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Objective: To investigate the impact of varus malalignment of the knee on pain reduction achieved by an ankle-foot orthosis and a laterally wedged insole in patients with medial knee osteoarthritis. Design: Secondary analysis of a randomized, clinically prospective cross-over study. Patients: Twenty-eight participants with medial knee osteoarthritis. Methods: All participants wore a 5-mm laterally wedged insole and an ankle-foot orthosis for a period of 6 weeks each in a randomized order. Pain was reported on a numerical rating scale and was correlated with limb alignment, as defined by the mechanical axis deviation in full-leg standing radiographs. Results: Insole and orthosis use reduced pain compared with baseline (median knee pain change: insole –0.5 (–5 to +6), orthosis –1.5 (–7 to +5). A higher mechanical axis deviation (greater varus) correlated significantly with smaller pain reduction for both aids (insole p = 0.003, orthosis p < 0.001). A cut-off to predict pain response was found at a mechanical axis deviation of 14–15 mm for both aids, i.e. > 3° knee varus. Conclusion: There is a correlation between varus malalignment and pain reduction. There seems to be a mechanical axis deviation cut-off that predicts the response to treatment with the aids with good sensitivity. LAY ABSTRACT Osteoarthritis of the knee can be treated using orthoses and insoles to unload the most damaged and painful inner (medial) part of the knee. However, patients do not benefit equally from these devices and there is not enough scientific data to predict which patients will benefit from an orthosis or insole. This study investigated whether the genu varum (degree of bow-leggedness) correlates with pain reduction when using an insole or an ankle-foot orthosis. A total of 28 patients with knee osteoarthritis received both aids, each for a period of 6 weeks, in random order. They documented knee pain before and after using the devices. Radiographs of the leg were analysed to determine the degree of genu varum. Statistical analysis showed that patients with straighter legs experienced better pain reduction with both aids than did bow-legged patients. In conclusion, ankle-foot orthoses and insoles are less effective in bow-legged patients.

Background:. Management of patients with rectal cancer can be complex, requiring significant care coordination and decisions that balance functional and oncologic outcomes. Objective:. To characterize care coordination occurring during surgical consultation for rectal cancer and consequences of using face-to-face time in clinic for care coordination. Methods:. Secondary analysis was performed on audio recordings of clinic visits with colorectal surgeons to discuss surgery for rectal cancer at 5 academic medical centers. Analysis included the content of communication related to types of care coordination, specific details and conditions under which care coordination was conducted, and consequences. Results:. The cohort included 18 patients seen by 8 surgeons. Care coordination consumed much of the conversation; on average 23.7% (SD 14.6) of content. Communication about care coordination included gathering information from work-up already performed, logistics for completing further work-up, gathering multidisciplinary opinions, and logistics for treatment planning. Obtaining imaging results was particularly challenging and surgeons went to great lengths to gather this information. To mitigate information gaps, surgeons asked patients about critical clinical details. Patients expressed remorse when they could not provide needed information, relay technical details, or had missing reports. Surgeons voiced frustration at the system related to the need to gather information from multiple sources and coordinate logistics. Surgeons worked to inform patients about their disease and discuss important lifestyle and cancer-related tradeoffs. However, the ability to solicit patient input and engage in shared decision making was often limited by incomplete data or conditioned on approval by a multidisciplinary tumor board. Conclusion:. Much of the conversation between surgeons and patients with rectal cancer is consumed by care coordination. Organizing care coordination outside of the clinic visit would likely improve the experience for both patients and surgeons, addressing both clinician burnout and variation in management and outcomes.

Microbial deterioration of wood has gradually destroyed precious historic musical instruments. The Serpentino (English: serpent/little snake) is a wind instrument used for over 400 years and is considered the godfather of modern instruments such as the saxophone and the tuba. Many original instruments have been totally destroyed due to colonization and degradation by bacteria and fungi. Reconstructing the serpent in particular and other ancient instruments in general requires the preservation of wood against bio-deterioration. Conventional chemical preservatives based on copper and boron compounds have been used in the wood processing industry; however, they are not ideal for protecting musical instruments and may pose a negative impact on the health and safety of musicians with direct mouth contact. Non-biocidal preservatives, such as plant oils, have attracted a lot of attention. Herein, we report the antimicrobial efficacy of plant oils, alone and in combination with fungal melanin, for protecting walnut wood that is used to make the serpent, against oral bacteria and wood-decay fungi. Linseed and tea tree oils were found to have a strong antibacterial effect, reducing the survival rate of Streptococcus mutans, a bacterium commonly found in human saliva, to below 1%. Impregnation of wood with plant oils and melanin significantly increased the antibacterial effect when compared to that of the oil(s) alone. A satisfactory antifungal effect was also achieved after 2 weeks as indicated by a reduction (

Background Intratumoral (IT) myeloid dendritic cells (myDCs) play a pivotal role in initiating antitumor immune responses and relicensing of anti-tumor cytotoxic T lymphocytes within the tumor microenvironment. Talimogene laherparepvec (T-VEC) induces immunogenic cell death, thereby providing maturation signals and enhancing the release of tumor antigens that can be captured and processed by CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDCs, in order to reinvigorate the cancer-immunity cycle.Methods In this phase I trial, patients with advanced melanoma who failed standard therapy were eligible for IT injections of ≥1 non-visceral metastases with T-VEC on day 1 followed by IT injection of CD1c (BDCA-1)+ myDCs +/- CD141 (BDCA-3)+ myDCs on day 2. T-VEC injections were repeated on day 21 and every 14 days thereafter. The number of IT administered CD1c (BDCA-1)+ myDCs was escalated from 0.5×106, to 1×106, to a maximum of 10×106 cells in three sequential cohorts. In cohort 4, all isolated CD1c (BDCA-1)+ / CD141 (BDCA-3)+ myDCs were used for IT injection. Primary objectives were safety and feasibility. Repetitive biopsies of treated lesions were performed.Results In total, 13 patients were enrolled (cohort 1 n=2; cohort 2 n=2; cohort 3 n=3; cohort 4 n=6). Patients received a median of 6 (range 3–8) T-VEC injections. The treatment was safe with most frequent adverse events being fatigue (n=11 (85%)), fever (n=8 (62%)), and chills/influenza-like symptoms (n=6 (46%)). Nine (69%) and four patients (31%), respectively, experienced pain or redness at the injection-site. Clinical responses were documented in injected and non-injected lesions. Two patients (cohort 3) who previously progressed on anti-PD-1 therapy (and one patient also on anti-CTLA-4 therapy) developed a durable, pathologically confirmed complete response that is ongoing at 33 and 35 months following initiation of study treatment. One additional patient treated (cohort 4) had an unconfirmed partial response as best response; two additional patients had a mixed response (with durable complete responses of some injected and non-injected lesions). On-treatment biopsies revealed a strong infiltration by inflammatory cells in regressing lesions.Conclusions IT coinjection of autologous CD1c (BDCA-1)+ +/- CD141 (BDCA-3)+ myDCs with T-VEC is feasible, tolerable and resulted in encouraging early signs of antitumor activity in immune checkpoint inhibitor-refractory melanoma patients.Trial registration number NCT03747744.

Abstract Introduction It is now widely acknowledged that there are serious shortcomings in allergy care provision for patients seen in primary care. We sought to assess the feasibility of delivering and evaluating a new nurse‐led allergy service in primary care, measured by recruitment, retention and estimates of the potential impact of the intervention on disease‐specific quality of life. Methods Mixed‐methods evaluation of a nurse‐led primary care‐based allergy clinic in Edinburgh, UK undertaken during the period 2017–2021 with a focus on suspected food allergy and atopic eczema in young children, allergic rhinitis in children and young people, and suspected anaphylaxis in adults. Prior to March 2020, patients were seen face‐to‐face (Phase 1). Due to COVID‐19 pandemic restrictions, recruitment was halted between March–August 2020, and a remote clinic was restarted in September 2020 (Phase 2). Disease‐specific quality of life was measured at baseline and 6–12 weeks post intervention using validated instruments. Quantitative data were descriptively analysed. We undertook interviews with 16 carers/patients and nine healthcare professionals, which were thematically analysed. Results During Phase 1, 426/506 (84%) referred patients met the eligibility criteria; 40/46 (87%) of Phase 2 referrals were eligible. Males and females were recruited in approximately equal numbers. The majority (83%) of referrals were for possible food allergy or anaphylaxis. Complete data were available for 338/426 (79%) patients seen in Phase 1 and 30/40 (75%) in Phase 2. Compared with baseline assessments, there were improvements in disease‐specific quality of life for most categories of patients. Patients/carers and healthcare professionals reported high levels of satisfaction, this being reinforced by the qualitative interviews in which convenience and speed of access to expert opinion, the quality of the consultation, and patient/care empowerment were particularly emphasised. Conclusion This large feasibility trial has demonstrated that it is possible to recruit, deliver and retain individuals into a nurse‐led allergy clinic with both face‐to‐face and remote consultations. Our data indicate that the intervention was considered acceptable to patients/carers and healthcare professionals. The before‐after data of disease‐specific quality of life suggest that the intervention may prove effective, but this now needs to be confirmed through a formal randomised controlled trial. Trial Registration ClinicalTrials.gov reference NCT03826953.

Background Acral melanoma is a rare melanoma subtype with poor prognosis. Importantly, these patients were not identified as a specific subgroup in the landmark melanoma trials involving ipilimumab and the anti-programmed cell death protein-1 (PD-1) agents nivolumab and pembrolizumab. There is therefore an absence of prospective clinical trial evidence regarding the efficacy of checkpoint inhibitors (CPIs) in this population. Acral melanoma has lower tumor mutation burden (TMB) than other cutaneous sites, and primary site is associated with differences in TMB. However the impact of this on the effectiveness of immune CPIs is unknown. We examined the efficacy of CPIs in acral melanoma, including by primary site.Methods Patients with unresectable stage III/IV acral melanoma treated with CPI (anti-PD-1 and/or ipilimumab) were studied. Multivariable logistic and Cox regression analyses were conducted. Primary outcome was objective response rate (ORR); secondary outcomes were progression-free survival (PFS) and overall survival (OS).Results In total, 325 patients were included: 234 (72%) plantar, 69 (21%) subungual and 22 (7%) palmar primary sites. First CPI included: 184 (57%) anti-PD-1, 59 (18%) anti-PD-1/ipilimumab combination and 82 (25%) ipilimumab. ORR was significantly higher with initial anti-PD-1/ipilimumab compared with anti-PD-1 (43% vs 26%, HR 2.14, p=0.0004) and significantly lower with ipilimumab (15% vs 26%, HR 0.49, p=0.0016). Landmark PFS at 1 year was highest for anti-PD-1/ipilimumab at 34% (95% CI 24% to 49%), compared with 26% (95% CI 20% to 33%) with anti-PD-1 and 10% (95% CI 5% to 19%) with ipilimumab. Despite a trend for increased PFS, anti-PD-1/ipilimumab combination did not significantly improve PFS (HR 0.85, p=0.35) or OS over anti-PD-1 (HR 1.30, p=0.16), potentially due to subsequent therapies and high rates of acquired resistance. No outcome differences were found between primary sites.Conclusion While the ORR to anti-PD-1/ipilimumab was significantly higher than anti-PD-1 and PFS numerically higher, in this retrospective cohort this benefit did not translate to improved OS. Future trials should specifically include patients with acral melanoma, to help determine the optimal management of this important melanoma subtype.

Background: Systematic assessment of childhood asthma is challenging in low- and middle-income country (LMIC) settings due to the lack of standardised and validated methodologies. We describe the contextual challenges and adaptation strategies in the implementation of a community-based asthma assessment in four resource-constrained settings in Bangladesh, India, and Pakistan. Method: We followed a group of children of age 6–8 years for 12 months to record their respiratory health outcomes. The study participants were enrolled at four study sites of the ‘Aetiology of Neonatal Infection in South Asia (ANISA)’ study. We standardised the research methods for the sites, trained field staff for uniform data collection and provided a ‘Child Card’ to the caregiver to record the illness history of the participants. We visited the children on three different occasions to collect data on respiratory-related illnesses. The lung function of the children was assessed in the outreach clinics using portable spirometers before and after 6-minute exercise, and capillary blood was examined under light microscopes to determine eosinophil levels. Results: We enrolled 1512 children, 95.5% (1476/1512) of them completed the follow-up, and 81.5% (1232/1512) participants attended the lung function assessment tests. Pre- and post-exercise spirometry was performed successfully in 88.6% (1091/1232) and 85.7% (1056/1232) of children who attempted these tests. Limited access to health care services, shortage of skilled human resources, and cultural diversity were the main challenges in adopting uniform procedures across all sites. Designing the study implementation plan based on the local contexts and providing extensive training of the healthcare workers helped us to overcome these challenges. Conclusion: This study can be seen as a large-scale feasibility assessment of applying spirometry and exercise challenge tests in community settings of LMICs and provides confidence to build capacity to evaluate children’s respiratory outcomes in future translational research studies.

Many years ago, twelve principles were defined for carrying out chemical reactions and processes from a green chemistry perspective. It is everyone’s endeavor to take these points into account as far as possible when developing new processes or improving existing ones. Especially in the field of organic synthesis, a new area of research has thus been established: micellar catalysis. This review article addresses the question of whether micellar catalysis is green chemistry by applying the twelve principles to micellar reaction media. The review shows that many reactions can be transferred from an organic solvent to a micellar medium, but that the surfactant also has a crucial role as a solubilizer. Thus, the reactions can be carried out in a much more environmentally friendly manner and with less risk. Moreover, surfactants are being reformulated in their design, synthesis, and degradation to add extra advantages to micellar catalysis to match all the twelve principles of green chemistry.

Higher levels of automated driving may offer the possibility to sleep in the driver’s seat in the car, and it is foreseeable that drivers will voluntarily or involuntarily fall asleep when they do not need to drive. Post-sleep performance impairments due to sleep inertia, a brief period of impaired cognitive performance after waking up, is a potential safety issue when drivers need to take over and drive manually. The present study assessed whether sleep inertia has an effect on driving and cognitive performance after different sleep durations. A driving simulator study with n = 13 participants was conducted. Driving and cognitive performance were analyzed after waking up from a 10–20 min sleep, a 30–60 min sleep, and after resting without sleep. The study’s results indicate that a short sleep duration does not reliably prevent sleep inertia. After the 10–20 min sleep, cognitive performance upon waking up was decreased, but the sleep inertia impairment faded within 15 min. Although the driving parameters showed no significant difference between the conditions, participants subjectively felt more tired after both sleep durations compared to resting. The small sample size of 13 participants, tested in a within-design, may have prevented medium and small effects from becoming significant. In our study, take-over was offered without time pressure, and take-over times ranged from 3.15 min to 4.09 min after the alarm bell, with a mean value of 3.56 min in both sleeping conditions. The results suggest that daytime naps without previous sleep deprivation result in mild and short-term impairments. Further research is recommended to understand the severity of impairments caused by different intensities of sleep inertia.

In the original publication [...]

(1) Background: Prior to revision hip (THA) or knee arthroplasty (TKA), periprosthetic low-grade infection (PJI) should be ruled out. Despite advances in preoperative diagnosis, unsuspected positive cultures (UPCs) may occur in initially planned aseptic revisions. Particularly, single UPCs pose a diagnostic and therapeutic dilemma, as their impact on outcome is unclear and recommendations are heterogeneous. This review investigates the frequency of single UPCs and their impact on implant survivorship. (2) Methods: In July 2022, a comprehensive literature search was performed using PubMed and Cochrane Library search. In total, 197 articles were screened. Seven retrospective studies with a total of 5821 cases were able to be included in this review. (3) Results: Based on the cases included, UPCs were found in 794/5821 cases (14%). In 530/794 cases (67%), the majority of the UPCs were single positive. The most commonly isolated pathogens were coagulase negative Staphylococci and Cutibacterium acnes. Five of seven studies reported no influence on revision- or infection-free survival following a single positive culture. In two studies, single UPCs following THA revision were correlated with subsequent re-revision for PJI. (4) Conclusions: Single UPCs of a non-virulent pathogen following presumed aseptic TKA revision may be interpreted as contaminants. A single UPC following THA revision may be a risk factor for subsequent PJI. The role of systemic antibiotic treatment remains unclear, but it should be considered if other risk factors for PJI are present.

Abstract The accurate preoperative diagnosis of periprosthetic joint infection (PJI) of total knee arthroplasty (TKA) can be difficult despite the use of a combination of serum and synovial markers. In such inconclusive cases, incisional open biopsy might be considered. This study investigates the usefulness of biopsies in patients with inconclusive diagnostic findings. We retrospectively identified 63 patients who underwent incisional biopsy for chronic PJI in the operation theatre following TKA revision between 2010 and 2018 after inconclusive preoperative diagnostics for PJI. In all cases, 5 independent biopsies were taken. Results from open biopsy for PJI were analyzed for diagnostic accuracy using the intraoperative results from following revision surgery as gold standard. 27 patients (43%) had a positive culture taken during biopsy. 15 cases (24%) met the diagnostic criteria for a chronic PJI. Most common organisms were Coagulase-negative staphylococci (67%) and Cutibacterium acnes (30%). Compared to the findings during revision surgery, biopsies showed a sensitivity of 47% and a specificity of 77% for PJI. Open incisional biopsy following inconclusive serum- and synovial diagnostics for low grade PJI may be considered for identification of microorganisms. Due to its low sensitivity and moderate specificity found in the present cohort, microbiological analysis should be combined with additional diagnostic markers and histological investigation. Level of Evidence. Retrospective cohort study (Level III).

For evaluating unclear tumorous lesions, contrast-enhanced ultrasonography (CEUS) is an important imaging modality in addition to contrast-enhanced computed tomography and magnetic resonance imaging, and may provide valuable insights into the microvascularization of tumors in dynamic examinations. In interventional procedures, CEUS can make a valuable contribution in pre-, peri-, and post-interventional settings, reduce radiation exposure and, under certain circumstances, decrease the number of interventions needed for patients.

Abstract D-dimer has been included in the criteria by the Musculoskeletal Infection Society in 2018 as a novel parameter to diagnose prosthetic joint infection (PJI). However, it is unclear how D-dimer levels change in between stages of a two-stage exchange. We prospectively investigated 30 patients who underwent a two-stage exchange using a spacer for PJI. D-Dimer, CRP and IL-6 were collected before first and second stage surgery and the difference (Δ) in between stages was calculated. The levels of plasma D-Dimer did not change from first to second stage surgery (2770 ng/ml (IQR, 1600–3770 ng/ml) versus 2340 ng/ml (IQR, 1270–4100 ng/ml); p = 0.8) while CRP (4.0 mg/dl (IQR, 1.7–5.5 mg/dl) versus 0.6 mg/dl (IQR, 0.5–0.8 mg/dl); p

Borderline personality disorder (BOR) is determined by environmental and genetic factors, and characterized by affective instability and impulsivity, diagnostic symptoms also observed in manic phases of bipolar disorder (BIP). Up to 20% of BIP patients show comorbidity with BOR. This report describes the first case-control genome-wide association study (GWAS) of BOR, performed in one of the largest BOR patient samples worldwide. The focus of our analysis was (i) to detect genes and gene sets involved in BOR and (ii) to investigate the genetic overlap with BIP. As there is considerable genetic overlap between BIP, major depression (MDD) and schizophrenia (SCZ) and a high comorbidity of BOR and MDD, we also analyzed the genetic overlap of BOR with SCZ and MDD. GWAS, gene-based tests and gene-set analyses were performed in 998 BOR patients and 1545 controls. Linkage disequilibrium score regression was used to detect the genetic overlap between BOR and these disorders. Single marker analysis revealed no significant association after correction for multiple testing. Gene-based analysis yielded two significant genes: DPYD (P=4.42 × 10-7) and PKP4 (P=8.67 × 10-7); and gene-set analysis yielded a significant finding for exocytosis (GO:0006887, PFDR=0.019; FDR, false discovery rate). Prior studies have implicated DPYD, PKP4 and exocytosis in BIP and SCZ. The most notable finding of the present study was the genetic overlap of BOR with BIP (rg=0.28 [P=2.99 × 10-3]), SCZ (rg=0.34 [P=4.37 × 10-5]) and MDD (rg=0.57 [P=1.04 × 10-3]). We believe our study is the first to demonstrate that BOR overlaps with BIP, MDD and SCZ on the genetic level. Whether this is confined to transdiagnostic clinical symptoms should be examined in future studies.

The rapid development, approval, and production of vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in less than 1 year after the first reports of a new infectious disease was a real game changer, providing 80%–90% efficacy in preventing severe etiopathologies of the coronavirus disease 2019 (COVID-19). These vaccines induce an immune response against the SARS-CoV-2 spike (S) protein located on the surface of the virus particle. Antibodies (Abs) recognizing the S-protein can inhibit binding of the virus via the S-protein to the angiotensin-converting enzyme-2 (ACE-2) receptor expressed on different human cells, especially when these Abs bind to the interaction site, the so-called receptor-binding domain (RBD). We have expressed the RBDs of wild-type SARS-CoV-2 and five variants of concern (VOCs) to test the immune response in people before vaccination with mRNA vaccines BNT162b2 and mRNA-1273 and after up to three vaccinations using in-house ELISA and inhibition assays. The methods of both assays are provided. Both vaccines initiated similarly high IgG titers after two vaccinations against the wild-type and even two VOC-RBDs (alpha and delta) and strongly inhibited the corresponding RBD-ACE-2 binding. The IgG titers and inhibition of ACE-2 binding were lower for beta and gamma RBDs and much lower for omicron RBD. The third vaccination after 6 months strongly increased both the IgG titers and the neutralizing effect against all variants, especially for omicron, leading to 63% ± 13% neutralization potential. Importantly, neutralization linearly increased with the IgG titers.

In this paper we present the results of a systematic review aimed at investigating what the literature reports on cyberbullying and cyberhate, whether and to what extent the connection between the two phenomena is made explicit, and whether it is possible to identify overlapping factors in the description of the phenomena. Specifically, for each of the 24 selected papers, we have identified the predictors of cyberbullying behaviors and the consequences of cyberbullying acts on the victims; the same analysis has been carried out with reference to cyberhate. Then, by comparing what emerged from the literature on cyberbullying with what emerged from the literature on cyberhate, we verify to what extent the two phenomena overlap in terms of predictors and consequences. Results show that the cyberhate issue related to adolescents is less investigated than cyberbullying, and most of the papers focusing on one of them do not refer to the other. Nevertheless, by comparing the predictors and outcomes of cyberbullying and cyberhate as reported in the literature, an overlap between the two concepts emerges, with reference to: the parent-child relationship to reduce the risk of cyber-aggression; the link between sexuality and cyber-attacks; the protective role of the families and of good quality friendship relationships; the impact of cyberbullying and cyberhate on adolescents' individuals' well-being and emotions; meaningful analogies between the coping strategies put in practice by victims of cyberbullying and cyberhate. We argue that the results of this review can stimulate a holistic approach for future studies on cyberbullying and cyberhate where the two phenomena are analyzed as two interlinked instances of cyber-aggression. Similarly, prevention and intervention programs on a responsible and safe use of social media should refer to both cyberbullying and cyberhate issues, as they share many predictors as well as consequences on adolescents' wellbeing, thus making it diminishing to afford them separately.Systematic Review Registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier: CRD42021239461.

The modeling of fresh concrete flow is still very challenging. Nevertheless, it is of highest relevance to simulate these industrially important materials with sufficient accuracy. Often, fresh concrete is assumed to show a Bingham-behavior. In numerical simulations, regularization must be used to prevent singularities. Two different regularization models, namely the 1) Bi-viscous, and 2) Bingham-Papanastasiou are investigated. Those models can be applied to complex flows with common simulation methods, such as the Finite Volume Method (FVM), Finite Element Method (FEM) and Smoothed Particle Hydrodynamics (SPH). Within the scope of this investigation, two common software packages from the field of FVM, namely Ansys Fluent and OpenFOAM, COMSOL Multiphysics (COMSOL) from FEM side, and HOOMD-blue.sph from the field of SPH are used to model a reference experiment and to evaluate the modeling quality. According to the results, a good agreement of data with respect to the velocity profiles for all software packages is achieved, but on the other side there are remarkable difficulties in the viscosity calculation especially in the shear- to plug-flow transition zone. Also, a minor influence of the regularization model on the velocity profile is observed.

Abstract Background Characteristics of COVID-19 patients have mainly been reported within confirmed COVID-19 cohorts. By analyzing patients with respiratory infections in the emergency department during the first pandemic wave, we aim to assess differences in the characteristics of COVID-19 vs. Non-COVID-19 patients. This is particularly important regarding the second COVID-19 wave and the approaching influenza season. Methods We prospectively included 219 patients with suspected COVID-19 who received radiological imaging and RT-PCR for SARS-CoV-2. Demographic, clinical and laboratory parameters as well as RT-PCR results were used for subgroup analysis. Imaging data were reassessed using the following scoring system: 0 – not typical, 1 – possible, 2 – highly suspicious for COVID-19. Results COVID-19 was diagnosed in 72 (32,9%) patients. In three of them (4,2%) the initial RT-PCR was negative while initial CT scan revealed pneumonic findings. 111 (50,7%) patients, 61 of them (55,0%) COVID-19 positive, had evidence of pneumonia. Patients with COVID-19 pneumonia showed higher body temperature (37,7 ± 0,1 vs. 37,1 ± 0,1 °C; p = 0.0001) and LDH values (386,3 ± 27,1 vs. 310,4 ± 17,5 U/l; p = 0.012) as well as lower leukocytes (7,6 ± 0,5 vs. 10,1 ± 0,6G/l; p = 0.0003) than patients with other pneumonia. Among abnormal CT findings in COVID-19 patients, 57 (93,4%) were evaluated as highly suspicious or possible for COVID-19. In patients with negative RT-PCR and pneumonia, another third was evaluated as highly suspicious or possible for COVID-19 (14 out of 50; 28,0%). The sensitivity in the detection of patients requiring isolation was higher with initial chest CT than with initial RT-PCR (90,4% vs. 79,5%). Conclusions COVID-19 patients show typical clinical, laboratory and imaging parameters which enable a sensitive detection of patients who demand isolation measures due to COVID-19.

Four commercial titanium dioxide (TiO2) photocatalysts, namely P25, P90, PC105, and PC500, were immobilized onto steel plates using a sol-gel binder and investigated for phenol degradation under 365 nm UV-LED irradiation. High-performance liquid chromatography (HPLC) and total organic carbon (TOC) analyses were performed to study the impact of three types of oxygen sources (air, dispersed synthetic air, and hydrogen peroxide) on the photocatalytic performance. The photocatalyst films were stable and there were significant differences in their performance. The best result was obtained with the P90/UV/H2O2 system with 100% degradation and about 70% mineralization within 3 h of irradiation. The operating conditions varied, showing that water quality is crucial for the performance. A wastewater treatment plant was developed based on the lab-scale results and water treatment costs were estimated for two cases of irradiation: UV-LED (about 600 EUR/m3) and sunlight (about 60 EUR/m3). The data show the high potential of immobilized photocatalysts for pollutant degradation under advanced oxidation process (AOP) conditions, but there is still a need for optimization to further reduce treatment costs.

Rapeseed meal (RSM), a by-product of rapeseed oil extraction, is currently used for low-value purposes. With a biorefinery approach, rapeseed proteins may be extracted and recovered for high-end uses to fully exploit their nutritional and functional properties. This study reports the application of RSM protein isolate, the main output of a biorefining process aimed at recovering high-value molecules from rapeseed meal, as a supplement to texture-modified (TM) food designed for elderly people with mastication and dysphagia problems. The compositional (macronutrients by Official Methods of Analyses, and mineral and trace element profiles using Inductively Coupled Plasma Optical Emission Spectrometry ICP-OES), nutritional and sensory evaluations of TM chicken breast, carrots and bread formulated without and with RSM protein supplementation (5% w/w) are hereby reported. The results show that the texture modification of food combined with rapeseed protein isolate supplementation has a positive impact on the nutritional and sensory profile of food, meeting the special requirements of seniors. TM chicken breast and bread supplemented with RSM protein isolate showed unaltered or even improved sensory properties and a higher nutrient density, with particular regard to proteins (+20–40%) and minerals (+10–16%). Supplemented TM carrots, in spite of the high nutrient density, showed a limited acceptability, due to poor sensory properties that could be overcome with an adjustment to the formulation. This study highlights the potentialities of RSM as a sustainable novel protein source in the food sector. The application of RSM protein proposed here is in line with the major current challenges of food systems such as the responsible management of natural resources, the valorization of agri-food by-products, and healthy nutrition with focus on elderly people.

When overmoulding optoelectronic devices with optical elements, precise alignment of the overmoulded part and the mould is of great importance. However, mould-integrated positioning sensors and actuators are not yet available as standard components. As a solution, we present a mould-integrated optical coherence tomography (OCT) device that is combined with a piezo-driven mechatronic actuator, which is capable of performing the necessary displacement correction. Because of the complex geometric structure optoelectronic devices may have, a 3D imaging method was preferable, so OCT was chosen. It is shown that the overall concept leads to sufficient alignment accuracy and, apart from compensating for the in-plane position error, provides valuable additional information about the sample both before and after the injection process. The increased alignment accuracy leads to better energy efficiency, improved overall performance and less scrap parts, and thus even a zero-waste production process might be feasible.

The luminal A-subtype of breast cancer, where the oestrogen receptor α (ERα) is overexpressed, is the most frequent one. The prodrug tamoxifen (1) is the clinically used agent, inhibiting the ERα activity via the formation of several active metabolites, such as 4-hydroxytamoxifen (2) or 4,4′-dihydroxytamoxifen (3). In this study, we present the tamoxifen derivative 4-[1,1-bis(4-methoxyphenyl)but-1-en-2-yl]-2,2′-bipyridine (4), which was combined with platinum or palladium dichloride, the former a well-known scaffold in anticancer treatment, to give [PtCl2(4-κ2N,N′)] (5) or [PdCl2(4-κ2N,N′] (6). To prevent fast exchange of weakly coordinating chlorido ligands in aqueous solution, a bulky, highly stable and hydrophobic nido-carborate(−2) ([C2B9H11]2−) was incorporated. The resulting complexes [3-(4-κ2N,N′)-3,1,2-PtC2B9H11] (7) and [3-(4-κ2N,N′)-3,1,2-PdC2B9H11] (8) exhibit a dramatic change in electronic and biological properties compared to 5 and 6. Thus, 8 is highly selective for triple-negative MDA-MB-231 cells (IC50 = 3.7 μM, MTT test), while 7 is completely inactive against this cell line. The observed cytotoxicity of compounds 4–6 and 8 against this triple-negative cell line suggests off-target mechanisms rather than only ERα inhibition, for which these compounds were originally designed. Spectroscopic properties and electronic structures of the metal complexes were investigated for possible explanations of the biological activities.

G protein-coupled receptors can adopt many different conformational states, each of them exhibiting different restraints towards downstream signaling pathways. One promising strategy to identify and quantify this conformational landscape is to introduce a cysteine at a receptor site sensitive to different states and label this cysteine with a probe for detection. Here, the application of NMR of hyperpolarized 129Xe for the detection of the conformational states of human neuropeptide Y2 receptor is introduced. The xenon trapping cage molecule cryptophane-A attached to a cysteine in extracellular loop 2 of the receptor facilitates chemical exchange saturation transfer experiments without and in the presence of native ligand neuropeptide Y. High-quality spectra indicative of structural states of the receptor–cage conjugate were obtained. Specifically, five signals could be assigned to the conjugate in the apo form. After the addition of NPY, one additional signal and subtle modifications in the persisting signals could be detected. The correlation of the spectroscopic signals and structural states was achieved with molecular dynamics simulations, suggesting frequent contact between the xenon trapping cage and the receptor surface but a preferred interaction with the bound ligand.

Background: Instrument-assisted soft tissue mobilization (IASTM) is thought to alter fluid dynamics in human soft tissue. The aim of this study was to investigate the influence of IASTM on the thoracolumbar fascia (TLF) on the water content of the lumbar myofascial tissue. Methods: In total, 21 healthy volunteers were treated with IASTM. Before and after the procedure and 5 and 10 min later, lumbar bioimpedance was measured by bioimpedance analysis (BIA) and TLF stiffness was measured by indentometry. Tissue temperature was recorded at the measurement time points using an infrared thermometer. Results: Bioimpedance increased significantly from 58.3 to 60.4 Ω (p < 0.001) at 10-min follow-up after the treatment. Temperature increased significantly from 36.3 to 36.6 °C from 5 to 10 min after treatment (p = 0.029), while lumbar myofascial stiffness did not change significantly (p = 0.84). Conclusions: After the IASTM intervention, there was a significant increase in bioimpedance, which was likely due to a decrease in water content in myofascial lumbar tissue. Further studies in a randomized control trial design are needed to extrapolate the results in healthy subjects to a symptomatic population as well and to confirm the reliability of BIA in myofascial tissue.

Surgeons face unique challenges in perioperative decision-making and communication with patients and families. In cardiothoracic surgery, the stakes are high, life and death decisions must be made quickly, and surgeons often lack a longstanding relationship with patients and families prior to intervention. This review considers specific challenges in the preoperative period followed by those faced postoperatively. While preoperative deliberation and informed consent focus on reaching a decision between 2 or more alternative approaches, the most vexing postoperative decisions often involve the patient's discontent with the best-case outcome or how to ensure goal-concordant care when complications arise. This review explores the preoperative ethical and legal requirement for informed consent by describing the contemporary preferred method, shared decision-making. We also present a framework to optimize surgeon communication and promote patient and family engagement in the setting of high-risk surgery for older patients with serious illness. In the postoperative period the family is often tasked with deciding what to do about major complications when the patient has lost decision-making capacity. We discuss several examples and offer strategies for surgeons to navigate these challenging situations. We also explore the concepts of clinical heroism and futility in relation to communicating with patients and families about the outcomes of surgery. Persistent ethical challenges in decision-making suggest that surgeons should improve their skills in communicating with patients to better engage with them, both before and after surgery. [ABSTRACT FROM AUTHOR]

We present the case of a 55-year-old female patient with metamizole-induced agranulocytosis after total knee arthroplasty, leading to septic periprosthetic joint infections (PJIs). Owing to metamizole-induced agranulocytosis, the synovial leukocyte count was negative. Here, we discuss the diagnostic challenges evolving from sepsis and neutropenia in patients with suspected PJIs. We suggest an urgent surgical approach, mainly focusing on the clinical presentation preoperatively. Later, our patient developed candidemia and periprosthetic tissue samples were positive for Candida albicans. For fungal PJIs, long-term follow-up studies are lacking and therapeutic recommendations differ. Here, we present our therapeutic approach, including staged revision and 12 weeks of systemic antifungal therapy, and discuss recent findings regarding the therapy of fungal PJIs.

Recent research on growth machines, in a prominent theme, has focused on how mobilized discourses promote urban redevelopment projects. Pushed to the margins, in this work, has been the issue of how alternative growth visions and voices are silenced or muffled. This article examines the notion of “silencing” in urban growth discourses. Silencing, it is argued, should not be understood as censorship but rather as attempts by growth machines to relativize the importance of critical and dissent voices in redevelopment projects. We believe that to understand how redevelopment projects operate and transform (urban) spaces, such rhetorical peripherialization is as important as pro-growth discourses. In developing this argument, the article focuses on the case study of the Obama Presidential Center (OPC) on Chicago's Southeast Side. An OPC growth machine consisting of the Obama Foundation, the city mayor, the University of Chicago, and a coalition of local business and community organizations practices this simultaneity of offering their voice and undercutting alternative voices in adroit ways. Race, it is argued, is at the center of this systematic suppression. The OPC development provides an important example of how current redevelopment in cities across the global west currently proceeds.

Summary: Background: Many repurposed drugs have progressed rapidly to Phase 2 and 3 trials in COVID19 without characterisation of Pharmacokinetics /Pharmacodynamics including safety data. One such drug is nafamostat mesylate. Methods: We present the findings of a phase Ib/IIa open label, platform randomised controlled trial of intravenous nafamostat in hospitalised patients with confirmed COVID-19 pneumonitis. Patients were assigned randomly to standard of care (SoC), nafamostat or an alternative therapy. Nafamostat was administered as an intravenous infusion at a dose of 0.2 mg/kg/h for a maximum of seven days. The analysis population included those who received any dose of the trial drug and all patients randomised to SoC. The primary outcomes of our trial were the safety and tolerability of intravenous nafamostat as an add on therapy for patients hospitalised with COVID-19 pneumonitis. Findings: Data is reported from 42 patients, 21 of which were randomly assigned to receive intravenous nafamostat. 86% of nafamostat-treated patients experienced at least one AE compared to 57% of the SoC group. The nafamostat group were significantly more likely to experience at least one AE (posterior mean odds ratio 5.17, 95% credible interval (CI) 1.10 – 26.05) and developed significantly higher plasma creatinine levels (posterior mean difference 10.57 micromol/L, 95% CI 2.43–18.92). An average longer hospital stay was observed in nafamostat patients, alongside a lower rate of oxygen free days (rate ratio 0.55–95% CI 0.31–0.99, respectively). There were no other statistically significant differences in endpoints between nafamostat and SoC. PK data demonstrated that intravenous nafamostat was rapidly broken down to inactive metabolites. We observed no significant anticoagulant effects in thromboelastometry. Interpretation: In hospitalised patients with COVID-19, we did not observe evidence of anti-inflammatory, anticoagulant or antiviral activity with intravenous nafamostat, and there were additional adverse events. Funding: DEFINE was funded by LifeArc (an independent medical research charity) under the STOPCOVID award to the University of Edinburgh. We also thank the Oxford University COVID-19 Research Response Fund (BRD00230).

Summary: Background: Long-term exposure to ambient air pollution has been associated with premature mortality, but associations at concentrations lower than current annual limit values are uncertain. We analysed associations between low-level air pollution and mortality within the multicentre study Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE). Methods: In this multicentre longitudinal study, we analysed seven population-based cohorts of adults (age ≥30 years) within ELAPSE, from Belgium, Denmark, England, the Netherlands, Norway, Rome (Italy), and Switzerland (enrolled in 2000–11; follow-up until 2011–17). Mortality registries were used to extract the underlying cause of death for deceased individuals. Annual average concentrations of fine particulate matter (PM2·5), nitrogen dioxide (NO2), black carbon, and tropospheric warm-season ozone (O3) from Europe-wide land use regression models at 100 m spatial resolution were assigned to baseline residential addresses. We applied cohort-specific Cox proportional hazard models with adjustment for area-level and individual-level covariates to evaluate associations with non-accidental mortality, as the main outcome, and with cardiovascular, non-malignant respiratory, and lung cancer mortality. Subset analyses of participants living at low pollutant concentrations (as per predefined values) and natural splines were used to investigate the concentration-response function. Cohort-specific effect estimates were pooled in a random-effects meta-analysis. Findings: We analysed 28 153 138 participants contributing 257 859 621 person-years of observation, during which 3 593 741 deaths from non-accidental causes occurred. We found significant positive associations between non-accidental mortality and PM2·5, NO2, and black carbon, with a hazard ratio (HR) of 1·053 (95% CI 1·021–1·085) per 5 μg/m3 increment in PM2·5, 1·044 (1·019–1·069) per 10 μg/m3 NO2, and 1·039 (1·018–1·059) per 0·5 × 10−5/m black carbon. Associations with PM2·5, NO2, and black carbon were slightly weaker for cardiovascular mortality, similar for non-malignant respiratory mortality, and stronger for lung cancer mortality. Warm-season O3 was negatively associated with both non-accidental and cause-specific mortality. Associations were stronger at low concentrations: HRs for non-accidental mortality at concentrations lower than the WHO 2005 air quality guideline values for PM2·5 (10 μg/m3) and NO2 (40 μg/m3) were 1·078 (1·046–1·111) per 5 μg/m3 PM2·5 and 1·049 (1·024–1·075) per 10 μg/m3 NO2. Similarly, the association between black carbon and non-accidental mortality was highest at low concentrations, with a HR of 1·061 (1·032–1·092) for exposure lower than 1·5× 10−5/m, and 1·081 (0·966–1·210) for exposure lower than 1·0× 10−5/m. Interpretation: Long-term exposure to concentrations of PM2·5 and NO2 lower than current annual limit values was associated with non-accidental, cardiovascular, non-malignant respiratory, and lung cancer mortality in seven large European cohorts. Continuing research on the effects of low concentrations of air pollutants is expected to further inform the process of setting air quality standards in Europe and other global regions. Funding: Health Effects Institute.

This study explores the risk for cancer by level of antibodies to the anaerobe oral bacteria of periodontitis Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all three collectively termed the red complex, and the facultative anaerobe bacterium Aggregatibacter actinomycetemcomitans (AA). The prospective cohort, the Oslo II-study from 2000, the second screening of the Oslo study of 1972/73, has been followed for 17 ½ years with regard to cancer incidence and mortality. A random sample of 697 elderly men comprised the study cohort. The antibody results measured by enzyme linked immunosorbent assay (ELISA) were used in the Cox proportional hazards analyses, and quartile risk on cancer incidence in a 17 ½ years follow-up. Among the 621 participants with no prior cancer diagnoses, 221 men developed cancer. The incidence trend was inverse, and the results are shown as 1st quartile of highest value and 4th as lowest of antibody levels. The results of the Cox proportional regression analyses showed that TF inversely predicts bladder cancer (n = 22) by Hazard Ratio (HR) = 1.71 (95% CI: 1.12, 2.61). TD inversely predicts colon cancer (n = 26) by HR = 1.52 (95% CI: 1.06, 2.19) and bladder cancer (n = 22) by HR = 1.60 (95% CI: 1.05, 2.43). Antibodies to two oral bacteria, TF and TD, showed an inverse risk relationship with incidence of specific cancers: TF bladder cancer, TD bladder and colon cancer. Lowered immunological response to the oral infection, periodontitis, is shown to be a risk factor in terms of cancer aetiology.

In this paper, we study the behavior of feasible rounding approaches for mixed-integer optimization problems when integrated into branch-and-bound methods. Our research addresses two important aspects. First, we develop insights into how an (enlarged) inner parallel set, which is the main component for feasible rounding approaches, behaves when we move down a search tree. Our theoretical results show that the number of feasible points obtainable from the inner parallel set is nondecreasing with increasing depth of the search tree. Thus, they hint at the potential benefit of integrating feasible rounding approaches into branch-and-bound methods. Second, based on those insights, we develop a novel primal heuristic for MILPs that fixes variables in a way that promotes large inner parallel sets of child nodes.Our computational study shows that combining feasible rounding approaches with the presented diving ideas yields a significant improvement over their application in the root node. Moreover, the proposed method is able to deliver best solutions for the MIP solver SCIP for a significant share of problems which hints at its potential to support solving MILPs.