (PF), PROMIS upper extremity (UE), PROMIS pain interference (PI), demographic variables, and range of motion were collected and analyzed over 12-month follow-up. Results: Radial head arthroplasty (RHA) was performed on 89 patients, open reduction and internal fixation (ORIF) was performed on 47 patients, and radial head excision was performed on 7 patients. Among the RHA patients, PROMIS PF, PI and UE demonstrated a change of -1.33 (p < 0.05), -1.48 (p < 0.05), and 2.23 (p < 0.05) respectively from injury to 12-months. Among the ORIF patients, PROMIS PF, PI and UE demonstrated a change of 3.22 (p < 0.05), -1.56 (p < 0.05), and 2.09 (p < 0.05) respectively from injury to 12-months. At the pre-operative and 12-month visits, the RHA group demonstrated lower PROMIS PF scores 34.75 vs 38.02 (p < 0.05) and 33.42 vs 41.24 (p < 0.05) respectively. Ther was no difference in PROMIS PI, UE, or elbow range of motion between the two groups at 6- or 12-month follow-up (p > 0.05). Conclusion: Comparing the RHA and ORIF groups, there was no difference in PROMIS PI or UE scores nor was there a clinically significant improvement at the 6- or 12-month mark. The ORIF group demonstrated improved PROMIS PF at all follow-up periods and did show a clinically significant improvement. Patient Acceptable Symptom State (PASS) correlated only with PROMIS UE at 6- and 12- months for both groups.

6.
J Biotechnol ; 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38642816

RESUMO

Bioprocess scale-up and technology transfer can be challenging due to multiple variables that need to be optimized during process development from laboratory scale to commercial manufacturing. Cell cultures are highly sensitive to key factors during process transfer across scales, including geometric variability in bioreactors, shear stress from impeller and sparging activity, and nutrient gradients that occur due to increasing blend times. To improve the scale-up and scale-down of these processes, it is important to fully characterize bioreactors to better understand the differences that will occur within the culture environment, especially the hydrodynamic profiles that will vary in vessel designs across scales. In this study, a comprehensive hydrodynamic characterization of the Ambr® 250 mammalian single-use bioreactor was performed using time-accurate computational fluid dynamics simulations conducted with M-Star computational fluid dynamics software, which employs lattice-Boltzmann techniques to solve the Navier-Stokes transport equations at a mesoscopic scale. The single-phase and two-phase fluid properties within this small-scale vessel were analyzed in the context of agitation hydrodynamics and mass transfer (both within the bulk fluid and the free surface) to effectively characterize and understand the differences that scale-down models possess when compared to their large-scale counterparts. The model results validate the use of computational fluid dynamics as an in-silico tool to characterize bioreactor hydrodynamics and additionally identify important free-surface transfer mechanics that need to be considered during the qualification of a scale-down model in the development of mammalian bioprocesses.

7.
Cureus ; 16(2): e53623, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38449952

RESUMO

Acute vision loss is a prevalent clinical manifestation associated with a broad spectrum of differential diagnoses, encompassing demyelinating diseases, neoplastic processes, autoimmune disorders, and infectious conditions. A rare but noteworthy infectious etiology contributing to acute vision loss is neurological Lyme disease (Lyme neuroborreliosis)-induced optic neuritis. Lyme disease, a vector-borne illness caused by the spirochete Borrelia burgdorferi, has the potential to affect multiple physiological systems and unfolds in three distinct stages. Another significant contributor to acute vision loss is giant cell arteritis, an autoimmune vasculitis that commonly affects large- and medium-sized vessels, including the temporal and ophthalmic arteries. This relatively common condition may manifest with symptoms, such as jaw claudication, headaches, and visual disturbances. The precise identification of the underlying cause of acute visual loss is of utmost importance for physicians, as it is instrumental in averting undesirable complications. An 80-year-old female presents to the emergency room with a sudden onset of blurry vision of the left eye, right-sided weakness, dysarthria, jaw pain, headache, and left facial droop. Following consultations with rheumatology and ophthalmology specialists, giant cell arteritis emerged as a primary consideration in the differential diagnosis for the observed vision loss. Subsequently, a temporal artery biopsy was conducted, definitively confirming the diagnosis of giant cell arteritis. Considering the patient's residence in an area endemic to Lyme disease, a Lyme immunoglobulin G (IgG) titer was ordered. The results returned positive, suggesting the presence of Lyme neuroborreliosis.

8.
Cells ; 13(5)2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38474333

RESUMO

A large portion of the heterogeneity in coronavirus disease 2019 (COVID-19) susceptibility and severity of illness (SOI) remains poorly understood. Recent evidence suggests that SARS-CoV-2 infection-associated damage to alveolar epithelial type 2 cells (AT2s) in the distal lung may directly contribute to disease severity and poor prognosis in COVID-19 patients. Our in vitro modeling of SARS-CoV-2 infection in induced pluripotent stem cell (iPSC)-derived AT2s from 10 different individuals showed interindividual variability in infection susceptibility and the postinfection cellular viral load. To understand the underlying mechanism of the AT2's capacity to regulate SARS-CoV-2 infection and cellular viral load, a genome-wide differential gene expression analysis between the mock and SARS-CoV-2 infection-challenged AT2s was performed. The 1393 genes, which were significantly (one-way ANOVA FDR-corrected p ≤ 0.05; FC abs ≥ 2.0) differentially expressed (DE), suggest significant upregulation of viral infection-related cellular innate immune response pathways (p-value ≤ 0.05; activation z-score ≥ 3.5), and significant downregulation of the cholesterol- and xenobiotic-related metabolic pathways (p-value ≤ 0.05; activation z-score ≤ -3.5). Whilst the effect of post-SARS-CoV-2 infection response on the infection susceptibility and postinfection viral load in AT2s is not clear, interestingly, pre-infection (mock-challenged) expression of 238 DE genes showed a high correlation with the postinfection SARS-CoV-2 viral load (FDR-corrected p-value ≤ 0.05 and r2-absolute ≥ 0.57). The 85 genes whose expression was negatively correlated with the viral load showed significant enrichment in viral recognition and cytokine-mediated innate immune GO biological processes (p-value range: 4.65 × 10-10 to 2.24 × 10-6). The 153 genes whose expression was positively correlated with the viral load showed significant enrichment in cholesterol homeostasis, extracellular matrix, and MAPK/ERK pathway-related GO biological processes (p-value range: 5.06 × 10-5 to 6.53 × 10-4). Overall, our results strongly suggest that AT2s' pre-infection innate immunity and metabolic state affect their susceptibility to SARS-CoV-2 infection and viral load.


Assuntos
COVID-19 , Células-Tronco Pluripotentes Induzidas , Humanos , SARS-CoV-2 , Carga Viral , Imunidade Inata , Colesterol
9.
J Hand Surg Glob Online ; 6(1): 58-61, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38313628

RESUMO

Purpose: Perilunate fracture dislocation (PLFD) injuries are associated with the development of acute carpal tunnel syndrome (CTS). The purpose of our study was to identify the factors that increase the likelihood of developing CTS in patients with PLFD. Additionally, we attempted to classify patients who did not initially undergo carpal tunnel release (CTR) at the time of injury but eventually underwent CTR within the follow-up period. Methods: Patients presenting to a level-1 trauma center with isolated PLFDs (Mayfield III-IV) were retrospectively identified by using CPT and ICD-10 codes. Polytraumatized patients, those with a history of previous wrist trauma, or those with previous carpal tunnel symptoms or surgery were excluded. Outcomes of interest included the development of acute CTS, pre- and post-reduction changes in CTS symptoms, and associated hand and wrist fractures. Chi-square tests, Kruskal-Wallis tests, and multivariate logistic regression were used to examine the predictors of developing CTS after a PLFD. Results: In total, 43 patients were included in the final cohort, with a mean age of 44 years, of which 77% were men. The most common fracture of the carpus included scaphoid fractures (9/43, 21%). The average time from presentation to reduction was 636 minutes. Acute CTS symptoms before reduction were present in 26% of the patients and increased post-reduction to 28%. No difference exists between the time to sedation and the presence of acute carpal tunnel symptoms (P >.05). During initial surgical intervention, 79% underwent CTR (27/34). Of the seven patients who did not initially undergo a CTR, 57% (4/7) required a CTR within the follow-up period. Conclusion: Reduction of PLFDs did not significantly improve the number of patients with acute CTS. More than 50% of the patients who did not undergo a CTR at the initial surgery required a CTR within the follow-up period. Type of study/level of evidence: Prognostic III.

10.
J Indian Assoc Pediatr Surg ; 29(1): 19-22, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405251

RESUMO

Aims: Intussusception is a common pediatric surgical emergency and an indicator for primary healthcare. We report our experience with childhood intussusception at a tertiary care hospital in the private sector in Central Kerala and add our refinement to the technique of hydrostatic saline reduction which had more desirable outcome. Settings and Design: Children presenting with the diagnosis of intussusception which were managed in our department of pediatric surgery at a private hospital in Kerala, India. Subjects and Methods: Eighty children, up to 15 years of age, (43 boys, 37 girls) confirmed to have intussusception on ultrasound and managed in our institution from October 2016 to July 2020 with hydrostatic saline reduction. Sixty-two (77%) of them were aged 3 months to 3 years (numbers <10 to be written in words); the age of idiopathic intussusception. Statistical Analysis Used: SPSS V25. Association between variables using Chi square test and independent t test. Results: A total of 80 children met the criteria out of that (n = 79) had successful nonoperative reduction. Hydrostatic saline enema 73, One Barium and five air enema. A child presented in shock was taken up for laparotomy and reduced operatively. Six recurred within 24 h (7% early recurrence) and a second attempt at nonoperative reduction succeeded in all six of them. (numbers <10 in words). Eleven children (14%) had a late recurrence, the attempt at saline hydrostatic reduction was successful in only 3 (27%) and 8 went on to have surgery. Six were successfully reduced operatively and 2 had resection anastomosis. Conclusions: After excluding those who need surgery on clinical grounds, we report a 98.7% success with nonoperative reduction for the first instance of intussusception, a 24 h recurrence of 7%, with successful repeat reductions in all. With the refinement in the technique, we could achieve a desirable outcome. At the first presentation, surgery was indicated in 1 of the 80 children. We report a late recurrence rate of 14%, with a 27% success rate for nonoperative reduction. No pathological lead points were identified even in this group. All the children had an uneventful and a faster recovery. In our series, we had 97.5% follow-up rate.

11.
Brain ; 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38325327

RESUMO

We evaluated whether spike ripples, the combination of epileptiform spikes and ripples, provide a reliable and improved biomarker for the epileptogenic zone (EZ) compared to other leading interictal biomarkers in a multicenter, international study. We first validated an automated spike ripple detector on intracranial EEG recordings. We then applied this detector to subjects from four centers who subsequently underwent surgical resection with known 1-year outcomes. We evaluated the spike ripple rate in subjects cured after resection (ILAE 1 outcome) and those with persistent seizures (ILAE 2-6) across sites and recording types. We also evaluated available interictal biomarkers: spike, spike-gamma, wideband high frequency oscillation (HFO, 80-500 Hz), ripple (80-250 Hz), and fast ripple (250-500 Hz) rates using previously validated automated detectors. The proportion of resected events was computed and compared across subject outcomes and biomarkers. 109 subjects were included. Most spike ripples were removed in subjects with ILAE 1 outcome (P < 0.001), and this was qualitatively observed across all sites and for depth and subdural electrodes (P < 0.001, P < 0.001). Among ILAE 1 subjects, the mean spike ripple rate was higher in the RV (0.66/min) than in the non-removed tissue (0.08/min, P < 0.001). A higher proportion of spike ripples were removed in subjects with ILAE 1 outcomes compared to ILAE 2-6 outcomes (P = 0.06). Among ILAE 1 subjects, the proportion of spike ripples removed was higher than the proportion of spikes (P < 0.001), spike-gamma (P < 0.001), wideband HFOs (P < 0.001), ripples (P = 0.009) and fast ripples (P = 0.009) removed. At the individual level, more subjects with ILAE 1 outcomes had the majority of spike ripples removed (79%, 38/48) than spikes (69%, P = 0.12), spike-gamma (69%, P = 0.12), wideband HFOs (63%, P = 0.03), ripples (45%, P = 0.01), or fast ripples (36%, P < 0.001) removed. Thus, in this large, multicenter cohort, when surgical resection was successful, the majority of spike ripples were removed. Further, automatically detected spike ripples have improved specificity for epileptogenic tissue compared to spikes, spike-gamma, wideband HFOs, ripples, and fast ripples.

12.
PLoS Negl Trop Dis ; 18(2): e0011956, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38359089

RESUMO

BACKGROUND: Chagas disease is caused by the protozoan parasite Trypanosoma cruzi and leads to ~10,000 deaths each year. Nifurtimox and benznidazole are the only two drugs available but have significant adverse effects and limited efficacy. New chemotherapeutic agents are urgently required. Here we identified inhibitors of the acidic M17 leucyl-aminopeptidase from T. cruzi (LAPTc) that show promise as novel starting points for Chagas disease drug discovery. METHODOLOGY/PRINCIPAL FINDINGS: A RapidFire-MS screen with a protease-focused compound library identified novel LAPTc inhibitors. Twenty-eight hits were progressed to the dose-response studies, from which 12 molecules inhibited LAPTc with IC50 < 34 µM. Of these, compound 4 was the most potent hit and mode of inhibition studies indicate that compound 4 is a competitive LAPTc inhibitor, with Ki 0.27 µM. Compound 4 is selective with respect to human LAP3, showing a selectivity index of >500. Compound 4 exhibited sub-micromolar activity against intracellular T. cruzi amastigotes, and while the selectivity-window against the host cells was narrow, no toxicity was observed for un-infected HepG2 cells. In silico modelling of the LAPTc-compound 4 interaction is consistent with the competitive mode of inhibition. Molecular dynamics simulations reproduce the experimental binding strength (-8.95 kcal/mol), and indicate a binding mode based mainly on hydrophobic interactions with active site residues without metal cation coordination. CONCLUSIONS/SIGNIFICANCE: Our data indicates that these new LAPTc inhibitors should be considered for further development as antiparasitic agents for the treatment of Chagas disease.


Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Humanos , Leucil Aminopeptidase/química , Leucil Aminopeptidase/farmacologia , Leucil Aminopeptidase/uso terapêutico , Doença de Chagas/tratamento farmacológico , Descoberta de Drogas , Antiparasitários/uso terapêutico , Tripanossomicidas/uso terapêutico
13.
Sci Adv ; 10(8): eadj2630, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38381813

RESUMO

In semiconductors, exciton or charge carrier diffusivity is typically described as an inherent material property. Here, we show that the transport of excitons among CsPbBr3 perovskite nanocrystals (NCs) depends markedly on how recently those NCs were occupied by a previous exciton. Using transient photoluminescence microscopy, we observe a striking dependence of the apparent exciton diffusivity on excitation laser power that does not arise from nonlinear exciton-exciton interactions or thermal heating. We interpret our observations with a model in which excitons cause NCs to transition to a long-lived metastable configuration that markedly increases exciton transport. The exciton diffusivity observed here (>0.15 square centimeters per second) is considerably higher than that observed in other NC systems, revealing unusually strong excitonic coupling between NCs. The finding of a persistent enhancement in excitonic coupling may help explain other photophysical behaviors observed in CsPbBr3 NCs, such as superfluorescence, and inform the design of optoelectronic devices.

14.
Int J Nurs Stud ; 151: 104690, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38237324

RESUMO

BACKGROUND: Patient safety is threatened when early signs of clinical deterioration are missed or not acted upon. This research began as a clinical-academic partnership established around a shared concern of nursing physical assessment practices on general wards and delayed recognition of clinical deterioration. The outcome was the development of a complex intervention facilitated at the ward level for proactive nursing surveillance. METHODS: The evidence-based nursing core assessment (ENCORE) trial was a pragmatic cluster-randomised controlled trial. We hypothesised that ward intervention would reduce the incidence of patient rescue events (medical emergency team activations) and serious adverse events. We randomised 29 general wards in a 1:2 allocation, across 5 Australian hospitals to intervention (n = 10) and usual care wards (n = 19). Skilled facilitation over 12 months enabled practitioner-led, ward-level practice change for proactive nursing surveillance. The primary outcome was the rate of medical emergency team activations and secondary outcomes were unplanned intensive care unit admissions, on-ward resuscitations, and unexpected deaths. Outcomes were prospectively collected for 6 months following the initial 6 months of implementation. Analysis was at the patient level using generalised linear mixed models to account for clustering by ward. RESULTS: We analysed 29,385 patient admissions to intervention (n = 11,792) and control (n = 17,593) wards. Adjusted models for overall effects suggested the intervention increased the rate of medical emergency team activations (adjusted incidence rate ratio 1.314; 95 % confidence interval 0.975, 1.773), although the confidence interval was compatible with a marginal decrease to a substantial increase in rate. Confidence intervals for secondary outcomes included a range of plausible effects from benefit to harm. However, considerable heterogeneity was observed in intervention effects by patient comorbidity. Among patients with few comorbid conditions in the intervention arm there was a lower medical emergency team activation rate and decreased odds of unexpected death. Among patients with multimorbidity in the intervention arm there were higher rates of medical emergency team activation and intensive care unit admissions. CONCLUSION: Trial outcomes have refined our assumptions about the impact of the ENCORE intervention. The intervention appears to have protective effects for patients with low complexity where frontline teams can respond locally. It also appears to have redistributed medical emergency team activations and unplanned intensive care unit admissions, mobilising higher rates of rescue for patients with multimorbidity. TRIAL REGISTRATION NUMBER: ACTRN12618001903279 (Date of registration: 22/11/2018; First participant recruited: 01/02/2019).


Assuntos
Deterioração Clínica , Humanos , Austrália , Enfermagem Baseada em Evidências , Hospitalização , Hospitais
15.
Fluids Barriers CNS ; 21(1): 7, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212763

RESUMO

BACKGROUND: Perivascular spaces (PVSs) carry cerebrospinal fluid (CSF) around the brain, facilitating healthy waste clearance. Measuring those flows in vivo is difficult, and often impossible, because PVSs are small, so accurate modeling is essential for understanding brain clearance. The most important parameter for modeling flow in a PVS is its hydraulic resistance, defined as the ratio of pressure drop to volume flow rate, which depends on its size and shape. In particular, the local resistance per unit length varies along a PVS and depends on variations in the local cross section. METHODS: Using segmented, three-dimensional images of pial PVSs in mice, we performed fluid dynamical simulations to calculate the resistance per unit length. We applied extended lubrication theory to elucidate the difference between the calculated resistance and the expected resistance assuming a uniform flow. We tested four different approximation methods, and a novel correction factor to determine how to accurately estimate resistance per unit length with low computational cost. To assess the impact of assuming unidirectional flow, we also considered a circular duct whose cross-sectional area varied sinusoidally along its length. RESULTS: We found that modeling a PVS as a series of short ducts with uniform flow, and numerically solving for the flow in each, yields good resistance estimates at low cost. If the second derivative of area with respect to axial location is less than 2, error is typically less than 15%, and can be reduced further with our correction factor. To make estimates with even lower cost, we found that instead of solving for the resistance numerically, the well-known resistance of a circular duct could be scaled by a shape factor. As long as the aspect ratio of the cross section was less than 0.7, the additional error was less than 10%. CONCLUSIONS: Neglecting off-axis velocity components underestimates the average resistance, but the error can be reduced with a simple correction factor. These results could increase the accuracy of future models of brain-wide and local CSF flow, enabling better prediction of clearance, for example, as it varies with age, brain state, and pathological conditions.


Assuntos
Encéfalo , Imageamento Tridimensional , Animais , Camundongos , Encéfalo/irrigação sanguínea , Imageamento Tridimensional/métodos , Hidrodinâmica , Cinética
16.
Environ Sci Process Impacts ; 26(2): 221-232, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990603

RESUMO

Gut probiotic bacteria play a significant role in the host health, immunity, and survival. In aquaculture, changes in the gut microbiome of fishes affect the overall productivity and product quality. In the scenario of growing plastic pollution and associated microplastic prevalence, the current study was designed to investigate the interactions and impact of prepared polystyrene microplastics (PS-MPs) of irregular surface morphology on a probiotic bacteria Bacillus tropicus ACS1, isolated from the gut of Oreochromis mossambicus (commonly called as Tilapia). The cell viability was significantly increased along with changes in bacterial growth kinetics upon exposure to varying concentrations of PS-MPs. The microplastic exposure also increased the production of exopolysaccharides (EPS) and induced slight changes in the IR spectra of the EPS. A peak representing a carbonyl linkage that could be attributed to the glycosidic linkages between sugars disappeared following exposure to higher concentrations of PS-MPs. The interaction between the bacteria and the microplastics was visualized using scanning electron microscopy (SEM) and the colonization of the bacteria with active biofilm formation was observed. The investigation of PS-MP induced oxidative stress in the bacteria revealed the generation of reactive oxygen species (ROS) and increase in anti-oxidant enzyme concentrations, superoxide dismutase (SOD), and catalase. The study provides new insights into the effect of microplastics on gut probiotics of an economically significant aquaculture species.


Assuntos
Bacillus , Probióticos , Tilápia , Animais , Tilápia/metabolismo , Microplásticos/toxicidade , Poliestirenos , Plásticos
17.
Biotechnol Bioeng ; 121(2): 655-669, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38031493

RESUMO

A physics-based model for predicting cell culture fluid properties inside a stirred tank bioreactor with embedded PID controller logic is presented. The model evokes a time-accurate solution to the fluid velocity field and overall volumetric mass transfer coefficient, as well as the ongoing effects of interfacial mass transfer, species mixing, and aqueous chemical reactions. The modeled system also includes a direct coupling between process variables and system control variables via embedded controller logic. Satisfactory agreement is realized between the model prediction and measured bioreactor data in terms of the steady-state operating conditions and the response to setpoint changes. Simulation runtimes are suitable for industrial research and design timescales.


Assuntos
Reatores Biológicos , Oxigênio , Oxigênio/química , Técnicas de Cultura de Células , Simulação por Computador , Concentração de Íons de Hidrogênio
18.
Telemed J E Health ; 30(2): 430-437, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37499094

RESUMO

Purpose: Extension for Community Health Outcomes (ECHO) is a model of continuing medical education meant to connect academic medical center-based specialists with community providers to increase capacity in managing complex health conditions. The purpose of this study was to evaluate the effectiveness of a shortened "bootcamp" ECHO model in increasing participant competence with topics related to transgender and gender diverse (TGD) health care and the impact of "bootcamp" participation on enrollment in an ongoing ECHO series. Methods: An ongoing monthly ECHO series was instituted on topics of TGD health. After 2 years, the team implemented a four-session "bootcamp" for four consecutive weeks during March 2022 to introduce foundational topics for new participants who had joined or were considering joining the ongoing series. Qualitative and quantitative results were collected from self-reported pre-/post-surveys as well as from in-session quizzes. Results: There were 71 participants in the "bootcamp" including health care providers and support staff. Attendees reported a 10.3% increase (p = 0.02) in self-reported comfort providing care to transgender patients. Pre-/post-knowledge improved in areas of health inequities (50% vs. 74% correct pre/post), surgical requirements (33% vs. 74%), and effects of masculinizing (55% vs. 70%) and feminizing (64% vs. 89%) hormone therapy. Prescribing providers reported a significant change across four areas of practice competency. Among 71 "bootcamp" participants, 15 registered for the ongoing program. Conclusion: Use of a "bootcamp" highlights ways to increase participant comfort and knowledge in providing TGD health care in a shortened timeframe and recruit new participants to an ongoing ECHO curriculum.


Assuntos
Minorias Sexuais e de Gênero , Pessoas Transgênero , Humanos , Currículo , Inquéritos e Questionários , Autorrelato
19.
Sleep ; 47(2)2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-37658793

RESUMO

Seminal animal studies demonstrated the role of sleep oscillations such as cortical slow waves, thalamocortical spindles, and hippocampal ripples in memory consolidation. In humans, whether ripples are involved in sleep-related memory processes is less clear. Here, we explored the interactions between sleep oscillations (measured as traits) and general episodic memory abilities in 26 adults with drug-resistant temporal lobe epilepsy who performed scalp-intracranial electroencephalographic recordings and neuropsychological testing, including two analogous hippocampal-dependent verbal and nonverbal memory tasks. We explored the relationships between hemispheric scalp (spindles, slow waves) and hippocampal physiological and pathological oscillations (spindles, slow waves, ripples, and epileptic spikes) and material-specific memory function. To differentiate physiological from pathological ripples, we used multiple unbiased data-driven clustering approaches. At the individual level, we found material-specific cerebral lateralization effects (left-verbal memory, right-nonverbal memory) for all scalp spindles (rs > 0.51, ps < 0.01) and fast spindles (rs > 0.61, ps < 0.002). Hippocampal epileptic spikes and short pathological ripples, but not physiological oscillations, were negatively (rs > -0.59, ps < 0.01) associated with verbal learning and retention scores, with left lateralizing and antero-posterior effects. However, data-driven clustering failed to separate the ripple events into defined clusters. Correlation analyses with the resulting clusters revealed no meaningful or significant associations with the memory scores. Our results corroborate the role of scalp spindles in memory processes in patients with drug-resistant temporal lobe epilepsy. Yet, physiological and pathological ripples were not separable when using data-driven clustering, and thus our findings do not provide support for a role of sleep ripples as trait-like characteristics of general memory abilities in epilepsy.


Assuntos
Epilepsia do Lobo Temporal , Epilepsia , Consolidação da Memória , Memória Episódica , Adulto , Animais , Humanos , Couro Cabeludo , Eletroencefalografia/métodos , Hipocampo/fisiologia , Sono/fisiologia
20.
Evolution ; 78(3): 442-452, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38113239

RESUMO

The largest cells are orders of magnitude bigger than the smallest cells. Organelle content scales to maintain cell function, with different organelles increasing in volume, length, or number as cells increase in size. Scaling may also reflect functional demands placed on organelles by increased cell size. Amphibians exhibit exceptional diversity in cell size. Using transmission electron microscopy, we analyzed 3 species whose enterocyte cell volumes range from 228 to 10,593 µm3. We show that nuclear volume increases by an increase in radius while mitochondrial volume increases by an increase in total network length; the endoplasmic reticulum and Golgi apparatus, with their complex shapes, are intermediate. Notably, all 4 organelle types increase in total volume proportional to cell volume, despite variation in functional (i.e., metabolic, transport) demands. This pattern suggests that organellar building blocks are incorporated into more or larger organelles following the same rules across species that vary ~50-fold in cell sizes, consistent with a "limited precursor" model for organellar scaling that, in turn, assumes equivalent cytoplasmic concentrations of organellar building block proteins. Taken together, our results lead us to hypothesize that salamanders have evolved increased biosynthetic capacity to maintain functional protein concentrations despite huge cell volumes.


Assuntos
Retículo Endoplasmático , Complexo de Golgi , Animais , Retículo Endoplasmático/metabolismo , Complexo de Golgi/metabolismo , Tamanho Celular
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