Longitudinal single-subject neuroimaging study reveals effects of daily environmental, physiological, and lifestyle factors on functional brain connectivity.

Our behavior and mental states are constantly shaped by our environment and experiences. However, little is known about the response of brain functional connectivity to environmental, physiological, and behavioral changes on different timescales, from days to months. This gives rise to an urgent need for longitudinal studies that collect high-frequency data. To this end, for a single subject, we collected 133 days of behavioral data with smartphones and wearables and performed 30 functional magnetic resonance imaging (fMRI) scans measuring attention, memory, resting state, and the effects of naturalistic stimuli. We find traces of past behavior and physiology in brain connectivity that extend up as far as 15 days. While sleep and physical activity relate to brain connectivity during cognitively demanding tasks, heart rate variability and respiration rate are more relevant for resting-state connectivity and movie-watching. This unique data set is openly accessible, offering an exceptional opportunity for further discoveries. Our results demonstrate that we should not study brain connectivity in isolation, but rather acknowledge its interdependence with the dynamics of the environment, changes in lifestyle, and short-term fluctuations such as transient illnesses or restless sleep. These results reflect a prolonged and sustained relationship between external factors and neural processes. Overall, precision mapping designs such as the one employed here can help to better understand intraindividual variability, which may explain some of the observed heterogeneity in fMRI findings. The integration of brain connectivity, physiology data and environmental cues will propel future environmental neuroscience research and support precision healthcare.

Motor cortex is responsible for motoric dynamics in striatum and the execution of both skilled and unskilled actions.

Striatum and its predominant input, motor cortex, are responsible for the selection and performance of purposive movement, but how their interaction guides these processes is not understood. To establish its neural and behavioral contributions, we bilaterally lesioned motor cortex and recorded striatal activity and reaching performance daily, capturing the lesion's direct ramifications within hours of the intervention. We observed reaching impairment and an absence of striatal motoric activity following lesion of motor cortex, but not parietal cortex control lesions. Although some aspects of performance began to recover after 8-10 days, striatal projection and interneuronal dynamics did not-eventually entering a non-motor encoding state that aligned with persisting kinematic control deficits. Lesioned mice also exhibited a profound inability to switch motor plans while locomoting, reminiscent of clinical freezing of gait (FOG). Our results demonstrate the necessity of motor cortex in generating trained and untrained actions as well as striatal motoric dynamics.

Bilateral Anterior Capsulotomy for Treatment-Resistant Obsessive-Compulsive Disorder.

INTRODUCTION: Ablative surgery is an intervention of last resort for treatment-resistant obsessive-compulsive disorder (TROCD). Our center has been using bilateral anterior capsulotomy (BAC) for the past 20 years for patients eligible for limbic surgery. This report details our experience with BAC for TROCD. METHOD: Five patients with OCD met eligibility criteria for BAC. Entry protocols were complex and took around 6 months to complete. Stereotactic radiofrequency was used to produce the capsulotomies. Lesion length varied between 5.7 and 16.9 mm in the coronal plane. Patients were followed between 4 and 20 years. RESULTS: All 5 patients (100%) were responders as defined by the widely accepted criteria of a reduction of ≥35% in Yale-Brown Obsessive Compulsive Scale (YBOCS) score at 18-month follow-up. Four patients remained responders at the 48 months. One patient was lost to follow-up. Responder status when viewed from the perspective of the YBOCS was sustained over the 4- to 20-year follow-up with one relapse 19 years postsurgery when medications were discontinued. Real-world psychiatric outcomes were different as other vulnerabilities surfaced illustrating the multifactorial determinants of mental health. No patient had any significant long-term neurocognitive or physical side effects. CONCLUSION: BAC should remain an option of last resort for patients with severe OCD who remain unresponsive to all other interventions.

Changes in the Johne's disease situation in GB dairy herds over 10 years, as revealed by regular milk ELISA data.

Effective management of cattle infected with Johne's Disease (JD) is crucial to minimizing transmission and within-herd prevalence. Within Great Britain (GB), the voluntary National Johne's Management Plan (NJMP) requires farmers and a certified vet to conduct a risk assessment to determine the herd risk, examine the herd JD status and formulate a management plan. Individual milk ELISA tests for JD antibodies are widely used to monitor infection. The JD Tracker application, available within the dairy data management software InterHerd+ and other web-based environments, is being used by farmers and veterinarians to facilitate the practical use of milk ELISA data to aid JD-related management decisions. The JD Tracker application uses a herd's milk ELISA data to calculate a collection of 'JD parameters' that are indicative of the current JD status of the herd alongside contemporary and retrospective drivers linked to transmission and maintenance of infection. Herein, we use milk ELISA data from 154 regularly testing herds to review the temporal trends in JD parameters from 2013 to 2022. Since 2015, JD Tracker parameters have improved in these herds, most notably average test value (ATV) and within-herd prevalence (%Pos30). Trends in driver parameters suggest that farmers are progressively less likely to serve repeat test-positive (J5) cows and are more readily removing them. The data also reveal that the burden of JD is disproportionately greater in herds with higher ATV. In 2022, the 25 % of herds with the highest ATVs accounted for 42 % of positive tests and 42 % of repeat ELISA positive (J5) cows. Retrospectively, it is not possible to identify with certainty factors that directly contributed to the trends in JD parameters, but it is notable that the introduction of the NJMP was coincided with the improving JD situation. In 2019, participation in the NJMP or an equivalent scheme became mandatory for dairy farms to be compliant with the food and farms standards assurance scheme Red Tractor, with the result that JD management plans are now completed by 95 % of UK dairy farms. As far as we know, the UK is unique in its development of a tool (the JD Tracker) which adds utility to milk ELISA data using specifically designed JD parameters. Anticipated further work includes the development of a national database of JD testing herds and application of the JD Tracker at national scale to enable more comprehensive industry-level monitoring of JD within GB dairy farms.

Interleukin-13 Treatment of Living Lung Tissue Model Alters the Metabolome and Proteome-A Nano-DESI MS Metabolomics and Shotgun Proteomics Study.

Asthma is a chronic respiratory disease with one of the largest numbers of cases in the world; thus, constant investigation and technical development are needed to unravel the underlying biochemical mechanisms. In this study, we aimed to develop a nano-DESI MS method for the in vivo characterization of the cellular metabolome. Using air-liquid interface (ALI) cell layers, we studied the role of Interleukin-13 (IL-13) on differentiated lung epithelial cells acting as a lung tissue model. We demonstrate the feasibility of nano-DESI MS for the in vivo monitoring of basal-apical molecular transport, and the subsequent endogenous metabolic response, for the first time. Conserving the integrity of the ALI lung-cell layer enabled us to perform temporally resolved metabolomic characterization followed by "bottom-up" proteomics on the same population of cells. Metabolic remodeling was observed upon histamine and corticosteroid treatment of the IL-13-exposed lung cell monolayers, in correlation with alterations in the proteomic profile. This proof of principle study demonstrates the utility of in vivo nano-DESI MS for characterizing ALI tissue layers, and the new markers identified in our study provide a good starting point for future, larger-scale studies.

Knowledge and Perceptions of the Public vis-a-vis Colorectal Cancer Information in Newspapers in Malaysia.

OBJECTIVE: The study examines knowledge and perceptions of colorectal cancer vis-à-vis colorectal cancer information in newspapers in Malaysia. METHODS: A total of 152 respondents filled in a 76-item questionnaire based on the Health Belief Model. Articles on colorectal cancer in three English newspapers in Malaysia from 1 January to 30 June 2022 were analysed. RESULT: A majority of the Malaysian respondents had low experiential knowledge of colorectal cancer, high perceived severity, low perceived susceptibility, and low to moderate susceptibility based on self-reported lifestyle and health conditions. The diet factor puts a majority of respondents at risk but smoking, alcohol drinking, and large intestine problems are risk factors for less than 10% of the group. The respondents believed in the benefits of seeking treatment but they were only marginally positive as to whether quitting smoking and losing weight could reduce colorectal cancer risk. They reported strong response efficacy and self-efficacy but the top barriers were lack of knowledge and cost. The strongest cue to action for their health protective intentions was news about colorectal cancer in newspapers, magazines, television and youtube. There were positive moderate correlations among perceived severity, benefits, response efficacy, self-efficacy, cues to action, and intention. Little salience was given to colorectal cancer in the three English newspapers based on the number of articles (N=10). The high frequency of information on severity, susceptibility, and benefits of lifestyle changes and screening in the newspaper articles are reflected in questionnaire results on better knowledge. Lack of information and cost prevented respondents from seeking screening or treatment, despite attempts by the newspaper articles to address barriers. CONCLUSION: The study suggests a need to heighten cues to action in the mass media and social media by providing information on cost and practical details of colorectal cancer screening and benefits of diet-related risk factors.

Neuroscience meets behavior: A systematic literature review on magnetic resonance imaging of the brain combined with real-world digital phenotyping.

A primary goal of neuroscience is to understand the relationship between the brain and behavior. While magnetic resonance imaging (MRI) examines brain structure and function under controlled conditions, digital phenotyping via portable automatic devices (PAD) quantifies behavior in real-world settings. Combining these two technologies may bridge the gap between brain imaging, physiology, and real-time behavior, enhancing the generalizability of laboratory and clinical findings. However, the use of MRI and data from PADs outside the MRI scanner remains underexplored. Herein, we present a Preferred Reporting Items for Systematic Reviews and Meta-Analysis systematic literature review that identifies and analyzes the current state of research on the integration of brain MRI and PADs. PubMed and Scopus were automatically searched using keywords covering various MRI techniques and PADs. Abstracts were screened to only include articles that collected MRI brain data and PAD data outside the laboratory environment. Full-text screening was then conducted to ensure included articles combined quantitative data from MRI with data from PADs, yielding 94 selected papers for a total of N = 14,778 subjects. Results were reported as cross-frequency tables between brain imaging and behavior sampling methods and patterns were identified through network analysis. Furthermore, brain maps reported in the studies were synthesized according to the measurement modalities that were used. Results demonstrate the feasibility of integrating MRI and PADs across various study designs, patient and control populations, and age groups. The majority of published literature combines functional, T1-weighted, and diffusion weighted MRI with physical activity sensors, ecological momentary assessment via PADs, and sleep. The literature further highlights specific brain regions frequently correlated with distinct MRI-PAD combinations. These combinations enable in-depth studies on how physiology, brain function and behavior influence each other. Our review highlights the potential for constructing brain-behavior models that extend beyond the scanner and into real-world contexts.

A practical method to simulate realistic reduced-exposure CT images by the addition of computationally generated noise.

Computed tomography (CT) scanning protocols should be optimized to minimize the radiation dose necessary for imaging. The addition of computationally generated noise to the CT images facilitates dose reduction. The objective of this study was to develop a noise addition method that reproduces the complexity of the noise texture present in clinical images with directionality that varies over images according to the underlying anatomy, requiring only Digital Imaging and Communications in Medicine (DICOM) images as input data and commonly available phantoms for calibration. The developed method is based on the estimation of projection data by forward projection from images, the addition of Poisson noise, and the reconstruction of new images. The method was validated by applying it to images acquired from cylindrical and thoracic phantoms using source images with exposures up to 49 mAs and target images between 39 and 5 mAs. 2D noise spectra were derived for regions of interest in the generated low-dose images and compared with those from the scanner-acquired low-dose images. The root mean square difference between the standard deviations of noise was 4%, except for very low exposures in peripheral regions of the cylindrical phantom. The noise spectra from the corresponding regions of interest exhibited remarkable agreement, indicating that the complex nature of the noise was reproduced. A practical method for adding noise to CT images was presented, and the magnitudes of noise and spectral content were validated. This method may be used to optimize CT imaging.

Connectivity alterations of mesostriatal pathways in first episode psychosis.

BACKGROUND AND HYPOTHESIS: Pathogenic understanding of the psychotic disorders converges on regulation of dopaminergic signaling in mesostriatocortical pathways. Functional connectivity of the mesostriatal pathways may inform us of the neuronal networks involved. STUDY DESIGN: This longitudinal study of first episode psychosis (FEP) (49 patients, 43 controls) employed seed-based functional connectivity analyses of fMRI data collected during a naturalistic movie stimulus. STUDY RESULTS: We identified hypoconnectivity of the dorsal striatum with the midbrain, associated with antipsychotic medication dose in FEP, in comparison with the healthy control group. The midbrain regions that showed hypoconnectivity with the dorsal striatum also showed hypoconnectivity with cerebellar regions suggested to be involved in regulation of the mesostriatocortical dopaminergic pathways. None of the baseline hypoconnectivity detected was seen at follow-up. CONCLUSIONS: These findings extend earlier resting state findings on mesostriatal connectivity in psychotic disorders and highlight the potential for cerebellar regulation of the mesostriatocortical pathways as a target of treatment trials.

Attention to Stimuli of Learned versus Innate Biological Value Relies on Separate Neural Systems.

The neural bases of attention, a set of neural processes that promote behavioral selection, is a subject of intense investigation. In humans, rewarded cues influence attention, even when those cues are irrelevant to the current task. Because the amygdala plays a role in reward processing, and the activity of amygdala neurons has been linked to spatial attention, we reasoned that the amygdala may be essential for attending to rewarded images. To test this possibility, we used an attentional capture task, which provides a quantitative measure of attentional bias. Specifically, we compared reaction times (RTs) of adult male rhesus monkeys with bilateral amygdala lesions and unoperated controls as they made a saccade away from a high- or low-value rewarded image to a peripheral target. We predicted that: (1) RTs will be longer for high- compared with low-value images, revealing attentional capture by rewarded stimuli; and (2) relative to controls, monkeys with amygdala lesions would exhibit shorter RT for high-value images. For comparison, we assessed the same groups of monkeys for attentional capture by images of predators and conspecifics, categories thought to have innate biological value. In performing the attentional capture task, all monkeys were slowed more by high-value relative to low-value rewarded images. Contrary to our prediction, amygdala lesions failed to disrupt this effect. When presented with images of predators and conspecifics, however, monkeys with amygdala lesions showed significantly diminished attentional capture relative to controls. Thus, separate neural pathways are responsible for allocating attention to stimuli with learned versus innate value.SIGNIFICANCE STATEMENT Valuable objects attract attention. The amygdala is known to contribute to reward processing and the encoding of object reward value. We therefore examined whether the amygdala is necessary for allocating attention to rewarded objects. For comparison, we assessed the amygdala's contribution to attending to objects with innate biological value: predators and conspecifics. We found that the macaque amygdala is necessary for directing attention to images with innate biological value, but not for directing attention to recently learned reward-predictive images. These findings indicate that the amygdala makes selective contributions to attending to valuable objects. The data are relevant to mental health disorders, such as social anxiety disorders and small animal phobias, that arise from biased attention to select categories of objects.

CMU Array: A 3D nanoprinted, fully customizable high-density microelectrode array platform.

Microelectrode arrays provide the means to record electrophysiological activity critical to brain research. Despite its fundamental role, there are no means to customize electrode layouts to address specific experimental or clinical needs. Moreover, current electrodes demonstrate substantial limitations in coverage, fragility, and expense. Using a 3D nanoparticle printing approach that overcomes these limitations, we demonstrate the first in vivo recordings from electrodes that make use of the flexibility of the 3D printing process. The customizable and physically robust 3D multi-electrode devices feature high electrode densities (2600 channels/cm2 of footprint) with minimal gross tissue damage and excellent signal-to-noise ratio. This fabrication methodology also allows flexible reconfiguration consisting of different individual shank lengths and layouts, with low overall channel impedances. This is achieved, in part, via custom 3D printed multilayer circuit boards, a fabrication advancement itself that can support several biomedical device possibilities. This effective device design enables both targeted and large-scale recording of electrical signals throughout the brain.

Trileucine as a dispersibility enhancer of spray-dried inhalable microparticles.

The formation of trileucine-containing spray-dried microparticles intended for pulmonary delivery was studied in depth. A single-particle method was employed to study the shell formation characteristics of trileucine in the presence of trehalose as a glass former, and an empirical correlation was proposed to predict the instance of shell formation. A droplet chain instrument was used to produce and collect monodisperse particles to examine morphology and calculate particle density for different levels of trileucine. It was observed that the addition of only 0.5 mg/mL (10% w/w) trileucine to a trehalose system could lower dried particle densities by approximately 1 g/cm3. In addition, a laboratory-scale spray dryer was used to produce batches of trileucine/trehalose powders in the respirable range. Raman spectroscopy demonstrated that both components were completely amorphous. Scanning electron microscopy and time-of-flight secondary ion mass spectrometry were used to study the particle morphologies and surface compositions. For all cases with trileucine, highly rugose particles with trileucine coverages of more than 60% by mass were observed with trileucine feed fractions of as little as 2% w/w. Moreover, it was seen that at lower trileucine content, smaller and larger particles of a polydisperse powder had slightly different surface compositions. The surface activity of trileucine was also modeled via a modified form of the diffusion equation inside an evaporating droplet that took into account initial surface adsorption and eventual surface desorption due to droplet shrinkage. Finally, using the Flory-Huggins theory, it was estimated that at room temperature, liquid-liquid phase separation would start when the trileucine reached an aqueous concentration of about 18 mg/mL. Besides the surface activity of trileucine, this low concentration was assumed to explain the substantial effect of trileucine on the morphology of spray-dried particles due to early phase separation. The methodology proposed in this study can be used in the rational design of trileucine-containing microparticles.

Successful Postnatal Cardiopulmonary Resuscitation Due to Defibrillation.

An asphyxiated term neonate required postnatal resuscitation. After six minutes of cardio-pulmonary resuscitation (CPR) and two doses of epinephrine, spontaneous circulation returned, but was shortly followed by ventricular fibrillation. CPR and administration of magnesium, calcium gluconate, and sodium bicarbonate did not improve the neonate's condition. A counter shock of five Joule was delivered and the cardiac rhythm immediately converted to sinus rhythm. The neonate was transferred to the neonatal intensive care unit and received post-resuscitation care. Due to prolonged QTc and subsequently suspected long-QT syndrome propranolol treatment was initiated. The neonate was discharged home on day 14 without neurological sequelae.

Controlling the performance of adhesive mixtures for inhalation using mixing energy.

A concept of mixing energy, ME, has been developed and applied to blending of adhesive mixtures for inhalation in a high shear blender. Six different systems were investigated, four of which included a coating agent. For blends containing a coating agent, it is shown that the applied ME is key to the control of two important functional mechanisms: i) coating of the carrier by the coating agent, and ii) the dispersibility of the active pharmaceutical ingredient (API). The mass of the carrier was identified to be the mass which is relevant to the forces acting during mixing. The dispersibility in terms of the fine particle fraction (FPF) can be expressed as the product of two exponentials which both are functions of ME. The first factor accounts for the initial increase in FPF, while the second accounts for the decrease observed at extensive mixing. For adhesive mixtures without a coating agent, a similar decrease in FPF is observed when high forces are applied during mixing. Mechanistic interpretation of the behavior is provided.

On the particle formation of leucine in spray drying of inhalable microparticles.

The particle formation of L-leucine, a dispersibility-enhancing amino acid used in the spray drying of inhalable pharmaceutical aerosols, was extensively studied using three experimental methods, and the results were interpreted with the aid of theory. A comparative-kinetics electrodynamic balance was used to study the shell formation behavior in single evaporating microdroplets containing leucine and trehalose. Different concentration thresholds of solidification and shell formation were determined for trehalose and leucine, which were then used in the particle formation model to predict the properties of spray-dried particles. Furthermore, a droplet chain instrument was used to study the particle morphologies and particle densities that were not accessible in the single particle experiments. Lab-scale spray drying was also used to produce powders typical for actual pharmaceutical applications. Raman spectroscopy confirmed that a glass former, such as trehalose, can inhibit the crystallization of leucine. The surface compositions of these spray-dried powders were analyzed via time-of-flight secondary ion mass spectrometry. The leucine surface coverage in a polydisperse powder was determined to be a function of the particle size or the initial droplet diameter of each respective particle. This observation confirms the important role of leucine crystallization kinetics in its shell-forming capabilities. A critical supersaturation ratio of 3.5 was also calculated for leucine, at which it is assumed to instantaneously nucleate out of solution. This ratio was used as the threshold for the initiation of crystallization. Crystallinity predictions for the leucine-trehalose particles based on this supersaturation ratio were in good agreement with the solid-state characterizations obtained by Raman spectroscopy. This study improves the fundamental understanding of the particle formation process of leucine-containing formulations, which can apply to other crystallizing systems and potentially facilitate the rational design of such formulations with reduced experimental effort.

Histological demonstration of BSEP/ABCB11 inhibition in transient neonatal cholestasis: a case report.

BACKGROUND: Idiopathic or transient neonatal cholestasis (TNC) represents a group of cholestatic disorders with unidentified origin and remains a diagnosis of exclusion. Dysfunction of hepatobiliary transporters mediating excretion of biliary constituents from hepatocytes may play a central role in the pathogenesis of cholestasis. Despite variants of bile salt (BS) export pump (BSEP/ABCB11) have already been described in TNC, the pathogenic role of BSEP dysfunction in TNC remained so far elusive. CASE PRESENTATION: We report on a newly-identified heterozygous ABCB11 missense variant (c.1345G > A, p.Glu449Lys) which was associated with prolonged cholestasis in a term infant after a complicated neonatal period. Moreover, we show for the first time almost completely abolished BSEP expression on the hepatocellular membrane in TNC. CONCLUSION: This report demonstrates for the first time a close association between the prolonged cholestasis in infancy and impaired BSEP expression on the hepatocyte canalicular membrane in a heterozygous carrier of newly-identified ABCB11 variant.

Quantification of surface composition and surface structure of inhalation powders using TOF-SIMS.

A multivariate TOF-SIMS methodology has been developed and applied to quantify surface composition and chemical distribution for dry powder blends. Surface properties are often critical to the behavior of powder formulations, especially in the case of dry powders for inhalation, as surface properties directly affect inter-particulate forces and, hence, the dispersibility of the formulation. The mass spectrum at each pixel was fit to a linear combination of reference spectra obtained by non-negatively constrained alternating least squares. From the pixel compositions, average surface coverage and a range of other image features were calculated. Two kinds of systems have been examined: 1) binary blends of lactose particles and coating agents, and 2) blends of different inhalation drugs with carrier lactose. For both kinds of systems, detailed insight into the surface composition and structure could be derived. For the former study, TOF-SIMS results were compared with a complementary surface analysis technique, XPS.

Open-Source Joystick Manipulandum for Decision-Making, Reaching, and Motor Control Studies in Mice.

To make full use of optogenetic and molecular techniques in the study of motor control, rich behavioral paradigms for rodents must rise to the same level of sophistication and applicability. We describe the layout, construction, use and analysis of data from joystick-based reaching in a head-fixed mouse. The step-by-step guide is designed for both experienced rodent motor labs and new groups looking to enter into this research space. Using this platform, mice learn to consistently perform large, easily-quantified reaches, including during a two-armed bandit probabilistic learning task. The metrics of performance (reach trajectory, amplitude, speed, duration, and inter-reach interval) can be used to quantify behavior or administer stimulation in closed loop with behavior. We provide a highly customizable, low cost and reproducible open-source behavior training platform for studying motor control, decision-making, and reaching reaction time. The development of this software and hardware platform enables behavioral work to complement recent advances in rodents, while remaining accessible to smaller institutions and labs, thus providing a high-throughput method to study unexplored features of action selection, motivation, and value-based decisions.

Correlations between surface composition and aerosolization of jet-milled dry powder inhaler formulations with pharmaceutical lubricants.

Co-jet-milling drugs and lubricants may enable simultaneous particle size reduction and surface coating to achieve satisfactory aerosolization performance. This study aims to establish the relationship between surface lubricant coverage and aerosolization behavior of a model drug (ciprofloxacin HCl) co-jet-milled with lubricants [magnesium stearate (MgSt) or l-leucine]. The co-jet-milled formulations were characterized for particle size, morphology, cohesion, Carr's index, and aerosolization performance. The surface lubricant coating was assessed by probing surface chemical composition using X-ray photoelectron spectroscopy (XPS) and time-of-flight secondary-ion mass spectrometry (ToF-SIMS). The effects of co-jet-milling on the surface energy and in vitro dissolution of ciprofloxacin were also evaluated. Our results indicated that, in general, the ciprofloxacin co-jet-milled with l-leucine at >0.5% w/w showed a significant higher fine particle fraction (FPF) compared with the ciprofloxacin jet-milled alone. The FPF values plateau at or above 5% w/w for both MgSt and l-leucine. We have established the quantitative correlations between surface lubricant coverage and aerosolization in the tested range for each of the lubricants. More importantly, our results suggest different mechanisms to improve aerosolization for MgSt-coating and l-leucine-coating, respectively: MgSt-coating reduces inter-particulate interactions through the formation of low surface energy coating films, while l-leucine-coating not only reduces the surface energy but also creates rough particle surfaces that reduce inter-particulate contact area. Furthermore, surface coatings with 5% w/w MgSt (which is hydrophobic) did not lead to substantial changes in in vitro dissolution. Our findings have shown that the coating structure/quality and their effects could be highly dependent on the process and the coating material. The findings from this mechanistic study provide fundamental understanding of the critical effects of MgSt and l-leucine surface coverages on aerosolization and powder flow properties of inhalation particles.