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Our ability to edit genomes lags behind our capacity to sequence them, but the growing understanding of CRISPR biology and its application to genome, epigenome and transcriptome engineering is narrowing this gap. In this Review, we discuss recent developments of various CRISPR-based systems that can transiently or permanently modify the genome and the transcriptome. The discovery of further CRISPR enzymes and systems through functional metagenomics has meaningfully broadened the applicability of CRISPR-based editing. Engineered Cas variants offer diverse capabilities such as base editing, prime editing, gene insertion and gene regulation, thereby providing a panoply of tools for the scientific community. We highlight the strengths and weaknesses of current CRISPR tools, considering their efficiency, precision, specificity, reliance on cellular DNA repair mechanisms and their applications in both fundamental biology and therapeutics. Finally, we discuss ongoing clinical trials that illustrate the potential impact of CRISPR systems on human health.

The Pulmonary Embolism-Syncope, Anemia, and Renal Dysfunction (PE-SARD) bleeding score was derived to predict very early major bleeding (MB) in patients with acute pulmonary embolism (PE). Before adoption into practice, the score requires external validation in different populations.

Here, we report six novel, easily accessible BODIPY-based agents for cancer treatment. In contrast to established photodynamic therapy (PDT) agents, these BODIPY-based compounds show additional photothermal activity and their cytotoxicity is not dependent on the generation of reactive oxygen species (ROS). The agents show high photocytotoxicity upon irradiation with light and low dark toxicity in different cancer cell lines in 2D culture as well as in 3D multicellular tumor spheroids (MCTSs). The ratio of dark to light toxicity (phototoxic index, PI) of these agents reaches striking values exceeding 830,000 after irradiation with energetically low doses of light at 630 nm. The oxygen-dependent mechanism of action (MOA) of established photosensitizers (PSs) hampers effective clinical deployment of these agents. Under hypoxic conditions (0.2% O2), which are known to limit the efficiency of conventional PSs in solid tumors, photocytotoxicity was induced at the same concentration levels, indicating an oxygen-independent photothermal MOA. With a PI exceeding 360,000 under hypoxic conditions, both PI values are the highest reported to date. We anticipate that small molecule agents with a photothermal MOA, such as the BODIPY-based compounds reported in this work, may overcome this barrier and provide a new avenue to cancer therapy.

Psychedelics are experiencing a renaissance in mental healthcare. In recent years, more and more early phase trials on psychedelic-assisted therapy have been conducted, with promising results overall. However, ethical analyses of this rediscovered form of treatment remain rare. The present paper contributes to the ethical inquiry of psychedelic-assisted therapy by analysing the ethical implications of its therapeutic mechanisms proposed by the relaxed beliefs under psychedelics (REBUS) hypothesis. In short, the REBUS hypothesis states that psychedelics make rigid beliefs revisable by increasing the influence of bottom-up input. Put differently, patients become highly suggestible and sensitive to context during a psychedelic session, amplifying therapeutic influence and effects. Due to that, patients are more vulnerable in psychedelic-assisted therapy than in other therapeutic interventions; they lose control during a psychedelic session and become dependent on the therapeutic setting (including the therapist). This enhanced vulnerability is ethically relevant and has been exploited by some therapists in the past. Therefore, patients in current research settings and starting mainstream medical settings need to be well informed about psychedelics’ mechanisms and their implications to give valid informed consent to treatment. Furthermore, other security measures are warranted to protect patients from the vulnerability coming with psychedelic-assisted therapy.

Imaging through optical multimode fiber (MMF) has the potential to enable hair-thin endoscopes that reduce the invasiveness of imaging deep inside tissues and organs. Active wavefront shaping and fluorescent labeling have recently been exploited to overcome modal scrambling and enable MMF imaging. Here, we present a computational approach that circumvents the need for active wavefront control and exogenous fluorophores. We demonstrate the reconstruction of depth-gated confocal images through MMF using a raster-scanned, focused input illumination at the fiber proximal end. We show the compatibility of this approach with quantitative phase, dark-field, and polarimetric imaging. Computational imaging through MMF opens a new pathway for minimally invasive imaging in medical diagnosis and biological investigations.

Photothermal optical coherence tomography (PT-OCT) is an emerging extension of OCT, which forms images based on both scattering and absorption of light. The speed of PT-OCT, however, has been limited by the necessity for lock-in detection with extensive temporal sampling of the sample’s PT response. Here, we demonstrate transient-mode PT-OCT (TM-PT-OCT), which increases the effective A-line rate by orders of magnitude from 10–100 Hz to 1.5–7.5 kHz, by interrogating the sample’s transient thermal response to a single diode laser pulse. Functional imaging of moving samples with TM-PT-OCT at video rate is also presented. This significant improvement in imaging speed is expected to open the door for downstream integration of PT-OCT in clinical systems for in vivo imaging.

Polarization-sensitive optical coherence tomography (PS-OCT) reveals the subsurface microstructure of biological tissue and provides information regarding the polarization state of light backscattered from tissue. Complementing OCT’s structural signal with molecular imaging requires strategies to simultaneously detect multiple exogenous contrast agents with high specificity in tissue. Specific detection of molecular probes enables the parallel visualization of physiological, cellular, and molecular processes. Here we demonstrate that, by combining PS-OCT and spectral contrast (SC)-OCT measurements, we can distinguish signatures of different gold nanobipyramids (GNBPs) in lymphatic vessels from the surrounding tissue and blood vessels in live mouse models. This technique could well be extended to other anisotropic nanoparticle-based OCT contrast agents and presents significant progress toward enabling OCT molecular imaging.

Adequate tumor yield in core-needle biopsy (CNB) specimens is essential in lung cancer for accurate histological diagnosis, molecular testing for therapeutic decision-making, and tumor biobanking for research. Insufficient tumor sampling in CNB is common, primarily due to inadvertent sampling of tumor-associated fibrosis or atelectatic lung, leading to repeat procedures and delayed diagnosis. Currently, there is no method for rapid, non-destructive intraprocedural assessment of CNBs. Polarization-sensitive optical coherence tomography (PS-OCT) is a high-resolution, volumetric imaging technique that has the potential to meet this clinical need. PS-OCT detects endogenous tissue properties, including birefringence from collagen, and degree of polarization uniformity (DOPU) indicative of tissue depolarization. Here, PS-OCT birefringence and DOPU measurements were used to quantify the amount of tumor, fibrosis, and normal lung parenchyma in 42 fresh, intact lung CNB specimens. PS-OCT results were compared to and validated against matched histology in a blinded assessment. Linear regression analysis showed strong correlations between PS-OCT and matched histology for quantification of tumors, fibrosis, and normal lung parenchyma in CNBs. PS-OCT distinguished CNBs with low tumor content from those with higher tumor content with high sensitivity and specificity. This study demonstrates the potential of PS-OCT as a method for rapid, non-destructive, label-free intra-procedural tumor yield assessment.

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Study design: Clinimetric cross-sectional cohort study in adults with paraplegic spinal cord injury (SCI) and neuropathic pain (NP). Objective: To assess the reliability of standardized quantitative pain drawings in patients with NP following SCI. Setting: Hospital-based research facility at the Spinal Cord Injury Center, Balgrist University Hospital, Zurich, Switzerland. Methods: Twenty individuals with chronic thoracic spinal cord injury and neuropathic pain were recruited from a national and local SCI registry. A thorough clinical examination and pain assessments were performed. Pain drawings were acquired at subsequent timepoints, 13 days (IQR 7.8–14.8) apart, in order to assess test-retest reliability. Results: The average extent [%] and intensity [NRS 0–10] of spontaneous NP were 11.3% (IQR 4.9–35.8) and 5 (IQR 3–7), respectively. Pain extent showed excellent inter-session reliability (intraclass correlation coefficient 0.96). Sensory loss quantified by light touch and pinprick sensation was associated with larger pain extent (rpinprick= −0.47, p= 0.04; rlight touch= −0.64, p< 0.01). Conclusion: Assessing pain extent using quantitative pain drawings is readily feasible and reliable in human SCI. Relating information of sensory deficits to the presence of pain may provide distinct insights into the interaction of sensory deafferentation and the development of neuropathic pain after SCI.

Recent progress has enabled the reconstruction of the local (i.e., depth-resolved) optic axis (OAx) of biological tissue from measurements made with polarization-sensitive optical coherence tomography (PS-OCT). Here we demonstrate local OAx imaging in healthy human skin in vivo. The images reveal dense, weaving patterns that are imperceptible in OCT intensity tomograms or conventional PS-OCT metrics and that suggest a mesh-like tissue organization, consistent with the morphology of dermal collagen. Using co-registered polarization-sensitive optical coherence microscopy, we furthermore investigated the impact of spatial resolution on the recovered OAx patterns and confirmed their consistency. OAx orientation as a contrast mechanism merits further exploration for applications in dermatology.

Quantitative blood flow measurements using optical coherence tomography (OCT) have a wide potential range of medical research and clinical applications. Flowmetry based on the temporal dynamics of the OCT signal may have the ability to measure three-dimensional flow profiles regardless of the flow direction. State-of-the-art models describing the OCT signal temporal statistics are based on dynamic light scattering (DLS), a model which is inherently limited to single scattering regimes. DLS methods continue to be applied to OCT despite the knowledge that red blood cells produce strong forward multiple scattering. Here, we postulate that forward multiple scattering is the primary mechanism causing the rate of speckle-decorrelation derived from data acquired in vivo to deviate from the rate of decorrelation determined in phantom experiments. We also postulate that multiple scattering contributions to decorrelation are only present when the sample exhibits velocity field inhomogeneities larger than the scale of a resolution volume and are thus absent in rigid bulk motion. To test these hypotheses, we performed a systematic study of the effects of forward multiple scattering on OCT signal decorrelation with phantom experiments under physiologically relevant flow conditions and relative bulk motion. Our experimental results confirm that the amount of forward multiple scattering affects the proportionality between lateral flow and decorrelation. We propose that multiply scattered light carries information from different locations in the sample and each location imprints scattering dynamics on the scattered light causing increased decorrelation rates. Our analysis confirms that the detection of forward scattered light inside the vessel lumen causes an increase in the rate of decorrelation which results in an overestimation of blood flow velocities at depths as shallow as 40 µm into whole blood for OCT systems with typical numerical apertures used in retinal imaging.

The organization of fibrillar tissue on the micrometer scale carries direct implications for health and disease but remains difficult to assess in vivo. Polarization-sensitive optical coherence tomography measures birefringence, which relates to the microscopic arrangement of fibrillar tissue components. Here, we demonstrate a critical improvement in leveraging this contrast mechanism by employing the improved spatial resolution of focus-extended optical coherence microscopy (1.4 µm axially in air and 1.6 µm laterally, over more than 70 µm depth of field). Vectorial birefringence imaging of sheep cornea ex vivo reveals its lamellar organization into thin sections with distinct local optic axis orientations, paving the way to resolving similar features in vivo.

We observed that the polarization state of light after round-trip propagation through a birefringent medium frequently aligns with the employed input polarization state ‘mirrored’ by the horizontal plane of the Poincaré sphere. We explored the predisposition for this mirror state and evidence that it constrains the evolution of polarization states as a function of the round-trip depth into weakly scattering birefringent samples, as measured with polarization-sensitive optical coherence tomography (PS-OCT). Combined with spectral variations in the polarization state transmitted through system components, we demonstrate how this constraint enables measurement of depth-resolved birefringence using only a single input polarization state, which offers a critical simplification compared to conventional PS-OCT employing two input states.

Stromal collagen organization has been identified as a potential prognostic indicator in a variety of cancers and other diseases accompanied by fibrosis. Changes in the connective tissue are increasingly considered for grading dysplasia and progress of oral squamous cell carcinoma, investigated mainly ex vivo by histopathology. In this study, polarization-sensitive optical coherence tomography (PS-OCT) with local phase retardation imaging is used for the first time to visualize depth-resolved (i.e., local) birefringence of healthy human oral mucosa in vivo. Depth-resolved birefringence is shown to reveal the expected local collagen organization. To demonstrate proof-of-principle, 3D image stacks were acquired at labial and lingual locations of the oral mucosa, chosen as those most commonly affected by cancerous alterations. To enable an intuitive evaluation of the birefringence images suitable for clinical application, color depth-encoded en-face projections were generated. Compared to en-face views of intensity or conventional cumulative phase retardation, we show that this novel approach offers improved visualization of the mucosal connective tissue layer in general, and reveals the collagen fiber architecture in particular. This study provides the basis for future prospective pathological and comparative in vivo studies non-invasively assessing stromal changes in conspicuous and cancerous oral lesions at different stages.

We present a microscopic image guidance platform for radiofrequency ablation (RFA) using a clinical balloon-catheter-based optical coherence tomography (OCT) system, currently used in the surveillance of Barrett’s esophagus patients. Our integrated thermal therapy delivery and monitoring platform consists of a flexible, customized bipolar RFA electrode array designed for use with a clinical balloon OCT catheter and a processing algorithm to accurately map the thermal coagulation process. Non-uniform rotation distortion was corrected using a feature tracking-based technique, which enables robust, frame-to-frame analysis of the temporal fluctuation of the complex OCT signal. With proper noise calibration, precise delineation of the thermal therapy zone was demonstrated using cumulative complex differential variance in porcine esophagus ex vivo with the integrated OCT-RFA system, as validated by nitroblue tetrazolium chloride (NBTC) histology. The ability to directly and accurately visualize the thermal coagulation process at high resolution is critical to the precise delivery of thermal energy to a wide range of epithelial lesions.

Males outperformed females in all split disciplines, overall race times, and all age groups.Variations in sex differences were observed across different disciplines, with swimming displaying lower differences compared to cycling and running.Sex differences in performance decreased with age.

Background: Giant cell arteritis (GCA) is primarily treated with glucocorticoids (GCs), which have substantial toxicity. Tocilizumab, an interleukin-6-receptor inhibitor (IL-6Ri), showed beneficial effects in GCA, leading to its approval. This study investigated the efficacy and safety of sarilumab (another IL-6Ri) in GCA. Methods: This Phase 3, double-blind study comprised a 52-week treatment period and a 24-week follow-up phase. Eligible GCA patients were randomized to receive sarilumab 200 mg (SAR200 + 26W) or 150 mg (SAR150 + 26W) with a 26-week GC taper, or placebo with a 52-week (PBO + 52W) or 26-week (PBO + 26W) GC taper. The primary efficacy endpoint was sustained remission (SR) at week 52. Additional endpoints were SR at week 24, cumulative GC dose, and safety. The study was discontinued prematurely due to protracted recruitment timelines, because of the impact of COVID-19. Therefore, only descriptive statistics were summarized. Results: Of the planned 360 subjects, only 83 were randomized and 36 were included in the week 52 analysis. At week 52, 46% (n= 6/13) of patients in SAR200 + 26W, 43% (n= 3/7) in SAR150 + 26W, 30% (n= 3/10) in PBO + 52W, and 0 (n= 0/6) in PBO + 26W taper groups achieved SR. Sensitivity analyses, excluding acute-phase reactants from the SR definition, showed similar results for SAR groups, but 60% (n= 6/10) in PBO + 52W and 17% (n= 1/6) in PBO + 26W taper groups achieved SR at week 52. Similar findings were noted at week 24. The proportions of patients who adhered to GC taper from week 12 through week 52 in each group were as follows: 46% (n= 6/13, SAR200 + 26W), 43% (n= 3/7, SAR150 + 26W), 60% (n= 6/10, PBO + 52W), and 33% (n= 2/6, PBO + 26W). The median actual cumulative GC dose received in the SAR200 + 26W group was lower than other groups. Most patients (80–100%) experienced treatment-emergent adverse events, with similar incidences reported across groups. Conclusions: Owing to the small sample size due to the early termination, it is difficult to draw clear conclusions from this study. There were no unexpected safety findings. Trial registration: ClinicalTrials.gov NCT03600805. Registered on July 26, 2018.

La Maison des Fondateurs in Le Brassus Switzerland is going to represent the watch making manufacture Audemars Piguet. Audemars Piguet stands for the finest quality, precision as well as innovation based on traditional watchmaking expertise and craftsmanship. La Maison des Fondateurs has been developed from a competition proposal to the execution project by the architects BIG—Bjarke Ingels Group. The created interlocking all glass spiral evolves the building volume out of the rough, natural landscape providing a perfect linear museum path for the building program. Despite the severe loading and weather conditions, inspired by the high values of Audemars Piguet the project team designed the building to the technical limits. The curved and very large insulated façade glass units as well as the curved glass partition walls of the interlocking glass spiral are forming the load bearing structure. All vertical and horizontal loads are transferred by these glass components making solid columns and shear wall obsolete. The article reflects the close collaboration of the designers, engineers, specialist contractor and industry. The global structural concept, transfer of the concentrated point loading into the curved structural glass element, testing procedures as well as the structural bonding beyond standards and the context of energy efficiency are discussed and elaborated.

Interstitial lung disease in systemic sclerosis (SSc-ILD) is a major cause of SSc-related death. Imunosuppressive treatment (IS) is used in patients with SSc for various organ manifestations mainly to ameliorate progression of SSc-ILD. Data on everyday IS prescription patterns and clinical courses of lung function during and after therapy are scarce. We analysed patients fulfilling American College of Rheumatology (ACR)/European League against Rheumatism (EULAR) 2013 criteria for SSc-ILD and at least one report of IS. Types of IS, pulmonary function tests (PFT) and PFT courses during IS treatment were evaluated. EUSTAR contains 3778/11,496 patients with SSc-ILD (33%), with IS in 2681/3,778 (71%). Glucocorticoid (GC) monotherapy was prescribed in 30.6% patients with GC combinations plus cyclophosphamide (CYC) (11.9%), azathioprine (AZA) (9.2%), methotrexate (MTX) (8.7%), or mycophenolate mofetil (MMF) (7.3%). Intensive IS (MMF + GC, CYC or CYC + GC) was started in patients with the worst PFTs and ground glass opacifications on imaging. Patients without IS showed slightly less worsening in forced vital capacity (FVC) when starting with FVC 50–75% or >75%. GC showed negative trends when starting with FVC <50%. Regarding diffusing capacity for carbon monoxide (DLCO), negative DLCO trends were found in patients with MMF. IS is broadly prescribed in SSc-ILD. Clusters of clinical and functional characteristics guide individualised treatment. Data favour distinguished decision-making, pointing to either watchful waiting and close monitoring in the early stages or start of immunosuppressive treatment in moderately impaired lung function. Advantages of specific IS are difficult to depict due to confounding by indication. Data do not support liberal use of GC in SSc-ILD.

Nailfold capillaroscopy (NC) is an important tool for the diagnosis of systemic sclerosis (SSc). The capillaroscopic skin ulcer risk index (CSURI) was suggested to identify patients at risk of developing digital ulcers (DUs). This study aims to assess the reliability of the CSURI across assessors, the CSURI change during follow-up and the value of the CSURI in predicting new DUs. This multicentre, longitudinal study included SSc patients with a history of DUs. NC images of all eight fingers were obtained at baseline and follow-up and were separately analysed by two trained assessors. Sixty-one patients were included (median observation time 1.0 year). In about 40% of patients (assessor 1, n= 24, 39%; assessor 2, n= 26, 43%) no megacapillary was detected in any of the baseline or follow-up images; hence the CSURI could not be calculated. In those 34 patients in whom CSURI scores were available from both assessors (26% male; median age 57 years) the median baseline CSURI was 5.3 according to assessor 1 (IQR 2.6–16.3), increasing to 5.9 (IQR 1.3–12.0) at follow-up. According to assessor 2, the CSURI diminished from 6.4 (IQR 2.4–12.5) to 5.0 (IQR 1.7–10.0). The ability of a CSURI ≥ 2.96 category to predict new DUs was low (for both assessors, positive predictive value 38% and negative predictive value 50%) and the inter-assessor agreements for CSURI categories were fair to moderate. In this study, around 40% of patients could not be evaluated with the CSURI due to the absence of megacapillaries. Clinical decisions based on the CSURI should be made with caution. Current Controlled Trials, ISRCTN04371709. Registered on 18 March 2011.

It is challenging to recover local optic axis orientation from samples probed with fiber-based polarization-sensitive optical coherence tomography (PS-OCT). In addition to the effect of preceding tissue layers, the transmission through fiber and system elements, and imperfect system alignment, need to be compensated. Here, we present a method to retrieve the required correction factors from measurements with depth-multiplexed PS-OCT, which accurately measures the full Jones matrix. The correction considers both retardation and diattenuation and is applied in the wavenumber domain, preserving the axial resolution of the system. The robustness of the method is validated by measuring a birefringence phantom with a misaligned system. Imaging ex-vivo lamb trachea and human bronchus demonstrates the utility of reconstructing the local optic axis orientation to assess smooth muscle, which is expected to be useful in the assessment of airway smooth muscle thickness in asthma, amongst other fiber-based applications.

Birefringence offers an intrinsic contrast mechanism related to the microstructure and arrangement of fibrillary tissue components. Here we present a reconstruction strategy to recover not only the scalar amount of birefringence, but also its optic axis orientation as a function of depth in tissue from measurements with catheter-based polarization-sensitive optical coherence tomography. A polarization symmetry constraint, intrinsic to imaging in the backscatter direction, facilitates the required compensation for wavelength-dependent transmission through the system elements, the rotating catheter, and overlying tissue layers. Applied to the intravascular imaging of coronary atherosclerosis in human patients, the optic axis affords refined interpretation of plaque architecture.

•A large number (n> 13,000) of cross-country skiers participate in the Vasaloppet every year.•Males have a more even pacing than females in cross-country skiing, which contrasts with findings in studies of marathon running.•Fast cross-country skiers adopt a more even pacing than their slower counterparts, which is in agreement with observations in other endurance sports.

CRISPR–Cas-based genome editing holds great promise for targeting genetic disorders, including inborn errors of hepatocyte metabolism. Precise correction of disease-causing mutations in adult tissues in vivo, however, is challenging. It requires repair of Cas9-induced double-stranded DNA (dsDNA) breaks by homology-directed mechanisms, which are highly inefficient in nondividing cells. Here we corrected the disease phenotype of adult phenylalanine hydroxylase (Pah)enu2mice, a model for the human autosomal recessive liver disease phenylketonuria (PKU)1, using recently developed CRISPR–Cas-associated base editors2–4. These systems enable conversion of C·G to T·A base pairs and vice versa, independent of dsDNA break formation and homology-directed repair (HDR). We engineered and validated an intein-split base editor, which allows splitting of the fusion protein into two parts, thereby circumventing the limited cargo capacity of adeno-associated virus (AAV) vectors. Intravenous injection of AAV-base editor systems resulted in Pahenu2gene correction rates that restored physiological blood phenylalanine (l-Phe) levels below 120 µmol/l [5]. We observed mRNA correction rates up to 63%, restoration of phenylalanine hydroxylase (PAH) enzyme activity, and reversion of the light fur phenotype in Pahenu2mice. Our findings suggest that targeting genetic diseases in vivo using AAV-mediated delivery of base-editing agents is feasible, demonstrating potential for therapeutic application.

Evaluating and testing hydration status is increasingly requested by rehabilitation, sport, military and performance-related activities. Besides commonly used biochemical hydration assessment markers within blood and urine, which have their advantages and limitations in collection and evaluating hydration status, there are other potential markers present within saliva, sweat or tear. This literature review focuses on body fluids saliva, sweat and tear compared to blood and urine regarding practicality and hydration status influenced by fluid restriction and/or physical activity. The selected articles included healthy subjects, biochemical hydration assessment markers and a well-described (de)hydration procedure. The included studies (n=16) revealed that the setting and the method of collecting respectively accessing body fluids are particularly important aspects to choose the optimal hydration marker. To obtain a sample of saliva is one of the simplest ways to collect body fluids. During exercise and heat exposures, saliva composition might be an effective index but seems to be highly variable. The collection of sweat is a more extensive and time-consuming technique making it more difficult to evaluate dehydration and to make a statement about the hydration status at a particular time. The collection procedure of tear fluid is easy to access and causes very little discomfort to the subject. Tear osmolarity increases with dehydration in parallel to alterations in plasma osmolality and urine-specific gravity. But at the individual level, its sensitivity has to be further determined.

Objective.To investigate sex differences in connection with the effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with ankylosing spondylitis (AS).Methods.A total of 440 patients with AS (294 men; 146 women) initiating a first TNFi in the prospective Swiss Clinical Quality Management Cohort were included. We evaluated the proportion of patients achieving the 20% and 40% improvement in the Assessment of Spondyloarthritis international Society criteria (ASAS20 and ASAS40) as well as Ankylosing Spondylitis Disease Activity Score (ASDAS) improvement and status scores at 1 year. Patients having discontinued TNFi were considered nonresponders. Logistic regression analyses were performed to adjust for important predictors of response.Results.Compared to men, female patients had lower mean C-reactive protein levels, better spinal mobility, and more peripheral disease at the start. There was no sex disparity with regard to the ASDAS, the Bath Ankylosing Spondylitis Disease Activity and Functional indices, and the quality of life. At 1 year, 52% of women and 63% of men achieved an ASAS20 response (OR 0.63, 95% CI 0.37–1.07, p = 0.09). An inactive disease status (ASDAS < 1.3) was reached by 18% of women and 26% of men (OR 0.65, 95% CI 0.32–1.27, p = 0.22). These sex differences in response to TNFi were more pronounced in adjusted analyses (OR 0.34, 95% CI 0.16–0.71, p = 0.005 for ASAS20 and OR 0.10, 95% CI 0.03–0.31, p < 0.001 for ASDAS < 1.3) and confirmed for all the other outcomes assessed.Conclusion.In AS, fewer women respond to TNFi and women show a reduced response in comparison to men.

During pregnancy, patients with rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA) can experience active disease, which might be influenced by adjustment of treatment around conception. The aim of this study was to identify possible risk factors of disease flares during pregnancy and to evaluate the effect of treatment in pregnant patients experiencing a flare. Pregnant patients with RA and axSpA were prospectively followed before, during, and after pregnancy. Disease activity and flares of disease activity were analyzed in regard to medication. Among 136 pregnant patients, disease flares during pregnancy occurred in 29% of patients with RA and in 25% of patients with axSpA. In both diseases, active disease and tumor necrosis factor inhibitor (TNFi) discontinuation in early pregnancy were identified as risk factors for disease flares during pregnancy. Of 75 patients with RA, 15 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. After stopping TNFi, disease activity increased, which was reflected by peaking C-reactive protein levels at the first trimester. The relative risk of flare in patients with RA stopping TNFi was 3.33 (95% CI 1.8–6.1). Initiation of TNFi or glucocorticosteroid (GC) treatment in 60% of these patients resulted in disease improvement at the second and third trimesters. In comparison, patients with RA without TNFi in the preconception period, most of whom had used pregnancy-compatible antirheumatic drugs, showed mild and stable disease activity before and during pregnancy. Of 61 patients with axSpA, 24 patients were on TNFi and discontinued the treatment at the time of the positive pregnancy test. In patients with axSpA stopping TNFi, a disease aggravation at the second trimester could be observed. The relative risk of flare in this group was 3.08 (95% CI 1.2–7.9). In spite of initiated TNFi or GC treatment in 62.5% of these patients, disease activity remained elevated throughout pregnancy. Patients with axSpA without TNFi in the preconception period showed persistent high disease activity from prepregnancy until the postpartum period. On the basis of a risk-benefit analysis, to stabilize disease activity and to prevent a flare during pregnancy in patients with RA and axSpA, tailored medication including TNF inhibitors should be considered beyond conception.

Birefringence imaging, including polarization sensitive optical coherence tomography (PS-OCT), can provide valuable insight into the microscopic structure and organization of many biological tissues. In this paper, we report on a method to fabricate tissue-like birefringence phantoms for such imaging modalities. We utilize the photo-elastic effect, wherein birefringence is induced by stretching a polymer sample after heating it above its glass-transition temperature. The cooled samples stably exhibit homogeneous birefringence, and were assembled into phantoms containing multiple well-defined regions of distinct birefringence. We present planar slab phantoms for microscopy applications and cylindrical phantoms for catheter-based imaging and demonstrate quantitative analysis of the birefringence within individual regions of interest. Birefringence phantoms enable testing, validating, calibrating, and improving PS-OCT acquisition systems and reconstruction strategies.

Owing to their electromagnetic properties, tunability and biocompatibility, gold nanorods are being investigated as multifunctional probes for a range of biomedical applications. However, detection beyond the reach of traditional fluorescence and two-photon approaches and quantitation of their concentration in biological tissue remain challenging tasks in microscopy. Here, we show how the size and aspect ratio that impart gold nanorods with their plasmonic properties also make them a source of entropy. We report on how depolarization can be exploited as a strategy to visualize gold nanorod diffusion and distribution in biologically relevant scenarios ex vivo, in vitro and in vivo. We identify a deterministic relation between depolarization and nanoparticle concentration. As a result, some of the most stringent experimental conditions can be relaxed, and susceptibility to artefacts is reduced, enabling microscopic and macroscopic applications.

Großgefäßvaskulitiden umfassen gemäß Chapel-Hill-Klassifikation die Riesenzellarteriitis (RZA) und die histologisch verwandte Takayasu-Arteriitis (TAK). Den Großgefäßvaskulitiden gemeinsam ist das Fehlen von Autoantikörpern und das Vorliegen einer systemischen Entzündung bei aktiver Erkrankung. Die RZA beginnt oft perakut mit ausgeprägtem Krankheitsgefühl und temporalen Kopfschmerzen. Das initiale Hauptrisiko besteht in der Erblindung. Um dieser meist irreversiblen Komplikation vorzubeugen, muss die Abklärung unverzüglich durchgeführt und die Therapie schnellstmöglich begonnen werden. Es besteht eine enge Assoziation zwischen der RZA und der Polymyalgia rheumatica. Die TAK beginnt meist im Kindes‑/Adoleszentenalter und geht in der Regel mit einer moderaten systemischen Entzündung einher, die wenige Symptome verursacht. Die TAK wird meist erst im Stadium der fortgeschrittenen Gefäßstenose im Sinne einer belastungsinduzierten Claudicatio gestellt. According to the Chapel Hill Classification, large vessel vasculitides encompass giant cell arteritis (GCA) and the histologically related Takakaysu arteritis (TAK). The two diseases lack autoantibodies and present with a systemic inflammatory response. GCA typically shows a sudden onset with profound sickness, loss of appetite and of body weight, and temporal headache. Due to the substantial risk of sudden blindness, diagnostic work-up has to be performed immediately and treatment started without delay. A close association between polymyalgia rheumatica (PMR) and GCA is well established. Takayasu arteritis very often begins in adolescence. In contrast to GCA, the general symptoms are much less pronounced and aside from occasional carotidodynia there is a lack of diagnostic symptoms. TAK is often diagnosed in late stages due to exercise-induced claudication.

Shortly after the first demonstration of optical coherence tomography for imaging the microstructure of the human eye, work began on developing systems and catheters suitable for intravascular imaging in order to diagnose and investigate atherosclerosis and potentially to monitor therapy. This review covers the driving considerations of the clinical application and its constraints, the major engineering milestones that enabled the current, high-performance commercial imaging systems, the key studies that laid the groundwork for image interpretation, and the clinical research that traces intravascular optical coherence tomography (OCT) from early human pilot studies to current clinical trials.

Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes.

Der Beitrag zeigt auf, dass von 1952 bis 2003 in der Schweiz für hoch gebildete Frauen die höchste Scheidungswahrscheinlichkeit bestand. Von 2004 bis 2013 hingegen sind keine bildungsspezifischen Unterschiede hinsichtlich des Scheidungsverhaltens mehr festzustellen, da die Scheidungswahrscheinlichkeit vor allem für tief, aber auch für mittel gebildete Frauen zugenommen hat. Folglich ist der Zusammenhang zwischen dem Bildungsniveau der Frauen und dem Scheidungsverhalten in der Schweiz zwischen 1952 und 2013 verschwunden.