Divergent brainstem opioidergic pathways that coordinate breathing with pain and emotions.

Breathing can be heavily influenced by pain or internal emotional states, but the neural circuitry underlying this tight coordination is unknown. Here we report that Oprm1 (µ-opioid receptor)-expressing neurons in the lateral parabrachial nucleus (PBL) are crucial for coordinating breathing with affective pain in mice. Individual PBLOprm1 neuronal activity synchronizes with breathing rhythm and responds to noxious stimuli. Manipulating PBLOprm1 activity directly changes breathing rate, affective pain perception, and anxiety. Furthermore, PBLOprm1 neurons constitute two distinct subpopulations in a "core-shell" configuration that divergently projects to the forebrain and hindbrain. Through non-overlapping projections to the central amygdala and pre-Bötzinger complex, these two subpopulations differentially regulate breathing, affective pain, and negative emotions. Moreover, these subsets form recurrent excitatory networks through reciprocal glutamatergic projections. Together, our data define the divergent parabrachial opioidergic circuits as a common neural substrate that coordinates breathing with various sensations and behaviors such as pain and emotional processing.

Dosimetry of a novel converging X-ray source for kilovoltage radiotherapy.

PURPOSE: The objective of this work was to evaluate phantom dosimetry of a novel kilovoltage (kV) X-ray source, which employs a stationary tungsten anode and a linearly swept scanning electron beam. The source utilizes converging X-ray collimation along with orthogonal mechanical rotation to distribute surface flux over large area. In this study, this was investigated as a potential solution to fast-falloff limitations expected with kV radiotherapy. This was done with the aim of future clinical development of a lower cost radiotherapy alternative to megavoltage (MV) linac systems. METHODS: Radiochromic film was employed for dosimetry on the kV X-ray source of the linear-converging radiotherapy system (LCRS). The source utilizes charge particle optics to magnetically deflect and focus an electron beam along a stationary, reflection tungsten target in an ultra-high-vacuum stainless-steel chamber. Resulting X-rays were collimated into converging beamlets that span a large planar angle and converge at the system isocenter. In this study, radiochromic film dosimetry was done at 140 and 145 kVp for a designated planning treatment volume (PTV) of 4 cm diameter. An acrylic phantom was employed for dose distribution measurements of stationary and rotational delivery. Film dosimetry was evaluated in planes parallel to the source X-ray window at various depths, as well as in the plane of gantry rotation. RESULTS: At 140 and 145 kVp and using a collimated 4 cm square field at depth, lesion-to-skin dose ratio was shown to improve with additional beams from different relative source positions, where the different beams are focused at the same isocenter and do not overlap at the phantom surface. It was only possible to achieve a 1:1 Dmax -to-surface ratio with four delivery beams, but the ratio improved to 4:1 with 12 beams, focused at the same isocenter depth of 7.8 cm in an acrylic phantom. For the tests conducted, the following Dmax -to-surface ratios were obtained: 0.4:1 lesion-to-skin ratio for stationary delivery from one entry beam, 0.71:1 lesion-to-skin ratio was obtained for two beams, 1.07:1 ratio for four beams, and 4:1 for 12 beams. Dose-depth profiles were evaluated for stationary and rotational dosimetry. Additionally, rotational dosimetry was measured for a case more analogous to a clinical scenario, where the isocenter was located at an off-center simulated lesion. CONCLUSIONS: The results demonstrate potential dose-depth improvements with kV arc therapy by distributing the surface flux with a wide converging beam along with perpendicular mechanical source rotation of the LCRS. The system delivered tolerable dose to a large surface area when a threshold of multiple, separated beams was reached. The radiochromic film data support the feasibility of the construct of the LCRS kV radiotherapy system design.

Monte Carlo calculated kilovoltage x-ray arc therapy plans for three lung cancer patients.

Purpose: The intent of this work was to evaluate the ability of our 200 kV kilovoltage arc therapy (KVAT) system to treat realistic lung tumors without exceeding dose constraints to organs-at-risk (OAR).Methods and Materials: Monte Carlo (MC) methods and the McO optimization framework generated and inversely optimized KVAT treatment plans for 3 SABR lung cancer patients. The KVAT system was designed to treat deep-seated lesions with kilovoltage photons. KVAT delivers dose to roughly spherical PTVs and therefore non-spherical PTVs were divided into spherical sub-volumes. A prescription dose of 12 Gy/fx × 4 fractions was planned to 90% of the PTV volume. KVAT plans were compared to VMC++ calculated, 6 MV stereotactic ablative radiotherapy (SABR) treatment plans. Dose distributions, dose volume histograms, gradient index (GI), planned mean doses and plan treatment times were calculated. Dose constraints for organs-at-risk (OAR) were taken from RTOG 101.Results: All plans, with the exception of the rib dose calculated in one of the KVAT plans for a peripheral lesion, were within dose-constraints. In general, KVAT plans had higher planned doses to OARs. KVAT GI values were 5.7, 7.2 and 8.9 and SABR values were 4.6, 4.1, and 4.7 for patient 1, 2 and 3, respectively. KVAT plan treatment times were 49, 65 and 17 min for patients 1, 2 and 3, respectively.Conclusions: Inverse optimization and MC methods demonstrated the ability of KVAT to produce treatment plans without exceeding TG 101 dose constraints to OARs for 2 out of 3 investigated lung cancer patients.

Confocal laser method for quantitative evaluation of critical optical properties of toric intraocular lenses.

PURPOSE: To present a proof-of-concept study on the development and implementation of an innovative confocal laser method platform for precise quantitative evaluation of critical optical properties unique to toric intraocular lenses (IOLs). SETTING: U.S. Food and Drug Administration, Optical Therapeutics and Medical Nanophotonics Laboratory, Silver Spring, Maryland, USA. DESIGN: Experimental study. METHODS: The optical properties of hydrophobic toric IOLs were evaluated with a confocal laser method that was modified to isolate the 2 planes of focus that are observed with toric IOLs. RESULTS: The results show the confocal laser method has the potential to measure the orthogonally separated optical powers and then calculate them to the commonly referenced spherical equivalent and cylinder powers of toric IOLs with high accuracy (≤1 µm of focal length measurement). Furthermore, the proposed confocal laser method design includes a new component for precise differentiation of the 2 focal planes and isolation of the 2 focal points, and thus for accurate measurement of the anterior cylinder axis of toric IOLs. CONCLUSION: The modifications to the confocal laser method platform enabled the quantitative evaluation of optical properties attributed to toric IOLs. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Quantitative air-trapping analysis in children with mild cystic fibrosis lung disease.

The purpose of this study was to compare quantitative computed tomography air trapping (AT) and pulmonary function measurements between subjects with mild cystic fibrosis lung disease (MCF; forced expiratory volume in 1 sec (FEV1) > 70% predicted) and normal age-matched controls. Quantitative AT measurements at different levels of expiration were evaluated. Ten subjects from the MCF group and 10 normal subjects underwent inspiratory and expiratory spirometer-triggered chest high-resolution computed tomography (HRCT) and pulmonary function tests. Six matched CT images were obtained at full inflation and at a lung volume near residual volume (nRV). Quantitative measurements of AT were determined by evaluating expiratory CT lung density and by the percent of segmented lung which demonstrated AT on expiratory scans. Percent AT was evaluated for all lung slices combined (global AT), and also by regional assessment. Additional comparisons of lung density and percent air trapping were made in 10 CF subjects with three matched axial HRCT images at lung volumes corresponding to full inflation, near functional residual capacity (nFRC), and nRV. All measurements of expiratory lung density in CF subjects were significantly lower and % AT significantly higher than normal controls. Significant correlations for all subjects were observed between % global AT and RV/TLC as well as forced expiratory flow between 25-75% of forced vital capacity (FEF(25-75)) % predicted. Pulmonary density measurements and % AT better discriminated differences between groups than PFTs. Measurements made on expiratory scans near FRC showed significantly higher values for AT than those made near RV.

Effect of contaminating red blood cells on OKT3-mediated polyclonal activation of peripheral blood mononuclear cells.

Erythrocytes are typically present as impurities in the majority of peripheral blood mononuclear cell (PBMC) preparations. This study was undertaken to investigate the effects of contaminating red blood cells (RBC) on the ability of OKT3 to activate CD4(+) and CD8(+) T cells. Surprisingly, the levels of gamma interferon, tumor necrosis factor alpha, and interleukin-1 beta (IL-1 beta) produced by PBMC upon stimulation by OKT3 were increased (P < 0.05) in a dose-dependent manner when increasing amounts of autologous RBC (RBC-to-PBMC ratios of 2:1, 10:1, and 50:1) were spiked into PBMC preparations. The OKT3-driven induction of the IL-2 receptor (CD25) and the proliferation of T lymphocytes in response to phorbol myristate acetate were not affected by the addition of RBC.