Outcomes of patients with ST-segment myocardial infarction admitted during the COVID-19 pandemic : A prospective, observational study from a tertiary care center in Germany.

BACKGROUND: Since the beginning of the SARS-CoV­2 outbreak, healthcare professionals reported that patients admitted with ST-segment myocardial infarction (STEMI) were in worse condition compared to STEMI patients admitted before the outbreak. However, data on their outcomes are sparse. METHODS: We conducted a prospective, observational, cohort study of STEMI patients admitted during the COVID-19 pandemic from March 21, 2020 to July 31, 2020 (COVID-19 group). Clinical outcomes, 30-day mortality, and reasons potentially related to a delay in patient presentation were assessed and compared with STEMI patients admitted between November 1, 2019 and March 20, 2020 (pre-COVID-19 group). RESULTS: A total of 124 patients were enrolled, comprising 57 patients in the pre-COVID-19 group and 67 patients in the COVID-19 group. Significantly more patients in the COVID-19 group had a time to first medical contact of greater than 24 h. Additionally, those admitted during the pandemic had a significantly lower left ventricular ejection fraction (LVEF), worse thrombolysis in myocardial infarction (TIMI) flow, received circulatory support significantly more often, and had a significantly higher 30-day mortality. Furthermore, significantly more patients stated that "information by the media" made them hesitate to contact the emergency medical services as soon as possible. CONCLUSION: Here, we show that STEMI patients admitted during the COVID-19 pandemic had significantly prolonged times to first medical contact, were in worse condition at admission, and had an increased 30-day mortality. Additionally, we found that "information by the media" made patients during COVID-19 hesitate to contact the emergency medical services. Consequently, public health strategies have to be developed to avoid potential excess mortality of STEMI patients during the pandemic.

Characterization of the Scattering and Absorption of Colored Zein Colloids in Optically Dense Dispersions.

In this research, we model the color of optically dense colloidal dispersions of dyed and undyed zein particles using results from multiple light scattering theory. These particles, as well as monodisperse silica colloids, were synthesized and characterized to obtain particle properties such as particle size, particle size distribution, refractive index, and absorption spectrum of the dye. This information was used to model the diffuse transmission of concentrated particle dispersions, which was measured using a specially designed variable path length quartz glass cuvette. For the nonabsorbing silica dispersions, a transport mean-free path throughout the visible range was obtained. Results showed a difference of less than 5% from the values calculated with a multiple scattering model using the single-particle properties as an input. For undyed zein particles, which are off-white, the deviation between the model and the experiment was about 30% because of slight absorption at wavelengths below 550 nm but <7% at higher wavelengths. From these results, it was concluded that the model correctly describes diffuse transmission and that the measurements are sensitive to absorption. Finally, this method was applied to dispersions of dyed zein particles. Here, the transport mean-free path was first determined for wavelengths at which there is no absorption, which agreed with the theory better than 4%. The modeled transport mean-free path was then used to extract the reciprocal absorption mean-free path in the remaining parts of the visible spectrum, and a reasonable agreement with the absorption spectrum of the dye solution was obtained.

Fast-track versus long-term hospitalizations for patients with non-disabling acute ischaemic stroke.

BACKGROUND AND PURPOSE: The aim was to assess the feasibility and safety of fast-track hospitalizations in a selected cohort of patients with stroke. METHODS: Patients hospitalized at the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischaemic stroke confirmed on magnetic resonance diffusion-weighted imaging were included. Neurological deficits of the included patients were non-disabling, i.e. not interfering with activities of daily living and compatible with a direct discharge home. Patients with premorbid disability were excluded. All patients were admitted to the Stroke Center for ≥24 h. Two study groups were compared - fast-track hospitalizations (≤72 h) and long-term hospitalizations (>72 h). The primary end-point was a composite of any unplanned rehospitalization for any reason within 3 months since hospital discharge and a modified Rankin Scale 3-6 at 3 months. Adjustment for confounders was done using the inverse probability of treatment weights (IPTW). RESULTS: Amongst the 521 patients who met the inclusion criteria, fast-track hospitalizations were performed in 79 patients (15%). In the fast-track group, seven patients (8.9%) met the primary end-point, compared to 37 (8.4%) in the long-term group [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.42-2.34, P = 0.88]. After weighting for IPTW, the odds of the primary end-point remained similar between the two arms (ORIPTW 1.27, 95% CI 0.51-3.16, P = 0.61). The costs of fast-track hospitalizations were lower, on average, by $4994. CONCLUSIONS: Fast-track hospitalizations including a full workup proved to be feasible, showed no increased risk and were less expensive than long-term hospitalizations.

White zein colloidal particles: synthesis and characterization of their optical properties on the single particle level and in concentrated suspensions.

Growing interest in using natural, biodegradable ingredients for food products leads to an increase in research for alternative sources of functional ingredients. One alternative is zein, a water-insoluble protein from corn. Here, a method to investigate the optical properties of white zein colloidal particles is presented in both diluted and concentrated suspensions. The particles are synthesized, after purification of zein, by anti-solvent precipitation. Mean particle diameters ranged from 35 to 135 nm based on dynamic light scattering. The value of these particles as white colorant is examined by measuring their optical properties. Dilute suspensions are prepared to measure the extinction cross section of individual particles and this was combined with Mie theory to determine a refractive index (RI) of 1.49 ± 0.01 for zein particles dispersed in water. This value is used to further model the optical properties of concentrated suspensions. To obtain full opacity of the suspension, comparable to 0.1-0.2 wt% suspensions of TiO2, concentrations of 2 to 3.3 wt% of zein particles are sufficient. The optimal size for maximal scattering efficiency is explored by modeling dilute and concentrated samples with RI's matching those of zein and TiO2 particles in water. The transport mean free path of light was determined experimentally and theoretically and the agreement between the transport mean free path calculated from the model and the measured value is better than 30%. Such particles have the potential to be an all-natural edible alternative for TiO2 as white colorant in wet food products.

Determination of the positions and orientations of concentrated rod-like colloids from 3D microscopy data.

Confocal microscopy in combination with real-space particle tracking has proven to be a powerful tool in scientific fields such as soft matter physics, materials science and cell biology. However, 3D tracking of anisotropic particles in concentrated phases remains not as optimized compared to algorithms for spherical particles. To address this problem, we developed a new particle-fitting algorithm that can extract the positions and orientations of fluorescent rod-like particles from three dimensional confocal microscopy data stacks. The algorithm is tailored to work even when the fluorescent signals of the particles overlap considerably and a threshold method and subsequent clusters analysis alone do not suffice. We demonstrate that our algorithm correctly identifies all five coordinates of uniaxial particles in both a concentrated disordered phase and a liquid-crystalline smectic-B phase. Apart from confocal microscopy images, we also demonstrate that the algorithm can be used to identify nanorods in 3D electron tomography reconstructions. Lastly, we determined the accuracy of the algorithm using both simulated and experimental confocal microscopy data-stacks of diffusing silica rods in a dilute suspension. This novel particle-fitting algorithm allows for the study of structure and dynamics in both dilute and dense liquid-crystalline phases (such as nematic, smectic and crystalline phases) as well as the study of the glass transition of rod-like particles in three dimensions on the single particle level.

LSD1 controls metastasis of androgen-independent prostate cancer cells through PXN and LPAR6.

Lysine-specific demethylase 1 (LSD1) was shown to control gene expression and cell proliferation of androgen-dependent prostate cancer (PCa) cells, whereas the role of LSD1 in androgen-independent metastatic prostate cancer remains elusive. Here, we show that depletion of LSD1 leads to increased migration and invasion of androgen-independent PCa cells. Transcriptome and cistrome analyses reveal that LSD1 regulates expression of lysophosphatidic acid receptor 6 (LPAR6) and cytoskeletal genes including the focal adhesion adaptor protein paxillin (PXN). Enhanced LPAR6 signalling upon LSD1 depletion promotes migration with concomitant phosphorylation of PXN. In mice LPAR6 overexpression enhances, whereas knockdown of LPAR6 abolishes metastasis of androgen-independent PCa cells. Taken together, we uncover a novel mechanism of how LSD1 controls metastasis and identify LPAR6 as a promising therapeutic target to treat metastatic prostate cancer.

Epigenetic reprogramming of cortical neurons through alteration of dopaminergic circuits.

Alterations of the dopaminergic system are associated with the cognitive and functional dysfunctions that characterize complex neuropsychiatric disorders. We modeled a dysfunctional dopaminergic system using mice with targeted ablation of dopamine (DA) D2 autoreceptors in mesencephalic dopaminergic neurons. Loss of D2 autoreceptors abolishes D2-mediated control of DA synthesis and release. Here, we show that this mutation leads to a profound alteration of the genomic landscape of neurons receiving dopaminergic afferents at distal sites, specifically in the prefrontal cortex. Indeed, we observed a remarkable downregulation of gene expression in this area of ~2000 genes, which involves a widespread increase in the histone repressive mark H3K9me2/3. This reprogramming process is coupled to psychotic-like behaviors in the mutant mice. Importantly, chronic treatment with a DA agonist can revert the genomic phenotype. Thus, cortical neurons undergo a profound epigenetic reprogramming in response to dysfunctional D2 autoreceptor signaling leading to altered DA levels, a process that may underlie a number of neuropsychiatric disorders.

Prevalence of risk factors for liver disease in a random population sample in southern Germany.

BACKGROUND: Chronic liver disease leads to fibrosis and cirrhosis of the liver. This may, in turn, result in chronic liver failure or the development of hepatocellular carcinoma (HCC). Main risk factors for chronic liver disease are viral hepatitis and alcoholism. The present study assessed a randomly selected population in southern Germany for risk factors for chronic liver disease such as fatty liver disease, viral hepatis infection and life-style factors. In addition, the potential association with elevated liver enzymes was investigated. METHODS: A total of 2256 subjects (1182 females, 1074 males), aged 18 - 65 years, participated in the study. Each subject underwent a standardized ultrasound examination, and anthropometric and biochemical assessments. Test subjects were randomly selected from the general population of a town in southwestern Germany. Data were acquired from November to December 2002 without further follow-up. RESULTS: Several factors were found to be associated with chronic liver disease in the study population. Alcohol consumption >20 g/d was seen in 18.1% (n=409). Metabolic syndrome was diagnosed in 5.9% (n=132). The number of people with a BMI greater than 25 kg/m(2) was 45.1% (n=1017). The prevalence of subjects with chronic hepatitis B was 0.7% (n=15), that of anti-HCV positive patients, 0.6%(n=15). Elevated gGT was seen in 10.4% (n=14) of the patients. Prevalence of hepatic steatosis was 25.0% (n=564). CONCLUSIONS: Many cases of chronic liver disease could be prevented by healthy nutrition, optimized medical treatment of associated disorders, and prevention strategies such as routine vaccination, in particular, against hepatitis B virus (HBV).

Associations of fatty liver disease and other factors affecting serum SHBG concentrations: a population based study on 1657 subjects.

Sex hormone binding globulin (SHBG) is a glycoprotein expressed predominantly in the hepatocytes. It regulates the transport of sex steroid hormones in the blood stream to their target tissues. The expression of the SHBG gene is subject to multifactorial regulation including hormonal, metabolic, and nutritional aspects. Against this background, we investigated the effect of fatty liver and metabolic syndrome, together with other parameters, on serum SHBG concentrations in a population-based cohort in Germany. This cross-sectional study included 870 women and 787 men (average age 42.3±12.8 years), who underwent ultrasound screening for fatty liver in addition to providing a complete medical history and undergoing physical and laboratory examination. Fatty liver was diagnosed on ultrasound criteria in 159 women (18.3%) and 287 men (36.5%). Fatty liver was shown to exert a significant influence on serum SHBG concentrations in men and in premenopausal women. Men with grade 1 fatty liver had a 1.96-fold increased risk (95%-confidence interval=1.28-3.02; p=0.0022) and postmenopausal women with grade 1 fatty liver a 2.4-fold risk (95%-confidence interval=1.11-5.27; p=0.0267) for low SHBG concentrations. Among metabolic parameters, HDL-C represented as affecting factor in men (p=0.0058) and premenopausal women (p=0.0002), while cholesterol only showed an association in premenopausal women (p=0.0439) and triglyceride in postmenopausal women (p=0.0436). No association of concentrations of SHBG and metabolic syndrome was observed. Age, BMI and waist-to-hip ratio also influence the SHBG concentration. Based on these findings, we conclude that fat accumulation in the liver influences SHBG concentrations in men and premenopausal women.

Study of colloids transport during two-phase flow using a novel polydimethylsiloxane micro-model.

As a representation of a porous medium, a closed micro-fluidic device made of polydimethylsiloxane (PDMS), with uniform wettability and stable hydrophobic properties, was designed and fabricated. A flow network, with a mean pore size of 30 µm, was formed in a PDMS slab, covering an area of 1 mm × 10 mm. The PDMS slab was covered and bonded with a 120-µm-thick glass plate to seal the model. The glass plate was first spin-coated with a thin layer, roughly 10 µm, of PDMS. The micro-model was treated with silane in order to make it uniformly and stably hydrophobic. Fluorescent particles of 300 µm in diameter were used as colloids. It is known that more removal of colloids occurs under unsaturated conditions, compared to saturated flow in soil. At the same time, the change of saturation has been observed to cause remobilization of attached colloids. The mechanisms for these phenomena are not well understood. This is the first time that a closed micro-model, made of PDMS with uniform and stable wettability, has been used in combination with confocal microscopy to study colloid transport under transient two-phase flow conditions. With confocal microscopy, the movement of fluorescent particles and flow of two liquids within the pores can be studied. One can focus at different depths within the pores and thus determine where the particles exactly are. Thus, remobilization of attached colloids by moving fluid-fluid interfaces was visualized. In order to allow for the deposition and subsequent remobilization of colloids during two-phase flow, three micro-channels for the injection of liquids with and without colloids were constructed. An outlet channel was designed where effluent concentration breakthrough curves can be quantified by measuring the fluorescence intensity. A peak concentration also indicated in the breakthrough curve with the drainage event. The acquired images and breakthrough curve successfully confirmed the utility of the combination of such a PDMS micro-model and confocal microscopy for the visualization of colloid transport in a flow network filled with two fluids, and in particular, the colloids retention, mobilization, and transport under transient flow conditions.

Fatal outcome after heart transplantation caused by Aspergillus lentulus.

Opportunistic invasive fungal infections are a major cause of mortality in immunocompromised patients. Early diagnosis of invasive aspergillosis and proper identification of the causative agent is crucial for guidance of therapy. Accurate differentiation of Aspergillus lentulus, a filamentous fungus often misidentified as atypical Aspergillus fumigatus, is of concern as multiple antifungal drugs show a reduced susceptibility. This is the first report, to our knowledge, of a proven pulmonary invasive fungal infection caused by A. lentulus after heart transplantation.

MESNA (sodium 2-mercaptoethanesulfonate) for prevention of contrast medium-induced nephrotoxicity - controlled trial.

BACKGROUND: The purpose of this study was to examine the efficacy of sodium 2-mercaptoethanesulfonate (MESNA), a reactive oxygen scavenger, in at-risk patients given radiographic contrast agents. Contrast-induced nephropathy (CIN) is a common complication of radiographic procedures; reactive oxygen species (ROS) could play a key role. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial in 100 patients with stable serum creatinine levels ≥ 150 µmol/l. They received an infusion of either 1,600 mg of MESNA (n = 51) or placebo (n = 49) plus 0.9% saline prior to and after contrast administration. CIN was defined as a ≥ 25% increase in serum creatinine after 48 h compared to baseline. RESULTS: CIN occurred in 7 patients in the placebo group and none in the MESNA group (p = 0.005). The adjusted odds ratio for CIN was 0.17 (95% confidence interval 0.03 - 0.80, p = 0.026) in the MESNA group compared to the placebo group. Cystatin C concentrations decreased slightly in the MESNA group but increased in the control group (p < 0.05). CONCLUSION: MESNA plus volume expansion before and during contrast exposure was effective in this single-center study for preventing CIN compared to volume expansion alone.

Survey of aspergillosis in non-neutropenic patients in Swiss teaching hospitals.

Invasive aspergillosis (IA) is a live-threatening opportunistic infection that is best described in haematological patients with prolonged neutropenia or graft-versus-host disease. Data on IA in non-neutropenic patients are limited. The aim of this study was to establish the incidence, disease manifestations and outcome of IA in non-neutropenic patients diagnosed in five Swiss university hospitals during a 2-year period. Case identification was based on a comprehensive screening of hospital records. All cases of proven and probable IA were retrospectively analysed. Sixty-seven patients were analysed (median age 60 years; 76% male). Sixty-three per cent of cases were invasive pulmonary aspergillosis (IPA), and 17% of these were disseminated aspergillosis. The incidence of IPA was 1.2/10 000 admissions. Six of ten cases of extrapulmonary IA affected the brain. There were six cases of invasive rhinosinusitis, six cases of chronic pulmonary aspergillosis, and cases three of subacute pulmonary aspergillosis. The most frequent underlying condition of IA was corticosteroid treatment (57%), followed by chronic lung disease (48%), and intensive-care unit stays (43%). In 38% of patients with IPA, the diagnosis was established at autopsy. Old age was the only risk factor for post-mortem diagnosis, whereas previous solid organ transplantation and chronic lung disease were associated with lower odds of post-mortem diagnosis. The mortality rate was 57%.

Validation of the digital pressure application measurement (PAM) device for detection of primary mechanical hyperalgesia in rat and mouse antigen-induced knee joint arthritis.

Several tests have been developed to obtain mechanical nociceptive withdrawal thresholds for arthritis-associated pain research in preclinical animal models, which are routinely used for testing the efficacy of antinociceptive pharmaceutical candidates. Here, we aimed to validate a recently introduced and commercially available digital pressure application measurement (PAM) device for the detection of primary mechanical hyperalgesia in a model of antigen-induced knee joint arthritis (AIA) in rats and mice. Two particular advantages of the PAM device are visual feedback control of the force increase rate and the detection of the complete threshold range. Using PAM, we were able to quantify mechanical thresholds at the knee joint in rats and mice (400 and 350 g, respectively) before and during the time course of AIA (approximately 100 g for rats and mice in the acute phase). Inter-observer agreement was generally higher when using PAM instead of an analog dynamometer. In conclusion, the digital PAM device is a suitable apparatus to detect primary mechanical hyperalgesia in experimental knee joint arthritis in rats and mice. The use of this device allows visual feedback control of the stimulus rate, thus minimizing the chances of confounding factors arising from differences in ramp speed.

Air suctioning during colon biopsy forceps removal reduces bacterial air contamination in the endoscopy suite.

BACKGROUND AND STUDY AIMS: Bacterial contamination of endoscopy suites is of concern; however studies evaluating bacterial aerosols are lacking. We aimed to determine the effectiveness of air suctioning during removal of biopsy forceps in reducing bacterial air contamination. PATIENTS AND METHODS: This was a prospective single-blinded trial involving 50 patients who were undergoing elective nontherapeutic colonoscopy. During colonoscopy, endoscopists removed the biopsy forceps first without and then with suctioning following contact with the sigmoid mucosa. A total of 50 L of air was collected continuously for 30 seconds at 30-cm distance from the biopsy channel valve of the colonoscope, with time starting at forceps removal. Airborne bacteria were collected by an impactor air sampler (MAS-100). Standard Petri dishes with CNA blood agar were used to culture Gram-positive bacteria. Main outcome measure was the bacterial load in endoscopy room air. RESULTS: At the beginning and end of the daily colonoscopy program, the median (and interquartile [IQR] range) bioaerosol burden was 4 colony forming units (CFU)/m (3) (IQR 3 - 6) and 16 CFU/m (3) (IQR 13 - 18), respectively. Air suctioning during removal of the biopsy forceps reduced the bioaerosol burden from a median of 14 CFU/m (3) (IQR 11 - 29) to a median of 7 CFU/m (3) (IQR 4 - 16) ( P = 0.0001). Predominantly enterococci were identified on the agar plates. CONCLUSION: The bacterial aerosol burden during handling of biopsy forceps can be reduced by applying air suction while removing the forceps. This simple method may reduce transmission of infectious agents during gastrointestinal endoscopies.

Brain aging in the oldest-old.

Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also significantly lower than those reported in younger AD cases. Overall, there is evidence that pathological substrates of cognitive deterioration in the oldest-old are different from those observed in the younger-old. Microvascular parameters such as mean capillary diameters may be key factors to consider for the prediction of cognitive decline in the oldest-old. Neuropathological particularities of the oldest-old may be related to "longevity-enabling" genes although little or nothing is known in this promising field of future research.

High-resolution soft X-ray beamline ADRESS at the Swiss Light Source for resonant inelastic X-ray scattering and angle-resolved photoelectron spectroscopies.

The concepts and technical realisation of the high-resolution soft X-ray beamline ADRESS operating in the energy range from 300 to 1600 eV and intended for resonant inelastic X-ray scattering (RIXS) and angle-resolved photoelectron spectroscopy (ARPES) are described. The photon source is an undulator of novel fixed-gap design where longitudinal movement of permanent magnetic arrays controls not only the light polarization (including circular and 0-180 degrees rotatable linear polarizations) but also the energy without changing the gap. The beamline optics is based on the well established scheme of plane-grating monochromator operating in collimated light. The ultimate resolving power E/DeltaE is above 33000 at 1 keV photon energy. The choice of blazed versus lamellar gratings and optimization of their profile parameters is described. Owing to glancing angles on the mirrors as well as optimized groove densities and profiles of the gratings, the beamline is capable of delivering high photon flux up to 1 x 10(13) photons s(-1) (0.01% BW)(-1) at 1 keV. Ellipsoidal refocusing optics used for the RIXS endstation demagnifies the vertical spot size down to 4 microm, which allows slitless operation and thus maximal transmission of the high-resolution RIXS spectrometer delivering E/DeltaE > 11000 at 1 keV photon energy. Apart from the beamline optics, an overview of the control system is given, the diagnostics and software tools are described, and strategies used for the optical alignment are discussed. An introduction to the concepts and instrumental realisation of the ARPES and RIXS endstations is given.