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This work describes the development of a system that combines a derivatization protocol based on the Katritzky reaction with paper spray ionization mass spectrometry (PSI-MS) for the analysis of amino acid neurotransmitters in mouse brain tissues. The system is relatively simple, consisting of spraying the derivatization solution onto a mouse brain section mounted on a glass slide, applying a small volume of solvent to moisten the sample, pressing a triangular paper onto the sample surface to transfer the sample constituents to the paper surface, and using the paper as a substrate for PSI-MS analysis. The Katritzky reaction facilitated the ionization of the amino acids by reacting a pyrylium salt with the amino group of the analytes, forming very stable pyridinium cations, which greatly increased the sensitivity of the PSI-MS analysis. Most of the intensities of the amino acids modified by the Katritzky reaction were more than 10 times greater than the nonderivatized ones. The system was applied for the analysis of brain sections obtained from mice with Parkinson's disease, and the amino acids gamma-aminobutyric acid (GABA) and glycine (Gly), two compounds very well-known in studies of Parkinson's disease, were readily detected. The results suggest that the Katritzky reaction combined with PSI-MS might offer a significant advance in the knowledge on protocols that improve the sensitivity of detection of crucial biological compounds.

BackgroundRecovery in schizophrenia is a complex process, involving clinical, societal and personal recovery. Until now, studies analysed these domains separately, without examining their mutual relations and changes over time.AimsThis study aimed to examine different states of recovery and transition rates between states.MethodThe Pharmacotherapy Monitoring and Outcome Survey (2006–2017) yearly assesses patients with schizophrenia in the Northern Netherlands. Data from 2327 patients with one up to 11 yearly measurements on clinical, societal and personal recovery were jointly analysed with a mixture latent Markov model (MLMM).ResultsThe selected MLMM had four states that differed in degree and pattern of recovery outcomes. Patients in state 1 were least recovered on any domain (16% of measurements), and partly recovered in states 2 (25%; featured by negative symptoms) and 3 (21%; featured by positive symptoms). Patients in state 4 (38%) were most recovered, except for work, study and housekeeping. At the subsequent measurement, the probability of remaining in the same state was 77–89%, transitioning to a better state was 4–12% and transitioning to a worse state was 4–6%; no transitions occurred between states 1 and 4. Female gender, shorter illness duration and less schizophrenia were more prevalent in better states.ConclusionsQuite a high recovery rate was present among a substantial part of the measurements (38%, state 4), with a high probability (89%) of remaining in this state. Transition rates in the other states might increase to a more favourable state by focusing on adequate treatment of negative and positive symptoms and societal problems.

Isothermal amplification strategies capable of rapid, inexpensive, and accurate nucleic acid detection provide new options for large-scale pathogen detection, disease diagnosis, and genotyping. Here we report a highly sensitive multicomponent XNA-based nucleic acid detection platform that combines analyte preamplification with X10-23-mediated catalysis to detect the viral pathogen responsible for COVID-19. The platform, termed RNA-Encoded Viral Nucleic Acid Analyte Reporter (REVEALR), functions with a detection limit of ≤20 aM (∼10 copies/μL) using conventional fluorescence and paper-based lateral flow readout modalities. With a total assay time of 1 h, REVEALR provides a convenient nucleic acid alternative to equivalent CRISPR-based approaches, which have become popular methods for SARS-CoV-2 detection. The assay shows no cross-reactivity for other in vitro transcribed respiratory viral RNAs and functions with perfect accuracy against COVID-19 patient-derived clinical samples.

The aim of this study is to implement lifetime attributable risk (LAR) predictions for radiation induced cancers for Swedish cohorts of patients of various age and sex, undergoing diagnostic investigations by nuclear medicine methods. Methods: Calculations are performed on Swedish groups of patients with Paget's disease and with bone metastases from prostatic cancer and diagnosed with bone scintigraphy with an administration of 500 MBq 99mTc-phosphonate. Results: The inclusion of patient survival rates into the calculations lowers the induced radiation cancer risk, as it takes into account that cohorts of patients have shorter predicted survival times than the general population. Conclusion: LAR estimations could be valuable for referring physicians, nuclear medicine physicians, nurses, medical physicists, radiologists, and oncologists and as well as ethical committees for risk estimates for specific subgroups of patients. Caution is however advised with respect to application of LAR predictions to individuals (because of individual sensitivities, circumstances, etc.).

Background: Patient-reported outcomes (PROS) are widely accepted measures for evaluating outcomes of surgical interventions. As patient-reported information is stored in electronic health records, it is essential that there are valid electronic PRO (ePRO) instruments available for clinicians and researchers. The aim of this study was to evaluate the validity of electronic versions of five widely used foot and ankle specific PRO instruments. Methods: Altogether 111 consecutive elective foot/ankle surgery patients were invited face-to-face to participate in this study. Patients completed electronic versions of the Foot and Ankle Ability Measure (FAAM), the Foot and Ankle Outcome Score (FAOS), the modified Lower Extremity Function Scale (LEFS), the Manchester-Oxford Foot Questionnaire (MOXFQ), and the Visual Analogue Scale Foot and Ankle (VAS-FA) on the day of elective foot and/or ankle surgery. Construct validity, coverage, and targeting of the scales were assessed. Results: Based on general and predefined thresholds, construct validity, coverage, and targeting of the ePRO versions of the FAAM, the FAOS, the MOXFQ, and the VAS-FA were acceptable. Major issues arose with score distribution and convergent validity of the modified LEFS instrument. Conclusions: The ePRO versions of the FAAM, the FAOS, the MOXFQ and the VAS-FA provide valid scores for foot and ankle patients. However, our findings do not support the use of the modified LEFS as an electronic outcome measure for patients with orthopedic foot and/or ankle pathologies. (C) 2020 European Foot and Ankle Society. Published by Elsevier Ltd. All rights reserved.

Mineralized polymer scaffolds have proven to be effective biomaterials for inducing osteoinductivity in bone tissue engineering. Sequential mineralization is a promising technique for depositing minerals in three-dimensional (3D) scaffolds. Paper, which is made of cellulose fibers, can be used as a tissue scaffold due to its highly porous structure and flexibility, as well as its excellent ability to wick fluids and support the growth of bone cells. In this study, paper-based, mineralized scaffolds were fabricated using sequential mineralization. We conducted experiments with two groups of scaffolds based on different incubation times in the mineralization solutions (30 min and 24 h). Ten cycles of mineralization were performed for each group. We found that the mineral content increased as the cycle number increased and that the 24-h group scaffolds consistently had more mineralization than did the 30-min group scaffolds when measured at the same cycle number. A quantitative reverse transcription-polymerase chain reaction was performed for two osteogenic differentiation markers of the preosteoblasts that were grown on the mineralized paper scaffolds. The gene expression results for bone-specific markers revealed that the mineralized scaffolds were osteoinductive. Subcutaneous implantation of the scaffolds in rats demonstrated favorable biocompatibility, high vascularization, and non-immunogenicity in vivo. The overall results suggest that the sequentially mineralized paper scaffolds are promising materials for use in bone tissue engineering.

Objectives: The study aimed to estimate the incidence and prevalence of feline lymphoma in cats attending primary-care practices across the UK and to identify patient-based and environmental (radon and pesticide exposure) risk factors. Materials and methods: Case records from the VetCompassTM programme from primary-care veterinary practices in the UK were searched for a diagnosis of lymphoma in cats in 2016. Cases were required to have had an external laboratory confirmed diagnosis based on cytology and/or histopathology. A nested case-control study design was used to identify risk factors for lymphoma using multivariable logistic regression. Results: From a cohort of 562,446 cats under veterinary care at VetCompass participating practices in 2016, a total of 271 lymphoma cases were identified (prevalence: 48/100,000, 95% CI 44- 56/100,000; incidence 32/100,000, 95% CI 26- 35/100,000). There was 180 incident lymphoma cases and 803 controls, all aged 2 years and older. Male (OR 1.7, 95% CI 1.2-2.4, P=0.004), insured (OR 3.6, 95% CI 2.3-5.6, P=

Changes in ecosystems after the removal of stress provide a rich source of information for conservation science. We used a long-term regional data set on the performance of white sucker (Catostomus commersonii) collected before and after the closure of a pulp mill to explore recovery in fish. Physiological indicators, including liver enzymes and plasma steroids, showed some compelling changes after the closure of the mill consistent with reduced exposure to pulp mill effluent but did not unequivocally demonstrate recovery. However, persistent signals in these fish may indicate effects of impoundment or discharge of sewage. We also used quantile regression with environmental covariates and bootstrap iteration to determine if systematic variation remained in relative body weight, liver weight, and gonad weight. In fish formerly exposed to pulp mill effluent, we found evidence of improvements (male gonad weight and liver weight of males and females), degradation (gonad weight of females), and no change (body weight). Although the observed patterns may be associated with closure of the mill, some differences were also found at regional locations, suggesting roles of additional stressors and challenging the clear association of change at the Mattagami River exposure site with the closure of the mill. However, fish captured at this location show responses consistent with regional locations, suggesting no residual impacts and highlights the challenges of identifying changes in fish even after large and known interventions. Environ Toxicol Chem 2021;40:162-176. © 2020 SETAC.

OBJECTIVE: This waiting-list randomized controlled trial examined the effectiveness of a self-management mHealth app in improving fatigue and quality of life (QoL) in cancer patients and survivors.METHODS: Persons with cancer-related fatigue (CRF) were recruited across four English speaking countries, via social media, and randomized into intervention (n = 519) and control (n = 280) groups. Whereas the intervention group received immediate access to the Untire app, the control group received access only after 12-weeks. Primary outcomes fatigue severity and interference, and secondary outcome QoL were assessed at baseline, 4, 8, and 12-weeks. We ran generalized linear mixed models for all outcomes to determine the effects of app access (yes/no), over 12-weeks, following the intention-to-treat principle.RESULTS: Compared with the control group, the intervention group showed significantly larger improvements in fatigue severity (d = 0.40), fatigue interference (d = 0.35), and overall QoL on average (d = 0.32) (P's 56). Effects did not depend on education and cancer status. Reliable change analyses indicated that significantly more people showed full recovery for fatigue in the intervention vs the control group (P's = .02).CONCLUSIONS: The Untire app can be an effective mHealth solution for cancer patients and survivors with moderate to severe CRF.

BackgroundDepression is associated with lower educational attainment, but there has been little investigation of long-term educational trajectories in large cohorts with diagnosed depression.AimsTo describe the educational attainment trajectories of children with a depression diagnosis in secondary care, and to investigate whether these trajectories vary by sociodemographic characteristics.MethodWe identified new referrals to South London and Maudsley's NHS Foundation Trust between 2007 and 2013 who received a depression diagnosis at under 18 years old. Linking their health records to the National Pupil Database, we standardised their performance on three assessments (typically undertaken at ages 6–7 years (school Year 2), 10–11 (Year 6) and 15–16 (Year 11)) relative to the local reference population in each academic year. We used mixed models for repeated measures to estimate attainment trajectories.ResultsIn our sample of 1492 children, the median age at depression diagnosis was 15 years (interquartile range = 14–16). Their attainment showed a decline between school Years 6 and 11. Attainment was consistently lower among males and those eligible for free school meals. Black ethnic groups also showed lower attainment than White ethnic groups between Years 2 and 6, but showed a less pronounced drop in attainment at Year 11.ConclusionsThose who receive a depression diagnosis during their school career show a drop in attainment in Year 11. Although this pattern was seen among multiple sociodemographic groups, gender, ethnicity and socioeconomic status predict more vulnerable subgroups within this clinical population who might benefit from additional educational support or more intensive treatment.

Objective Fear of cancer recurrence (FCR) is a common psychosocial sequela among cancer survivors, but data on patients with multiple myeloma are scarce. This study calculated the prevalence of FCR and identified family and social factors that predict FCR in the study population. Methods We recruited 127 myeloma patients and their partners to participate in a cross‐sectional survey from a regional tertiary cancer centre in China. The questionnaires included items on demographic characteristics and from the fear of disease progression simplified scale, family hardiness index and Social Support Scale. Univariate and multivariate regression was used to identify predictors of FCR. Results Of the participants, 56.4% patients reported high‐level FCR, which was similar to the partner‐reported proportion. The partners' FCR was positively associated with the patients' FCR, while family hardiness and social support were statistically significant, negative predictors. Conclusions Interventions to mitigate partners' FCR and improve family hardiness and social support may help with the psychological adjustment and well‐being of myeloma patients.

The effect of low-level laser therapy (LLLT) on an experimental model of ventilator-induced lung injury (VILI) was evaluated in this study. 24 adult Wistar rats were randomized into four groups: protective mechanical ventilation (PMV), PMV + laser, VILI and VILI + laser. The animals of the PMV and VILI groups were ventilated with tidal volumes of 6 and 35 ml kg−1, respectively, for 90 minutes. After the first 60 minutes of ventilation, the animals in the laser groups were irradiated (808 nm, 100 mW power density, 20 J cm−2 energy density, continuous emission mode, and exposure time of 5 s) and after 30 minutes of irradiation, the animals were euthanized. Lung samples were removed for morphological analysis, bronchoalveolar lavage (BAL) and real time quantitative polynucleotide chain reaction (RT-qPCR). The VILI group showed a greater acute lung injury (ALI) score with an increase in neutrophil infiltration, higher neutrophil count in the BAL fluid and greater cytokine mRNA expression compared to the PMV groups (p < 0.05). The VILI ± laser group when compared to the VILI group showed a lower ALI score (0.35 ± 0.08 vs. 0.54 ± 0.13, p < 0.05), alveolar neutrophil infiltration (7.00 ± 5.73 vs. 21.50 ± 9.52, p < 0.05), total cell count (1.90 ± 0.71 vs. 4.09 ± 0.96 × 105, p < 0.05) and neutrophil count in the BAL fluid (0.60 ± 0.37 vs. 2.28 ± 0.48 × 105, p < 0.05). Moreover, LLLT induced a decrease in pro-inflammatory and an increase of anti-inflammatory mRNA levels compared to the VILI group (p < 0.05). In conclusion, LLLT was found to reduce the inflammatory response in an experimental model of VILI.

Objective: The purpose of this study was to evaluate whether the complexity of the corneal pulse (CP) signal can be used to differentiate patients with primary open-angle glaucoma (POAG) from healthy subjects. Approach: The study sample consisted of 28 patients with POAG and a control, age-matched group of 30 subjects. After standard ophthalmic examination, the CP signal from a randomly selected eye of each participant was measured using non-contact ultrasonic micro-displacement measurement technology. After pre-processing, the complexity of the CP signal was estimated using refined composite multiscale fuzzy entropy (RCMFE) up to scale factor 50. The average RCMFE values were computed from three repeated measurements of the CP signals for each participant and each scale factor. Main results: The complexity of the CP signal in glaucomatous eyes was higher than that observed in healthy ones. Also, RCMFE of the CP signal was found to differentiate (statistically significantly) between the two groups for scales in the range from 26 to 43. For these scales, the one for which the lowest p-value (t-test, p = 0.017) was obtained when comparing RCMFE between the two groups was selected as the optimal scale. Next, a receiver operating characteristic analysis for the optimal scale showed that the proposed approach of calculating the multiscale entropy of the CP signal has some potential to discriminate between patients with POAG and healthy controls (sensitivity, specificity and accuracy of 0.643, 0.700 and 0.672, respectively). Significance: In conclusion, RCMFE, as a complexity measure, may be considered an auxiliary indicator to support glaucoma diagnostics.

Objective Patients with cancer are at high risk of depression. However, the risk of major depressive disorder (MDD) after cancer diagnosis has not been studied in a population setting in Japan. This cohort study used a Japanese medical claims database to examine time to MDD in cancer patients and the risk of MDD (hazard ratio; HR) compared with matched cancer‐free controls. Methods Primary endpoint was time to MDD (starting 6 months before cancer diagnosis) in adult (18–74 years) cancer patients; secondary endpoint was time to MDD (6 months before to 12 months after cancer diagnosis) in a matched cohort of cancer patients and cancer‐free controls. Multivariate analyses were performed to determine HRs for all cancers and for each cancer site. Results Of 35 008 cancer patients (mean age, 53.3 years), 2201 (6.3%) were diagnosed with MDD within 66 months. Matched cancer patients (n = 30 372) had an elevated risk of MDD compared with cancer‐free controls (n = 303 720; HR [95% confidence interval] 2.96 [2.77–3.16]). MDD risk was highest in patients with multiple cancers, pancreatic cancer, and brain cancer. Compared with middle‐aged patients, risk was higher in patients

Objectives Numerous authors have expressed their interest in adjustment and social support in the context of cancer. However, none of the previous studies has directly examined the models describing the links between daily social support and adjustment fluctuation, particularly at the relational level. This study aimed to verify the additive and buffering models of daily received support regarding the relational level of patient‐caregiver relationship, that is, the relationship‐related stress and relationship satisfaction following hematopoietic cell transplantation (HCT). Methods Two hundred patient‐caregiver dyads participated in a 28‐day diary study that was started on the first day after post‐HCT discharge. The participants rated the extent of daily relationship‐related stress, relationship satisfaction, and received support every evening during the study. The analyses were based on the actor‐partner interdependence moderation model. Results Daily deviations in received support were directly associated with concurrent and lagged daily deviations in relationship satisfaction, regardless of relationship‐related stress level in both patients and caregivers. In addition, in caregivers, the effect of daily deviations in received support on relationship satisfaction depended on deviations in relationship‐related stress and was significant on the days with higher relationship‐related stress. Conclusions The findings supported both the additive (in patients and caregivers) and the buffering hypotheses (in caregivers) of daily received support in patient‐caregiver dyads during the first month following HCT. The theoretical and practical implications of the findings are further highlighted.

Postmortem computed tomography (PMCT) is integrated into the evaluation of decedents in several American medical examiner offices and medicolegal death investigative centers in many other countries. We retrospectively investigated the value of PMCT in a series of firearm homicide cases from a statewide centralized medical examiner’s office that occurred during 2016. Autopsies were performed or supervised by board‐certified forensic pathologists who reviewed the PMCT scans prior to autopsy. PMCT scans were re‐evaluated by a forensic radiologist blinded to the autopsy findings and scored by body region (head–neck, thoracoabdominal, and extremities). Injury discrepancies were scored using a modified Goldman classification and analyzed with McNemar’s test. We included 60 males and 20 females (median age 31 years, range 3–73). Based on PMCT, 56 (79.1%) cases had injuries relevant to the cause of death in a single body region (24 head–neck region, 32 thoracoabdominal region). Out of these 56 cases, 9 had a missed major diagnosis by PMCT outside that region, including 6 extremity injuries visible during standard external examination. Yet all had evident lethal firearm injury. We showed that PMCT identifies major firearm injuries in homicide victims and excludes injuries related to the cause of death in other regions when a single body region is injured. Although PMCT has a known limited sensitivity for soft tissue and vascular pathology, it can be combined with external examination to potentially reduce or focus dissections in some of these cases depending on the circumstances and medicolegal needs.

Objective This study aimed to assess psychological functioning, quality of life, and regret about screening after a positive fecal immunochemical test (FIT) and subsequent colonoscopy, and to evaluate changes over time. Methods This is a prospective cohort study. Individuals aged 55 to 75 with a positive FIT that were referred for colonoscopy between July 2017 and November 2018, were invited to complete questionnaires related to psychological distress and health‐related quality of life at three predefined time points: before colonoscopy, after histopathology result notification, and after 6 months. Four questionnaires were used: the Psychological Consequences Questionnaire (PCQ), the six‐item Cancer Worry Scale (CWS), the Decision Regret Scale (DRS), and the 36‐item Short‐Form (SF‐36). Results A total of 1066 participants out of 2151 eligible individuals were included. Patients with cancer showed a significant increase in psychological dysfunction (P = .01) and cancer worry (P = .008) after colonoscopy result notification, and a decline to pre‐colonoscopy measurements after 6 months. In the no‐cancer groups, psychological dysfunction and cancer worry significantly decreased over time (P 25). A good global quality of life was reported in participants with no cancer. Conclusion Some psychological distress remains up to 6 months after colonoscopy in participants who tested false‐positive in the Dutch bowel cancer screening program.

The use of iodine-131 S values based on reference computational phantoms with fixed thyroid model may lead to significant dosimetric errors in patients who may have different thyroid location from the reference phantoms. In the present study, we investigated individual thyroid location variation by examining the computed tomography image sets of 40 adult male and female patients. Subsequently, the thyroid location of the adult male and female mesh-type reference phantoms of the International Commission on Radiological Protection (ICRP) was adjusted to match each the highest, mean and the lowest locations of the thyroid observed in this dataset. The thyroid-adjusted phantoms were implemented into the Geant4 Monte Carlo code to calculate thyroid location-dependent iodine-131 S values (rT ← thyroid) for a total of 30 target regions. The maximum variation among the observed thyroid locations was 39 mm and 36 mm for male and female patients, respectively. The mean thyroid locations of both male and female patients showed a good agreement with the ICRP reference phantoms. The thyroid location-dependent Iodine-131 S values were significantly different from the reference phantoms for most target regions by up to a factor of 3. The use of thyroid location-dependent S values in dose reconstructions should help quantify the dosimetric uncertainty in epidemiologic investigations of patients receiving iodine-131 therapy for hyperthyroidism and thyroid cancer.

Background Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15–20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study. Methods Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8–13 years) and adolescent (14–18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up. Results A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4–20] vs. 7(3–13] vs. 7(3–14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous ( p = 0.025), musculoskeletal ( p = 0.029), renal ( p = 0.027) and cardiorespiratory ( p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive ( p = 0.034) and exhibited higher anti-dsDNA titres ( p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia ( p = 0.002), thrombocytopenia ( p = 0.004) or low complement ( p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up. Conclusions Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and “classic” autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.

Made available in DSpace on 2020-12-10T20:03:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-15 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Study Design. Cross-sectional study. Objective. To investigate the equivalence of electronic and paper version of self-report questionnaires for the assessment of disability, pain, fear of movement, depression, and physical activity of patients with chronic low back pain (LBP). Summary of Background Data. Paper and electronic versions of self-report questionnaires are commonly used for assessment of patients with LBP. However, the equivalence of self-report questionnaires commonly used for assessment of patients with chronic LBP remains unclear. Methods. Seventy-nine individuals with chronic LBP seeking physiotherapy care were recruited. Participants attended the clinic twice with an interval of 1 week and completed the self-reported questionnaires in a random order. The following questionnaires were administered: Roland Morris Disability Questionnaire (RMDQ); 11-point numerical rating scale (NRS); Tampa Scale for Kinesiophobia (TSK); Center for Epidemiological Studies-Depression (CES-D), and Baecke Habitual Physical Activity Questionnaire (BPAQ). To investigate the equivalence between the two questionnaire versions, intraclass correlation coefficient with 95% confidence interval and Bland-Altman plotting was used. Results. The paper and electronic versions of the RMDQ, TSK, and CES-D showed good reliability and the showed moderate reliability. In contrast, the NRS showed poor reliability between the electronic and paper versions. Conclusion. Our findings support that the electronic version of the RMDQ, TSK, CES-D, and BPAQ can be administered in clinical and research settings for assessment of patients with chronic LBP. Nevertheless, electronic version of the NRS for assessment of pain intensity should not be used interchangeably in clinical practice in patients with chronic LBP. Univ Estadual Paulista, Dept Fisioterapia, Fac Ciencias & Tecnol, Presidente Prudente, Brazil Univ Fed Minas Gerais UFMG, Dept Phys Therapy, Belo Horizonte, MG, Brazil Univ Estadual Paulista, Dept Educ Fis, Fac Ciencias & Tecnol, Presidente Prudente, Brazil Univ Estadual Paulista, Dept Fisioterapia, Fac Ciencias & Tecnol, Presidente Prudente, Brazil Univ Estadual Paulista, Dept Educ Fis, Fac Ciencias & Tecnol, Presidente Prudente, Brazil FAPESP: 2017/21336-8 FAPESP: 2016/03826-5 FAPESP: 2017/12246-5

Objective: Clinical options for managing nonmetastatic prostate cancer (PCa) vary. Each option has side effects associated with it, leading to difficulty in decision‐making. This study aimed to assess the relationship between patient involvement in treatment decision‐making and subsequent decision regret (DR), and quantify the impact of health‐related quality of life (HRQL) outcomes on DR. Methods: Men living in the United Kingdom, 18 to 42 months after diagnosis of PCa, were identified from cancer registration data and sent a questionnaire. Measures included the Decision Regret Scale (DRS), Expanded Prostate cancer Index Composite short form (EPIC‐26), EQ‐5D‐5L, and an item on involvement in treatment decision‐making. Multivariable ordinal regression was utilized, with DR categorized as none, mild, or moderate/severe regret. Results: A total of 17 193 men with stage I‐III PCa completed the DRS: 36.6% reported no regret, 43.3% mild regret, and 20.0% moderate/severe regret. The odds of reporting DR were greater if men indicated their views were not taken into account odds ratio ([OR] = 6.42, 95% CI: 5.39‐7.64) or were involved “to some extent” in decision‐making (OR = 4.63, 95% CI: 4.27‐5.02), compared with men who were “definitely” involved. After adjustment, including for involvement, men reporting moderate/big problems with urinary, bowel, or sexual function were more likely to experience regret compared with men with no/small problems. Better HRQL scores were associated with lower levels of DR. Conclusions: This large‐scale study demonstrates the benefit of patient involvement in treatment decision‐making for nonmetastatic PCa. However, men experiencing side effects and poorer HRQL report greater DR. Promoting engagement in clinical decision‐making represents good practice and may reduce the risk of subsequent regret.

Purpose Several studies have explored factors causing depression in cancer survivors, including perceived physical symptoms. Another critical factor in the depression symptomatology of cancer survivors is activity restriction (AR). We investigated how AR mediate the effects of perceived pain and fatigue on depression in cancer survivors. Methods Cancer survivors (n = 61; mean age 56.16 years) that were recruited through cancer support groups in Japan participated in this study. Participants completed a battery of questionnaires comprising demographic and clinical information, the Pain Catastrophizing Scale, the Cancer Fatigue Scale, the Activity Restriction Scale for Cancer Patients, and the Hospital Anxiety and Depression Scale. Results Mediation analysis indicated that AR partially mediates the effect of pain on depression. Direct paths from pain to AR, AR to depression, and pain to depression were significant (P

Objective: Meaning-centered group psychotherapy for cancer survivors (MCGP-CS) is an effective intervention to improve personal meaning, psychological well-being, and depressive symptoms until 6 months after the intervention. In this study, the long-term effects of MCGP-CS (i.e., at 1- and 2-year follow-up) on meaning, psychological well-being and posttraumatic growth were assessed, in comparison to supportive group psychotherapy (SGP) and care as usual (CAU). Methods: Cancer survivors (n = 170) were randomized into MCGP-CS, SGP, or CAU. Assessments were scheduled at baseline, 1 week, 3 months, 6 months, 1 year, and 2 years postintervention. Outcome measures were the Personal Meaning Profile, Ryff's Scales of Psychological Well-Being (SPWB), the Posttraumatic Growth Inventory, and their subscales. Linear mixed models (LMM) were used and results were both reported on an intention-to-treat (ITT) basis, as well as for intervention completers only. Results: LMM and post hoc analyses with Bonferroni correction revealed that MCGP-CS participants reported more improvement on positive relations (subscale of SPWB) than CAU participants of 2-year postintervention (ITT analysis, Cohen's d =.82). Completers also reported more personal growth (subscale of SPWB) after MCGP-CS than after SGP 1-year postintervention (Cohen's d =.94). No long-term effects were found on the other outcome measures. Conclusions: In the 2 years after MCGP-CS, the short-term significant effects on personal meaning and most positive effects related to psychological well-being faded. However, MCGP-CS had a long-term positive effect on positive relations with others and on survivors' sense of personal growth. Trial registration: Netherlands Trial Register: NTR3571.

A developmental validation was performed to demonstrate reliability, reproducibility, and robustness of the ANDE Rapid DNA Identification System for processing of crime scene and disaster victim identification (DVI) samples. A total of 1705 samples were evaluated, including blood, oral epithelial samples from drinking containers, samples on FTA and untreated paper, semen, bone, and soft tissues. This study was conducted to address the FBI’s Quality Assurance Standards on developmental validation and to accumulate data from a sufficient number of unique donors and sample types to meet NDIS submission requirements for acceptance of the ANDE Expert System for casework use. To date, no Expert System has been approved for such samples, but the results of this study demonstrated that the automated Expert System performs similarly to conventional laboratory data analysis. Furthermore, Rapid DNA analysis demonstrated accuracy, precision, resolution, concordance, and reproducibility that were comparable to conventional processing along with appropriate species specificity, limit of detection, performance in the presence of inhibitors. No lane‐to‐lane or run‐to‐run contamination was observed, and the system correctly identified the presence of mixtures. Taken together, the ANDE instrument, I‐Chip consumable, FlexPlex chemistry (a 27‐locus STR assay compatible with all widely used global loci, including the CODIS core 20 loci), and automated Expert System successfully processed and interpreted more than 1200 unique samples with over 99.99% concordant CODIS alleles. This extensive developmental validation data provides support for broad use of the system by agencies and accredited forensic laboratories in single‐source suspect‐evidence comparisons, local database searches, and DVI.

Bruises are often difficult to detect on victims of violence, potentially impacting investigation and prosecution. The purpose of our randomized controlled trial was to measure the effectiveness of an alternate light source (ALS) within visible and long ultraviolet spectrums at improving bruise detection compared to white light over time. We also examined the effects of skin color, age, gender, localized fat, and injury mechanism on bruise detection. Participants included 157 healthy adults with balanced sampling across six skin color categories. Bruises were created under the controlled application of a paintball pellet and dropped weight to one upper and lower arm, respectively. Using a crossover design, both bruises were examined 21 times over 4 weeks. Ten different wavelength (350–535 nm) and filter (yellow, orange, red) combinations were used. Multilevel models were used to analyze 2903 examinations on both upper and lower arms. Results in multivariable models showed after controlling for other covariates 415 and 450 nm using a yellow filter had greater odds of detecting evidence of bruising than white light (Upper Arm: 415 nm: OR = 5.34, 95% CI: 4.35–6.56; 450 nm: OR = 4.08, 95% CI: 3.36–4.96). Under either light source, being female and having more localized fat had increased odds of detecting bruises created by the dropped weight (female: OR = 2.96, 95% CI: 2.37–3.70; fat: OR = 1.21, 95% CI: 1.09–1.34). Our results support ALS as an appropriate tool to enhance concurrent physical assessment of bruises in the presence of known history of injury. Future development and evaluation of clinical practice guidelines for ALS application are needed.

Objective Male breast cancer (MBC) is rare. Information about breast cancer is usually designed for female patients. However, in males this disease and some side effects differ from its female counterpart. Therefore, there is a need for male‐specific information. The aim was to assess unmet information needs of (a) MBC patients and (b) health professionals. Methods Dutch MBC patients (diagnosed between 2011 and 2016 in 21 hospitals), patient advocates and partners were invited to participate in focus groups and/or complete a paper‐based questionnaire on information needs. In addition, an online questionnaire on information needs was sent to health professionals involved in MBC patient care. Results In three focus groups with MBC patients (N = 12) and partners (N = 2) the following unmet information themes were identified: patients' experiences/photographs, symptoms, (delay of) diagnosis, treatments, side effects, follow‐up, psychological impact/coping, genetics and family, research and raising awareness. 77 of 107 MBC patients (72%) completed the questionnaire: most patients lacked information about acute (65%) or late (56%) side effects, particularly sexual side effects. Among health professionals, 110 of 139 (79%) had searched for MBC‐related information, specifically: patient information, anti‐hormonal therapy, genetic testing, research, and psychosocial issues. Conclusions Unmet information needs in MBC patients and health professionals were identified. Specific information on MBC should be developed to improve timely diagnosis, quality of life, treatment, and survival. A targeted website is an ideal tool to meet these needs. Therefore, we integrated these results into a user‐centered design to develop an informative website, www.mannenmetborstkanker.nl.

Contains fulltext : 219877.pdf (Publisher’s version ) (Open Access) OBJECTIVE: It was previously determined that group-based face-to-face Mindfulness-Based Cognitive Therapy (MBCT) and individual internet-based MBCT (eMBCT) are equally efficacious compared with treatment as usual (TAU) in reducing psychological distress. In this study, the incremental cost-utility of both interventions compared with TAU was assessed. METHODS: This cost-utility study included 245 self-referred heterogeneous cancer patients with psychological distress who were randomized to MBCT, eMBCT or TAU. Healthcare costs and (informal) work-related productivity losses were assessed by interview. Outcomes were expressed in EuroQol-5D-3L utility scores and quality-adjusted life years (QALY). An economic evaluation with a time-horizon of 3 months was conducted from the societal perspective in the intention-to-treat sample. In addition, secondary explorative analyses of costs and quality of life during the 9-month follow-up were conducted based on linear extrapolation of TAU. RESULTS: Paid work-related productivity losses and societal costs were lower in both intervention conditions compared with TAU during the 3-month intervention period. Moreover, quality of life (utility scores) improved in eMBCT versus TAU (Cohen's d: .54) and MBCT versus TAU (.53). At a willingness to pay of euro20000 per QALY, the mean incremental net monetary benefit was euro1916 (SD=euro783) in eMBCT and euro2365 (SD=euro796) in MBCT versus TAU. Exploration of costs demonstrated an equal pattern of eMBCT and MBCT being superior to TAU. Quality of life at 9-month follow-up remained improved in both interventions. CONCLUSIONS: Results indicate that eMBCT and MBCT are cost-saving treatments whilst simultaneously improving quality of life for distressed cancer patients.

Improvements have been made in identifying the prevalence of risk factors/indicators for violent extremism. A consistent problem is the lack of base rates. How to develop base rates is of equal concern. This study has two aims: (i) compare two methods for developing base rates; the Unmatched Count Technique (UCT) and direct questioning, (ii) generate base rates in a general population sample and compare these to a sample of lone‐actor terrorists (n = 125). We surveyed 2108 subjects from the general population. Participants were recruited from an online access panel and randomly assigned to one of three conditions; direct survey, control, or UCT. Survey items were based on a lone‐actor terrorist codebook developed from the wider literature. Direct questioning was more suitable under our study conditions where UCT resulted in deflation effects. Comparing the base rates identified a number of significant differences: (i) lone‐actor terrorists demonstrated propensity indicators related to a cognitive susceptibility, and a crime‐ and/or violence‐supportive morality more often; the general sample demonstrated protective factors more often, (ii) lone‐actor terrorists demonstrated situational indicators related to a crime‐ and/or violence‐supportive morality more often, whereas the general sample experienced situational stressors more often, (iii) lone‐actor terrorists demonstrated indicators related to exposure to extremism more often. Results suggest there are measurable differences in the prevalence of risk factors between lone‐actor terrorists and the general population. However, no single factor “predicts” violent extremism. This bears implications for our understanding of the interrelation of risk and protective factors, and for the risk assessment of violent extremism.

The use of synthetic stimulants, including designer cathinones, remains a significant concern worldwide. Thus, the detection and identification of synthetic cathinones in biological matrices is of paramount importance for clinical and forensic laboratories. In this study, distribution of mephedrone and its metabolites was investigated in fingerprints. Following a controlled human mephedrone administration (100 mg nasally insufflated), two mass spectrometry-based methods for fingerprint analysis have been evaluated. The samples deposited on triangular pieces of chromatography paper were directly analysed under ambient conditions by paper spray-mass spectrometry (PS-MS) while those deposited on glass cover slips were extracted and analysed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The LC-MS/MS method was 5-6 times more sensitive than PS-MS but required sample preparation and longer analysis time. Mephedrone was detected in 62% and in 38% of all post-administration samples analysed by LC-MS/MS and PS-MS, respectively. Nor-mephedrone was the only metabolite detected in 3.8% of all samples analysed by LC-MS/MS. A large inter- and intra-subject variation was observed for mephedrone which may be due to several factors, such as the applied finger pressure, angle and duration of contact with the deposition surface and inability to control the 'amount' of collected fingerprint deposits. Until these limitations are addressed, we suggest that the sole use of fingerprints can be a useful diagnostic tool in qualitative rather than quantitative analysis, and requires a confirmatory analysis in a different biological matrix.

The gut microbiota is recognized as having major impact in health and disease. Sample storage is an important aspect to obtain reliable results. Mostly recommended is immediate freezing, however, this is not always feasible. Faecal occult blood test (FOBT) papers are an appealing solution in such situations, and most studies find these to be applicable, showing no major changes within 7 days storage at room temperature (RT). As fieldwork often requires RT storage for longer periods, evaluation of this is warranted. We performed 16S rRNA gene sequencing of 19 paired faecal samples immediately frozen or kept five weeks and five months at RT on FOBT papers. Alpha-diversity evaluation revealed no effect of FOBT storage, and evaluation of beta-diversity showed that host explained 65% of community variation, while storage method explained 5%. Evaluation of community dispersion and the Firmicutes/Bacteroidetes ratio revealed a larger effect of storage time for fresh-frozen samples. Single taxa evaluation (order-to-genus level) showed significant alterations of four (of 37) genera after five weeks and five genera after five months. When comparing the two timepoints, alterations were only detectable for fresh-frozen samples. Our findings reveal that long term storage on FOBT papers is an applicable approach for microbiota research.

Objective Post‐traumatic stress disorder (PTSD) is a severe psychiatric disorder, which might develop after a traumatic event, like cancer diagnosis, and threatens the patient's psychological and/or physiological integrity. Anxiety, depression, and mental distress are known to be common in cancer patients; however, the frequency of PTSD was not investigated thoroughly in this patient group so far. Here, we aim to screen cancer patients for PTSD symptoms and determine a possible correlation with anxiety, depression, and distress. Methods The study was performed at the Divisions of Hematology and Oncology of the Medical University of Vienna from 2010 to 2018. Following written consent, patients were asked to fill out the validated self‐assessment questionnaire for PTSS‐10 and HADS. The study was approved by the institutional ethics committee of the Medical University of Vienna (EC Nr: 2255/2016). Results A total of 1017 adult cancer patients (513 male, 504 female) were included in a cross‐sectional single‐center study. Mean age was 57.6 years (SD 14.4 years); 31.7%, 14.6%, 13.2%, and 27.4% of patients outscored the predefined thresholds for self‐assessed cases of PTSD, anxiety, depression, and distress, respectively. Compared with men, women showed a higher prevalence of symptoms for PTSD (38.9% vs 24.5%; P

Objective \ud Depression and anxiety lead to reduced treatment adherence, poorer quality of life, and increased care costs amongst cancer patients. Mindfulness‐based cognitive therapy (MBCT) is an effective treatment, but dropout reduces potential benefits. Smart‐message reminders can prevent dropout and improve effectiveness. However, smart‐messaging is untested for MBCT in cancer. This study evaluates smart‐messaging to reduce dropout and improve effectiveness in MBCT for cancer patients with depression or anxiety.MethodsFifty‐one cancer patients attending MBCT in a psycho‐oncology service were offered a smart‐messaging intervention, which reminded them of prescribed between‐session activities. Thirty patients accepted smart‐messaging and 21 did not. Assessments of depression and anxiety were taken at baseline, session‐by‐session, and one‐month follow‐up. Logistic regression and multilevel modelling compared the groups on treatment completion and clinical effectiveness. Fifteen post‐treatment patient interviews explored smart‐messaging use.ResultsThe odds of programme completion were eight times greater for patients using smart‐messaging compared with non‐users, controlling for age, gender, baseline depression, and baseline anxiety (OR = 7.79, 95% CI 1.75 to 34.58, p = .007). Smart‐messaging users also reported greater improvement in depression over the programme (B = ‐2.33, SEB = .78, p = .004) when controlling for baseline severity, change over time, age, and number of sessions attended. There was no difference between groups in anxiety improvement (B = ‐1.46, SEB = .86, p = .097). In interviews, smart‐messaging was described as a motivating reminder and source of personal connection. ConclusionsSmart‐messaging may be an easily integrated telehealth intervention to improve MBCT for cancer patients.

Recent reports have demonstrated that genetically variant peptides derived from human hair shaft proteins can be used to differentiate individuals of different biogeographic origins. We report a method involving direct extraction of hair shaft proteins more sensitive than previously published methods regarding GVP detection. It involves one step for protein extraction and was found to provide reproducible results. A detailed proteomic analysis of this data is presented that led to the following four results: (i) A peptide spectral library was created and made available for download. It contains all identified peptides from this work, including GVPs that, when appropriately expanded with diverse hair‐derived peptides, can provide a routine, reliable, and sensitive means of analyzing hair digests; (ii) an analysis of artifact peptides arising from side reactions is also made using a new method for finding unexpected modifications; (iii) detailed analysis of the gel‐based method employed clearly shows the high degree of cross‐linking or protein association involved in hair digestion, with major GVPs eluting over a wide range of high molecular weights while others apparently arise from distinct non‐cross‐linked proteins; and (v) finally, we show that some of the specific GVP identifications depend on the sample preparation method.

Background The implementation of an electronic health record (EHR) with structured and standardized recording of patient data can improve data quality and reusability. Whether and how users perceive these advantages may depend on the preimplementation situation. Objective To determine whether the influence of implementing a structured and standardized EHR on perceived EHR use, data quality, and data reuse differed for users working with paper-based records versus a legacy EHR before implementation. Methods We used an electronic questionnaire to measure users' perception before implementation (2014), expected change, and perceived change after implementation (2016) on three themes. We included all health care professionals in two university hospitals in the Netherlands. Before jointly implementing the same structured and standardized EHR, one hospital used paper-based records and the other a legacy EHR. We compared perceptions before and after implementation for both centers. Additionally, we compared expected benefit with perceived benefit. Results We received 7,611 responses (4,537 before and 3,074 after implementation) of which 5,707 (75%) were from professionals reading and recording patient data. A total of 975 (13%) professionals responded to both before and after implementation questionnaires. In the formerly paper-based center staff perceived improvement in all themes after implementation. The legacy EHR center experienced deterioration of perceived EHR use and data reuse, and only one improvement in EHR use. In both centers, for half of the aspects at least 45% of responders experienced results worse than expected preimplementation. Conclusion Our results indicate that the preimplementation recording practice impacts the perceived effect of the implementation of a structured and standardized EHR. For almost half of the respondents the new EHR did not meet their expectations. Especially legacy EHR centers need to investigate the expectations as these might be different and less clear cut than those in paper-based centers. These expectations need to be addressed appropriately to achieve a successful implementation.

Significance Prostate cancer is the most common cancer among men. An accurate diagnosis of its severity at detection plays a major role in improving their survival. Recently, machine learning models using biomarkers identified from Raman micro-spectroscopy discriminated intraductal carcinoma of the prostate (IDC-P) from cancer tissue with a ≥85 % detection accuracy and differentiated high-grade prostatic intraepithelial neoplasia (HGPIN) from IDC-P with a ≥97.8 % accuracy. Aim To improve the classification performance of machine learning models identifying different types of prostate cancer tissue using a new dimensional reduction technique. Approach A radial basis function (RBF) kernel support vector machine (SVM) model was trained on Raman spectra of prostate tissue from a 272-patient cohort (Centre hospitalier de l'Universite de Montreal, CHUM) and tested on two independent cohorts of 76 patients [University Health Network (UHN)] and 135 patients (Centre hospitalier universitaire de Quebec-Universite Laval, CHUQc-UL). Two types of engineered features were used. Individual intensity features, i.e., Raman signal intensity measured at particular wavelengths and novel Raman spectra fitted peak features consisting of peak heights and widths. Results Combining engineered features improved classification performance for the three aforementioned classification tasks. The improvements for IDC-P/cancer classification for the UHN and CHUQc-UL testing sets in accuracy, sensitivity, specificity, and area under the curve (AUC) are (numbers in parenthesis are associated with the CHUQc-UL testing set): +4 % (+8 % ), +7 % (+9 % ), +2 % (6%), +9 (+9) with respect to the current best models. Discrimination between HGPIN and IDC-P was also improved in both testing cohorts: +2.2 % (+1.7 % ), +4.5 % (+3.6 % ), +0 % (+0 % ), +2.3 (+0). While no global improvements were obtained for the normal versus cancer classification task [+0 % (-2 % ), +0 % (-3 % ), +2 % (-2 % ), +4 (+3)], the AUC was improved in both testing sets. Conclusions Combining individual intensity features and novel Raman fitted peak features, improved the classification performance on two independent and multicenter testing sets in comparison to using only individual intensity features.

BackgroundMental health policy makers require evidence-based information to optimise effective care provision based on local need, but tools are unavailable.AimsTo develop and validate a population-level prediction model for need for early intervention in psychosis (EIP) care for first-episode psychosis (FEP) in England up to 2025, based on epidemiological evidence and demographic projections.MethodWe used Bayesian Poisson regression to model small-area-level variation in FEP incidence for people aged 16–64 years. We compared six candidate models, validated against observed National Health Service FEP data in 2017. Our best-fitting model predicted annual incidence case-loads for EIP services in England up to 2025, for probable FEP, treatment in EIP services, initial assessment by EIP services and referral to EIP services for ‘suspected psychosis’. Forecasts were stratified by gender, age and ethnicity, at national and Clinical Commissioning Group levels.ResultsA model with age, gender, ethnicity, small-area-level deprivation, social fragmentation and regional cannabis use provided best fit to observed new FEP cases at national and Clinical Commissioning Group levels in 2017 (predicted 8112, 95% CI 7623–8597; observed 8038, difference of 74 [0.92%]). By 2025, the model forecasted 11 067 new treated cases per annum (95% CI 10 383–11 740). For every 10 new treated cases, 21 and 23 people would be assessed by and referred to EIP services for suspected psychosis, respectively.ConclusionsOur evidence-based methodology provides an accurate, validated tool to inform clinical provision of EIP services about future population need for care, based on local variation of major social determinants of psychosis.

Significance: Our work demonstrates in preclinical models that continuous-wave transrectal diffuse optical tomography (TRDOT) can be used to accurately monitor photothermal therapy (PTT) and, in particular, the progression of the photocoagulation boundary toward the rectum. When used in patients, this should prevent rectal damage during PTT, thereby achieving maximum treatment efficacy while ensuring safety, using a technology platform suitable for wide dissemination. Aim: We aim to validate that TRDOT measurements analyzed using a shape-based image-reconstruction algorithm (SBDOT) allow localization of the photocoagulation boundary during PTT within ±1 mm toward the rectum in the transverse plane. Approach: TRDOT measurements were performed in tissue-simulating phantoms, ex vivo tissues, and an in vivo canine prostate model. The accuracy and sensitivity of reconstructing the size and location of the coagulation zone were determined, based on changes in the tissue absorption and reduced scattering coefficients upon photocoagulation. The reconstruction also yields the native and coagulated tissue optical properties. Results: The TRDOT measurements and SBDOT reconstruction algorithm were confirmed to perform sufficiently well for clinical translation in PTT monitoring, recovering the location of the coagulation boundary within ±1 mm compared to the true value as determined by direct visualization postexcision and/or MRI. Conclusions: Implementing previously described TRDOT instrumentation and SBDOT image reconstruction in different tissue models confirms the potential for clinincal translation, including required refinements of the system and reconstruction algorithm.

Pancreatic beta-cells synthesize and secrete insulin maintaining an organism's energy homeostasis. In humans, beta-cell dysfunction and death contribute to the pathogenesis of type 2 diabetes (T2D). Although the causes of beta-cell dysfunction are complex, obesity-induced low-grade systemic inflammation plays a role. For example, obese individuals exhibiting increased levels of proinflammatory cytokines IL-6 and IL-1beta have a higher risk of beta-cell dysfunction and T2D. Interestingly, obesity-induced inflammation changes the expression of several cellular metal regulating genes, prompting this study to examine changes in the beta-cell metallome after exposure to proinflammatory-cytokines. Primary mouse beta-cells were exposed to a combination of IL-6 and IL-1beta for 48 hours, were chemically fixed and imaged by synchrotron X-ray fluorescent microscopy. Quantitative analysis showed a surprising 2.4-fold decrease in the mean total cellular content of zinc from 158 ± 57.7 femtograms (fg) to 65.7 ± 29.7 fg; calcium decreased from 216 ± 67.4 to 154.3 ± 68.7 fg (control vs. cytokines, respectively). The mean total cellular iron content slightly increased from 30.4 ± 12.2 to 47.2 ± 36.4 fg after cytokine treatment; a sub-population of cells (38%) exhibited larger increases of iron density. Changes in the subcellular distributions of zinc and calcium were observed after cytokine exposure. Beta-cells contained numerous iron puncta that accumulated still more iron after exposure to cytokines. These findings provide evidence that exposure to low levels of cytokines is sufficient to cause changes in the total cellular content and/or subcellular distribution of several metals known to be critical for normal beta-cell function.

This report provides perspectives concerning dual roles of serum ferritin as a measure of both iron status and of inflammation. We suggest benefits of a lower range of serum ferritin as has occurred for total serum cholesterol and fasting blood glucose levels. Observations during a prospective randomized study using phlebotomy in patients with peripheral arterial disease (PAD) offered unique insights into dual roles of serum ferritin both as an iron status marker and acute phase reactant. Robust positive associations between serum ferritin, interleukin 6 [IL-6], tissue necrosis factor-alpha (TNF-a), and high sensitivity C-reactive protein (hsCRP) were discovered. Elevated serum ferritin and IL-6 levels associated with increased mortality and with reduced mortality at ferritin levels < 100 ng/mL. Epidemiologic studies demonstrate similar outcomes. Extremely elevated ferritin and IL-6 levels also occur in individuals with high mortality due to SARS-CoV-2 infection. Disordered iron metabolism reflected by a high range of serum ferritin level signals disease severity and outcomes. Based upon experimental and epidemiologic data, we suggest testing the hypotheses that optimal ferritin levels for cardiovascular mortality reduction range from 20—100 ng/mL with % transferrin levels from 20–50%, to ensure adequate iron status and that ferritin levels above 194 ng/mL associate with all-cause mortality in population cohorts., Graphical Abstract Graphical Abstract

OBJECTIVES/HYPOTHESIS The aim of the study was to investigate the healing rates, the restoration of hearing, and the time for complete healing of paper patching versus watchful waiting for traumatic tympanic membrane perforations (TTMPs). STUDY DESIGN Systematic review with meta analysis. METHODS Publications were selected by a search on "PubMed," "Embase," and "Web of Science." A meta-analysis of risk ratios for paper patching (intervention arm) and watchful waiting (control arm) was performed. RESULTS Five studies describing 393 TTMPs were included in the quantitative meta-analysis. TTMP healing rates ranged between 84.2% and 95.2% in the intervention arm and between 76.7% and 84.8% in the control arm. The pooled risk ratio of healed TTMPs was significantly higher in the intervention arm than in the control arm (risk ratio: 1.12, 95% confidence interval: 1.04-1.21). CONCLUSIONS TTMPs have high healing potential with and without intervention. The healing rate of paper patching was superior to that of watchful waiting alone. LEVEL OF EVIDENCE NA Laryngoscope, 131:2091-2097, 2021.

Purpose To study respiratory effects of exposure to soft paper dust exposure, a relationship that is rarely studied. Methods Soft tissue paper mill workers at a Swedish paper mill were investigated using a questionnaire and lung function and atopy screening. Spirometry without bronchodilation was performed with a dry wedge spirometer, and forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were obtained and expressed as percent predicted. Exposure to soft paper dust was assessed from historical stationary and personal measurements of total dust, in addition to historical information about the work, department, and production. The impact of high exposure to soft paper dust (> 5 mg/m3) vs. lower exposure ≤ 5 mg/m3, as well as cumulative exposure, was analyzed using multiple linear regression models. Multivariate models were adjusted for smoking, atopy, gender, and body mass index. Results One hundred ninety-eight current workers (124 male and 74 female) were included. There were significant associations between both cumulative exposure and years of high exposure to soft paper dust and impaired lung function. Each year of high exposure to soft paper dust was associated with a 0.87% decrease in FEV1 [95% confidence interval (CI) − 1.39 to − 0.35] and decreased FVC (− 0.54%, 95% CI − 1.00 to − 0.08) compared to the lower exposed workers. Conclusions The present study shows that occupational exposure to soft paper dust (years exceeding 5 mg/m3 total dust) is associated with lung function impairment and increased prevalence of obstructive lung function impairment.

The aim of this study was to assess postures and movements of the trunk and upper arm during paper mill work, and to determine the extent to which they differ depending on method of assessment. For each of 28 paper mill workers, postures and movements were assessed during three full shifts using inclinometer registration and observation from video. Summary metrics for each shift, e.g., 10th, 50th, and 90th posture percentile, were averaged across shifts and across workers. In addition, the standard deviation between workers, and the standard deviation between shifts within worker were computed. The results showed that trunk and arm postures during paper mill work were similar to other occupations involving manual materials handling, but the velocities of arm movements were lower. While postures determined by inclinometry and observation were similar on a group level, substantial differences were found between results obtained by the two methods for individual workers, particularly for extreme postures. Thus, measurements by either method on individuals or small groups should be interpreted with caution.

Objective: The aim of this study was to explore TT men’s pre-diagnosis experiences of prostate cancer (PCa). This study is part of a wider project that examined men and their partners’ experiences of routes to diagnosis for PCa in TT. Methods: Men (n=51) were voluntarily recruited to semi-structured interviews from four centres. Data were analysed following principles of Grounded Theory. Results: Major barriers to medical help-seeking were highlighted as lack of knowledge and awareness of the prostate gland and symptoms of PCa, the digital rectal exam (DRE), PSA, cultural and religious beliefs and hegemonic masculinity norms and non-reporting of bodily changes to GPs. Fear of DRE, distrust in providers and misinterpretation of bodily changes as related to ageing and diabetes mellitus also contributed to delays towards seeking medical help. Men’s interactions with pharmacists and traditional healers lengthened the time taken to consult with Health Care Providers for prostate concerns. Conclusions: TT men’s PCa pre-diagnosis experiences are important to unearth barriers and facilitators to care along routes to diagnosis for this disease. This can help target specific health promotion strategies to motivate men to seek medical care for symptoms in a timely manner.

This article analyses the role of social protection programmes in contributing to people's resilience to climate risks. Drawing from desk-based and empirical studies in Ethiopia, Kenya and Uganda, it finds that social transfers make a strong contribution to the capacity of individuals and households to absorb the negative impacts of climate-related shocks and stresses. They do so through the provision of reliable, national social safety net systems-even when these are not specifically designed to address climate risks. Social protection can also increase the anticipatory capacity of national disaster response systems through scalability mechanisms, or pre-emptively through linkages to early action and early warning mechanisms. Critical knowledge gaps remain in terms of programmes' contributions to the adaptive capacity required for long-term resilience. The findings offer insights beyond social protection on the importance of robust, national administrative systems as a key foundation to support people's resilience to climate risks.

Objective: Depression and anxiety symptoms are common among patients with epilepsy, but are relatively under-researched in patients with both epilepsy and intellectual disability (ID). The aim was to investigate whether epilepsy and ID characteristics are associated with mood, anxiety, and quality of life. Materials and Methods: Adult patients with epilepsy and ID who rely on tertiary epilepsy care were included (N = 189). Mood, anxiety, and quality of life were assessed by standardized questionnaires. Epilepsy and ID characteristics were retrieved from patient charts or determined by psychometric instruments. Results: Elevated levels of depressive and anxiety symptoms were present in 21.7% and 12.7%, respectively. Anxiety was significantly associated with a focal epilepsy type and ID domain discrepancy (substantial difference between two domains of adaptive behavior), but was negatively related to seizure frequency and drug load of mood-stabilizing antiepileptic drugs. Depressive symptoms were not significantly related to epilepsy characteristics, but a severe ID and ID domain discrepancy was associated with more depressive symptoms. Quality of life was significantly worse in those with multiple seizure types and ID domain discrepancy. Conclusion: Whereas anxiety and quality of life are associated with individual epilepsy characteristics, this could not be confirmed for depressive symptoms in patients with epilepsy and ID, despite its high prevalence.

This paper describes an approach for colorimetric detection of salivary α-amylase, one of the potential biomarkers of autonomic nervous system (ANS) activity, for enabling assessment of fatigue. The ability of α-amylase to cleave α-bonds of polysaccharides is utilized for developing a colorimetric assay. In the proposed approach, 2-chloro-4-nitrophenyl-α-d-maltotrioside as substrate releases a colored byproduct upon cleavage by salivary α-amylase. Introduction of maltose as a noncompetitive inhibitor yields desirable linear responses in the physiologically relevant concentration range (20–500 μg/mL) with a limit of detection (LOD) of 8 μg/mL (in aqueous solution). The concentrations of substrate and noncompetitive inhibitor are subsequently optimized for colorimetric detection of salivary α-amylase. A facile paper-based “strip” assay is proposed for analysis of human saliva samples with marginal interference from saliva components. The proposed assay is rapid, specific, and easy-to-implement for colorimetric detection of salivary α-amylase between 20 and 500 μg/mL. Complementary RGB (red, green, blue components) analysis offers quantitative detection with a LOD of 11 μg/mL. The two assay formats are benchmarked against the Phadebas test, a state of the art method for spectrophotometric detection of α-amylase. The reported paper-based methodology possesses a high potential for estimation of altered ANS responses toward stressors that possibly could find applications in assessment of fatigue and for monitoring onset of fatigue. Nanyang Technological University Accepted version This work is supported by Provost’s office and Institute for Sports Research (ISR), School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore.

Over the past decades, the application of single-photon emission computed tomography and positron emission tomography in neuroimaging has markedly increased. In the current study, we used a series of Korean computational head phantoms with detailed cranial structures for 6-, 9-, 12-, 15-y-old children and adult and a Monte Carlo transport code, MCNPX, to calculate age-dependent specific absorbed fraction (SAF) for mono-energetic electrons ranging from 0.01 to 4 MeV and S values for seven radionuclides widely used in nuclear medicine neuroimaging for the combination of ten source and target regions. Compared to the adult phantom, the 6-y phantom showed up to 1.7-fold greater SAF (cerebellum < cerebellum) and up to 1.4-fold greater S values (vitreous body < lens) for 123I. The electron SAF data, combined with our previous photon SAF data, will facilitate absorbed dose calculations for various cranial structures in patients undergoing neuroimaging procedures.

Objective The incidence of lung cancer is four times higher in people with chronic obstructive pulmonary disease (COPD) compared with the general population. Promotion of a shorter time from symptom onset to presentation is one potential strategy for earlier lung cancer diagnosis, but distinguishing respiratory symptoms can be difficult. We investigated how the experience of COPD influences symptom appraisal and help seeking for potential lung cancer symptoms. Methods We conducted qualitative interviews with men (n = 17) and women (n = 23) aged 40 to 83 years with COPD. Topic guides drew on the integrated symptom‐response framework and covered symptom experience, interpretation, action, recognition, help seeking, evaluation, and reevaluation. We used the framework method to analyse the data. Results Participants said that they attributed chest symptoms to their COPD; no other cause was considered. Participants said that family/friends noticed changes in their symptoms and encouraged help seeking. Others felt isolated by their COPD because they could not get out, were fatigued, or were embarrassed. Participants visited health professionals frequently, but increased risk of lung cancer was not discussed. Conclusions Our study provides insight into different levels of influence on symptom appraisal and targets for intervention. Greater awareness of increased lung cancer risk and support to act on symptom changes is essential and could be achieved through a concerted information campaign. Health professionals working with people with COPD could also optimise appointments to support symptom appraisal of potential lung cancer symptoms.

Paper patching, a method that places cigarette paper over the most mobile quadrants of the tympanic membrane, is one of the treatment options for patulous eustachian tube (PET).The objective of this study was to compare the outcomes of two different treatment strategies for PET.Twenty-three patients underwent paper patching of the tympanic membrane and 16 patients were treated with nasal saline irrigation with or without ipratropium bromide nasal spray. Medical records were reviewed for resolution of PET symptoms as categorical variables (complete remission, partial remission, or no improvement) with a minimum follow-up of 3 months.Immediately after undergoing paper patching, 20 of the 23 patients (87.0%) reported complete remission (CR). The percentage of CR after paper patching was 82.6% at 1 month and 65.2% at 3 months. A greater percentage of patients reported CR of aural symptoms in the paper patching group than in the nasal irrigation group at both 1 and 3 months after treatment (p .05).Repetitive paper patching resolves aural discomfort in most PET patients for at least 3 months and can be considered as a first-line treatment option for PET in the outpatient setting.