Sleep quality according to chronotype in nurses working 8-hour shifts.

BACKGROUND: To date, studies have been focused on sleep disturbances of nurses working during night shifts. There is a lack of understanding regarding the sleep quality of nurses working in the rapid rotation system for each type of shift work. AIMS: To determine the relationship between chronotype and sleep quality according to shift type (i.e. day, evening and night shifts) in nurses working 8-hour rotating shifts. METHODS: A cross-sectional, descriptive study was conducted from two tertiary hospitals in South Korea from December 2021 to September 2022, including nurses working 8-hour rotating shifts (N = 74). They completed questionnaires to measure general, occupational and sleep-related characteristics, chronotype, insomnia severity and daytime sleepiness. Additionally, sleep parameters were collected from actigraphy and sleep diaries for 7 days. RESULTS: A total of 64% of nurses had an evening chronotype and 37% of nurses had an intermediate chronotype. Nurses had significantly less total sleep time and worsened sleep latency and efficiency during the day shift compared to other shift types. Compared to nurses with an intermediate chronotype, those with an evening chronotype had poorer sleep quality during day shift work. CONCLUSIONS: Strategies to enhance nurses' sleep quality during day shifts should consider a two-level approach: individual approaches, such as improving sleep hygiene, and administrative approaches, such as establishing a chronotype-based shift system for scheduling.

Association of body mass index and bloodstream infections in patients on extracorporeal membrane oxygenation: a single-centre, retrospective, cohort study.

BACKGROUND: Obesity is associated with poor clinical outcomes in critically ill patients. However, under some clinical conditions, obesity has protective effects. Bloodstream infections (BSI) are among the most common nosocomial infections associated with extracorporeal membrane oxygenation (ECMO). BSI during ECMO is associated with higher mortality rates and poorer clinical outcomes. AIM: To analyse whether body mass index (BMI) is associated with BSI during ECMO or with in-hospital mortality. METHODS: All adult patients who had received ECMO support for >48 h were included in the analysis. The analysis of total duration of ECMO support, in-hospital mortality and BSI was stratified by BMI category. The Cox proportional hazards model was used to compare the risk of BSI among BMI categories. FINDINGS: In total, 473 patients were enrolled in the study. The average age was 56.5 years and 65.3% were men. The total duration of ECMO was approximately 11.8 days, with a mortality rate of 47.1%. The incidence rates of BSI and candidaemia were 20.5% and 5.5%, respectively. The underweight group required ECMO for respiratory support, whereas the overweight and obese groups required ECMO for cardiogenic support (P<0.0001). No significant difference in BSI rate was found (P=0.784). However, after adjusting for clinical factors, patients in Group 4 (BMI 25.0-<30.0 kg/m2) exhibited lower mortality compared with patients in Group 2 (normal BMI) (P=0.004). CONCLUSION: BMI was not associated with risk of BSI, but patients with higher BMI showed lower in-hospital mortality associated with ECMO support.

Process evaluation of a kindergarten-based intervention for obesity prevention in early childhood: the Toybox study Malaysia.

BACKGROUND: Toybox is a kindergarten-based intervention program that targets sedentary behavior, snacking and drinking habits, as well as promoting physical activity in an effort to improve healthy energy balance-related behaviors among children attending kindergartens in Malaysia. The pilot of this program was conducted as a randomized controlled trial (RCT) involving 837 children from 22 intervention kindergartens and 26 control kindergartens respectively. This paper outlines the process evaluation of this intervention. METHODS: We assessed five process indicators: recruitment, retention, dosage, fidelity, and satisfaction for the Toybox program. Data collection was conducted via teachers' monthly logbooks, post-intervention feedback through questionnaires, and focus group discussions (FGD) with teachers, parents, and children. Data were analyzed using quantitative and qualitative data analysis methods. RESULTS: A total of 1072 children were invited. Out of the 1001 children whose parents consented to join, only 837 completed the program (Retention rate: 88.4%). As high as 91% of the 44 teachers and their assistants engaged positively in one or more of the process evaluation data collection methods. In terms of dosage and fidelity, 76% of parents had received newsletters, tip cards, and posters at the appropriate times. All teachers and their assistants felt satisfied with the intervention program. However, they also mentioned some barriers to its implementation, including the lack of suitable indoor environments to conduct activities and the need to make kangaroo stories more interesting to captivate the children's attention. As for parents, 88% of them were satisfied with the family-based activities and enjoyed them. They also felt that the materials provided were easy to understand and managed to improve their knowledge. Lastly, the children showed positive behaviors in consuming more water, fruits, and vegetables. CONCLUSIONS: The Toybox program was deemed acceptable and feasible to implement by the parents and teachers. However, several factors need to be improved before it can be expanded and embedded as a routine practice across Malaysia.

Women in Orthopaedics: A Perspective from Malaysian Female Orthopaedic Surgeons.

Introduction: The awareness of under-representation of female surgeons in orthopaedics has been increasing in this decade. We aim to investigate the reasons why female surgeons chose orthopaedic, the barriers that possibly hinder female surgeons into orthopaedics and analyse the obstacles that they encountered in their career in Malaysian context. Materials and methods: A total of 101 registered female orthopaedic surgeons registered with the Malaysian Medical Council, during the period 1980 to 2020, were contacted for a cross-sectional survey, consisting of thirty-four questions on their experience in the orthopaedic career. Eighty-two responses were received (81.2%). Questions in this survey consisted of four sections: (1) demographic details, (2) current clinical practice environment, (3) orthopaedics training experience, and (4) career experience. Results: A total of 49% of respondents had subspeciality training, highest in paediatric orthopaedic (30%). Enjoyment of manual tasks (64.6%) and professional satisfaction (64.6%) were the top reasons for choosing orthopaedic as a career. Primary barriers to orthopaedic were physical strength required (56.0%) and public gender bias (52.4%). Twenty-eight percent reported gender discrimination in career opportunities while 60% reported similar in daily work. Thirty-three percent reported verbal and 11% physical sexual harassment in their career. Forty-four percent of respondents reported benefits as female orthopaedic surgeon in their work. Conclusion: The reasons for Malaysian female orthopaedic surgeons to choose orthopaedic as their career and the barriers perceived to hinder other females from choosing orthopaedics were similar to reports worldwide with no exception to gender discrimination and sexual harassment. The support given by male colleagues to married female surgeons marked a unique phenomenon in Malaysian culture.

Comparing the efficacy of different methods of faecal microbiota transplantation via oral capsule, oesophagogastroduodenoscopy, colonoscopy, or gastric tube.

BACKGROUND: The increasing prevalence of multidrug-resistant organism (MDRO) carriage poses major challenges to medicine as healthcare costs increase. Recently, faecal microbiota transplantation (FMT) has been discussed as a novel and effective method for decolonizing MDRO. AIM: To compare the efficacy of different FMT methods to optimize the success rate of decolonization in patients with MDRO carriage. METHODS: This prospective cohort study enrolled patients with MDRO carriages from 2018 to 2021. Patients underwent FMT via one of the following methods: oral capsule, oesophagogastroduodenoscopy (EGD), colonoscopy, or gastric tube. FINDINGS: A total of 57 patients underwent FMT for MDRO decolonization. The colonoscopy group required the shortest time for decolonization, whereas the EGD group required the longest (24.9 vs 190.4 days, P = 0.022). The decolonization rate in the oral capsule group was comparable to that in the EGD group (84.6% vs 85.7%, P = 0.730). An important clinical factor associated with decolonization failure was antibiotic use after FMT (odds ratio = 6.810, P = 0.008). All four groups showed reduced proportions of MDRO species in microbiome analysis after FMT. CONCLUSION: Compared to other conventional methods, the oral capsule is an effective FMT method for patients who can tolerate an oral diet. The discontinuation of antibiotics after FMT is a key factor in the success of decolonization.

Development and validation of an automatic commissioning tool for the Monte Carlo dose engine in myQA iON.

Independent dose verification with Monte Carlo (MC) simulations is an important feature of proton therapy quality assurance (QA). However, clinical integration of such tools often generates an additional and complex workload for medical physicists. The preparation of the necessary clinical inputs, such as the machine beam model, should therefore be automated. In this work, a methodology for automatic MC commissioning has been devised, validated, and developed into a MATLAB tool for the users of myQA iON, the recent QA platform of IBA Dosimetry. With this workflow, all necessary parameters can easily be tuned using dedicated optimization methods. For the geometrical beam parameters (phase space), the assumption of a single or double Gaussian is made. To model the energy spectrum, a Gaussian function is assumed and parameters are optimized using either MC simulations or a library of pre-computed Bragg peaks. For the absolute dose calibration, commissioning fields can be reproduced with the dose engine to retrieve the necessary parameters. We discuss in a first time the tool efficiency and show that one can optimize all parameters in less than 4 min per energy with excellent accuracy. We then validate a beam model obtained with the tool by simulating homogeneous spread-out Bragg peaks (SOBPs) and patient QA plans previously measured in water. An average range agreement of 0.29 ± 0.34 mm is achieved for the SOBPs while 3%/3 mm local gamma passing rates reach 99.3% on average over all 62 measured patient QA planes, which is well within clinical tolerances.

Variations in the Course of the Carotid Arteries in Patients with Retropharyngeal Parathyroid Adenomas.

The carotid arteries, classically described as taking a relatively straight course through the neck, deviate medially in a minority of patients. At the extreme, the internal carotid arteries may "kiss" in the midline, coming extremely close to the pharyngeal wall. In this clinical report, we describe 5 patients with primary hyperparathyroidism, all with ectopic retropharyngeal parathyroid adenomas but all with varying carotid artery anatomy. We describe these variations using a previously developed clinical grading system that highlights 1) the relationship between carotid artery location and risk of injury during pharyngeal procedures and 2) the importance of universal, objective criteria to classify carotid anatomy. Radiologists should be familiar with variations in carotid anatomy and communicate them to the operative team.

Development of robustness evaluation strategies for enabling statistically consistent reporting.

Robustness evaluation of proton therapy treatment plans is essential for ensuring safe treatment delivery. However, available evaluation procedures feature a limited exploration of the actual robustness of the plan and generally do not provide confidence levels. This study compared established and more sophisticated robustness evaluation procedures, with quantified confidence levels. We have evaluated several robustness evaluation methods for 5 bilateral head-and-neck patients optimized considering spot scanning delivery and with a conventional CTV-to-PTV margin of 4 mm. Method (1) good practice scenario selection (GPSS) (e.g. +/- 4 mm setup error 3% range uncertainty); (2) statistically sound scenario selection (SSSS) either only on or both on and inside isoprobability hypersurface encompassing 90% of the possible errors; (3) statistically sound dosimetric selection (SSDS). In the last method, the 90% best plans were selected according to either target coverage quantified by D 95 (SSDS_D 95) or to an approximation of the final objective function (OF) used during treatment optimization (SSDS_OF). For all methods, we have considered systematic setup and systematic range errors. A mix of systematic and random setup errors were also simulated for SSDS, but keeping the same conventional margin of 4 mm. All robustness evaluations have been performed using the fast Monte Carlo dose engine MCsquare. Both SSSS strategies yielded on average very similar results. SSSS and GPSS yield comparable values for target coverage (within 0.5 Gy). The most noticeable differences were found for the CTV between GPSS, on the one hand, and SSDS_D 95 and SSDS_OF, on the other hand (average worst-case D 98 were 2.8 and 2.0 Gy larger than for GPSS, respectively). Simulating explicitly random errors in SSDS improved almost all DVH metrics. We have observed that the width of DVH-bands and the confidence levels depend on the method chosen to sample the scenarios. Statistically sound estimation of the robustness of the plan in the dosimetric space may provide an improved insight on the actual robustness of the plan for a given confidence level.

Cognition and cerebrovascular function in primary hyperparathyroidism before and after parathyroidectomy.

PURPOSE: There are cognitive changes in primary hyperparathyroidism (PHPT) that improve with parathyroidectomy, but the mechanism of cognitive dysfunction has not been delineated. We assessed if cerebrovascular function is impaired in PHPT, improves post-parathyroidectomy and is associated with PTH level and cognitive dysfunction. METHODS: This is an observational study of 43 patients with mild hypercalcemic or normocalcemic PHPT or goiter. At baseline, cerebrovascular function (dynamic cerebral autoregulation and vasomotor reactivity) by transcranial Doppler and neuropsychological function were compared between all three groups. A subset underwent parathyroidectomy or thyroidectomy, and was compared 6 months post-operatively. RESULTS: Mean cerebrovascular and neuropsychological function was normal and no worse in PHPT compared to controls preoperatively. Higher PTH was associated with worse intracerebral autoregulation (r = - 0.43, p = 0.02) and worse cognitive performance on some tests. Post-parathyroidectomy, mood improved significantly, but changes did not differ compared to those having thyroidectomy (p = 0.84). There was no consistent improvement in cognition or change in vascular function in either surgical group. CONCLUSIONS: Although higher PTH was associated with worse intracerebral autoregulation, cerebrovascular function, cognition and mood were normal in mild PHPT. PTX did not improve vascular or cognitive function. The observed improvement in mood cannot be clearly attributed to PTX. Notwithstanding the small sample size, the results do not support changing current criteria for parathyroidectomy to include cognitive complaints. However, the associations between PTH, cognition and cerebral autoregulation merit future studies in those with more severe hyperparathyroidism.

Computational wear prediction of insert conformity and material on mobile-bearing unicompartmental knee arthroplasty.

OBJECTIVES: Unicompartmental knee arthroplasty (UKA) is an alternative to total knee arthroplasty with isolated medial or lateral compartment osteoarthritis. However, polyethylene wear can significantly reduce the lifespan of UKA. Different bearing designs and materials for UKA have been developed to change the rate of polyethylene wear. Therefore, the objective of this study is to investigate the effect of insert conformity and material on the predicted wear in mobile-bearing UKA using a previously developed computational wear method. METHODS: Two different designs were tested with the same femoral component under identical kinematic input: anatomy mimetic design (AMD) and conforming design inserts with different conformity levels. The insert materials were standard or crosslinked ultra-high-molecular-weight polyethylene (UHMWPE). We evaluated the contact pressure, contact area, wear rate, wear depth, and volumetric wear under gait cycle loading conditions. RESULTS: Conforming design inserts had the lower contact pressure and larger contact area. However, they also had the higher wear rate and volumetric wear. The improved wear performance was found with AMD inserts. In addition, the computationally predicted volumetric wear of crosslinked UHMWPE inserts was less than half that of standard UHMWPE inserts. CONCLUSION: Our results showed that increasing conformity may not be the sole predictor of wear performance; highly crosslinked mobile-bearing polyethylene inserts can also provide improvement in wear performance. These results provide improvements in design and materials to reduce wear in mobile-bearing UKA.Cite this article: Bone Joint Res 2019;8:563-569.

Early major complications after bariatric surgery in the USA, 2003-2014: a systematic review and meta-analysis.

The effectiveness of bariatric surgery has been well-studied. However, complications after bariatric surgery have been understudied. This review assesses <30-d major complications associated with bariatric procedures, including anastomotic leak, myocardial infarction and pulmonary embolism. This review included 71 studies conducted in the USA between 2003 and 2014 and 107,874 patients undergoing either gastric bypass, adjustable gastric banding or sleeve gastrectomy, with mean age of 44 years and pre-surgery body mass index of 46.5 kg m-2 . Less than 30-d anastomotic leak rate was 1.15%; myocardial infarction rate was 0.37%; pulmonary embolism rate was 1.17%. Among all patients, mortality rate following anastomotic leak, myocardial infarction and pulmonary embolism was 0.12%, 0.37% and 0.18%, respectively. Among surgical procedures, <30-d after surgery, sleeve gastrectomy (1.21% [95% confidence interval, 0.23-2.19%]) had higher anastomotic leak rate than gastric bypass (1.14% [95% confidence interval, 0.84-1.43%]); gastric bypass had higher rates of myocardial infarction and pulmonary embolism than adjustable gastric banding or sleeve gastrectomy. During the review, we found that the quality of complication reporting is lower than the reporting of other outcomes. In summary, <30-d rates of the three major complications after either one of the procedures range from 0% to 1.55%. Mortality following these complications ranges from 0% to 0.64%. Future studies reporting complications after bariatric surgery should improve their reporting quality.

Combined influence of CT random noise and HU-RSP calibration curve nonlinearities on proton range systematic errors.

Proton range random and systematic uncertainties are the major factors undermining the advantages of proton therapy, namely, a sharp dose falloff and a better dose conformality for lower doses in normal tissues. The influence of CT artifacts such as beam hardening or scatter can easily be understood and estimated due to their large-scale effects on the CT image, like cupping and streaks. In comparison, the effects of weakly-correlated stochastic noise are more insidious and less attention is drawn on them partly due to the common belief that they only contribute to proton range uncertainties and not to systematic errors thanks to some averaging effects. A new source of systematic errors on the range and relative stopping powers (RSP) has been highlighted and proved not to be negligible compared to the 3.5% uncertainty reference value used for safety margin design. Hence, we demonstrate that the angular points in the HU-to-RSP calibration curve are an intrinsic source of proton range systematic error for typical levels of zero-mean stochastic CT noise. Systematic errors on RSP of up to 1% have been computed for these levels. We also show that the range uncertainty does not generally vary linearly with the noise standard deviation. We define a noise-dependent effective calibration curve that better describes, for a given material, the RSP value that is actually used. The statistics of the RSP and the range continuous slowing down approximation (CSDA) have been analytically derived for the general case of a calibration curve obtained by the stoichiometric calibration procedure. These models have been validated against actual CSDA simulations for homogeneous and heterogeneous synthetical objects as well as on actual patient CTs for prostate and head-and-neck treatment planning situations.

Experimental assessment of proton dose calculation accuracy in inhomogeneous media.

PURPOSE: Proton therapy with Pencil Beam Scanning (PBS) has the potential to improve radiotherapy treatments. Unfortunately, its promises are jeopardized by the sensitivity of the dose distributions to uncertainties, including dose calculation accuracy in inhomogeneous media. Monte Carlo dose engines (MC) are expected to handle heterogeneities better than analytical algorithms like the pencil-beam convolution algorithm (PBA). In this study, an experimental phantom has been devised to maximize the effect of heterogeneities and to quantify the capability of several dose engines (MC and PBA) to handle these. METHODS: An inhomogeneous phantom made of water surrounding a long insert of bone tissue substitute (1×10×10 cm3) was irradiated with a mono-energetic PBS field (10×10 cm2). A 2D ion chamber array (MatriXX, IBA Dosimetry GmbH) lied right behind the bone. The beam energy was such that the expected range of the protons exceeded the detector position in water and did not attain it in bone. The measurement was compared to the following engines: Geant4.9.5, PENH, MCsquare, as well as the MC and PBA algorithms of RayStation (RaySearch Laboratories AB). RESULTS: For a γ-index criteria of 2%/2mm, the passing rates are 93.8% for Geant4.9.5, 97.4% for PENH, 93.4% for MCsquare, 95.9% for RayStation MC, and 44.7% for PBA. The differences in γ-index passing rates between MC and RayStation PBA calculations can exceed 50%. CONCLUSION: The performance of dose calculation algorithms in highly inhomogeneous media was evaluated in a dedicated experiment. MC dose engines performed overall satisfactorily while large deviations were observed with PBA as expected.

[Robust treatment planning in proton therapy]. / Planification de traitement robuste en protonthérapie.

The concentration of the dose delivered by protons at the end of their path, the Bragg peak, has the potential to improve external radiotherapy treatments. Unfortunately, the main strength of the protons, their finite range, is also their greatest weakness. Any uncertainty on the range may lead to inadequate target coverage or excessive toxicity. The uncertainties have multiple origins and include, among others, ballistic errors, morphological modifications or inaccurate estimations of the physical quantities necessary to predict the proton range. Uncertainties have been part of daily practice in conventional radiotherapy with X-rays for a long time. However, dose distributions delivered with X-rays are much less sensitive to uncertainties than the ones delivered with protons. This relative insensitivity enabled the management of uncertainties through safety margins using a simple formalism. The conditions of validity of this formalism are much more restrictive for proton therapy, leading to the need of developing new tools and adapted strategies to manage accurately these uncertainties. The objective of this paper is to present a vision for the management of uncertainties in proton therapy in the continuity of formalisms established for X-rays. The latter are first summarized before discussing the necessary developments in order to consistently apply them to protons.

Effect of concomitant vitamin D deficiency or insufficiency on lumbar spine volumetric bone mineral density and trabecular bone score in primary hyperparathyroidism.

UNLABELLED: Lower vitamin D and higher parathyroid hormone (PTH) levels are associated with higher volumetric BMD and bone strength at the lumbar spine as measured by central quantitative computed tomography in primary hyperparathyroidism (PHPT), but there are no differences in bone microarchitecture as measured by trabecular bone score (TBS). INTRODUCTION: The purpose of this study was to evaluate the association between 25-hydroxyvitamin D (25OHD) and volumetric bone mineral density (vBMD) and the TBS at the lumbar spine (LS) in PHPT. METHODS: This is a cross-sectional analysis of PHPT patients with and without low 25OHD. We measured vBMD with quantitative computed tomography (cQCT) and TBS by dual-energy X-ray absorptiometry (DXA) at the LS in 52 and 88 participants, respectively. RESULTS: In the cQCT cohort, those with lower vitamin D (<20 vs. 20-29 vs. ≥30 ng/ml) tended to be younger (p = 0.05), were less likely to use vitamin D supplementation (p < 0.01), and had better renal function (p = 0.03). Those with 25OHD <20 ng/ml had 80 and 126 % higher serum PTH levels respectively vs. those with 25OHD 20-29 ng/ml (p = 0.002) and 25OHD ≥30 ng/ml (p < 0.0001). Covariate-adjusted integral and trabecular vBMD were higher in those with 25OHD 20-29 vs. those with 25OHD ≥30 ng/ml, but those with 25OHD <20 did not differ. Because there were few participants with 25OHD deficiency, we also compared those with vitamin D <30 vs. ≥30 ng/ml. Covariate-adjusted integral and trabecular vBMD were 23 and 30 % higher respectively (both p < 0.05) in those with vitamin D <30 vs. ≥30 ng/ml. TBS was in the partially degraded range but did not differ by vitamin D status. CONCLUSION: In mild PHPT, lower 25OHD is associated with higher PTH, but vitamin D deficiency and insufficiency using current clinical thresholds did not adversely affect lumbar spine skeletal health in PHPT. Further work is needed to determine if higher vBMD in those with lower vitamin D is due to an anabolic effect of PTH.

Low vitamin D levels have become less common in primary hyperparathyroidism.

UNLABELLED: We compared temporal trends in serum 25-hydroxyvitamin D and parathyroid hormone (PTH) in two primary hyperparathyroidism (PHPT) cohorts recruited 20 years apart. The prevalence of 25-hydroxyvitamin D levels <20 and <30 ng/mL declined by 30-50 %, respectively, and was accompanied by lower PTH. In the older cohort, higher PTH may be due to lower 25-hydroxyvitamin D. INTRODUCTION: Vitamin D deficiency may exacerbate PHPT. Whether there have been temporal trends in 25-hydroxyvitamin D (25OHD) levels in PHPT is unclear. The prevalence of low vitamin D levels (25OHD <20 and <30 ng/mL) and associated biochemical and bone mineral density (BMD) profiles were assessed in two PHPT cohorts recruited over 20 years apart. METHODS: This is a cross-sectional comparison of serum 25OHD levels, calciotropic hormones, and BMD between two PHPT cohorts recruited at the same hospital: the "old" (N = 103) and "new" (N = 100) cohorts were enrolled between 1984 and 1991 and between 2010 and 2014, respectively. RESULTS: Mean 25OHD levels were 26 % higher in the new cohort (23 ± 10 vs. 29 ± 10 ng/mL, p < 0.0001). Levels of 25OHD <20 and <30 ng/mL declined from 46 and 82 %, respectively, to 19 and 54 % (both p < 0.0001). Supplemental vitamin D use was common in the new (64 %) but not the old cohort (0 %). The new cohort demonstrated 33 % lower serum PTH levels (p < 0.0001). Neither serum nor urine calcium differed. BMD was higher in the new cohort at all skeletal sites (all p < 0.001). CONCLUSION: With the rise in vitamin D supplementation over the last two decades, low 25OHD levels are no longer common in PHPT patients in the New York area. Those with 25OHD <20 and <30 ng/mL have declined by over 50 and 30 %, respectively. The lower mean PTH levels in the new cohort are most likely accounted for by higher vitamin D intake. Whether improved vitamin D status also underlies the relatively higher BMD in the more vitamin D replete cohort of PHPT patients is unknown.

Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study.

BACKGROUND: Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. PATIENTS AND METHODS: Chemotherapy-receiving breast cancer patients (stages I-III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte-macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. RESULTS: Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1ß was associated with poorer response speed performance (estimate: -0.78; 95% confidence interval (CI) -1.34 to -0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1ß and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). CONCLUSIONS: While elevated concentrations of IL-6 and IL-1ß were observed in patients with poorer response speed performance and perceived cognitive disturbances, IL-4 may be protective against chemotherapy-associated cognitive impairment. This study is important because cytokines would potentially be mechanistic mediators of chemotherapy-associated cognitive changes.

Feasibility and robustness of dose painting by numbers in proton therapy with contour-driven plan optimization.

PURPOSE: To prove the ability of protons to reproduce a dose gradient that matches a dose painting by numbers (DPBN) prescription in the presence of setup and range errors, by using contours and structure-based optimization in a commercial treatment planning system. METHODS: For two patients with head and neck cancer, voxel-by-voxel prescription to the target volume (GTVPET) was calculated from (18)FDG-PET images and approximated with several discrete prescription subcontours. Treatments were planned with proton pencil beam scanning. In order to determine the optimal plan parameters to approach the DPBN prescription, the effects of the scanning pattern, number of fields, number of subcontours, and use of range shifter were separately tested on each patient. Different constant scanning grids (i.e., spot spacing = Δx = Δy = 3.5, 4, and 5 mm) and uniform energy layer separation [4 and 5 mm WED (water equivalent distance)] were analyzed versus a dynamic and automatic selection of the spots grid. The number of subcontours was increased from 3 to 11 while the number of beams was set to 3, 5, or 7. Conventional PTV-based and robust clinical target volumes (CTV)-based optimization strategies were considered and their robustness against range and setup errors assessed. Because of the nonuniform prescription, ensuring robustness for coverage of GTVPET inevitably leads to overdosing, which was compared for both optimization schemes. RESULTS: The optimal number of subcontours ranged from 5 to 7 for both patients. All considered scanning grids achieved accurate dose painting (1% average difference between the prescribed and planned doses). PTV-based plans led to nonrobust target coverage while robust-optimized plans improved it considerably (differences between worst-case CTV dose and the clinical constraint was up to 3 Gy for PTV-based plans and did not exceed 1 Gy for robust CTV-based plans). Also, only 15% of the points in the GTVPET (worst case) were above 5% of DPBN prescription for robust-optimized plans, while they were more than 50% for PTV plans. Low dose to organs at risk (OARs) could be achieved for both PTV and robust-optimized plans. CONCLUSIONS: DPBN in proton therapy is feasible with the use of a sufficient number subcontours, automatically generated scanning patterns, and no more than three beams are needed. Robust optimization ensured the required target coverage and minimal overdosing, while PTV-approach led to nonrobust plans with excessive overdose. Low dose to OARs can be achieved even in the presence of a high-dose escalation as in DPBN.

A study on seasonal variation of skin parameters in Korean males.

OBJECTIVE: The physiological characteristics of the skin are varied greatly, depending on gender, age, region and race, and many dermatologic researches have been performed through various research methods. This study aimed to examine how Korean men's skin conditions were influenced by temperature or humidity changes caused by seasonal rotations. METHODS: A total of 100 healthy Korean men, age range 20-59 years, participated in the study for both summer and winter. We compared on the characteristics of skin between summer and winter. The skin hydration, skin pH and TEWL were evaluated on the forehead, cheek and forearm. The skin sebum content of the glabella, nasal ala and cheek was measured using Sebumeter(®) (SM810, Courage+Khazaka, Germany). Cutometer(®) (MPA 580 Courage+Khazaka, Germany) the elasticity was measured by on the cheeks, and PRIMOS lite(®) (Phase shift Rapid in vivo Measurement of Skin, GFMesstechnik GmbH, Germany) was used to evaluate wrinkles on crow's feet. Lastly, in addition, the skin pore of the face was measured using the Janus(®) (PSI, Korea) which is a facial analysis system. RESULTS: The results were as follows: the comparison of hydration in summer and winter shows significant differences in their forehead, cheeks and forearm. The pH values of the skin surface were generally higher in winter, and significantly different on each site, and the sebum content was higher in summer than in winter. As a result of the pore measurement, the summer showed more pores compared to the winter, and there was a statistically significant difference in skin pores between summer and winter. The sensitivity measured by stinging test increases significantly more in winter than in summer. However, there were no seasonal differences in wrinkles and skin brightness. CONCLUSION: The skin surface pH, TEWL, sebum content, hydration, elasticity, wrinkles, skin pore and skin sensitivity vary with seasons and body regions in Korean men.