In-silico decongested trial effects on the impaired breathing function of a bulldog suffering from severe brachycephalic obstructive airway syndrome.

BACKGROUND AND OBJECTIVE: Brachycephalic obstructive airway syndrome (BOAS) susceptible dogs (e.g., French bulldog), suffer health complications related to deficient breathing primarily due to anatomical airway geometry. Surgical interventions are known to provide acceptable functional and cosmetic results; however, the long-term post-surgery outcome is not well known. In silico analysis provides an objective measure to quantify the respiratory function in postoperative dogs which is critical for successful long-term outcomes. A virtual surgery to open the airway can explore the ability for improved breathing in an obstructed airway of a patient dog, thus supporting surgeons in pre-surgery planning using computational fluid dynamics. METHODS: In this study five surgical interventions were generated with a gradual increment of decongested levels in a bulldog based on computed tomography images. The effects of the decongested airways on the breathing function of a patient bulldog, i.e., airflow characteristics, pressure drop, wall shear stress, and air-conditioning capacity, were quantified by benchmarking against a clinically healthy bulldog using computational fluid dynamics (CFD) method. RESULTS: Our findings demonstrated a promising decrease in excessive airstream velocity, pressure drop, and wall shear stress in virtual surgical scenarios, while constantly preserving adequate air-conditioning efficiency. A linear fit curve was proposed to correlate the reduction in the pressure drop and decongested level. CONCLUSIONS: The in silico analysis is a viable tool providing visual and quantitative insight into new unexplored surgical techniques.

Computational fluid dynamics comparison of impaired breathing function in French bulldogs with nostril stenosis and an examination of the efficacy of rhinoplasty.

BACKGROUND: Brachycephalic obstructive airway syndrome (BOAS) in dogs indicates a particular set of upper airway abnormalities found in brachycephalic dogs (e.g., French bulldogs). Stenotic nares is one of the primary BOAS-related abnormalities restricting the functional breathing of affected dogs. For severe stenosis, rhinoplasty is required to increase the accessibility of the external nostril to air; however, the specific improvement from surgery in terms of respiratory physiology and uptake of inhaled air has not been fully elucidated METHOD: This study employed Computational Fluid Dynamics (CFD) simulations to evaluate the effects of different stenotic intensities on airflow patterns in a total of eight French bulldog upper airways. A bulldog with severe stenosis after surgery was included to examine the efficacy of the surgical intervention. RESULTS: The results showed homogeneous airflow distributions in healthy and mild stenosis cases and significantly accelerated airstreams at the constricted positions in moderate and severe stenosis bulldogs. The airflow resistance was over 20-fold greater in severe stenosis cases than the healthy cases. After surgery, a decrease in airflow velocity was observed in the surgical region, and the percentage of reduced airflow resistance was approximately 4%. CONCLUSIONS: This study suggests impaired breathing function in brachycephalic dogs with moderate and severe stenosis. The results also serve as a reference for veterinarians in surgical planning and monitoring bulldogs' recuperation after surgery.

Real-time monitoring of NADPH levels in living mammalian cells using fluorescence-enhancing protein bound to NADPHs.

Nicotinamide adenine nucleotide phosphate (NADPH) has been known to be involved in the multiple pathways of cell metabolism. However, conventional quantification assays for NADPH have required breaking down the cell membranes of around one million cells per assay, and monitoring NADPH flux in living cells has been limited by a few available tools. Here, we visualized NADPH levels in human cervical cancer cells HeLa using metagenome-derived blue fluorescent protein (mBFP), which specifically binds to NADPH and enhances the intrinsic fluorescence of NADPH up to 10-fold when imaged by two-photon microscopy to reduce photodamage. Adding an oxidizing agent such as diamide to HeLa cells that expressed mBFP led to an immediate decrease of intracellular NADPH depending on glucose availability in culture media. Furthermore, inhibiting glucose-6-phosphate dehydrogenase (G6PD) in the pentose phosphate pathway with dehydroandrosterone (DHEA) and knockdown of G6PD transcripts gradually decreased NADPH when diamide was added to living cells. These results demonstrate that introducing a bacterial mBFP gene into mammalian cells is a straightforward approach to monitoring intracellular NADPH flux in real time at the single-cell level. Moreover, this strategy can be expanded to tracking the spatio-temporal changes in NADPH even in single-cell organelles such as mitochondria and chloroplasts, which will allow us to more precisely assess the efficacy of biochemically or biophysically metabolic perturbations in animal and plant cells.

The utility of magnetoencephalography in the presurgical evaluation of refractory insular epilepsy.

PURPOSE: To study the utility of magnetoencephalography (MEG) in patients with refractory insular epilepsy. Covered by highly functional temporal, frontal, and parietal opercula, insular-onset seizures can manifest a variety of ictal symptoms falsely leading to a diagnosis of temporal, frontal, or parietal lobe seizures. Lack of recognition of insular seizures may be responsible for some epilepsy surgery failures. METHODS: We retrospectively reviewed and analyzed MEG data in 14 patients with refractory insular seizures defined through intracranial electroencephalography (EEG) or by the presence of an epileptogenic lesion in the insula with compatible seizure semiology. MEG was performed as part of the noninvasive presurgical evaluation, using a 275-channel whole head MEG system. MEG data were analyzed using a single equivalent current dipole model. MEG localization was compared to interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) results and to the resection margin. KEY FINDINGS: Three patterns of MEG spike sources were observed. Seven patients showed an anterior operculoinsular clusters and two patients had a posterior operculoinsular cluster. No spikes were detected in one patient, and the remaining four patients showed a diffuse perisylvian distribution. Spike sources showed uniform orientation perpendicular to the sylvian fissure. Nine patients proceeded to insular epilepsy surgery with favorable surgical outcome. Among patients with anterior operculoinsular cluster who proceeded to have surgery, MEG provided superior information to ictal SPECT in four of six patients and to interictal PET in five of six patients. SIGNIFICANCE: MEG is useful in identifying patients who are likely to benefit from epilepsy surgery targeting the insula, particularly if a tight dipole cluster is identified even if other noninvasive modalities fail to produce localizing results.