Modelling Mucus Clearance in Sinuses: Thin-Film Flow Inside a Fluid-Producing Cavity Lined with an Active Surface.

The paranasal sinuses are a group of hollow spaces within the human skull, surrounding the nose. They are lined with an epithelium that contains mucus-producing cells and tiny hairlike active appendages called cilia. The cilia beat constantly to sweep mucus out of the sinus into the nasal cavity, thus maintaining a clean mucus layer within the sinuses. This process, called mucociliary clearance, is essential for a healthy nasal environment and disruption in mucus clearance leads to diseases such as chronic rhinosinusitis, specifically in the maxillary sinuses, which are the largest of the paranasal sinuses. We present here a continuum mathematical model of mucociliary clearance inside the human maxillary sinus. Using a combination of analysis and computations, we study the flow of a thin fluid film inside a fluid-producing cavity lined with an active surface: fluid is continuously produced by a wall-normal flux in the cavity and then is swept out, against gravity, due to an effective tangential flow induced by the cilia. We show that a steady layer of mucus develops over the cavity surface only when the rate of ciliary clearance exceeds a threshold, which itself depends on the rate of mucus production. We then use a scaling analysis, which highlights the competition between gravitational retention and cilia-driven drainage of mucus, to rationalise our computational results. We discuss the biological relevance of our findings, noting that measurements of mucus production and clearance rates in healthy sinuses fall within our predicted regime of steady-state mucus layer development.

Exploring the association between cognitive activity and symptom resolution following concussion in adolescents aged 11-17 years.

OBJECTIVE: As opposed to postconcussion physical activity, the potential influence of cognitive activity on concussion recovery is not well characterised. This study evaluated the intensity and duration of daily cognitive activity reported by adolescents following concussion and examined the associations between these daily cognitive activities and postconcussion symptom duration. METHODS: This study prospectively enrolled adolescents aged 11-17 years with a physician-confirmed concussion diagnosis within 72 hours of injury from the emergency department and affiliated concussion clinics. Participants were followed daily until symptom resolution or a maximum of 45 days postinjury to record their daily cognitive activity (intensity and duration) and postconcussion symptom scores. RESULTS: Participants (n=83) sustained their concussion mostly during sports (84%), had a mean age of 14.2 years, and were primarily male (65%) and white (72%). Participants reported an average of 191 (SD=148), 166 (SD=151) and 38 (SD=61) minutes of low-intensity, moderate-intensity and high-intensity daily cognitive activity postconcussion while still being symptomatic. Every 10 standardised minutes per hour increase in moderate-intensity or high-intensity cognitive activities postconcussion was associated with a 22% greater rate of symptom resolution (adjusted hazard ratio (aHR) 1.22, 95% CI 1.01 to 1.47). Additionally, each extra day's delay in returning to school postconcussion was associated with an 8% lower rate of symptom resolution (aHR 0.92, 95% CI 0.85 to 0.99). CONCLUSION: In adolescents with concussion, more moderate-high intensity cognitive activity is associated with faster symptom resolution, and a delayed return to school is associated with slower symptom resolution. However, these relationships may be bidirectional and do not necessarily imply causality. Randomised controlled trials are needed to determine if exposure to early cognitive activity can promote concussion recovery in adolescents.

Pituitary adenylate cyclase-activating polypeptide receptor activation in the hypothalamus recruits unique signaling pathways involved in energy homeostasis.

Pituitary adenylate cyclase activating polypeptide (PACAP) exerts pleiotropic effects on ventromedial nuclei (VMN) of the hypothalamus and its control of feeding and energy expenditure through the type I PAC1 receptor (PAC1R). However, the endogenous role of PAC1Rs in the VMN and the downstream signaling responsible for PACAP's effects on energy balance are unknown. Numerous studies have revealed that PAC1Rs are coupled to both Gαs/adenylyl cyclase/protein kinase A (Gαs/AC/PKA) and Gαq/phospholipase C/protein kinase C (Gαq/PLC/PKC), while also undergoing trafficking following stimulation. To determine the endogenous role of PAC1Rs and downstream signaling that may explain PACAP's pleiotropic effects, we used RNA interference to knockdown VMN PAC1Rs and pharmacologically inhibited PKA, PKC, and PAC1R trafficking. Knocking down PAC1Rs increased meal sizes, reduced total number of meals, and induced body weight gain. Inhibition of either PKA or PKC alone in awake male Sprague-Dawley rats, attenuated PACAP's hypophagic and anorectic effects during the dark phase. However, PKA or PKC inhibition potentiated PACAP's thermogenic effects during the light phase. Analysis of locomotor activity revealed that PKA inhibition augmented PACAP's locomotor effects, whereas PKC inhibition had no effect. Finally, PACAP administration in the VMN induces surface PAC1R trafficking into the cytosol which was blocked by endocytosis inhibitors. Subsequently, inhibition of PAC1R trafficking into the cytosol attenuated PACAP-induced hypophagia. These results revealed that endogenous PAC1Rs uniquely engage PKA, PKC, and receptor trafficking to mediate PACAP's pleiotropic effects in VMN control of feeding and metabolism.NEW & NOTEWORTHY Endogenous PAC1 receptors, integral to VMN management of feeding behavior and body weight regulation, uniquely engage PKA, PKC, and receptor trafficking to mediate the hypothalamic ventromedial nuclei control of feeding and metabolism. PACAP appears to use different signaling mechanisms to regulate feeding behavior from its effects on metabolism.

Biofilms at interfaces: microbial distribution in floating films.

Cellular motility is a key function guiding microbial adhesion to interfaces, which is the first step in the formation of biofilms. The close association of biofilms and bioremediation has prompted extensive research aimed at comprehending the physics of microbial locomotion near interfaces. We study the dynamics and statistics of microorganisms in a 'floating biofilm', i.e., a confinement with an air-liquid interface on one side and a liquid-liquid interface on the other. We use a very general mathematical model, based on a multipole representation and probabilistic simulations, to ascertain the spatial distribution of microorganisms in films of different viscosities. Our results reveal that microorganisms can be distributed symmetrically or asymmetrically across the height of the film, depending on their morphology and the ratio of the film's viscosity to that of the fluid substrate. Long-flagellated, elongated bacteria exhibit stable swimming parallel to the liquid-liquid interface when the bacterial film is less viscous than the underlying fluid. Bacteria with shorter flagella on the other hand, swim away from the liquid-liquid interface and accumulate at the free surface. We also analyze microorganism dynamics in a flowing film and show how a microorganism's ability to resist 'flow-induced-erosion' from interfaces is affected by its elongation and mode of propulsion. Our study generalizes past efforts on understanding microorganism dynamics under confinement by interfaces and provides key insights on biofilm initiation at liquid-liquid interfaces.

Hydrodynamics-mediated trapping of micro-swimmers near drops.

In this paper, we investigate the swimming characteristics and dynamics of a model micro-swimmer in the vicinity of a clean drop, and of a surfactant covered drop. We model the swimmer as a force dipole and utilize the image-singularity system to study the dynamical behavior of the swimmer. Motivated by bacterial bio-remediation of insoluble hydrocarbons (HCs) released during oil spills, we report the 'trapping characteristics' - critical trapping radius, basin of attraction and trapping time distribution - of deterministic and stochastic swimmers, as a function of viscosity ratio, and dimensionless surface viscosity. We find that addition of surfactant reduces the critical trapping radius of a drop by ∼30%. The basin of attraction though, is not affected acutely for any combination in the parameter space of viscosity ratio and surface viscosity. We also carry out a dynamical system analysis of our problem, for deterministic swimmers, to clarify the aforementioned concepts. For hydrodynamics combined with diffusion based motion, we note increments ranging from ∼5-25% in the interface-retention times of surfactant-laden drops, as compared to clean drops. These differences occur for low values of surface viscosity, and saturate rapidly as the surface viscosity increases. With potential applications in bioremediation, our results highlight the importance of considering dispersant-addition in oil spills involving insoluble hydrocarbons.

Modeling of active swimmer suspensions and their interactions with the environment.

In this article, we review mathematical models used to study the behaviour of suspensions of micro-swimmers and the accompanying biophysical phenomena, with specific focus on stimulus response. The methods discussed encompass a range of interactions exhibited by the micro-swimmers; including passive hydrodynamic (gyrotaxis) and gravitational (gravitaxis) effects, and active responses to chemical cues (chemotaxis) and light intensities (phototaxis). We introduce the simplest models first, and then build towards more sophisticated recent developments, in the process, identifying the limitations of the former and the new results obtained by the latter. We comment on the accuracy/validity of the models adopted, based on the agreement between theoretical results and experimental observations. We conclude by identifying some of the open problems and associated challenges faced by researchers in the realm of active suspensions.

Natural convection in the cytoplasm: Theoretical predictions of buoyancy-driven flows inside a cell.

The existence of temperature gradients within eukaryotic cells has been postulated as a source of natural convection in the cytoplasm, i.e. bulk fluid motion as a result of temperature-difference-induced density gradients. Recent computations have predicted that a temperature differential of ΔT ≈ 1 K between the cell nucleus and the cell membrane could be strong enough to drive significant intracellular material transport. We use numerical computations and theoretical calculations to revisit this problem in order to further understand the impact of temperature gradients on flow generation and advective transport within cells. Surprisingly, our computations yield flows that are an order of magnitude weaker than those obtained previously for the same relative size and position of the nucleus with respect to the cell membrane. To understand this discrepancy, we develop a semi-analytical solution of the convective flow inside a model cell using a bi-spherical coordinate framework, for the case of an axisymmetric cell geometry (i.e. when the displacement of the nucleus from the cell centre is aligned with gravity). We also calculate exact solutions for the flow when the nucleus is located concentrically inside the cell. The results from both theoretical analyses agree with our numerical results, thus providing a robust estimate of the strength of cytoplasmic natural convection and demonstrating that these are much weaker than previously predicted. Finally, we investigate the ability of the aforementioned flows to redistribute solute within a cell. Our calculations reveal that, in all but unrealistic cases, cytoplasmic convection has a negligible contribution toward enhancing the diffusion-dominated mass transfer of cellular material.

Headgear use in girls' lacrosse-stakeholders not ready for change.

Purpose: Mandating headgear for field players in girls' lacrosse to reduce head injuries, including concussion, has been heavily debated. However, research regarding the need and effectiveness of mandated headgear use in girls' lacrosse is still developing. Therefore, this qualitative study aimed to identify the need for and barriers to the development of mandated headgear use policies in girls' lacrosse in Ohio. Methods: We conducted six virtual focus groups, three with concussion experts (clinicians and researchers) and three with girls' lacrosse stakeholders (high school players, parents, coaches, and officials). A focus group guide was developed to explore study participants' perceptions and opinions on concussion in girls' lacrosse, headgear use among players, and policies and policy development related to headgear use or a headgear mandate. We developed the codebook using an inductive and iterative approach based on focus group transcripts and used ATLAS.TI to code and analyze the transcript data. Results: Concussion experts and stakeholders understood the potential consequences of concussion but did not perceive concussion as a pervasive problem in girls' lacrosse. The prevention of head and facial injuries was regarded as a potential benefit of headgear use. However, stakeholders expressed that the myriad of arguments discussed opposing mandated headgear use including increased aggressive play and/or targeting, concerns over changes in the game, and cost strongly outweighed the benefits. Finally, both concussion experts and stakeholders identified multiple organizations, including USA Lacrosse, who could act as facilitators and/or barriers to developing, enacting, and implementing headgear policies. Conclusions: Concussion experts and stakeholders identified possible reasons for headgear use related to injury prevention but also identified several important barriers to the development of a headgear mandate for girls' lacrosse in Ohio.

Grape Polyphenols May Prevent High-Fat Diet-Induced Dampening of the Hypothalamic-Pituitary-Adrenal Axis in Male Mice.

Context : Chronic high-fat diet (HFD) consumption causes obesity associated with retention of bile acids (BAs) that suppress important regulatory axes, such as the hypothalamic-pituitary-adrenal axis (HPAA). HFD impairs nutrient sensing and energy balance due to a dampening of the HPAA and reduced production and peripheral metabolism of corticosterone (CORT). Objective: We assessed whether proanthocyanidin-rich grape polyphenol (GP) extract can prevent HFD-induced energy imbalance and HPAA dysregulation. Methods: Male C57BL6/J mice were fed HFD or HFD supplemented with 0.5% w/w GPs (HFD-GP) for 17 weeks. Results: GP supplementation reduced body weight gain and liver fat while increasing circadian rhythms of energy expenditure and HPAA-regulating hormones, CORT, leptin, and PYY. GP-induced improvements were accompanied by reduced mRNA levels of Il6, Il1b, and Tnfa in ileal or hepatic tissues and lower cecal abundance of Firmicutes, including known BA metabolizers. GP-supplemented mice had lower concentrations of circulating BAs, including hydrophobic and HPAA-inhibiting BAs, but higher cecal levels of taurine-conjugated BAs antagonistic to farnesoid X receptor (FXR). Compared with HFD-fed mice, GP-supplemented mice had increased mRNA levels of hepatic Cyp7a1 and Cyp27a1, suggesting reduced FXR activation and more BA synthesis. GP-supplemented mice also had reduced hepatic Abcc3 and ileal Ibabp and Ostß, indicative of less BA transfer into enterocytes and circulation. Relative to HFD-fed mice, CORT and BA metabolizing enzymes (Akr1d1 and Srd5a1) were increased, and Hsd11b1 was decreased in GP supplemented mice. Conclusion: GPs may attenuate HFD-induced weight gain by improving hormonal control of the HPAA and inducing a BA profile with less cytotoxicity and HPAA inhibition, but greater FXR antagonism.

Malignant ameloblastoma: concurrent presentation of primary and distant disease and review of the literature.

Malignant ameloblastoma is a rare tumor of odontogenic origin with a metastatic focus. Distant metastatic disease is found most commonly in the lungs. A review of the literature shows that most cases of malignant ameloblastoma involve a disease-free period from primary tumor extirpation to the discovery of metastasis. This report describes the case of a 56-year-old man presenting with ameloblastoma of the maxilla and a solitary pulmonary metastasis concurrently. This represents a rare case in which there is a simultaneous diagnosis of primary ameloblastoma and a metastatic lesion. Appropriate workup for ameloblastoma includes surveillance for metastatic disease. Surgical resection of primary and distant disease is recommended. Chemotherapy and radiation may play a role in palliation when resection of metastatic disease is not feasible.

Epistaxis After Orthognathic Surgery: Literature Review and Three Case Studies.

Study Design: This is a literature review with 3 case studies. Objective: Intraoperative and postoperative bleeding are the most common complications of orthognathic surgery and have the potential to become life-threatening. The rarity of severe postoperative epistaxis has resulted in limited characterization of these cases in the literature. The purpose of this study is to 1) differentiate various presentations of epistaxis following orthognathic surgery in the literature, 2) identify management approaches, and 3) to synthesize a treatment algorithm to guide future management of postoperative epistaxis. Methods: A literature search of PubMed was conducted and 28 cases from 17 studies were assessed. Results: Bleeding within the first week may indicate isolated epistaxis, often resolved with local tamponade. Half of cases were attributed to pseudoaneurysm rupture (n = 14), with epistaxis onset ranging from postoperative day 6 to week 9. Angiography was used in most cases (n = 17), often as the primary imaging modality (n = 11). Nasal endoscopy is a less invasive and effective alternative to angiography with embolization. Proximal vessel ligation was used in 3 cases but is not preferred because collaterals may reconstitute flow through the defect and cause rebleeding. Repeat maxillary down-fracture with surgical exploration was described in 4 cases. Conclusions: As outlined in our management algorithm, nasal packing and tamponade should be followed by either local electrocautery or vascular imaging. Angiography with embolization is the preferred approach to diagnosis and management, whereas surgical intervention is reserved for cases of embolization failure or unavailability.

Hydrodynamic Interaction Enhances Colonization of Sinking Nutrient Sources by Motile Microorganisms.

In this study, we document hydrodynamics-mediated trapping of microorganisms around a moving spherical nutrient source such as a settling marine snow aggregate. There exists a range of size and excess density of the nutrient source, and motility and morphology of the microorganism under which hydrodynamic interactions enable the passive capture of approaching microorganisms onto a moving nutrient source. We simulate trajectories of chemotactic and non-chemotactic bacteria encountering a sinking marine snow particle effusing soluble nutrients. We calculate the average nutrient concentration to which the bacteria are exposed, under regimes of strong and weak hydrodynamic trapping. We find that hydrodynamic trapping can significantly amplify (by ≈40%) the nutrient exposure of bacteria, both chemotactic and non-chemotactic. The subtle interactions between hydrodynamic and chemotactic effects reveal non-trivial variations in this "hydrodynamic amplification," as a function of relevant biophysical parameters. Our study provides a consistent description of how microorganism motility, fluid flow and nutrient distribution affect foraging by marine microbes, and the formation of biofilms on spherical nutrient sources under the influence of fluid flow.

Combined influence of hydrodynamics and chemotaxis in the distribution of microorganisms around spherical nutrient sources.

We study how the interaction between hydrodynamics and chemotaxis affects the colonization of nutrient sources by microorganisms. We use an individual-based model and perform probabilistic simulations to ascertain the impact of important environmental and motility characteristics on the spatial distribution of microorganisms around a spherical nutrient source. In general, we unveil four distinct regimes based on the distribution of the microorganisms: (i) strong surface colonization, (ii) rotary-diffusion-induced "off-surface" accumulation, (iii) a depletion zone in the spatial distribution, and (iv) no appreciable aggregation, with their occurrence being contingent on the relative strengths of hydrodynamic and chemotactic effects. More specifically, we show that the extent of surface colonization first increases, then reaches a plateau, and finally decreases as the nutrient availability is increased. We also show that surface colonization reduces monotonically as the mean run length of the chemotactic microorganisms increases. Our study provides insight into the interplay of two important mechanisms governing microorganism behavior near nutrient sources, isolates each of their effects, and thus offers greater predictability of this nontrivial phenomenon.

Capillary filling under electro-osmotic effects in the presence of electromagneto-hydrodynamic effects.

We report various regimes of capillary filling dynamics under electromagneto-hydrodynamic interactions, in the presence of electrical double layer effects. Our chosen configuration considers an axial electric field and transverse magnetic field acting on an electrolyte. We demonstrate that for positive interfacial potential, the movement of the capillary front resembles capillary rise in a vertical channel under the action of gravity. We also evaluate the time taken by the capillary front to reach the final equilibrium position for positive interfacial potential and show that the presence of a transverse magnetic field delays the time of travel of the liquid front, thereby sustaining the capillary motion for a longer time. Our scaling estimates reveal that the initial linear regime starts, as well as ends, much earlier in the presence of electrical and magnetic body forces, as compared to the corresponding transients observed under pure surface tension driven flow. We further obtain a long time solution for the capillary imbibition for positive interfacial potential, and derive a scaling estimate of the capillary stopping time as a function of the applied magnetic field and an intrinsic length scale delineating electromechanical influences of the electrical double layer. Our findings are likely to offer alternative strategies of controlling dynamical features of capillary imbibition, by modulating the interplay between electromagnetic interactions, electrical double layer phenomena, and hydrodynamics over interfacial scales.