Stability Evaluation and Pharmacokinetic Profiling of Vepdegestrant in Rodents Using Liquid Chromatography-Tandem Mass Spectrometry.

Vepdegestrant (formerly ARV-471), a novel proteolysis-targeting chimera (PROTAC), targets estrogen receptor alpha (ERα) for degradation, offering a promising option to treat advanced ER-positive breast cancer. We developed and validated a sensitive and rapid liquid chromatography-tandem mass spectrometry method to quantify vepdegestrant in rodent plasma using bavdegalutamide (formerly ARV-110) as an internal standard. Plasma samples were prepared with protein precipitation using acetonitrile and analyzed using reverse-phase C18 columns and a mobile phase of 10 mM ammonium formate in distilled water and acetonitrile. The method demonstrated linearity from 1 to 1000 ng/mL in mouse and rat plasma, meeting all validation criteria, and successfully applied to in vivo and in vitro studies. Pharmacokinetic analysis revealed low-to-moderate clearance (313.3, 1053 mL/h/kg) and oral bioavailability (17.91, 24.12%) of vepdegestrant in mice and rats, respectively. It was unstable in buffer solutions across pH 2-10 and in phosphate-buffered saline (pH 7.4), likely due to adsorption, but remained stable in mouse and rat plasma at varying temperatures. In liver microsomes, vepdegestrant exhibited moderate stability in rats but was stable in mice, dogs, and humans. These findings enhance the understanding of pharmacokinetic properties of vepdegestrant supporting further development of PROTAC drugs.

Multi-class segmentation of temporomandibular joint using ensemble deep learning.

Temporomandibular joint disorders are prevalent causes of orofacial discomfort. Diagnosis predominantly relies on assessing the configuration and positions of temporomandibular joint components in magnetic resonance images. The complex anatomy of the temporomandibular joint, coupled with the variability in magnetic resonance image quality, often hinders an accurate diagnosis. To surmount this challenge, we developed deep learning models tailored to the automatic segmentation of temporomandibular joint components, including the temporal bone, disc, and condyle. These models underwent rigorous training and validation utilizing a dataset of 3693 magnetic resonance images from 542 patients. Upon evaluation, our ensemble model, which combines five individual models, yielded average Dice similarity coefficients of 0.867, 0.733, 0.904, and 0.952 for the temporal bone, disc, condyle, and background class during internal testing. In the external validation, the average Dice similarity coefficients values for the temporal bone, disc, condyle, and background were 0.720, 0.604, 0.800, and 0.869, respectively. When applied in a clinical setting, these artificial intelligence-augmented tools enhanced the diagnostic accuracy of physicians, especially when discerning between temporomandibular joint anterior disc displacement and osteoarthritis. In essence, automated temporomandibular joint segmentation by our deep learning approach, stands as a promising aid in refining temporomandibular joint disorders diagnosis and treatment strategies.

A retrospective evaluation of individual thigh muscle volume disparities based on hip fracture types in followed-up patients: an AI-based segmentation approach using UNETR.

Background: Hip fractures are a common and debilitating condition, particularly among older adults. Loss of muscle mass and strength is a common consequence of hip fractures, which further contribute to functional decline and increased disability. Assessing changes in individual thigh muscles volume in follow-up patients can provide valuable insights into the quantitative recovery process and guide rehabilitation interventions. However, accurately measuring anatomical individual thigh muscle volume can be challenging due to various, labor intensive and time-consuming. Materials and Methods: This study aimed to evaluate differences in thigh muscle volume in followed-up hip fracture patients computed tomography (CT) scans using an AI based automatic muscle segmentation model. The study included a total of 18 patients at Gyeongsang National University, who had undergone surgical treatment for a hip fracture. We utilized the automatic segmentation algorithm which we have already developed using UNETR (U-net Transformer) architecture, performance dice score = 0.84, relative absolute volume difference 0.019 ± 0.017%. Results: The results revealed intertrochanteric fractures result in more significant muscle volume loss (females: -97.4 cm3, males: -178.2 cm3) compared to femoral neck fractures (females: -83 cm3, males: -147.2 cm3). Additionally, the study uncovered substantial disparities in the susceptibility to volume loss among specific thigh muscles, including the Vastus lateralis, Adductor longus and brevis, and Gluteus maximus, particularly in cases of intertrochanteric fractures. Conclusions: The use of an automatic muscle segmentation model based on deep learning algorithms enables efficient and accurate analysis of thigh muscle volume differences in followed up hip fracture patients. Our findings emphasize the significant muscle loss tied to sarcopenia, a critical condition among the elderly. Intertrochanteric fractures resulted in greater muscle volume deformities, especially in key muscle groups, across both genders. Notably, while most muscles exhibited volume reduction following hip fractures, the sartorius, vastus and gluteus groups demonstrated more significant disparities in individuals who sustained intertrochanteric fractures. This non-invasive approach provides valuable insights into the extent of muscle atrophy following hip fracture and can inform targeted rehabilitation interventions.

Evaluating the Impact of Rotary Instrument Lubricants on Dental Implant Osseointegration: An Experimental Rabbit Tibia Study.

Purpose: The osseointegration in dental implants is greatly affected by various surface properties, such as chemistry, texture, and overall cleanliness. This study aimed to investigate the impact of mineral oil lubricants used in rotary instruments on osseointegration within rabbit tibiae, with a specific focus on potential contamination from dental handpices. Materials and Methods: Twelve New Zealand rabbits were included in this study, each receiving two implants in each tibia, resulting in a total of 48 implants across the study. Groups were organized based on the time until euthanasia and the degree of implant contamination. Three contamination levels were defined: the first group received implants without any lubricant in the handpiece (control group); the second group received implants with handpices managed as recommended; the third group had implants placed using fixtures pre-soaked in lubricant. These groups were further subdivided based on euthanization periods of two and four weeks. We measured and analyzed both the removal torque and the bone-implant contact. Results: We observed a non-significant inverse correlation between the severity of fixture contamination and removal torque. However, there was a significant reduction in bone-implant contact associated with higher contamination levels, particularly after four weeks. Conclusions: Even brief exposure to lubricants from handpieces can jeopardize the osseointegration of implants in bone. Therefore, it is imperative to implement thorough procedures for lubricant removal post-application and to employ precise cleaning and suction during implant drilling and placement to minimize residual oil on the implant surface.

User-Centric Cell-Free Massive MIMO with Low-Resolution ADCs for Massive Access.

This paper proposes a heuristic association algorithm between access points (APs) and user equipment (UE) in user-centric cell-free massive multiple-input-multiple-output (MIMO) systems, specifically targeting scenarios where UEs share the same frequency and time resources. The proposed algorithm prevents overserving APs and ensures the connectivity of all UEs, even when the number of UEs is significantly greater than the number of APs. Additionally, we assume the use of low-resolution analog-to-digital converters (ADCs) to reduce fronthaul capacity. While realistic massive access scenarios, such as those in Internet-of-Things (IoT) environments, often involve hundreds or thousands of UEs per AP using multiple access techniques to allocate different frequency and time resources, our study focuses on scenarios where UEs within each AP cluster share the same frequency and time resources to highlight the impact of pilot contamination in dense network environments. The proposed algorithm is validated through simulations, confirming that it guarantees the connection of all UEs and prevents overserving APs. Furthermore, we analyze the required fronthaul capacity based on quantization bits and confirm that the proposed algorithm outperforms existing algorithms in terms of SE and average SE performance for UEs.

A three-dimensional valve-on-chip microphysiological system implicates cell cycle progression, cholesterol metabolism and protein homeostasis in early calcific aortic valve disease progression.

BACKGROUND: Calcific aortic valve disease (CAVD) is one of the most common forms of valvulopathy, with a 50 % elevated risk of a fatal cardiovascular event, and greater than 15,000 annual deaths in North America alone. The treatment standard is valve replacement as early diagnostic, mitigation, and drug strategies remain underdeveloped. The development of early diagnostic and therapeutic strategies requires the fabrication of effective in vitro valve mimetic models to elucidate early CAVD mechanisms. METHODS: In this study, we developed a multilayered physiologically relevant 3D valve-on-chip (VOC) system that incorporated aortic valve mimetic extracellular matrix (ECM), porcine aortic valve interstitial cell (VIC) and endothelial cell (VEC) co-culture and dynamic mechanical stimuli. Collagen and glycosaminoglycan (GAG) based hydrogels were assembled in a bilayer to mimic healthy or diseased compositions of the native fibrosa and spongiosa. Multiphoton imaging and proteomic analysis of healthy and diseased VOCs were performed. RESULTS: Collagen-based bilayered hydrogel maintained the phenotype of the VICs. Proteins related to cellular processes like cell cycle progression, cholesterol biosynthesis, and protein homeostasis were found to be significantly altered and correlated with changes in cell metabolism in diseased VOCs. This study suggested that diseased VOCs may represent an early, adaptive disease initiation stage, which was corroborated by human aortic valve proteomic assessment. CONCLUSIONS: In this study, we developed a collagen-based bilayered hydrogel to mimic healthy or diseased compositions of the native fibrosa and spongiosa layers. When the gels were assembled in a VOC with VECs and VICs, the diseased VOCs revealed key insights about the CAVD initiation process. STATEMENT OF SIGNIFICANCE: Calcific aortic valve disease (CAVD) elevates the risk of death due to cardiovascular pathophysiology by 50 %, however, prevention and mitigation strategies are lacking, clinically. Developing tools to assess early disease would significantly aid in the prevention of disease and in the development of therapeutics. Previously, studies have utilized collagen and glycosaminoglycan-based hydrogels for valve cell co-cultures, valve cell co-cultures in dynamic environments, and inorganic polymer-based multilayered hydrogels; however, these approaches have not been combined to make a physiologically relevant model for CAVD studies. We fabricated a bi-layered hydrogel that closely mimics the aortic valve and used it for valve cell co-culture in a dynamic platform to gain mechanistic insights into the CAVD initiation process using proteomic and multiphoton imaging assessment.

Nonsurgical improvement of severe upper airway obstruction in infants with Robin sequence and cleft palate using Stanford Orthodontic Airway Plate treatment.

STUDY OBJECTIVES: Severe respiratory distress of neonates with Robin sequence (RS) is traditionally managed by surgery. Stanford Orthodontic Airway Plate treatment (SOAP) is a nonsurgical option. The study aimed to determine if SOAP can improve polysomnography (PSG) parameters of neonates with RS. METHODS: PSG of neonates with RS treated with SOAP at a single hospital were retrospectively analyzed. Patients without PSG at all 4 time points (pre-, start of-, mid-, and post-treatment) were excluded. Data were analyzed using a linear mixed effects model. RESULTS: Sixteen patients were included. All patients had cleft palate (CP). The median age (min, max) at the start of treatment was 1.1 months (0.5, 2.3) with the treatment duration of 4.5 months (3.5, 6.0). The mean obstructive apnea-hypopnea index (95% confidence interval) decreased from 39.3 events/hour (32.9, 45.7) to 12.2 events/hour (6.7, 17.7) (P < 0.001), obstructive apnea index decreased from 14.1 (11.2, 17.0) events/hour to 1.0 (-1.5, 3.5) events/hour (P < 0.001), and oxygen nadir increased from 79.9% (77.4, 82.5) to 88.2% (85.5, 90.8) (P < 0.001) between pre- and start of treatment. Respiratory improvements were sustained during and after the treatment. All patients avoided mandibular distraction osteogenesis or tracheostomy following SOAP. CONCLUSIONS: As being a rare diagnosis, the number of participants was, as expected, low. However, the current study demonstrates that SOAP can improve PSG parameters, demonstrating its potential utility before surgical interventions for neonates with RS and CP experiencing severe respiratory distress.

Nanoleakage of apical sealing using a calcium silicate-based sealer according to canal drying methods.

Objectives: This study investigated the nanoleakage of root canal obturations using calcium silicate-based sealer according to different drying methods. Materials and Methods: Fifty-two extracted mandibular premolars with a single root canal and straight root were selected for this study. After canal preparation with a nickel-titanium rotary file system, the specimens were randomly divided into 4 groups according to canal drying methods (1: complete drying, 2: blot drying/distilled water, 3: blot drying/NaOCl, 4: aspiration only). The root canals were obturated using a single-cone filling technique with a calcium silicate-based sealer. Nanoleakage was evaluated using a nanoflow device after 24 hours, 1 week, and 1 month. Data were collected twice per second at the nanoscale and measured in nanoliters per second. Data were statistically analyzed using the Kruskal-Wallis and Mann-Whitney U-tests (p < 0.05). Results: The mean flow rate measured after 24 hours showed the highest value among the time periods in all groups. However, the difference in the flow rate between 1 week and 1 month was not significant. The mean flow rate of the complete drying group was the highest at all time points. After 1 month, the mean flow rate in the blot drying group and the aspiration group was not significantly different. Conclusions: Within the limitations of this study, the canal drying method had a significant effect on leakage and sealing ability in root canal obturations using a calcium silicate-based sealer. Thus, a proper drying procedure is critical in endodontic treatment.

Salvia miltiorrhiza bunge extracts: a promising source for anti-atopic dermatitis activity.

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory condition characterized by the accumulation of reactive oxygen species and the expression of inflammatory factors. Regarding its anti-atopic activity, numerous traditional medicinal materials and secondary metabolic products play pivotal roles in modulating the associated mechanisms. METHODS: This study aimed to utilize Salvia miltiorrhiza Bunge (SMB) as an anti-AD source. In-vitro activity assessments and qualitative and quantitative analyses using UPLC-TQ-MS/MS and HPLC-DAD were conducted in two cultivars ('Dasan' and 'Kosan'). Statistical analysis indicated that the profiles of their secondary metabolites contribute significantly to their pharmacological properties. Consequently, bio-guided fractionation was undertaken to figure out the distinct roles of the secondary metabolites present in SMB. RESULTS: Comparative study of two cultivars indicated that 'Dasan', having higher salvianolic acid A and B, exhibited stronger antioxidant and anti-inflammatory activities. Meanwhile, 'Kosan', containing higher tanshinones, showed higher alleviating activities on anti-AD related genes in mRNA levels. Additionally, performed bio-guided fractionation re-confirmed that the hydrophilic compounds of SMB can prevent AD by inhibiting accumulation of ROS and suppressing inflammatory factors and the lipophilic components can directly inhibit AD. CONCLUSIONS: SMB was revealed as a good source for anti-AD activity. Several bioactive compounds were identified from the UPLC-TQ-MS/MS and different compounds content was linked to biological activities. Characterization of these compounds may be helpful to understand differential role of secondary metabolites from SMB on alleviation of AD.

Presurgical Reduction of the Cleft Palate: Serendipitous Benefit of the Stanford Orthodontic Airway Plate Treatment (SOAP) for Infants with Robin Sequence.

OBJECTIVE: Narrowing of the palatal cleft is often observed in infants with Robin sequence (RS) treated with the Stanford Orthodontic Airway Plate treatment (SOAP) even though SOAP is utilized primarily to establish airway patency. The current study quantified dimensional changes of the cleft palate (CP) in infants with RS treated with SOAP. DESIGN: A retrospective chart review. PATIENTS: Infants with RS and CP who completed SOAP and had maxillary arch models at both pre- and post-treatment time points at a single tertiary referral hospital between September 2019 and July 2023. SETTING AND OUTCOME MEASURE: Maxillary arch models were measured and analyzed using Bivariate statistical analysis. RESULTS: Seventeen infants were included in the study. The median age (min, max) was 6.7 weeks (1.1, 21.9) at pre-treatment and 26.6 weeks (18.7, 37.0) at post-treatment. The median Obstructive Apnea Hypopnea Index was 36.2 events/hour (8.1, 103.1) at pre-treatment and 4.1 events/hour (1.9, 8.6) at post-treatment. The pre-treatment width of CP decreased by an average (± standard diviation) of 6.37 mm (± 3.55, p < 0.001) at post-treatment. The ratio of the posterior cleft width to the total maxillary arch width decreased from 40% (± 9.1) at pre-treatment to 22% (± 11) at post-treatment (p < 0.001). CONCLUSION: The dimensions of CP reduced significantly during SOAP in infants with RS and CP treated for their severe upper airway obstruction. The findings highlight a potential benefit of SOAP that may contribute favorably to the palate repair surgery.

A preliminary study of super-resolution deep learning reconstruction with cardiac option for evaluation of endovascular-treated intracranial aneurysms.

OBJECTIVES: To investigate the usefulness of super-resolution deep learning reconstruction (SR-DLR) with cardiac option in the assessment of image quality in patients with stent-assisted coil embolization, coil embolization, and flow-diverting stent placement compared with other image reconstructions. METHODS: This single-centre retrospective study included 50 patients (mean age, 59 years; range, 44-81 years; 13 men) who were treated with stent-assisted coil embolization, coil embolization, and flow-diverting stent placement between January and July 2023. The images were reconstructed using filtered back projection (FBP), hybrid iterative reconstruction (IR), and SR-DLR. The objective image analysis included image noise in the Hounsfield unit (HU), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and full width at half maximum (FWHM). Subjectively, two radiologists evaluated the overall image quality for the visualization of the flow-diverting stent, coil, and stent. RESULTS: The image noise in HU in SR-DLR was 6.99 ± 1.49, which was significantly lower than that in images reconstructed with FBP (12.32 ± 3.01) and hybrid IR (8.63 ± 2.12) (P < .001). Both the mean SNR and CNR were significantly higher in SR-DLR than in FBP and hybrid IR (P < .001 and P < .001). The FWHMs for the stent (P < .004), flow-diverting stent (P < .001), and coil (P < .001) were significantly lower in SR-DLR than in FBP and hybrid IR. The subjective visual scores were significantly higher in SR-DLR than in other image reconstructions (P < .001). CONCLUSIONS: SR-DLR with cardiac option is useful for follow-up imaging in stent-assisted coil embolization and flow-diverting stent placement in terms of lower image noise, higher SNR and CNR, superior subjective image analysis, and less blooming artifact than other image reconstructions. ADVANCES IN KNOWLEDGE: SR-DLR with cardiac option allows better visualization of the peripheral and smaller cerebral arteries. SR-DLR with cardiac option can be beneficial for CT imaging of stent-assisted coil embolization and flow-diverting stent.

Sex-related disparities in cough-associated symptoms across different age groups.

BACKGROUND: Sex-related disparities in the prevalence of chronic cough have been consistently reported globally, with varying male-to-female ratios. OBJECTIVES: This study aimed to evaluate sex-related differences by comparing correlations between cough-related symptoms in males and females of different age groups. DESIGN: Adult patients with chronic cough who completed the Leicester Cough Questionnaire (LCQ) were recruited from 16 respiratory centers. METHODS: Correlation networks were constructed based on Spearman's correlation coefficients in males and females of various age groups. The distinct relationships of cough-related symptoms between subgroups were validated by an independent cohort. RESULTS: A total of 255 patients were enrolled in this study (male-to-female ratio, 1:1.71). The following LCQ items were highly correlated: embarrassment and interference with daily work, anxiety, and interference with overall life enjoyment/feeling of being fed up, interference with daily work and overall life enjoyment, interference with overall life enjoyment and feeling of being fed up, and feeling of being fed up and annoyance to partner/family/friends. The patterns of these correlations between LCQ items varied in males and females of different ages. The strongest interrelationship was observed in male patients aged >50 years old, which was similar to those in the validation cohort. CONCLUSION: The correlation patterns between cough-related symptoms vary significantly according to age and sex. Understanding the mechanisms underlying the development of cough-related symptoms may facilitate sex- and age-specific strategies for chronic cough.

A Study on Nanoleakage of Apical Retrograde Filling of Premixed Calcium Silicate-Based Cement Using a Lid Technique.

This study aimed to compare the nanoleakage of retrograde fillings with premixed calcium silicate-based putty and mineral trioxide aggregate (MTA), using two different techniques (traditional and Lid). Sixty-four extracted human teeth were decoronated, then root canals and ends were instrumented for retrograde filling and divided into four groups according to the retrograde filling technique: the traditional and the Lid technique. Each group (n = 15) was filled with Ceraseal + Well-Root putty, Well-Root putty, Ceraseal + ProRoot MTA, and ProRoot MTA. The nanoleakage was evaluated using the Nanoflow device (IB Systems) on days 1, 3, 7, 15 and 30. Data were collected twice per second at the nanoscale (nL/s) and calculated after archiving the stabilization of fluid flow. The Kruskal-Wallis and Mann-Whitney U-tests were used for statistical analysis. All groups showed enhanced sealing ability over time. Regardless of filling materials, the Well-Root putty, Ceraseal+Well-Root putty, and Ceraseal+ProRoot MTA groups indicated less nanoleakage than the ProRoot MTA group in the first week of evaluation (p < 0.05). Although all groups did not show significant differences after 2 weeks, the Ceraseal+ProRoot MTA group leaked less than ProRoot MTA on Days 3 and 7 (p < 0.05). The scanning electron microscopic examined good adaptation to the cavity wall, which was similar to nanoleakage results. Premixed calcium silicate-based putty retrograde filling material alone and using the "lid technique" were shown to be faster and less prone to nanoleakage when compared to MTA.

Adjunctive recombinant human parathyroid hormone agents for the treatment of medication-related osteonecrosis of the jaw: a report of three cases.

Teriparatide has been effective in treating people diagnosed with medication-related osteonecrosis of the jaw (MRONJ). However, its efficacy is not well established to be accepted as a standard of care. The objective of this paper was to investigate the efficacy of recombinant human parathyroid hormone for the treatment of MRONJ. We report three cases of MRONJ patients with osteoporosis as the primary disease who were treated with a teriparatide agent along with other adjunctive measures. Each patient was administered a teriparatide injection subcutaneously for 16 weeks, 36 weeks, or 60 weeks. Surgical intervention including partial resection, sequestrectomy, decortication, and saucerization took place during the teriparatide administration. Complete lesion resolution was identified clinically and radiographically in all three patients. In patients diagnosed with MRONJ, teriparatide therapy is an efficacious and safe therapeutic option to improve healing of bone lesions. These findings demonstrate that teriparatide in combination with another therapy, especially bone morphogenetic protein, platelet-rich fibrin, or antibiotic therapy, can be an effective protocol for MRONJ.

Intelligent Resource Allocation Scheme Using Reinforcement Learning for Efficient Data Transmission in VANET.

Vehicular ad hoc networks (VANETs) use multiple channels to communicate using wireless access in vehicular environment (WAVE) standards to provide a variety of vehicle-related applications. The current IEEE 802.11p WAVE communication channel structure is composed of one control channel (CCH) and several service channels (SCHs). SCHs are used for non-safety data transmission, while the CCH is used for broadcasting beacons, control, and safety. WAVE devices transmit data that alternate between CCHs and SCHs, and each channel is active for a duration called the CCH interval (CCHI) and SCH interval (SCHI), respectively. Currently, both intervals are fixed at 50 ms. However, fixed-length intervals cannot effectively respond to dynamically changing traffic loads. Additionally, when many vehicles are simultaneously using the limited channel resources for data transmission, the network performance significantly degrades due to numerous packet collisions. Herein, we propose an adaptive resource allocation technique for efficient data transmission. The technique dynamically adjusts the SCHI and CCHI to improve network performance. Moreover, to reduce data collisions and optimize the network's backoff distribution, the proposed scheme applies reinforcement learning (RL) to provide an intelligent channel access algorithm. The simulation results demonstrate that the proposed scheme can ensure high throughputs and low transmission delays.

Comparison of the Surgical Outcome between the Multiple Screw Fixation and Fixed Angle Devices for the Basicervical Femoral Neck Fractures.

Introduction: Basicervical femoral neck fracture (FNF) is an uncommon type of femoral neck fracture and is associated with an increased risk of fixation failure due to its inherent instability. The purpose of this study was to compare the surgical parameters and reoperation rate between the use of a multiple cannulated screw (MCS) and fixed angle device (FAD) in treating basicervical FNFs. Methods: We retrospectively reviewed the records of 885 patients who underwent internal fixation between May 2004 and August 2019 to determine basicervical FNF with at least 12 months of follow-up. Among the identified 77 patients with basicervical FNF, 17 patients who underwent multiple cannulated screw (MCS) fixation and 36 patients who underwent fixed angle device (FAD) fixation were included. We compared the rates of fracture-site collapse and reoperations according to the fixation device. Results: Among the 53 patients with basicervical FNF, 13 patients (24.5%) sustained surgical complications (8 collapses of fracture site and 5 reoperations). The reoperation rate in the MCS group was significantly higher than that in the FAD group (23.5% vs. 2.8%, p = 0.016), without any significant difference in the collapse of the fracture site (11.8% vs. 16.7%, p = 0.642). Conclusions: Although basicervical FNF was rare among hip fractures, fracture site collapse was prevalent and prone to fixation failure. Surgeons should keep this in mind, and consider FAD for basicervical FNF.

The Effect of Roflumilast on Lipopolysaccharide-induced Acute Lung Injury During Neutropenia Recovery in Mice.

BACKGROUND/AIM: Patients with pneumonia after prolonged neutropenia are at increased risk for acute respiratory distress syndrome (ARDS). The key molecule of endothelial barrier breakdown in sepsis is lipopolysaccharide (LPS), which is a component of the outer membrane of gram-negative bacterial cell walls. Maintaining increased cyclic adenosine monophosphate (cAMP) levels in endothelial cells is effective in preventing endothelial dysfunction and microvascular permeability. The aim of this study was to elucidate whether roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor, is effective in LPS-induced acute lung injury (ALI) during neutropenia recovery in a murine model. MATERIALS AND METHODS: To induce neutropenia, all mice were administered intraperitoneal cyclophosphamide. On day 2 after neutropenia, mice were administered LPS by intra-tracheal instillation. In the prevention group, roflumilast was given orally on day 0, when neutropenia was induced. In the treatment group, roflumilast was administered orally 1 hour after LPS injection. RESULTS: Roflumilast attenuated histopathological changes associated with LPS-induced lung injury. The accumulation of neutrophils and the concentrations of inflammatory cytokines IL-1ß, TNF-α, and IL-6 in bronchoalveolar lavage fluids were inhibited effectively by roflumilast. Also, MMP-9 and TGF-ß expression was attenuated in the roflumilast group. CONCLUSION: Roflumilast significantly attenuated LPS-induced ALI during neutropenia recovery.

Predicting Postoperative Lung Function in Patients with Lung Cancer Using Imaging Biomarkers.

There have been previous studies conducted to predict postoperative lung function with pulmonary function tests (PFTs). Computing tomography (CT) can quantitatively measure small airway walls' thickness, lung volume, pulmonary vessel volume, and emphysema area, which reflect the severity of respiratory diseases. These measurements are considered imaging biomarkers. This study aimed to predict postoperative lung function with imaging biomarkers. A retrospective analysis of 79 patients with lung cancer who had undergone lung surgery was completed. Postoperative lung function measured by forced expiratory volume in one second (FEV1) was defined as an outcome. Preoperative clinico-pathological parameters and imaging biomarkers representing airway walls' thickness, severity of emphysema, total lung volume, and pulmonary vessel volume were measured quantitatively in chest CT by an automated segmentation software, AVIEW COPD. Pi1 was defined as the first percentile along the histogram of lung attenuation that represents the degree of emphysema. Wafw was defined as the airway thickness, which was calculated by the full-width at half-maximum method. Logistic and linear regressions were used to assess these variables. If the actual postoperative FEV1 was higher than the postoperative FEV1 projected by a formula, the group was considered to be preserved. Among the 79 patients, 16 of the patients were grouped as a non-preserved group, and 63 of them were grouped as a preserved group. The patients in the preserved FEV1 group had a higher vessel volume than the non-preserved group. Pi1 and Wafw were independent predictors of postoperative lung function. Imaging biomarkers can be considered significant variables in predicting postoperative lung function in patients with lung cancer.

Digital Templating of Hip Arthroplasty Using Microsoft PowerPoint: A Pilot Study with Technical Details.

Templating is essential in hip arthroplasty preparation, facilitating implant size prediction and surgical rehearsal. It ensures the selection of suitable implants according to patient anatomy and disease, aiming to minimize post-operative complications. Various templating methods exist, including traditional acetate templating on both analog and digital images, alongside digital templating on digital images, which is categorized into 2D and 3D approaches. Despite the popularity of acetate templating on digital images, challenges such as the requirement for physical templates and result preservation persist. To address these limitations, digital templating with software like OrthoSize and Orthoview has been suggested, although not universally accessible. This technical note advocates for Microsoft PowerPoint as an effective alternative for 2D digital templating, highlighting its user-friendly features for image manipulation without needing specialized software. The described method involves scanning acetate templates, adjusting the images in PowerPoint 365 for size, position, and calibration on patient radiographs, and demonstrating reliability through preliminary assessments, with intraclass correlation coefficient (ICC) values indicating a high level of agreement for cup and stem size (ICC = 0.860, 0.841, respectively) but moderate for neck length (ICC = 0.592). We have introduced a method for performing 2D digital templating in the clinical field without the need for specialized software dedicated to digital templating. We believe this method significantly improves the accessibility to 2D digital templating, which was previously limited by the need for digital templating software. Additionally, it enables surgeons to easily establish arthroplasty plans and share them, overcoming the limitations of acetate templates.