Severe COVID-19 and its cardiopulmonary effects 6 and 18 months after hospital discharge.

Introduction: SARS-CoV-2 infection affects the cardiopulmonary system in the acute as well as long-term phase. The aim of the present study was to comprehensively assess symptoms and possible long-term impairments 6 and 18 months after hospitalization for severe COVID-19 infection. Methods: This prospective registry included patients with PCR-confirmed COVID-19 infection requiring hospitalization. Follow-up approximately 6 months post discharge comprised a detailed patient history, clinical examination, transthoracic echocardiography, electrocardiogram, cardiac magnetic resonance imaging (cMRI), chest computed tomography (CT) scan, pulmonary function test (PFT), six-minute walk test (6MWT) and a laboratory panel. At the time of the second follow-up visit at 18 months, patients without pathologic findings during the first study visit were contacted by phone to inquire about the course of their symptoms. In all other patients all initial examinations were repeated. Results: Two hundred Patients, who were hospitalized for COVID-19, were contacted by phone and were recruited for the study. Due to dropouts the second study visit was performed in 170 patients. A comparison between the two study visits at 6 and 18 months post discharge showed the following results: Six months after discharge, 73% and 18 months after discharge 52% fulfilled the criteria for Long COVID with fatigue being the most common symptom (49%). Echocardiography at 6 months post discharge showed an impaired left ventricular function in 8% of which 80% returned to normal. Six months post discharge, cMRI revealed pericardial effusion in 17% which resolved in 47% of the 15 patients who underwent a control cMRI. Signs of peri- or myocarditis were present in 5% of the patients and were resolved in all 4 patients who attended control studies. At 6 months, chest CT scans identified post-infectious residues in 24%. In the 25 repeated chest CT scans 20% showed full recovery. Length of in-hospital stay was identified as a significant predictor for persisting Long COVID (95% CI: 1.005-1.12, p = 0.03). Conclusion: Comparing 6 to 18 months, the prevalence of Long COVID decreased over time, but a high symptom burden remained. Structural and functional abnormalities were less frequent than the portrayed symptoms, and it thus remains a challenge to substantiate the symptoms.

Electronically excited states of formic acid investigated by theoretical and experimental methods.

Absolute cross-section values are reported from high-resolution vacuum ultraviolet (VUV) photoabsorption measurements of gas-phase formic acid (HCOOH) in the photon energy range 4.7-10.8 eV (265-115 nm), together with quantum chemical calculations to provide vertical energies and oscillator strengths. The combination of experimental and theoretical methods has allowed a comprehensive assignment of the electronic transitions. The VUV spectrum reveals various vibronic features not previously reported in the literature, notably associated with (3pa'←10a'), (3p'a'←10a'), (3sa'←2a″) and (3pa'←2a″) Rydberg transitions. The assignment of vibrational features in the absorption bands reveal that the C=O stretching, v3'a', the H'-O-C' deformation, v5'a', the C-O stretching, v6'a', and the O=C-O' deformation, v7'a' modes are mainly active. The measured absolute photoabsorption cross sections have also been used to estimate the photolysis lifetime of HCOOH in the upper stratosphere (30-50 km), showing that solar photolysis is an important sink at altitudes above 30 km but not in the troposphere. Potential energy curves for the lowest-lying electronic excited states, as a function of the C=O coordinate, are obtained employing time dependent density functional theory (TD-DFT). These calculations have shown the relevance of internal conversion from Rydberg to valence character governing the nuclear dynamics, yielding clear evidence of the rather complex multidimensional nature of the potential energy surfaces involved.

Hormonal and metabolic responses of older adults to resistance training in normobaric hypoxia.

PURPOSE: In young adults, the hormonal responses to resistance exercise are amplified by normobaric hypoxia. Hormone concentrations and metabolism are typically dysregulated with age, yet the impact of hypoxia on these responses to resistance exercise are uncharacterised. Therefore, this study aimed to characterise the acute and chronic hormonal and metabolic responses of older adults to resistance training in normobaric hypoxia. METHODS: Adults aged 60-75 years completed 8 weeks of resistance training in either normoxia (20.9% O2; n = 10) or normobaric hypoxia (14.4% O2, n = 10) twice weekly at 70% of their predicted 1-repetition maximum. Growth hormone, glucose, lactate, insulin, homeostatic model assessment of insulin resistance (HOMA-IR), cortisol, total testosterone, adrenaline, noradrenaline and dopamine were quantified at pre- and post-training, and in the 60 min following the first training session (untrained state) and the last training session (trained state). RESULTS: Eight weeks of training in hypoxia did not affect the resting levels of the hormones or physiological factors measured. However, hypoxia significantly blunted the acute growth hormone response in the 15 min following the last training session at week eight (43.87% lower in the hypoxic group; p = 0.017). This novel and unexpected finding requires further investigation. All other hormones were unaffected acutely by hypoxia in the 60 min following the first and the last training session. CONCLUSION: Chronic resistance training in normobaric hypoxia supresses the growth hormone response to exercise in older adults. All other hormones and metabolic markers were unaffected both acutely and chronically by hypoxia.

Methodological needs in the quality and safety characterisation of nanotechnology-based health products: Priorities for method development and standardisation.

Nanotechnology-based health products are providing innovative solutions in health technologies and the pharmaceutical field, responding to unmet clinical needs. However, suitable standardised methods need to be available for quality and safety assessments of these innovative products prior to their translation into the clinic and for monitoring their performance when manufacturing processes are changed. The question arises which technological solutions are currently available within the scientific community to support the requested characterisation of nanotechnology-based products, and which methodological developments should be prioritized to support product developers in their regulatory assessment. To this end, the work presented here explored the state-of-the-art methods to identify methodological gaps associated with the preclinical characterisation of nanotechnology-based medicinal products and medical devices. The regulatory information needs, as expressed by regulatory authorities, were extracted from the guidance documents released so far for nanotechnology-based health products and mapped against available methods, thus allowing an analysis of methodological gaps and needs. In the first step, only standardised methods were considered, leading to the identification of methodological needs in five areas of characterisation, including: (i) surface properties, (ii) drug loading and release, (iii) kinetic properties in complex biological media, (iv) ADME (absorption, distribution, metabolism and excretion) parameters and (v) interaction with blood and the immune system. In the second step, a detailed gap analysis included analytical approaches in earlier stages of development, and standardised test methods from outside of the nanotechnology field that could address the identified areas of gaps. Based on this analysis, three categories of methodological needs were identified, including (i) method optimisation/adaptation to nanotechnological platforms, (ii) method validation/standardisation and (iii) method development for those areas where no technological solutions currently exist. The results of the analysis presented in this work should raise awareness within the scientific community on existing and emerging methodological needs, setting priorities for the development and standardisation of relevant analytical and toxicological methods allowing the development of a robust testing strategy for nanotechnology-based health products.

Network-driven discovery yields new insight into Shox2-dependent cardiac rhythm control.

The homeodomain transcription factor SHOX2 is involved in the development and function of the heart's primary pacemaker, the sinoatrial node (SAN), and has been associated with cardiac conduction-related diseases such as atrial fibrillation and sinus node dysfunction. To shed light on Shox2-dependent genetic processes involved in these diseases, we established a murine embryonic stem cell (ESC) cardiac differentiation model to investigate Shox2 pathways in SAN-like cardiomyocytes. Differential RNA-seq-based expression profiling of Shox2+/+ and Shox2-/- ESCs revealed 94 dysregulated transcripts in Shox2-/- ESC-derived SAN-like cells. Of these, 15 putative Shox2 target genes were selected for further validation based on comparative expression analysis with SAN- and right atria-enriched genes. Network-based analyses, integrating data from the Mouse Organogenesis Cell Atlas and the Ingenuity pathways, as well as validation in mouse and zebrafish models confirmed a regulatory role for the novel identified Shox2 target genes including Cav1, Fkbp10, Igfbp5, Mcf2l and Nr2f2. Our results indicate that genetic networks involving SHOX2 may contribute to conduction traits through the regulation of these genes.

Perfluoro effect on the electronic excited states of para-benzoquinone revealed by experiment and theory.

We report a comprehensive study on the electronic excited states of tetrafluoro-1,4-benzoquinone, through high-resolution vacuum ultraviolet photoabsorption spectroscopy and time-dependent density functional theory calculations performed within the nuclear ensemble approach. Absolute cross section values were experimentally determined in the 3.8-10.8 eV energy range. The present experimental results represent the highest resolution data yet reported for this molecule and reveal previously unresolved spectral structures. The interpretation of the results was made in close comparison with the available data for para-benzoquinone [Jones et al., J. Chem. Phys., 2017, 146, 184303]. While the dominant absorption features for both molecules arise from analogous π* ← π transitions, some remarkable differences have been identified. The perfluoro effect manifests in different ways: shifts in band positions and cross sections, appearance of features associated with excitations to σCF* orbitals, and spectrum broadening by quenching of either vibrational or Rydberg progressions. The level of agreement between experiment and theory is very satisfactory, yet that required the inclusion of nuclear quantum effects in the calculations. We have also discussed the role of temperature on the absorption spectrum, as well as the involvement of core-excited resonances in promoting dissociative electron attachment reactions in the 3-5 eV range.

Treating patients with driving phobia by virtual reality exposure therapy - a pilot study.

OBJECTIVES: Virtual reality exposure therapy (VRET) is a promising treatment for patients with fear of driving. The present pilot study is the first one focusing on behavioral effects of VRET on patients with fear of driving as measured by a post-treatment driving test in real traffic. METHODS: The therapy followed a standardized manual including psychotherapeutic and medical examination, two preparative psychotherapy sessions, five virtual reality exposure sessions, a final behavioral avoidance test (BAT) in real traffic, a closing session, and two follow-up phone assessments after six and twelve weeks. VRE was conducted in a driving simulator with a fully equipped mockup. The exposure scenarios were individually tailored to the patients' anxiety hierarchy. A total of 14 patients were treated. Parameters on the verbal, behavioral and physiological level were assessed. RESULTS: The treatment was helpful to overcome driving fear and avoidance. In the final BAT, all patients mastered driving tasks they had avoided before, 71% showed an adequate driving behavior as assessed by the driving instructor, and 93% could maintain their treatment success until the second follow-up phone call. Further analyses suggest that treatment reduces avoidance behavior as well as symptoms of posttraumatic stress disorder as measured by standardized questionnaires (Avoidance and Fusion Questionnaire: p < .10, PTSD Symptom Scale-Self Report: p < .05). CONCLUSIONS: VRET in driving simulation is very promising to treat driving fear. Further research with randomized controlled trials is needed to verify efficacy. Moreover, simulators with lower configuration stages should be tested for a broad availability in psychotherapy.

Revisiting the photoabsorption spectrum of NH3 in the 5.4-10.8 eV energy region.

We present a comprehensive revisited experimental high-resolution vacuum ultraviolet (VUV) photoabsorption spectrum of ammonia, NH3, covering for the first time the full 5.4-10.8 eV energy-range, with absolute cross sections determined. The calculations on the vertical excitation energies and oscillator strengths were performed using the equation-of-motion coupled cluster method restricted to single and double excitation levels and used to help reanalyze the observed Rydberg structures in the photoabsorption spectrum. The VUV spectrum reveals several new features that are not previously reported in the literature, with particular reference to the vibrational progressions of the (D̃1E'←X̃1A1 '), the (F̃1E'←X̃1A1 '), and the (G̃1A2 ″←X̃1A1 ') absorption bands. In addition, new Rydberg members have been identified in nda1 '←1a2 ″D̃''1A2 ″←X̃1A1 ', where n > 3 has not been reported before as well as in nde″←1a2 ″F̃1E'←X̃1A1 ' and in nsa1 '←1a2 ″G̃1A2 ″←X̃1A1 '. The measured absolute photoabsorption cross sections have been used to calculate the photolysis lifetime of ammonia in the Earth's atmosphere (0-50 km).

Biomarkers of immune capacity, infection and inflammation are associated with poor outcome and mortality after stroke - the PREDICT study.

BACKGROUND: Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome. METHODS: In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed. RESULTS: Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time. CONCLUSIONS: SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset. TRIAL REGISTRATION: www.clinicaltrials.gov, NCT01079728 , March 3, 2010.

Electronic structure and VUV photoabsorption measurements of thiophene.

The absolute photoabsorption cross sections for thiophene in the 5.0-10.7 eV range were measured using synchrotron radiation. New theoretical calculations performed at the time-dependent density functional theory level were used to qualitatively interpret the recorded photoabsorption spectrum. The calculations facilitated a re-analysis of the observed vibronic and Rydberg structures in the photoabsorption spectrum. Here a number of features have been re-assigned, while a number of other features have been assigned for the first time. This represents the most comprehensive and self-consistent assignment of the thiophene high-resolution photoabsorption spectrum to date.

Thermal effects of a novel electrosurgical device for focused preparation in breast surgery tested in a specified porcine tissue ex vivo breast model using infrared measurement.

PURPOSE: This article investigates the qualities and thermal effects of a novel electrosurgical device (PT) which has been designed by ERBE Elektromedizin GmbH, Germany, for the preparation of critical locations such as in skin-sparing or nipple-sparing techniques and compares it to a standard device (SD) in a porcine ex vivo breast model using an heat map generated by infrared thermography. METHODS: In total, 42 abdominal wall specimens of porcine tissue consisting of the skin and the underlying subcutaneous and muscle layer were alternately dissected using one of the devices and pre-settings. During the preparation with the two devices, the epicutaneous temperature was measured by an infrared camera (VarioCam, Jenoptik, Germany) and the maximum temperature as well as the slope of the temperature rise was analysed. RESULTS: The use of PT shows significantly lower values for [Formula: see text] compared to SD. This effect was independent from the chosen mode. Using the same instrument in different modes, the use of AutoCut mode showed a significant reduction of [Formula: see text] at all indicated time points (SD: p < 0.0001 and PT: p < 0.0001). In summary, the combination of AutoCut + PT showed the lowest rise in temperature, whereas the combination of DryCut + SD led to the highest rise in temperature. The temperature difference between these two settings was 13.84 °C, which means a possible temperature reduction of 67% can be achieved by the right choice of device and its tailored mode. CONCLUSIONS: The novel PT shows a significant reduction in epicutaneous temperature and a significant reduction of the slope of temperature rise most probably by a more focused application of energy compared to SD.

Body and Pectoral Fin Kinematics During Routine Yaw Turning in Bonnethead Sharks (Sphyrna tiburo).

Maneuvering is a crucial locomotor strategy among aquatic vertebrates, common in routine swimming, feeding, and escape responses. Combinations of whole body and fin movements generate an imbalance of forces resulting in deviation from an initial path. Sharks have elongate bodies that bend substantially and, in combination with pectoral fin rotation, play a role in yaw (horizontal) turning, but previous studies focus primarily on maximal turning performance rather than routine maneuvers. Routine maneuvering is largely understudied in fish swimming, despite observations that moderate maneuvering is much more common than the extreme behaviors commonly described in the literature. In this study, we target routine maneuvering in the bonnethead shark, Sphyrna tiburo. We use video reconstruction of moving morphology to describe three-dimensional pectoral fin rotation about three axes to compare to those previously described on yaw turning by the Pacific spiny dogfish. We quantify kinematic variables to understand the impacts of body and fin movements on routine turning performance. We also describe the anatomy of bonnethead pectoral fins and use muscle stimulation to confirm functional hypotheses about their role in actuating the fin. The turning performance metrics we describe for bonnethead sharks are comparable to other routine maneuvers described for the Pacific spiny dogfish and manta rays. These turns were substantially less agile and maneuverable than previously documented for other sharks, which we hypothesize results from the comparison of routine turning to maneuvering under stimulated conditions. We suggest that these results highlight the importance of considering routine maneuvering in future studies. Cinemática del Cuerpo y de las Aletas Pectorales Durante el giro en el eje Vertical en la Cabeza del Tiburón Pala (Sphyrna tiburo) (Body and Pectoral Fin Kinematics During Routine Yaw Turning in Bonnethead Sharks [Sphyrna tiburo]).

Maniobrar es una estrategia locomotora crucial entre los vertebrados acuáticos, la usan communmente al nadar, alimentarse y escapar. Las combinación de movimientos de todo el cuerpo y las aletas generan un desequilibrio de fuerzas que resulta en una desviación de una trayectoria inicial. Los tiburones tienen cuerpos alargados que se doblan sustancialmente y, en combinación con la rotación de la aleta pectoral, desempeñan un papel en el giro de horizontal de la cabez. Estudios anteriores se centraron principalmente en el rendimiento máximo de giro en lugar de las maniobras de rutina. Las maniobras de rutina son poco estudiadas en la natación de peces, a pesar de las observaciones de que las maniobras moderadas son mucho más comunes que las conductas extremas comúnmente descritas en la literatura. Utilizamos la reconstrucción con video de la morfología en movimiento para describir la rotación de la aleta pectoral tridimensional en tres ejes para compararla con los descritos anteriormente en un estudio sobre el giro de rutina realizado por el tiburón espinoso del Pacífico. Cuantificamos las variables cinemáticas para comprender los impactos de los movimientos del cuerpo y las aletas en el rendimiento de giro de rutina. También describimos la anatomía de las aletas pectorales tiburón cabeza de pala y utilizamos la estimulación muscular para confirmar las hipótesis funcionales sobre su papel en la actuación de la aleta. Las métricas de rendimiento de giro que describimos para los tiburones cabeza de pala son comparables a otras maniobras de rutina descritas para el perrito espinoso del Pacífico y las mantas rayas. Estos giros fueron sustancialmente menos ágiles y maniobrables de lo que se documentó anteriormente para otros tiburones, lo cual, según nuestra hipótesis, resulta de la comparación del giro rutinario a la maniobra en condiciones estimuladas. Sugerimos que estos resultados resaltan la importancia de considerar maniobras rutinarias en estudios futuros. Translated to Spanish by J. Heras (herasj01@gmail.com).

Cinemática do Corpo e da Nadadeira Peitoral Durante a Rotação de Rotina em Tubarões Cabeça-de-Boné (Sphyrna tiburo) (Body and Pectoral Fin Kinematics During Routine Yaw Turning in Bonnethead Sharks [Sphyrna tiburo]) A manobra é uma estratégia locomotora crucial entre os vertebrados aquáticos, comum na natação rotineira, na alimentação e na resposta à ameaças. Combinações de movimentos do corpo e das nadadeiras geram um desequilíbrio de forças resultando em desvio do caminho inicial. Os tubarões têm corpos alongados que se dobram substancialmente e, em combinação com a rotação da nadadeira peitoral, desempenham um papel importante no giro horizontal (guinada), porém, estudos anteriores focaram principalmente no desempenho de giro máximo em vez de manobras rotineiras. A manobra rotineira é pouco estudada na natação de peixes, apesar das observações de que manobras moderadas são muito mais comuns do que os comportamentos extremos comumente reportados em literatura. Usamos a reconstrução de vídeo de morfologia móvel para descrever a rotação tridimensional da nadadeira peitoral para comparar com aqueles previamente descritos em um estudo sobre rotação rotineira pelo tubarão galhudo do Pacífico. Quantificamos as variáveis cinemáticas para entender os impactos dos movimentos do corpo e das nadadeiras no desempenho rotineiro de giro. Descrevemos também a anatomia das nadadeiras peitorais do tubarão martelo e utilizamos a estimulação muscular para confirmar hipóteses funcionais sobre o seu papel na movimentação da nadadeira. As métricas de desempenho de giro que descrevemos para os tubarões martelo são comparáveis a outras manobras de rotina descritas para o tubarão galhudo do Pacífico e raias-manta. Esses turnos foram substancialmente menos ágeis e manobráveis do que o anteriormente documentado para outros tubarões, dados dos quais nós criamos a hipótese com os resultados da comparação da rotação de rotina para manobrar sob condições estimuladas. Sugerimos que esses resultados ressaltem a importância de considerar manobras rotineiras em estudos futuros. Translated to Portuguese by Diego Vaz (dbistonvaz@vims.edu).

Probing the Lowest-Lying Electronic States of Acrylic Acid by Experimental and Theoretical Methods.

We report a combined experimental and theoretical study of the electronic state spectroscopy of acrylic acid (C3H4O2) in the gas phase, by high-resolution vacuum ultraviolet (VUV) photoabsorption measurements in the 4.0-10.8 eV energy range, together with ab initio calculations (vertical energies and oscillator strengths), which were used in the assignment of the valence transitions. We also discuss the Rydberg transitions for this molecular target, obtained using the experimental ionization energies available in the literature. The experimental spectrum presented in this paper represents the highest resolution data yet reported for acrylic acid and reveals new features not previously reported in the literature. The dominant transitions have been assigned to (π*(4a″) ← π(3a″)) and (π*(4a″) ← π(2a″)), the latter exhibiting excitation of the ν5'( a') C = O stretching mode with mean energy of 0.155 eV. The measured absolute photoabsorption cross sections have been used to calculate the photolysis lifetime of acrylic acid in the upper stratosphere (20-50 km).

Isolated impact of liver herniation on outcome in fetuses with congenital diaphragmatic hernia - A matched-pair analysis based on fetal MRI relative lung volume.

PURPOSE: To evaluate liver-herniation as individual parameter on outcome in children with congenital diaphragmatic hernia. MATERIALS AND METHODS: In a retrospective matched-pair analysis based on observed to expected fetal lung volume (o/e FLV), birth weight, gestational age at time-point of examination, status of tracheal occlusion therapy and side of the defect the individual impact of liver-herniation on survival, need for extracorporeal membrane oxygenation (ECMO) therapy and chronic lung disease (CLD) was investigated. In total 61 pairs (122 patients) were included. Fisher's exact test was used to evaluate influence of liver-herniation and a p-value of <0.05 was defined as statistically significant. The study was approved by the local review board. RESULTS: Children with liver-herniation have lower survival rates (78.7% vs. 95.1%; p = 0.0073), need ECMO-therapy more often (41.0% vs. 16.4%; p = 0.0027) and are more likely to develop CLD (71.7% vs. 37.9%; p = 0.0004) than their corresponding matched-pair without liver-herniation. CONCLUSION: Liver-herniation itself and not further lung-volume restriction due to liver-herniation is responsible for poor outcome in CDH.

Brain inflammasomes in stroke and depressive disorders: Regulation by oestrogen.

Neuroinflammation is a devastating pathophysiological process that results in brain damage and neuronal death. Pathogens, cell fragments and cellular dysfunction trigger inflammatory responses. Irrespective of the cause, inflammasomes are key intracellular multiprotein signalling platforms that sense neuropathological conditions. The activation of inflammasomes leads to the auto-proteolytic cleavage of caspase-1, resulting in the proteolysis of the pro-inflammatory cytokines interleukin (IL)1ß and IL18 into their bioactive forms. It also initiates pyroptosis, a type of cell death. The two cytokines contribute to the pathogenesis in acute and chronic brain diseases and also play a central role in human aging and psychiatric disorders. Sex steroids, in particular oestrogens, are well-described neuroprotective agents in the central nervous system. Oestrogens improve the functional outcome after ischaemia and traumatic brain injury, reduce neuronal death in Parkinson's and Alzheimer's disease, as well as in amyotrophic lateral sclerosis, attenuate glutamate excitotoxicity and the formation of radical oxygen species, and lessen the spread of oedema after damage. Moreover, oestrogens alleviate menopause-related depressive symptoms and have a positive influence on depressive disorders probably by influencing growth factor production and serotonergic brain circuits. Recent evidence also suggests that inflammasome signalling affects anxiety- and depressive-like behaviour and that oestrogen ameliorates depression-like behaviour through the suppression of inflammasomes. In the present review, we highlight the most recent findings demonstrating that oestrogens selectively suppress the activation of the neuroinflammatory cascade in the brain in acute and chronic brain disease models. Furthermore, we aim to describe putative regulatory signalling pathways involved in the control of inflammasomes. Finally, we consider that psychiatric disorders such as depression also contain an inflammatory component that could be modulated by oestrogen.

Comparison of blood pressure monitoring by applanation tonometry and invasively assessed blood pressure in cardiological patients.

The aim of this study was to evaluate the accuracy and precision of non-invasive continuous blood pressure measurement by applanation tonometry (AT) in awake or anaesthetised cardiological intensive care patients. Patients suffering from highly impaired left ventricular function atrial fibrillation or severe aortic valve stenosis were included into the study. Arterial blood pressure was recorded by applanation tonometry (T-Line 400, Tensys Medical®, USA) and an arterial line in awake or anaesthetised patients. Discrepancies in mean (MAP), systolic (SAP), and diastolic (DAP) arterial pressure between the two methods were assessed as bias, limits of agreement and percentage error respectively. In 31 patients a total of 27,900 measurements were analyzed. The concordance correlation coefficient was 0.23, 0.45 and 0.06 for MAP, SAP and DAP, respectively. For all patients bias for MAPAT compared to MAPAL was 14.96 mmHg (SAPAT 4.51 mmHg; DAPAT 19.12 mmHg) with limits of agreement for MAPAT of 46.25 and - 16.33 mm Hg (SAPAT 48.00 and - 38.98 mmHg; DAPAT 50.12 and - 11.89 mmHg). Percentage error for MAPAT was 56.8% (42.7% for SAPAT; 75.2% for DAPAT). We conclude that the AT method is not reliable in ICU patients with severe cardiac comorbidities.

MRI-Based Estimation of Scalar Cochlear-Implant Electrode Position.

The position of the cochlear-implant electrode is important to audiological outcomes after cochlear implantation. The common technique to evaluate the intracochlear electrode's position involves the use of ionized radiation in MSCT, DVT, or flat-panel tomography (FPT). Recent advances in knowledge regarding the handling of MRI artifacts in cochlear implantees indicate that estimating the intracochlear electrode's position with an MRI could be possible. This study's aim was to evaluate the ipsilaterally position of electrodes using MRI at 1.5 T. In a retrospective study of 10 implantees with postoperative need for MRI scanning, we evaluated the intrascalar electrode's position using a T2-weighted sequence at 1.5 T. We compared the resulting estimate of the intracochlear position with the estimates from the postoperative FPT scan and the intraoperative NRT ratio. For each ear, the MRI-estimated scalar position corresponded with the estimated positions from the FPT and NRT ratio. For eight ears, a scala tympani's position was observed in the MRI. In one case, an electrode scalar translocation was found. In one case, the scala vestibuli's position was observed. Thus, MRI-based estimation of the scalar position of a cochlear-implant electrode is possible. Limitations to this method include implant-specific magnet and fixation configurations, which can cause complications.

Orbitofrontal structural markers of negative affect in alcohol dependence and their associations with heavy relapse-risk at 6 months post-treatment.

BACKGROUND: Alcohol relapse is often occurring to regulate negative affect during withdrawal. On the neurobiological level, alcoholism is associated with gray matter (GM) abnormalities in regions that regulate emotional experience such as the orbitofrontal cortex (OFC). However, no study to our knowledge has investigated the neurobiological unpinning of affect in alcoholism at early withdrawal and the associations of OFC volume with long-term relapse risk. METHODS: One hundred and eighty-two participants were included, 95 recently detoxified alcohol dependent patients (ADP) and 87 healthy controls (HC). We measured affective states using the positive and negative affect schedule (PANAS). We collected T1-weighted brain structural images and performed Voxel-based morphometry (VBM). RESULTS: Findings revealed GM volume decrease in alcoholics in the prefrontal cortex (including medial OFC), anterior cingulate gyrus, and insula. GM volume in the medial OFC was positively associated with NA in the ADP group. Cox regression analysis predicted that risk to heavy relapse at 6 months increases with decreased GM volume in the medial OFC. CONCLUSIONS: Negative affect during alcohol withdrawal was positively associated with OFC volume. What is more, increased GM volume in the OFC also moderated risk to heavy relapse at 6 months. Reduced GM in the OFC poses as risk to recovery from alcohol dependence and provides valuable insights into transient negative affect states during withdrawal that can trigger relapse. Implications exist for therapeutic interventions signifying the OFC as a neurobiological marker to relapse and could explain the inability of ADP to regulate internal negative affective states.

The effect of pneumococcal conjugate vaccines on incidence and microbiology associated with complicated acute otitis media.

OBJECTIVES: The objectives of this study were to investigate the incidence of complicated acute otitis media (cAOM) as well as the associated microbiology before and after introduction of the 7- and 13-valent pneumococcal conjugate vaccines (PCV-7 and -13), respectively. CAOM comprises "heavy" AOM (AOM demanding hospitalization), mastodismus (M) and acute mastoiditis (AM). METHODS: A retrospective cohort study of the incidence and microbiology associated with cAOM during the non-PCV era, the PCV-7 and 13 eras, respectively. Clinical and microbiological data were prospectively registered in a local database. The incidences of cAOM as well as the distribution of various bacterial strains in the three eras were compared. RESULTS: A total of 246 cases of cAOM (125 in the pre-vaccine period (2001-2006), 50 in the PCV-7 period (2007-2010) and 71 in the PCV-13 period (2011-2015)) were identified. The incidence of hAOM decreased by 62% in the PCV7-era but increased to almost pre-vaccine levels in the PCV-13 era. In the M + AM group, a decrease by almost 21% in the PCV7-era was found compared to the pre vaccine era, whereas the decrease was only 12% in the PCV13-era. The three most common findings in both hAOM and M + AM were Streptococcus pneumonia (SP), group A streptococcus (GAS) and "no growth". In the hAOM group, SP decreased from 38% in the pre-vaccine era to 31% in the PCV7-era and further to 16% in the PCV13-era. GAS decreased from 17% in the pre-vaccine era to 0% in the PCV7-era and 16% in the PCV13-era. The percentage of "no growth" increased from 12% to 38% and 44%, respectively. In the M + AM group, SP decreased to 10% in the PCV13-era compared with 44% in the pre-vaccine era and 41% in the PCV7-era. An increase in GAS from 15% in the pre-vaccine era and PCV7-era to 30% in the PCV13-era was observed. The "no growth" percentage increased from 13% in the pre-vaccine era to 26% in the PCV7-era and 33% in the PCV13-era. CONCLUSION: Introduction of PCV7 and PCV13 has been associated with an overall reduction of cAOM in Central Region Denmark. Pneumococci were still one of the two most common bacteria species related to cAOM though a decrease in pneumococci positive cases was observed. We found an increase in M + AM induced by GAS and a relatively large increase in "no growth", which might be caused by a more aggressive pre-hospital approach to treatment with antibiotics. Consequently, it is not evident whether the reduction of incidences is caused by the vaccines or a more aggressive antimicrobial attitude to manage AOM. The shift to GAS from SP is worrisome, and therefore continuous surveillance of the microbiology associated with AOM is warranted.