Relaxation and creep response of the alveolar lung to diagnosis and treatments for respiratory and lung disorders.

BACKGROUND: The lung Extracellular Matrix (ECM) contains a considerable part of the parenchymal cells. It contains three essential components: elastin and collagen within a proteoglycan (PG) viscoelastic network. Elastin provides the lung's elasticity property, a necessity for normal breathing, while collagen prepares structural support and strength, and PGs give stability and cushioning within tissue loading. Bacterial and viral respiratory diseases are dependent on changes in the ECM ingredients, which result in an alteration of the lung tissue strength. PURPOSE: In the present study, this variation was investigated by changing the volume ratio of the ECM ingredients in the viscoelastic model. RESULTS: As a result, the relaxation curves continuously declined by reducing the volume ratios of elastin, collagen, and PGs; subsequently, the lung stiffness decreased. Also, the Standard Linear Solid (SLS) model-based results demonstrated excellent accordance with empirical data with only minor deviations. The resting relaxation modulus and the creep modulus for the ECM tissue were 51 kPa and approximately 0.02 kPa, respectively, and the maximum total modulus of elasticity reached 121 kPa. CONCLUSIONS: Moreover, this model demonstrates individual alveolar mechanical behaviours and adds another pathway to the generalized Kelvin-Voigt and Maxwell models in predicting the progress of lung diseases.

Efficacy of two different methods of cold air analgesia for pain relief in PDT of actinic keratoses of the head region - a randomized controlled comparison study.

BACKGROUND: Photodynamic therapy (PDT) is an effective method for treating actinic keratosis (AK) with pain during illumination representing the major side effect. The efficacy of two different cooling methods for pain relief in PDT of AK in the head region was compared. METHODS: Randomized, assessor-blinded, half side comparison study in 20 patients with symmetrically distributed AK on the head. Conventional PDT was performed on both halves of the scalp or face by applying 20% aminolevulinic acid cream (ALA) and subsequent illumination with incoherent red light. During illumination one side was cooled with a cold air blower (CAB) and the other with a standard fan (FAN) in a randomized fashion. Pain and skin temperature were recorded during and after PDT. The phototoxic skin reaction was evaluated up to seven days after PDT. The clearance rate of AK was assessed at 3 and 6 months after PDT. RESULTS: Mean pain (VASmean), maximum pain intensity (VASmax) and the mean skin temperature during PDT were significantly lower with CAB as compared to FAN (VASmean: 2.7 ± 1.4 vs. 3.7 ± 2.1, p = 0.003; VASmax: 3.8 ± 2.0 vs. 4.8 ± 2.5, p = 0.002; 26.8 ± 2.0 °C vs. 32.1 ± 1.7 °C; p=<0.001). The severity of the phototoxic skin reaction and the clearance rate of AK did not differ between the two cooling methods. CONCLUSION: Cooling with CAB during PDT has a greater analgesic effect than cooling with FAN. Patients with a lower skin temperature during illumination tended to experience less pain, however, this effect did not reach the level of statistical significance.

Design for All - Design for Disabled: How important is anthropometry?

BACKGROUND: Design for All or Universal Design is a relatively new domain in Ergonomics. With globally ageing populations, it has however recently gained significant interest. OBJECTIVE: This position paper summarizes the outcomes of a workshop held at the virtual 21st Triennial Congress of the International Ergonomics Association. The paper expands the horizon of traditional Ergonomics into a domain where people are differently abled and establishes a platform for the essential needs of future ergonomic standards which are required to inform inclusive design guidelines, or Design for All, extending the range of users. METHODS: The paper includes contributions from Asian, Australian, European and US workshop participants who are accessibility design experts in their respective geographic regions. The paper summarizes issues related to anthropometry in the Design for All, based on recent work in the US (Access board) and actual developments in various national and international accessibility standardization bodies, such as the Standards Australia/Standards New Zealand, the European Standardization Organization (EN 17210:2021; EN 17161:2019) and the International Organization for Standardization (ISO 21542:2021 and BS ISO 7176-5:2008). CONCLUSIONS: The paper concludes that despite the identification of a significant gap in knowledge of the anthropometry of people with disabilities as far back as 1990, work towards bridging the gap and enabling ergonomic standardization has not progressed since then globally. The lack of standardization in anthropometric data on people with a physical disability continues to complicate provision of data for mobility and accessibility design and hampers accessibility standardization efforts.

How severe acute respiratory syndrome coronavirus-2 aerosol propagates through the age-specific upper airways.

The recent outbreak of the COVID-19 causes significant respirational health problems, including high mortality rates worldwide. The deadly corona virus-containing aerosol enters the atmospheric air through sneezing, exhalation, or talking, assembling with the particulate matter, and subsequently transferring to the respiratory system. This recent outbreak illustrates that the severe acute respiratory syndrome (SARS) coronavirus-2 is deadlier for aged people than for other age groups. It is evident that the airway diameter reduces with age, and an accurate understanding of SARS aerosol transport through different elderly people's airways could potentially help the overall respiratory health assessment, which is currently lacking in the literature. This first-ever study investigates SARS COVID-2 aerosol transport in age-specific airway systems. A highly asymmetric age-specific airway model and fluent solver (ANSYS 19.2) are used for the investigation. The computational fluid dynamics measurement predicts higher SARS COVID-2 aerosol concentration in the airway wall for older adults than for younger people. The numerical study reports that the smaller SARS coronavirus-2 aerosol deposition rate in the right lung is higher than that in the left lung, and the opposite scenario occurs for the larger SARS coronavirus-2 aerosol rate. The numerical results show a fluctuating trend of pressure at different generations of the age-specific model. The findings of this study would improve the knowledge of SARS coronavirus-2 aerosol transportation to the upper airways which would thus ameliorate the targeted aerosol drug delivery system.

Effectiveness and clinical predictors of drug survival in psoriasis patients receiving apremilast: A registry analysis.

BACKGROUND: Little is known about the effectiveness and drug survival associated with apremilast under real-world conditions. OBJECTIVE: To investigate the influence of patient and disease characteristics on drug survival associated with apremilast and to elucidate clinical effectiveness with regard to the psoriasis area and severity index (PASI) reduction. METHODS: This was an observational, retrospective, multicenter analysis from the Austrian Psoriasis Registry. RESULTS: Data from 367 patients were eligible for analysis. The 12-month drug survival rate associated with apremilast (ie, the proportion of patients on the drug) was 57.3% and decreased significantly in patients younger than 40 years (relative hazard ratio = 1.49, P = .007918). Sex; concomitant arthritis; previous biologic therapy; obesity; and palmoplantar, scalp, nail, and intertriginous involvement did not significantly affect drug survival. At 12 months, the response rates in patients receiving apremilast per protocol with a PASI of 50, 75, 90, and 100 were 80.0%, 56.4%, 38.2%, and 22.7%, respectively. LIMITATIONS: Inclusion of a substantial number of patients with no record of absolute PASI at study entry and lack of PASI reduction follow-up data of 103 patients (28.1%) after starting apremilast treatment. CONCLUSION: Apremilast is a robust antipsoriatic drug for which the drug survival is not strongly influenced by most patient- or disease-related factors except age. Drug survival is significantly shorter in patients younger than 40 years.

A Review and Qualitative Meta-Analysis of Digital Human Modeling and Cyber-Physical-Systems in Ergonomics 4.0.

Occupational ApplicationsFounded in an empirical case study and theoretical work, this paper reviews the scientific literature to define the role of Digital Human Modeling (DHM), Digital Twin (DT), and Cyber-Physical Systems (CPS) to inform the emerging concept of Ergonomics 4.0. We find that DHM evolved into DT is a core element in Ergonomics 4.0. A solid understanding and agreement on the nature of Ergonomics 4.0 is essential for the inclusion of ergonomic values and considerations in the larger conceptual framework of Industry 4.0. In this context, we invite Ergonomists from various disciplines to broaden their understanding and application of DHM and DT.

Technical AbstractBackground Industry 4.0 presents itself as an ecosystem; a collection of elements endowed with Cyber-Physical Systems and Augmented Reality/Virtual Reality devices, which are connected through the Internet of Things, and uploaded to Cloud Platforms for analysis, knowledge extraction, and diagnostics through Cognitive Computing based on a large amount of data. The concept is centered around data: managing data, analyzing data, and controlling data. Many factors influence this interconnected working environment, and for that reason planning and implementing the digital transformation implies many challenges. Industry 4.0 and Ergonomics are being integrated using a variety of tools and approaches, thus supporting the development of an Ergonomics 4.0 concept.Purpose This paper reviews studies focusing on the determinants of Ergonomics 4.0, identifying the main elements and their interrelationships with a focus on Digital Human Modeling and Cyber-Physical Systems. We consider approaches such as Operator 4.0 and 'Modeling and Simulation for Digital Twin Creation', which aim to accelerate the decision-making and adaptation processes. We identify the leading technologies, operations, and worker-related aspects through a qualitative meta-analysis, to establish elements and interrelationships of Ergonomics 4.0 determinants.Methods Literature was selected from articles recent journal publications, and a qualitative evaluation was performed using semantic meta-analysis. The findings were then used to develop a theoretical taxonomy of determinants of Ergonomics 4.0 in Industry 4.0 based on various classifiers, which were structured and interlinked.Results The five areas categorized include: Industry 4.0 technology, Human-Cyber-Physical Systems, Operator 4.0, Human-Robot collaboration, Digital Twin and Digital Human Modeling. The proposed conceptual framework for Ergonomics 4.0 describes processes, technology, information, and structures, which occur in Industry 4.0 as Operator 4.0, Human-Robot collaboration, Digital Twin, Digital Human Modeling and eventually define Ergonomics 4.0. The concepts of Digital Twin and Digital Human Modeling are analyzed in detail, as they form the core of Ergonomics 4.0.Conclusions We propose a conceptual framework for Ergonomics 4.0 as a Cyber-Physical System and discuss aspects of Digital Human Modeling and Digital Twin that are essential to understanding the role of Ergonomics and the integration of Ergonomics into Industry 4.0.

Polydisperse Aerosol Transport and Deposition in Upper Airways of Age-Specific Lung.

A comprehensive understanding of airflow characteristics and particle transport in the human lung can be useful in modelling to inform clinical diagnosis, treatment, and management, including prescription medication and risk assessment for rehabilitation. One of the difficulties in clinical treatment of lung disorders lies in the patients' variable physical lung characteristics caused by age, amongst other factors, such as different lung sizes. A precise understanding of the comparison between different age groups with various flow rates is missing in the literature, and this study aims to analyse the airflow and aerosol transport within the age-specific lung. ANSYS Fluent solver and the large-eddy simulation (LES) model were employed for the numerical simulation. The numerical model was validated with the available literature and the computational results showed airway size-reduction significantly affected airflow and particle transport in the upper airways. This study reports higher deposition at the mouth-throat region for larger diameter particles. The overall deposition efficiency (DE) increased with airway size reduction and flow rate. Lung aging effected the pressure distribution and a higher pressure drop was reported for the aged lung as compared to the younger lung. These findings could inform medical management through individualised simulation of drug-aerosol delivery processes for the patient-specific lung.

SARS CoV-2 aerosol: How far it can travel to the lower airways?

The recent outbreak of the SARS CoV-2 virus has had a significant effect on human respiratory health around the world. The contagious disease infected a large proportion of the world population, resulting in long-term health issues and an excessive mortality rate. The SARS CoV-2 virus can spread as small aerosols and enters the respiratory systems through the oral (nose or mouth) airway. The SARS CoV-2 particle transport to the mouth-throat and upper airways is analyzed by the available literature. Due to the tiny size, the virus can travel to the terminal airways of the respiratory system and form a severe health hazard. There is a gap in the understanding of the SARS CoV-2 particle transport to the terminal airways. The present study investigated the SARS CoV-2 virus particle transport and deposition to the terminal airways in a complex 17-generation lung model. This first-ever study demonstrates how far SARS CoV-2 particles can travel in the respiratory system. ANSYS Fluent solver was used to simulate the virus particle transport during sleep and light and heavy activity conditions. Numerical results demonstrate that a higher percentage of the virus particles are trapped at the upper airways when sleeping and in a light activity condition. More virus particles have lung contact in the right lung than the left lung. A comprehensive lobe specific deposition and deposition concentration study was performed. The results of this study provide a precise knowledge of the SARs CoV-2 particle transport to the lower branches and could help the lung health risk assessment system.

Quality of Life, Anxiety, and Depression in Patients With Early-Stage Mycosis Fungoides and the Effect of Oral Psoralen Plus UV-A (PUVA) Photochemotherapy on it.

Background: Little is known about psychological discomfort and quality of life (QoL) in early stage mycosis fungoides (MF) and the effect of psoralen plus UV-A (PUVA) on it. Objective: To evaluate QoL, anxiety, and depression with validated instruments in early stage MF patients and whether PUVA treatment improves it. Methods: Patients with stage IA to IIA MF were treated with PUVA twice weekly for 12-24 weeks, followed by maintenance treatment or not, in a prospective randomized clinical trial. Patients completed a questionnaire on DLQI as well as the Hospital Anxiety and Depression Scale (HADS) prior to therapy, after their last PUVA exposure, and after the PUVA maintenance or observance phase. Results: For 24 patients with early stage MF, completed questionnaires were available and analyzed. Prior to treatment, 17% reported strong (DLQI > 10) and 29% moderate impairment (DLQI 6-10) in QoL; 33% of patients reported HADS scores indicating anxiety, and 21% reported scores indicating depression. PUVA significantly improved overall QoL by reducing mean DLQI scores by 58.6% (p = 0.003), HADS-A by 30% (p = 0.045), and HADS-D by 44% (p = 0.002). Improvements in QoL and psychological well-being seemed to be sustained, irrespective of maintenance treatment or not. Limitations: Small sample size. Conclusions: PUVA sustainably improves QoL and psychological well-being in patients with early stage MF. Clinical trial registration: ClinicalTrials.gov identifier: NCT01686594.

Secukinumab Use in Patients with Moderate to Severe Psoriasis, Psoriatic Arthritis and Ankylosing Spondylitis in Real-World Setting in Europe: Baseline Data from SERENA Study.

INTRODUCTION: Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has demonstrated robust efficacy in the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with a rapid onset of action, sustained long-term clinical responses and a consistently favourable safety profile across phase 3 trials. Here, we report the clinical data at enrolment from SERENA, designed to investigate the real-world use of secukinumab across all three indications. METHODS: SERENA is an ongoing, longitudinal, observational study conducted at 438 sites across Europe in patients with moderate to severe plaque PsO, active PsA or active AS. Patients should have received at least 16 weeks of secukinumab treatment before enrolment in the study. RESULTS: Overall 2800 patients were included in the safety set; patients with PsA (N = 541) were older than patients with PsO (N = 1799) and patients with AS (N = 460); patients with PsO had a higher mean body weight than patients with PsA and patients with AS; and patients with PsO and patients with AS were predominantly male. Time since diagnosis was longer in patients with PsO compared with patients with PsA and patients with AS, and about 40% of patients were either current or former smokers. The proportion of obese patients (body mass index ≥ 30 kg/m2) was similar across indications. Patients were treated with secukinumab for a mean duration of 1 year prior to enrolment (range 0.89-1.04). The percentages of patients with prior biologics exposure were 31.5% PsO, 59.7% PsA and 55% AS. The percentages of patients prescribed secukinumab monotherapy were 75% (n = 1349) in PsO, 48.2% (n = 261) in PsA and 48.9% (n = 225) in AS groups. CONCLUSION: Baseline demographics of the study population are consistent with existing literature. This large observational study across all secukinumab indications will provide valuable information on the long-term effectiveness and safety of secukinumab in the real-world setting.

Helium-Oxygen Mixture Model for Particle Transport in CT-Based Upper Airways.

The knowledge of respiratory particle transport in the extra-thoracic pathways is essential for the estimation of lung health-risk and optimization of targeted drug delivery. The published literature reports that a significant fraction of the inhaled aerosol particles are deposited in the upper airways, and available inhalers can deliver only a small amount of drug particles to the deeper airways. To improve the targeted drug delivery efficiency to the lungs, it is important to reduce the drug particle deposition in the upper airways. This study aims to minimize the unwanted aerosol particle deposition in the upper airways by employing a gas mixture model for the aerosol particle transport within the upper airways. A helium-oxygen (heliox) mixture (80% helium and 20% oxygen) model is developed for the airflow and particle transport as the heliox mixture is less dense than air. The mouth-throat and upper airway geometry are extracted from CT-scan images. Finite volume based ANSYS Fluent (19.2) solver is used to simulate the airflow and particle transport in the upper airways. Tecplot software and MATLAB code are employed for the airflow and particle post-processing. The simulation results show that turbulence intensity for heliox breathing is lower than in the case of air-breathing. The less turbulent heliox breathing eventually reduces the deposition efficiency (DE) at the upper airways than the air-breathing. The present study, along with additional patient-specific investigation, could improve the understanding of particle transport in upper airways, which may also increase the efficiency of aerosol drug delivery.

Air Pollution Emissions 2008-2018 from Australian Coal Mining: Implications for Public and Occupational Health.

Occupational exposure limits for respirable coal dust are based on exposure during working hours, but coal miners may experience additional community-based exposures during nonworking hours. We analyzed Australia National Pollutant Inventory (NPI) data for the years 2008-2018 to estimate air pollutants (metals, nitrogen oxides, particulate matter ≤ 10 micrometers (PM10) and ≤2.5 micrometers (PM2.5)) originating from coal mines. PM10 levels from community-based air monitors in Queensland and New South Wales were also compared between mining and nonmining communities. Results indicated that tons of coal mined increased over the study period, and that levels of particulate matter, metals, and nitrogen oxides increased significantly over time as well. Coal mines accounted for 42.1% of national PM10 air emissions from NPI sites. PM2.5 from coal mines accounted for 19.5% of the national total, metals for 12.1%, and nitrogen oxides for 10.1%. Coal mining occurred in 57 different post codes; the 20 coal-mining post codes with the highest PM10 emissions were home to 160,037 people. Emissions of all studied pollutants were significantly higher from coal mining sites than from other types of NPI sites. Results from community-based air monitoring stations indicated significantly higher population PM10 exposure in coal mining communities than in nonmining communities. The health of the public at large is impacted by coal mining, but to the extent that miners also live near coal mining operations, their total exposure is underestimated by consideration of exposure only during working hours.

Airflow and Particle Transport Prediction through Stenosis Airways.

Airflow and particle transport in the human lung system is influenced by biological and other factors such as breathing pattern, particle properties, and deposition mechanisms. Most of the studies to date have analyzed airflow characterization and aerosol transport in idealized and realistic models. Precise airflow characterization for airway stenosis in a digital reference model is lacking in the literature. This study presents a numerical simulation of airflow and particle transport through a stenosis section of the airway. A realistic CT-scan-based mouth-throat and upper airway model was used for the numerical calculations. Three different models of a healthy lung and of airway stenosis of the left and right lung were used for the calculations. The ANSYS FLUENT solver, based on the finite volume discretization technique, was used as a numerical tool. Proper grid refinement and validation were performed. The numerical results show a complex-velocity flow field for airway stenosis, where airflow velocity magnitude at the stenosis section was found to be higher than that in healthy airways. Pressure drops at the mouth-throat and in the upper airways show a nonlinear trend. Comprehensive pressure analysis of stenosis airways would increase our knowledge of the safe mechanical ventilation of the lung. The turbulence intensities at the stenosis sections of the right and left lung were found to be different. Deposition efficiency (DE) increased with flow rate and particle size. The findings of the present study increase our understanding of airflow patterns in airway stenosis under various disease conditions. More comprehensive stenosis analysis is required to further improve knowledge of the field.

A Review of Respiratory Anatomical Development, Air Flow Characterization and Particle Deposition.

The understanding of complex inhalation and transport processes of pollutant particles through the human respiratory system is important for investigations into dosimetry and respiratory health effects in various settings, such as environmental or occupational health. The studies over the last few decades for micro- and nanoparticle transport and deposition have advanced the understanding of drug-aerosol impacts in the mouth-throat and the upper airways. However, most of the Lagrangian and Eulerian studies have utilized the non-realistic symmetric anatomical model for airflow and particle deposition predictions. Recent improvements to visualization techniques using high-resolution computed tomography (CT) data and the resultant development of three dimensional (3-D) anatomical models support the realistic representation of lung geometry. Yet, the selection of different modelling approaches to analyze the transitional flow behavior and the use of different inlet and outlet conditions provide a dissimilar prediction of particle deposition in the human lung. Moreover, incorporation of relevant physical and appropriate boundary conditions are important factors to consider for the more accurate prediction of transitional flow and particle transport in human lung. This review critically appraises currently available literature on airflow and particle transport mechanism in the lungs, as well as numerical simulations with the aim to explore processes involved. Numerical studies found that both the Euler-Lagrange (E-L) and Euler-Euler methods do not influence nanoparticle (particle diameter ≤50 nm) deposition patterns at a flow rate ≤25 L/min. Furthermore, numerical studies demonstrated that turbulence dispersion does not significantly affect nanoparticle deposition patterns. This critical review aims to develop the field and increase the state-of-the-art in human lung modelling.

Parametric human modelling to determine body surface area covered by sun-protective clothing.

Solar ultraviolet radiation (UVR) is the main environmental risk-factor for cancer of the skin. Sun-protective clothing provides a physical barrier that reduces the UVR dose reaching the skin and European and Australian standards for sun-protective clothing set minimum clothing coverage requirements. Body Surface Area Coverage by clothing (BSAC) is calculated by means of indirect or direct methods, which are laborious and do not support computer-based apparel design. To support the sun-safe specification and design of garments, parametric digital human models and protective clothing mesh covering the minimum Body Surface Area specified in AS/NZS 4399:2017, were created making use of MakeHuman v1.1.1 and Blender software. The Whole Body Surface Area (WBSA) and the BSAC were calculated employing code developed in Blender. Thus, different groups of subjects were analysed to explore BSAC. The method assists in the evaluation of exposed body areas in a wider spectrum of different occupations. Practitioner summary: Sun-protective clothing provides a physical barrier that reduces the UVR dose reaching the skin's surface. Body Surface Area Coverage (BSAC) by clothing is an important determinant of the sun protective capabilities of a garment. In this study, BSAC is calculated using parametric digital human modelling. Abbreviation: UVR: (Solar) ultraviolet radiation; DHM: digital human modeling; BSA: body surface area; BSAC: body surface area coverage (by clothing); BSANC: body surface area not covered (by clothing); WBSA: whole body surface area; BCC: basal cell carcinoma; SCC: squamous cell carcinoma; UPF: ultraviolet protection factor; GPF: garment protection factor.

Evaluation of Low-Dose, Low-Frequency Oral Psoralen-UV-A Treatment With or Without Maintenance on Early-Stage Mycosis Fungoides: A Randomized Clinical Trial.

Importance: Psoralen-UV-A (PUVA) photochemotherapy is standard first-line treatment for skin-limited, early-stage mycosis fungoides capable of producing high initial complete response (CR) rates. However, much remains unknown about PUVA's therapeutic mechanisms, optimal duration and frequency of treatment, dose escalation, or use as maintenance therapy. Objectives: To evaluate low-dose, low-frequency PUVA, and whether maintenance treatment extends disease-free remission in patients with mycosis fungoides. Design, Setting, and Participants: This prospective randomized clinical trial with defined PUVA dosing regimen was carried out in 5 centers (Graz, Vienna, Hietzing, Innsbruck, and Salzburg) across Austria. Patients with stage IA to IIA mycosis fungoides (n = 27) were enrolled in the study beginning March 13, 2013, with the last patient enrolled March 21, 2016. These patients were treated with oral 8-methoxypsoralen followed by UV-A exposure 2 times per week for 12 to 24 weeks until CR. Patients with CR were randomized to PUVA maintenance for 9 months (14 total exposures) or no maintenance. The study was conducted from April 27, 2012, to July 27, 2018. Data analysis of the primary end point was of the intention-to-treat population, and the secondary end point analysis was of the evaluable population. Main Outcomes and Measures: Efficacy of the PUVA regimen was determined by the rate of CR as defined by a modified severity-weighted assessment tool (mSWAT) score reduction to 0. Levels of proinflammatory molecules in serum and histologic features and percentage of clonal T cells in skin were assessed to search for biomarkers of clinical response. Results: In 27 patients with mycosis fungoides, 19 (70%) were male with mean (range) age 61 (30-80) years. At baseline, patients with CR had a mean (range) mSWAT score of 18.6 (1-66) compared with 16.8 (3-46) in patients with partial response. The 12- to 24-week PUVA induction regimen reduced the mSWAT score in all patients and led to CR in 19 (70%) of 27 patients and a low mean cumulative UV-A dose of 78.5 J/cm2. The subsequent standardized 9-month PUVA maintenance phase prolonged median (range) disease-free remission from 4 (1-20) months to 15 (1-54) months (P = .02). High density of histologic infiltrate and high percentage of clonal TCR sequences in skin biopsy specimens at baseline were inversely associated with therapeutic response. No severe adverse effects were seen during the PUVA induction or maintenance phase. Conclusions and Relevance: This proof-of-concept study identifies potential biomarkers for therapeutic response to PUVA in mycosis fungoides; it also demonstrates that low-dose, low-frequency PUVA appears to be highly effective, and maintenance treatment may extend disease-free remission. Trial Registration: ClinicalTrials.gov identifier: NCT01686594.

Modulation of Tumor Cell Metabolism by Laser Photochemotherapy with Cisplatin or Zoledronic Acid In Vitro.

BACKGROUND/AIM: Laser photochemotherapy is a new approach in cancer treatment using low-level laser therapy (LLLT) to enhance the effect of chemotherapy. MATERIALS AND METHODS: In order to evaluate the effect of LLLT on tumor cells, HeLa cells were treated with cisplatin or zoledronic acid (ZA) followed by LLLT. Cell viability was evaluated with 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide assay. Oxidative phosphorylation and glycolysis were measured using extracellular flux analysis. Immunocytochemistry of heat-shock protein 70 (HSP70) and western blot analysis were performed. RESULTS: LLLT alone increased viability and was associated with lower oxidative phosphorylation but higher glycolysis rates. Cisplatin and ZA alone lowered cell viability, glycolysis and oxidative phosphorylation. This effect was significantly enhanced in conjunction with LLLT and was accompanied by reduced oxidative phosphorylation and collapse of glycolysis. CONCLUSION: Our observations indicate that LLLT may raise the cytotoxicity of cisplatin and ZA by modulating cellular metabolism, pointing to a possible application in cancer treatment.

Efficiency of soft tissue incision with a novel 445-nm semiconductor laser.

Using a 445-nm semiconductor laser for tissue incision, an effective cut is expected due to the special absorption properties of blue laser light in soft tissues. The aim of the present study was the histological evaluation of tissue samples after incision with a 445-nm diode laser. Forty soft tissue specimens were obtained from pork oral mucosa and mounted on a motorized linear translation stage. The handpiece of a high-frequency surgery device, a 970-nm semiconductor laser, and a 445-nm semiconductor laser were connected to the slide, allowing a constant linear movement (2 mm/s) and the same distance of the working tip to the soft tissue's surface. Four incisions were made each: (I) 970-nm laser with conditioned fiber tip, contact mode at 3-W cw; (II-III): 445-nm laser with non-conditioned fiber tip, contact mode at 2-W cw, and non-contact mode (1 mm) at 2 W; and (IV): high-frequency surgery device with straight working tip, 90° angulation, contact mode at 50 W. Histological analysis was performed after H&E staining of the embedded specimens at 35-fold magnification. The comparison of the incision depths showed a significant difference depending on the laser wavelength and the selected laser parameters. The highest incision depth was achieved with the 445-nm laser contact mode (median depth 0.61 mm, min 0.26, max 1.17, interquartile range 0.58) (p < 0.05) with the lowest amount of soft tissue denaturation (p < 0.05). The lowest incision depth was measured for the high-frequency surgical device (median depth 0.36 mm, min 0.12, max 1.12, interquartile range 0.23) (p < 0.05). Using a 445-nm semiconductor laser, a higher cutting efficiency can be expected when compared with a 970-nm diode laser and high-frequency surgery. Even the 445-nm laser application in non-contact mode shows clinically acceptable incision depths without signs of extensive soft tissue denaturation.

A novel method for quanitifying comfort in child passengers demonstrates an association between child restraint comfort and errors in use of booster seats.

OBJECTIVE: Misuse of child restraint systems is a widespread and long-standing problem impacting risk of injury and death in car crashes. Discomfort has been suggested as a causative factor for misuse, particularly in errors introduced by children while they use the restraints. However, the relationship between comfort and errors in use has never been studied. In this study we examine the reliability and sensitivity of a newly developed observational method for assessing comfort in children in vehicles. We then use this method to examine the relationship between comfort and errors in use of booster seats. METHODS: A novel method was developed for assessing comfort by counting fidgeting and postural adjustment behaviors to derive a Discomfort Avoidance Behavior (DAB) score. The sensitivity of the DAB score was examined by observing children in four different seating conditions designed as "comfortable" and "uncomfortable" (Part 1). Paired-samples t-tests were used to compare differences in DAB between seating conditions. The reliability of the DAB score was assessed by calculating the intraclass correlation coefficient (ICC) between DAB scores recorded by different researchers. The association between comfort and correctness of use was examined by observing children using booster seats (Part 2). The association between DAB score and number of usage errors was tested using linear regression analysis. Participants were children ages 4-8 years. Fourteen children participated in Part 1 and 15 children in Part 2. RESULTS: The DAB score was sensitive to changes in seat condition (p < 0.01), and was repeatable between different researchers (ICC 0.98, 95% confidence interval [CI] 0.954-0.991). Increases in DAB were associated with increases in the number of use errors among children using booster seats (errors in use = 3.89 × DAB - 2.18, p < 0.0001). CONCLUSION: The DAB score is a reliable and valid measure of comfort of children in child restraints but could be improved by incorporating a measurement of postural positioning. Comfort, as characterized by fidgeting and postural adjustment behaviors, is associated with correct use of child restraints. The broader implication is that this confirms ergonomic design of child restraints as important for minimizing errors in use. There is a need for further study of the impact of specific restraint design features on comfort experienced by children.