Nonlinear Convection in Reaction-diffusion Equations under dynamical boundary conditions

We investigate blow-up phenomena for positive solutions of nonlinear reaction-diffusion equations including a nonlinear convection term $\partial_t u = \Delta u - g(u) \cdot \nabla u + f(u)$ in a bounded domain of $\mathbb{R}^N$ under the dissipative dynamical boundary conditions $\sigma \partial_t u + \partial_\nu u =0$. Some conditions on $g$ and $f$ are discussed to state if the positive solutions blow up in finite time or not. Moreover, for certain classes of nonlinearities, an upper-bound for the blow-up time can be derived and the blow-up rate can be determinated.Comment: 20 page

Intubation Related Laryngeal Injuries in Pediatric Population.

Introduction: Laryngeal intubation related lesions (LIRL) in pediatric patients cause extreme morbidity in both elective and emergency settings. It has a wide range of presentations from minor laryngeal edema to a life-threatening airway obstruction. We report here our units' experience with LIRL in neonates, infants, and small children. Material and Methods: This is a retrospective monocentric cohort study between January 2013 and April 2019. Results: Thirty-nine patients with intubation lesions were included in the study. We looked at the lesions type, characteristics, management, and outcome. Half the patients were premature and having comorbidities. Main LIRL were subglottic stenosis (31%), ulcers (26%), granulations (18%), retention cysts (18%), posterior glottic stenosis (13%), and vocal cords edema (5%). Unfavorable lesions causing airway stenosis were associated with an intubation duration of over 1 week and were an important factor in causing airway stenosis (p < 0.05). The endoscopic treatment performed for these lesions was lesion and anatomical site-specific. Tracheostomy was needed in five patients, and was avoided in another two. Seven patients (18%) received open surgery prior to their decannulation. Conclusions: LIRL management is challenging and stressful in the pediatric population and optimal treatment could avoid extreme morbidity in them. Intubation duration and associated comorbidities are important factors in deciding the severity of these lesions. Protocols to prevent the formation of these lesions are critical

Low energy cost for optimal speed and control of membrane fusion

Membrane fusion is the cell’s delivery process, enabling its many compartments to receive cargo and machinery for cell growth and intercellular communication. The overall activation energy of the process must be large enough to prevent frequent and nonspecific spontaneous fusion events, yet must be low enough to allow it to be overcome upon demand by specific fusion proteins [such as soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs)]. Remarkably, to the best of our knowledge, the activation energy for spontaneous bilayer fusion has never been measured. Multiple models have been developed and refined to estimate the overall activation energy and its component parts, and they span a very broad range from 20 kBT to 150 kBT, depending on the assumptions. In this study, using a bulk lipid-mixing assay at various temperatures, we report that the activation energy of complete membrane fusion is at the lowest range of these theoretical values. Typical lipid vesicles were found to slowly and spontaneously fully fuse with activation energies of ∼30 kBT. Our data demonstrate that the merging of membranes is not nearly as energy consuming as anticipated by many models and is ideally positioned to minimize spontaneous fusion while enabling rapid, SNARE-dependent fusion upon demand

Kinetic barriers to SNAREpin assembly in the regulation of membrane docking/priming and fusion

Neurotransmission is achieved by soluble NSF attachment protein receptor (SNARE)-driven fusion of readily releasable vesicles that are docked and primed at the presynaptic plasma membrane. After neurotransmission, the readily releasable pool of vesicles must be refilled in less than 100 ms for subsequent release. Here we show that the initial association of SNARE complexes, SNAREpins, is far too slow to support this rapid refilling owing to an inherently high activation energy barrier. Our data suggest that acceleration of this process, i.e., lowering of the barrier, is physiologically necessary and can be achieved by molecular factors. Furthermore, under zero force, a low second energy barrier transiently traps SNAREpins in a half-zippered state similar to the partial assembly that engages calcium-sensitive regulatory machinery. This result suggests that the barrier must be actively raised in vivo to generate a sufficient pause in the zippering process for the regulators to set in place. We show that the heights of the activation energy barriers can be selectively changed by molecular factors. Thus, it is possible to modify, both in vitro and in vivo, the lifespan of each metastable state. This controllability provides a simple model in which vesicle docking/priming, an intrinsically slow process, can be substantially accelerated. It also explains how the machinery that regulates vesicle fusion can be set in place while SNAREpins are trapped in a half-zippered state

Hypothesis - buttressed rings assemble, clamp, and release SNAREpins for synaptic transmission

Neural networks are optimized to detect temporal coincidence on the millisecond timescale. Here, we offer a synthetic hypothesis based on recent structural insights into SNAREs and the C2 domain proteins to explain how synaptic transmission can keep this pace. We suggest that an outer ring of up to six curved Munc13 ‘MUN’ domains transiently anchored to the plasma membrane via its flanking domains surrounds a stable inner ring comprised of synaptotagmin C2 domains to serve as a work-bench on which SNAREpins are templated. This ‘buttressed-ring hypothesis’ affords straightforward answers to many principal and long-standing questions concerning how SNAREpins can be assembled, clamped, and then released synchronously with an action potential

How hard is a colloidal 'hard-sphere' interaction?

Poly-12-hydroxystearic acid (PHSA) is widely used as a coating on colloidal spheres to provide a "hard-sphere-type" interaction. These hard spheres have been widely used in fundamental studies of nucleation, crystallization, and glass formation. Most authors describe the interaction as "nearly" hard sphere. In this paper we directly measure this interaction, using layers of PHSA adsorbed onto mica sheets in a surfaces force apparatus. We find that the layers, in appropriate solvents, have no long-range interaction. When the solvent is decahydronaphthalene (decalin), the repulsion rises from zero to the maximum measurable over a distance range of 15-20 nm. The data is converted to equivalent forces between spheres of different diameters, and modeled using a hard core potential. Using zeroth-order perturbation theory and computer simulation, we demonstrate that the equation of state does not deviate from that of a perfect hard-sphere system under any relevant experimental conditions

Acute pulmonary edema induced by non-ionic low-osmolar radiographic contrast media.

Non-cardiogenic pulmonary edema (NCPE) after intravenous (iv) administration of non-ionic radiocontrast media (RCM) is a rare but life-threatening complication. In a context of emergency, its diagnosis is difficult. We report the case of a 55-year-old woman who developed an acute pulmonary edema following iv infusion of non-ionic, low-osmolar RCM during abdominal CT scan. She needed a 24-hour hospitalization in intensive care unit for an acute hypoxemic dyspnea. She was falsely treated at first for an anaphylactic reaction, and then for a cardiac failure. She improved with cortisone and diuretic treatment. Although NCPE has been rarely reported after RCM injection, it remains an acute severe complication that has to be considered. The differential diagnosis involves multiple pathogenic patterns giving furthermore complexity in choosing an appropriate treatment

Graves Disease Causing Pancytopenia: Case Report and Literature Review.

Graves disease or other causes of thyrotoxicosis are frequently associated with cytopenia. Although anemia is the most common, other cell lineage can be affected. Pancytopenia is a rare complication of thyrotoxicosis. We report a case of a 33-year-old Chinese man who presented a nonsevere pancytopenia in the context of a newly diagnosed Graves disease. Restauration of euthyroid state led to progressive correction of pancytopenia. Literature review shows other rare cases of pancytopenia. It is usually nonsevere with just extremely rare cases of transfusion reported. Evolution was always favorable after achievement of euthyroid state. Its mechanism remains poorly understood, especially because those patients have no vitamin or iron deficiency. The exact physiopathological process remains unclear but 2 causes seem to overlap: reduced production of hematopoietic cells from the bone marrow and increased destruction or sequestration of mature hematopoietic cells. Despite unclear mechanism, the presence of hematologic abnormalities including pancytopenia must not be considered as a contraindication to antithyroid drug therapy

Mucosal Melanoma of the Head and Neck: A Retrospective Review and Current Opinion

Introduction: Head and Neck Mucosal Melanoma (HNMM) is an uncommon malignancy that arises in decreasing order in the nasal cavity, the paranasal sinuses, and the oral cavity. Although radical surgery followed by eventual radiotherapy is acknowledged as the mainstay treatment, patients with advanced stages or multi-focal tumors benefit from new systemic therapies. We wish to share our experience with these treatments and review the current literature. Materials and Methods: We present a case review of every patient treated in our center for an HNMM over the past 10 years, including every patient treated in our center for an HNMM over the past 10 years. We analyzed clinical characteristics, treatment modalities, and outcomes. Results: We included eight patients aged from 62 to 85 years old. We found six MM in the nasal cavity, one in the sphenoidal sinus, and one in the piriform sinus. Six patients underwent endoscopic surgery with negative margins, six underwent radiotherapy with variable modalities. Immunotherapy or targeted therapy was given in cases extensive tumors without the possibility of a surgical treatment or in two patient as an adjuvant treatment after R0 surgery. The three-year overall survival was 50%, and three patients (37.5%) are in remission. Conclusions: HNMM is associated with poor oncologic outcomes regarding the concerned patients of our review, as reported in the literature. New treatments such as immunotherapies or targeted therapies have not significantly changed the prognosis, but they may offer new interesting perspectives. Our small series of cases seems to confirm that surgical resection with negative margins improves overall survival

FRAP to Characterize Molecular Diffusion and Interaction in Various Membrane Environments

Fluorescence recovery after photobleaching (FRAP) is a standard method used to study the dynamics of lipids and proteins in artificial and cellular membrane systems. The advent of confocal microscopy two decades ago has made quantitative FRAP easily available to most laboratories. Usually, a single bleaching pattern/area is used and the corresponding recovery time is assumed to directly provide a diffusion coefficient, although this is only true in the case of unrestricted Brownian motion. Here, we propose some general guidelines to perform FRAP experiments under a confocal microscope with different bleaching patterns and area, allowing the experimentalist to establish whether the molecules undergo Brownian motion (free diffusion) or whether they have restricted or directed movements. Using in silico simulations of FRAP measurements, we further indicate the data acquisition criteria that have to be verified in order to obtain accurate values for the diffusion coefficient and to be able to distinguish between different diffusive species. Using this approach, we compare the behavior of lipids in three different membrane platforms (supported lipid bilayers, giant liposomes and sponge phases), and we demonstrate that FRAP measurements are consistent with results obtained using other techniques such as Fluorescence Correlation Spectroscopy (FCS) or Single Particle Tracking (SPT). Finally, we apply this method to show that the presence of the synaptic protein Munc18-1 inhibits the interaction between the synaptic vesicle SNARE protein, VAMP2, and its partner from the plasma membrane, Syn1A