Light Induced Proton Coupled Charge Transfer Triggers Counterion Directional Translocation.

We demonstrate directed translocation of ClO4 - anions from cationic to neutral binding site along the synthetized BPym-OH dye molecule that exhibits coupled excited-state intramolecular proton-transfer (ESIPT) and charge-transfer (CT) reaction (PCCT). The results of steady-state and time-resolved spectroscopy together with computer simulation and modeling show that in low polar toluene the excited-state redistribution of electronic charge enhanced by ESIPT generates the driving force, which is much stronger than by CT reaction itself and provides more informative gigantic shifts of fluorescence spectra signaling on ultrafast ion motion. The associated with ion translocation red-shifted fluorescence band (at 750 nm, extending to near-IR region) appears at the time ~83 ps as a result of electrochromic modulation of PCCT reaction. It occurs at substantial delay to PCCT that displayed fluorescence band at 640 nm and risetime of <200 fs. Thus, it becomes possible to visualize the manifestations of light-triggered ion translocation and of its driving force by fluorescence techniques and to separate them in time and energy domains.

Hyperbaric Oxygen Therapy Attenuated the Motor Coordination and Cognitive Impairment of Polyglutamine Spinocerebellar Ataxia SCA17 Mice.

Spinocerebellar ataxias (SCAs) are a large and diverse group of autosomal-dominant neurodegenerative diseases. No drugs have been approved for these relentlessly progressive and fatal SCAs. Our previous studies indicate that oxidative stress, neuroinflammation, and neuronal apoptosis are elevated in the SCA17 mice, which are the main therapeutic targets of hyperbaric oxygen treatment (HBOT). HBOT is considered to be an alternative and less invasive therapy for SCAs. In this study, we evaluated the HBOT (2.2 ATA for 14 days) effect and the persistence for the management of SCA17 mice and their wild-type littermates. We found HBOT attenuated the motor coordination and cognitive impairment of SCA17 mice and which persisted for about 1 month after the treatment. The results of several biochemistry and liver/kidney hematoxylin and eosin staining show the HBOT condition has no obvious toxicity in the mice. Immunostaining analyses show that the neuroprotective effect of HBOT could be through the promotion of BDNF production and the amelioration of neuroinflammation. Surprisingly, HBOT executes different effects on the male and female SCA17 mice, including the reduction of neuroinflammation and activation of CaMKII and ERK. This study suggests HBOT is a potential alternative therapeutic treatment for SCA17. Accumulated findings have revealed the similarity in disease pathomechanisms and possible therapeutic strategies in polyQ diseases; therefore, HBOT could be an optional treatment as well as the other polyQ diseases.

Schizophrenia patients discharged on antipsychotic polypharmacy from a public psychiatric hospital in Taiwan, 2006-2021.

The aim of this study was to identify the factors associated with antipsychotic polypharmacy (APP), investigate whether APP could affect the risk of rehospitalization, and explore temporal trends in APP use. Schizophrenia patients discharged from the study hospital between 2006 and 2021 (n = 16,722) were included in the analysis. The logistic regression model was employed to determine the predictors significantly associated with APP use. Survival analysis was used to compare time to rehospitalization between APP and antipsychotic monotherapy (AMT). The temporal trend of APP use was analyzed using the Cochran-Armitage Trend test. In comparison with the patients (n = 10,909) who were discharged on AMT, those (n = 5,813) on APP were significantly more likely to be male gender, to receive LAIs, to take clozapine, to take anticholinergic agents, to have a greater number of previous hospitalizations, and to have a higher CPZ equivalent dose of antipsychotic prescription. The prescription rate of APP significantly increased from 18.4 % in 2006 to 44.9 % in 2021. Compared with AMT, APP was associated with more clozapine use, more LAI use, higher doses of antipsychotics, and an increased risk of rehospitalization. In addition, the prescription of APP continued to increase during the study period.

Schizophrenia Patients Discharged on Clozapine Plus Long-Acting Injectable Antipsychotics From a Public Psychiatric Hospital in Taiwan, 2006-2021.

BACKGROUND: Some schizophrenia patients treated with clozapine experience an inadequate response and adherence problems. The purpose of this study was to compare time to rehospitalization within 6 months in schizophrenia patients discharged on 3 clozapine regimens. Additionally, the temporal trend of prescription rate in each group was also explored. METHODS: Schizophrenia patients discharged from the study hospital from January 1, 2006, to December 31, 2021, (n = 3271) were included in the analysis. The type of clozapine prescribed at discharge was divided into 3 groups: clozapine plus long-acting injectable antipsychotics (clozapine + LAIs), clozapine plus other oral antipsychotics (clozapine + OAPs), and clozapine monotherapy. Survival analysis was used to compare time to rehospitalization within 6 months after discharge among the 3 groups. The temporal trend in the prescription rate of each group was analyzed using the Cochran-Armitage Trend test. RESULTS: Patients discharged on clozapine + LAIs had a significantly longer time to rehospitalization than those on clozapine + OAPs or clozapine monotherapy. The prescription rates of clozapine + LAIs and clozapine + OAPs significantly increased over time, whereas the prescription rates of clozapine monotherapy significantly decreased. CONCLUSIONS: Compared with the clozapine + OAPs group, the clozapine + LAIs group had a lower risk of rehospitalization and a lower dose of clozapine prescribed. Therefore, if a second antipsychotic is required for patients who are taking clozapine alone, LAIs should be considered earlier.

The relation between second-generation antipsychotics and laxative use in elderly patients with schizophrenia.

BACKGROUND: We aimed to investigate factors associated with concomitant laxative use among elderly patients with schizophrenia, discharged on second-generation antipsychotics (SGAs), from two large public psychiatric hospitals in Taiwan. METHODS: Elderly patients with schizophrenia who were discharged between 2006 and 2019 and received SGA monotherapy at discharge were included in the analysis. Multivariate logistic regression was used to identify factors associated with regular laxative use at discharge. The Cochrane-Armitage trend test was used to evaluate whether significant time trends existed for rates of laxative use at discharge. RESULTS: A total of 2591 elderly patients with schizophrenia were discharged during the study period, and 1727 of 2591 patients who met the inclusion criteria were included for analysis. Of these 1727 patients, 732 (42.4%) also received concomitant laxatives. Female gender, mood stabiliser use and concomitant diabetes mellitus were found to be associated with increased laxative use. Among SGAs, clozapine was associated with the highest rate of laxative use, followed by zotepine, quetiapine, olanzapine and risperidone. Additionally, risperidone, amisulpride, aripiprazole, paliperidone and sulpiride were associated with comparable rates of laxative use. Laxative use rates grew over time from 30.8% in 2006 to 46.6% in 2019 (z = 4.83, P < 0.001). CONCLUSIONS: Laxative use is common in elderly schizophrenia patients treated with SGAs. In cases of clinically significant constipation, switching to an SGA with a lower risk for constipation, or discontinuing the use of mood stabilisers should be considered, if clinically feasible.

Counterion Migration Driven by Light-Induced Intramolecular Charge Transfer.

A series of D-π-A + pyridinium compounds, in which D = -NPh2 and A+ = -PyMe+ are linked by various amounts of linear phenyl spacers, were strategically designed and synthesized. Their characterization revealed the presence of excited-state intramolecular charge transfer (ESICT) that triggers a corresponding response from the counterion. In medium and strong polar solvents, the fast solvent relaxation occurring after ESICT overwhelms the counterion effect, showing typical emission solvatochromism. In weakly polar solvents, ESICT induces counteranion migration for electrostatic stabilization, the time scale of which is dependent on the radius of the counteranion, the length of the π-linker, and the viscosity of the solvent. In low-viscosity organic solvents such as toluene, counteranion migration occurs within several tens to hundreds of picoseconds, resulting in a time-dependent continuous emission that can be resolved from the spectral temporal evolution. Concrete evidence for this is provided by the chemical synthesis of a D-π-A + pyridinium-sulfur trioxide- zwitterion, where anion migration is restricted due to its internally locked ion pair. As a result, only a single emission band can be observed. These comprehensive studies prove that the ion migration process may be significant for a wide range of ESICT-type ionic fluorophores. Such an ionic movement, triggered by optically pumped ESICT of the D-π-A + dyad, is similar to the molecular machine driven by the redox reaction, but with a facile access and fast response.

Inhibitory effect of PPARγ on NLRP3 inflammasome activation.

Rationale: Stimulation of the NLRP3 inflammasome by metabolic byproducts is known to result in inflammatory responses and metabolic diseases. However, how the host controls aberrant NLRP3 inflammasome activation remains unclear. PPARγ, a known regulator of energy metabolism, plays an anti-inflammatory role through the inhibition of NF-κB activation and additionally attenuates NLRP3-dependent IL-1ß and IL-18 production. Therefore, we hypothesized that PPARγ serves as an endogenous modulator that attenuates NLRP3 inflammasome activation in macrophages. Methods: Mouse peritoneal macrophages with exposure to a PPARγ agonist at different stages and the NLRP3 inflammasome-reconstituted system in HEK293T cells were used to investigate the additional anti-inflammatory effect of PPARγ on NLRP3 inflammasome regulation. Circulating mononuclear cells of obese patients with weight-loss surgery were used to identify the in vivo correlation between PPARγ and the NLRP3 inflammasome. Results: Exposure to the PPARγ agonist, rosiglitazone, during the second signal of NLRP3 inflammasome activation attenuated caspase-1 and IL-1ß maturation. Moreover, PPARγ interfered with NLRP3 inflammasome formation by decreasing NLRP3-ASC and NLRP3-NLRP3 interactions as well as NLRP3-dependent ASC oligomerization, which is mediated through interaction between the PPARγ DNA-binding domain and the nucleotide-binding and leucine-rich repeat domains of NLRP3. Furthermore, PPARγ was required to limit metabolic damage-associated molecular pattern-induced NLRP3 inflammasome activation in mouse macrophages. Finally, the mature caspase-1/PPARγ ratio was reduced in circulating mononuclear cells of obese patients after weight-loss surgery, which we define as an "NLRP3 accelerating index". Conclusions: These results revealed an additional anti-inflammatory role for PPARγ in suppressing NLRP3 inflammasome activation through interaction with NLRP3. Thus, our study highlights that PPARγ agonism may be a therapeutic option for targeting NLRP3-related metabolic diseases.

A Sensor Fusion Based Nonholonomic Wheeled Mobile Robot for Tracking Control.

In this paper, a detail design procedure of the real-time trajectory tracking for the nonholonomic wheeled mobile robot (NWMR) is proposed. A 9-axis micro electro-mechanical systems (MEMS) inertial measurement unit (IMU) sensor is used to measure the posture of the NWMR, the position information of NWMR and the hand-held device are acquired by global positioning system (GPS) and then transmit via radio frequency (RF) module. In addition, in order to avoid the gimbal lock produced by the posture computation from Euler angles, the quaternion is utilized to compute the posture of the NWMR. Furthermore, the Kalman filter is used to filter out the readout noise of the GPS and calculate the position of NWMR and then track the object. The simulation results show the posture error between the NWMR and the hand-held device can converge to zero after 3.928 seconds for the dynamic tracking. Lastly, the experimental results show the validation and feasibility of the proposed results.

Toward the Rational Design of Universal Dual Polarity Matrix for MALDI Mass Spectrometry.

A series of novel anthranilic acid derivatives I-IV, of which COOH-NH2 (I) and COOH-NHMe (IV) are endowed with acid and base bifunctionality, were designed and synthesized for matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry applications in dual polarity molecular imaging of biological samples, particularly for lipids. The heat of protonation, deprotonation, and proton transfer reaction as well as the capability of analyzing biomolecules in both positive and negative ion modes for I-IV were systematically investigated under standard 355 nm laser excitation. The results indicate correlation between dual polarity and acid-base property. Further, COOH-NHMe (IV) showed a unique performance and was successfully applied as the matrix for MALDI-TOF mass spectrometry imaging (MSI) for studying the mouse brain. Our results demonstrate the superiority of COOH-NHMe (IV) in detecting more lipid and protein species compared to commercially available matrices. Moreover, MALDI-TOF MSI results were obtained for lipid distributions, making COOH-NHMe (IV) a potential next generation universal matrix.

Human dendritic cell-specific ICAM-3-grabbing non-integrin downstream signaling alleviates renal fibrosis via Raf-1 activation in systemic candidiasis.

We generated a human dendritic cell-specific ICAM-3-grabbing non-integrin (DC-SIGN) transgenic mouse in which renal tubular epithelial cells expressed DC-SIGN. The transgenic mice were infected with Candida albicans intravenously to study how DC-SIGN expression affected the pathogenesis of systemic candidiasis. We discovered that, while C. albicans infection induced renal fibrosis in both transgenic and littermate control mice, the transgenic mice had significantly lower levels of Acta2, Col1a2, Col3a1, and Col4a1 mRNA transcripts compared to the controls. KIM-1, an emerging biomarker for kidney injury, along with Tnf, Il6, and Tgfb1 transcripts, were lower in infected transgenic mice, and yet, the levels of Il10 remained comparable to the controls. While renal CD45+ infiltrating cells were the source of Tnf, Il6, and Il10, LTL+ renal proximal tubular epithelial cells were TGF-ß1 producers in both infected transgenic and littermate controls. DC-SIGN-expressing tubular epithelial cells produced less TGF-ß1 in response to C. albicans infection. In vivo experiments demonstrated that renal proximal tubular epithelial cell production of TGF-ß1 was key to C. albicans-induced renal fibrosis and injury. Infection of transgenic mice induced a marked increase of phosphorylated Raf-1 and p38 in the kidney. However, ERK1/2 and JNK phosphorylation was more pronounced in the infected-littermate controls. Interestingly, treating the infected transgenic mice with a Raf-1 inhibitor increased the levels of the Tgfb1, Kim1, and Acta2 transcripts. These results indicate that DC-SIGN signaling, through activation of Raf-1 and p38 and suppression of JNK and ERK1/2 phosphorylation, reduces TGF-ß1 production and C. albicans-induced renal fibrosis. Our study reveals for the first time the effect of DC-SIGN expression on C. albicans-induced renal fibrosis.

The azatryptophan-based fluorescent platform for in vitro rapid screening of inhibitors disrupting IKKß-NEMO interaction.

The nuclear factor-κB (NF-κB) plays an important role in inflammatory and immune responses. Aberrant NF-κB signaling is implicated in multiple disorders, including cancer. Targeting the regulatory scaffold subunit IκB kinase γ (IKKγ/NEMO) as therapeutic interventions could be promising due to its specific involvement in canonical NF-κB activation without interfering with non-canonical signaling. In this study, the use of unnatural amino acid substituted IKKß with unique photophysical activity to sense water environment changes upon interaction with NEMO provides a powerful in vitro screening platform that would greatly facilitate the identification of compounds having the potential to disrupt IKKß-NEMO interaction, and thus specifically modulate the canonical NF-κB pathway. We then utilized a competitive binding platform to screen the binding ability of a number of potential molecules being synthesized. Our results suggest that a lead compound (-)-PDC-099 is a potent agent with ascertained potency to disrupt IKKß-NEMO complex for modulating NF-κB canonical pathway.

Excited-State Proton Transfer in 3-Cyano-7-azaindole: From Aqueous Solution to Ice.

We investigated the excited-state proton transfer (ESPT) reaction for 3-cyano-7-azaindole (3CAI) in aqueous solution and in ice. 3CAI undergoes water-catalyzed ESPT in the aqueous solution, giving normal (355 nm) and proton transfer tautomer (∼472 nm) emission bands. Detailed temperature-dependent studies showed that the values of activation free energy (Δ G‡) were similar between N-H and N-D isotopes. Therefore, water-catalyzed ESPT involves a stepwise mechanism incorporating solvation equilibrium ( Keq) to form a 1:1 (molar ratio) water:3CAI cyclic hydrogen-bonded complex as an intermediate, followed by perhaps proton tunneling reaction. In sharp contrast, 3CAI in ice undergoes entirely different photophysical properties, in which 3CAI self-organizes to form a double-hydrogen-bonded dimers at the grain boundary of the polycrystalline. Upon excitation, the dimer proceeds with a fast excited-state double proton transfer reaction, giving rise to solely a tautomer emission (∼450 nm). The distinct difference in ESPT properties between water and ice makes azaindoles feasible for the investigation of water-ice interface property.

Insight into the Amino-Type Excited-State Intramolecular Proton Transfer Cycle Using N-Tosyl Derivatives of 2-(2'-Aminophenyl)benzothiazole.

Studies have been carried out to gain insight in to an overall excited-state proton transfer cycle for a series of N-tosyl derivatives of 2-(2'-aminophenyl)benzothiazole. The results indicate that followed by ultrafast (<150 fs) excited-state intramolecular proton transfer (ESIPT), the titled compounds undergo rotational isomerization along the C1-C1' bond. For the model compound 2-(2'-tosylaminophenyl)benzothiazole (PBT-NHTs) the subsequent cis-trans isomerization process in both triplet and ground states are probed by nanosecond transient absorption (TA) and two-step laser-induced fluorescence (TSLIF) spectroscopy. Both TA and TSLIF results indicate the existence of a long-lived trans-tautomer species in the ground state with a lifetime of few microseconds. The experimental results correlate well with the theoretical approach, which suggests that PBT-NHTs proton transfer tautomer generated in the excited state undergoes intramolecular C1-C1' rotation to ∼100° between benzothiazole and phenyl moieties in which the energetics for the S1 and T1 states are nearly identical. As a result, the intersystem crossing between S1 and T1 states serves as a fast deactivation pathway for the excited-state cis-tautomer to channel into both cis- and trans-tautomer in their respective T1 states, followed by the dominant T1-S0 radiationless deactivation to populate the trans-tautomer in the ground state. The trans-tautomer species in the S0 state proceeds with intermolecular double proton transfer to regenerate the cis-normal form. An overall proton-transfer cycle describing the amino-type ESIPT and the subsequent isomerization processes is thus depicted in detail.

A new class of N-H proton transfer molecules: wide tautomer emission tuning from 590 nm to 770 nm via a facile, single site amino derivatization in 10-aminobenzo[h]quinoline.

Facile derivation of 10-aminobenzo[h]quinoline via replacing one of the N-H hydrogen atoms by various substituents generates a new series of excited-state intramolecular N-H proton-transfer molecules, for which the proton-transfer emission can be widely tuned from 590 nm to 770 nm simply by harnessing the electron-donating/withdrawing strength of the substituents.

Harnessing Excited-State Intramolecular Proton-Transfer Reaction via a Series of Amino-Type Hydrogen-Bonding Molecules.

A series of new amino (NH)-type hydrogen-bonding (H-bonding) compounds comprising 2-(2'-aminophenyl)benzothiazole and its extensive derivatives were designed and synthesized. Unlike in the hydroxyl (OH)-type H-bonding systems, one of the amino hydrogens can be replaced with electron-donating/withdrawing groups. This, together with a versatile capability for modifying the parent moiety, makes feasible the comprehensive spectroscopy and dynamics studies of amino-type excited-state intramolecular proton transfer (ESIPT), which was previously inaccessible in the hydroxyl-type ESIPT systems. Empirical correlations were observed among the hydrogen-bonding strength (the N-H bond distances and proton acidity), ESIPT kinetics, and thermodynamics, demonstrating a trend that the stronger N-H···N hydrogen bond leads to a faster ESIPT, as experimentally observed, and a more exergonic reaction thermodynamics. Accordingly, ESIPT reaction can be harnessed for the first time from a highly endergonic type (i.e., prohibition) toward equilibrium with a measurable ESIPT rate and then to the highly exergonic, ultrafast ESIPT reaction within the same series of amino-type intramolecular H-bond system.

In vitro characterization of magnetic electrospun IDA-grafted chitosan nanofiber composite for hyperthermic tumor cell treatment.

Magnetic nanoparticles were the thermoseeds under an alternating magnetic field and can be used to produce highly localized hyperthermia effect on deep-seated tumor. Nevertheless, effective and precisive delivery of nanoparticles to the treatment-intended site remains a challenge. In this study, Fe3O4 nanoparticles were incorporated onto the crosslinked electrospun chitosan nanofibers using chemical co-precipitation from the Fe ions adsorbed. Such magnetic nanoparticle-nanofiber composites could be delivered to the treatment site precisely by surgical or endoscopic method. Iminodiacetic acid (IDA) functionality was grafted onto the chitosan with an aim to increase the amount of magnetic nanoparticles formed in the electrospun magnetic nanofiber composite. The morphology, crystalline phase as well as the magnetism characteristic of the magnetic electrospun nanofiber matrixes, was analyzed. Results have indicated that, with the incorporation of IDA functionality, more magnetic nanoparticles were formed in the electrospun chitosan nanofiber matrix. In addition, the magnetic IDA-grafted chitosan nanofiber composite can effectively reduced the tumor cell proliferation under the application of magnetic field. This finding suggested the magnetic electrospun chitosan nanofiber composite can be of potential for hyperthermia treatment.

In vitro feasibility study of the use of a magnetic electrospun chitosan nanofiber composite for hyperthermia treatment of tumor cells.

Hyperthermia has been reported to be an effective cancer treatment modality, as tumor cells are more temperature-sensitive than their normal counterparts. Since the ambient temperature can be increased by placing magnetic nanoparticles in an alternating magnetic field it has become of interest to incorporate these magnetic nanoparticles into biodegradable nanofibers for possible endoscopic hyperthermia treatment of malignant tumors. In this preliminary investigation we have explored various characteristics of biodegradable electrospun chitosan nanofibers containing magnetic nanoparticles prepared by different methods. These methods included: (1) E-CHS-Fe(3)O(4), with electrospun chitosan nanofibers directly immersed in a magnetic nanoparticle solution; (2) E-CHS-Fe(2+), with the electrospun chitosan nanofibers initially immersed in Fe(+2)/Fe(+3) solution, followed by chemical co-precipitation of the magnetic nanoparticles. The morphology and crystalline phase of the magnetic electrospun nanofiber matrices were determined by scanning electron microscopy, transmission electron microscopy, selected area electron diffraction, and X-ray diffraction spectroscopy. The magnetic characteristics were measured using a superconducting quantum interference device. The heating properties of these magnetic electrospun nanofiber matrices in an alternating magnetic field were investigated at a frequency of 750 kHz and magnetic intensity of 6.4 kW. In vitro cell incubation experiments indicated that these magnetic electrospun nanofiber matrices are non-cytotoxic and can effectively reduce tumor cell proliferation upon application of a magnetic field.

Effects of crossed states on photoluminescence excitation spectroscopy of InAs quantum dots.

In this report, the influence of the intrinsic transitions between bound-to-delocalized states (crossed states or quasicontinuous density of electron-hole states) on photoluminescence excitation (PLE) spectra of InAs quantum dots (QDs) was investigated. The InAs QDs were different in size, shape, and number of bound states. Results from the PLE spectroscopy at low temperature and under a high magnetic field (up to 14 T) were compared. Our findings show that the profile of the PLE resonances associated with the bound transitions disintegrated and broadened. This was attributed to the coupling of the localized QD excited states to the crossed states and scattering of longitudinal acoustical (LA) phonons. The degree of spectral linewidth broadening was larger for the excited state in smaller QDs because of the higher crossed joint density of states and scattering rate.

Impacts of coulomb interactions on the magnetic responses of excitonic complexes in single semiconductor nanostructures.

We report on the diamagnetic responses of different exciton complexes in single InAs/GaAs self-assembled quantum dots (QDs) and quantum rings (QRs). For QDs, the imbalanced magnetic responses of inter-particle Coulomb interactions play a crucial role in the diamagnetic shifts of excitons (X), biexcitons (XX), and positive trions (X-). For negative trions (X-) in QDs, anomalous magnetic responses are observed, which cannot be described by the conventional quadratic energy shift with the magnetic field. The anomalous behavior is attributed to the apparent change in the electron wave function extent after photon emission due to the strong Coulomb attraction by the hole in its initial state. In QRs, the diamagnetic responses of X and XX also show different behaviors. Unlike QDs, the diamagnetic shift of XX in QRs is considerably larger than that of X. The inherent structural asymmetry combined with the inter-particle Coulomb interactions makes the wave function distribution of XX very different from that of X in QRs. Our results suggest that the phase coherence of XX in QRs may survive from the wave function localization due to the structural asymmetry or imperfections.

Positive expiratory pressure changes aerosol distribution in patients with cystic fibrosis.

HYPOTHESIS: We hypothesized that aerosol distribution in the lungs of patients with cystic fibrosis changes with positive expiratory pressure (PEP). METHODS: Eight patients were randomized to one of 2 conditions. On one study day, patients inhaled saline aerosol containing 99mtechnetium generated by a Pari LC Plus nebulizer and exhaled through a Pari PEP device. On another day, the same patients exhaled through a low-resistance Pari filter (no PEP). Afterwards, they underwent gamma-camera lung imaging. Images were analyzed for lung deposition fraction, expressed as a percent of the initial nebulizer activity, and deposition pattern, expressed in terms of inner-outer and apical-basal ratios. RESULTS: Lung deposition fraction was significantly lower with the Pari PEP device; the mean + SD deposition fraction was 6.10 + 3.05% (median 6.20%) with PEP, compared to 10.76 + 4.52% (median 10.32%) (p = 0.0078) without PEP. The inner-outer ratio was 2.01 + 0.69 (median 2.23) with PEP, which was significantly lower than without PEP (2.76 + 1.33, median 2.55) (p = 0.004). The apical-basal ratio was 0.82 + 0.31 (median 0.80) with PEP, which was not significantly different from no PEP (1.00 + 0.49, median 0.90). CONCLUSION: These results indicate that less aerosol is deposited in the lungs of patients with cystic fibrosis when the Pari LC Plus nebulizer is used with the Pari PEP device, as described in these experiments. Nevertheless, aerosol administration with this nebulizer and PEP device also results in a proportional redistribution of aerosol to the peripheral airways, compared to nebulization without the PEP device. The clinical relevance of this subtle redistribution of aerosol in cystic fibrosis patients will probably depend on the drug administered and disease severity.