Occurence of Post-Traumatic Stress Symptoms, Anxiety and Depression in the Acute Phase of Transient Ischemic Attack and Stroke

Rates of post-traumatic stress symptoms, anxiety and depression are increased in patients having experienced a transient ischemic attack (TIA) or stroke several months ago. However, data of psychiatric symptoms in the acute phase within the first days after ictus are lacking. In 20 patients with stroke and 33 patients with TIA we assessed disease severity by means of the NIHSS, levels of depression and anxiety by HADS, PTSD-like symptoms by PC-PTSD, quality of life (HrQoL) by SF-12, and coping style by brief COPE Inventory within the first 5 days after ictus. NIHSS on admission was lower in patients with TIA (0 ± 1) than in patients with stroke (3 ± 2, p  0.05). 5 and 3 of 33 TIA patients as well as 4 and 3 of 20 stroke patients had at least 11 points in the HADS anxiety and depression score respectively (p = 0.001). 2 of 33 TIA patients and 2 of 20 stroke patients had more than 2 points in the PC-PTSD (p = 0.646). We did not find consistent correlations between the NIHSS and the psychometric parameters. Within the first five days after patients having experienced a TIA or stroke PTSD-like, anxious and depressive symptoms are more common than in the general population. As the acute psychological status after ictus is predictive for psychiatric comorbidity years later physicians should pay attention and adequately treat psychiatric symptoms already in the acute phase of stroke. Trial Registration: German Clinical Trials Register, DRKS00021730, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00021730, registered 05/19/2020- Retrospectively registered

Acute Effects of Aerobic Exercise on Executive Function and Attention in Adult Patients With ADHD

Aerobic exercise can improve cognitive functions in healthy individuals and in various clinical groups, which might be particularly relevant for patients with ADHD. This study investigated the effects of a single bout of aerobic exercise on attention and executive functions in adult patients with ADHD, including functional MRI to examine the underlying neural mechanisms. On two different days, 23 adult patients with ADHD and 23 matched healthy controls performed in a flanker task, while functional MR images were collected, following 30 min of continuous stationary cycling with moderate intensity as well as after a control condition (watching a movie). Behavioral performance and brain activation were tested for differences between groups and conditions and for interactions to investigate whether exercise improves executive function to a greater extent in patients compared to healthy controls. Exercise significantly improved reaction times in congruent and incongruent trials of the flanker task in patients with ADHD but not in healthy controls. We found no changes in brain activation between the two conditions for either group. However, a subgroup analysis of ADHD patients with a higher degree of cardiorespiratory fitness revealed decreased activation in premotor areas during congruent trials and in premotor and medial frontal cortex during incongruent trials in the exercise compared to the control condition. Our results indicate exercise-induced improvements in attention and processing speed in patients with ADHD, demonstrating that adult patients with ADHD may benefit from an acute bout of exercise. These findings could be of high relevance for developing alternative treatment approaches for ADHD. In addition, results of the current study contribute to elucidate the neurophysiological mechanisms underlying the beneficial effects of exercise on cognition and to better understand the role of cardiorespiratory fitness on these effects

Consensus Guidelines for Perioperative Care in Neonatal Intestinal Surgery: Enhanced Recovery After Surgery (ERAS\u3csup\u3e®\u3c/sup\u3e) Society Recommendations

Background: Enhanced Recovery After Surgery (ERAS®) Society guidelines integrate evidence-based practices into multimodal care pathways that have improved outcomes in multiple adult surgical specialties. There are currently no pediatric ERAS® Society guidelines. We created an ERAS® guideline designed to enhance quality of care in neonatal intestinal resection surgery. Methods: A multidisciplinary guideline generation group defined the scope, population, and guideline topics. Systematic reviews were supplemented by targeted searching and expert identification to identify 3514 publications that were screened to develop and support recommendations. Final recommendations were determined through consensus and were assessed for evidence quality and recommendation strength. Parental input was attained throughout the process. Results: Final recommendations ranged from communication strategies to antibiotic use. Topics with poor-quality and conflicting evidence were eliminated. Several recommendations were combined. The quality of supporting evidence was variable. Seventeen final recommendations are included in the proposed guideline. Discussion: We have developed a comprehensive, evidence-based ERAS guideline for neonates undergoing intestinal resection surgery. This guideline, and its creation process, provides a foundation for future ERAS guideline development and can ultimately lead to improved perioperative care across a variety of pediatric surgical specialties

Precise mass determination for the keystone sub-Neptune planet transiting the mid-type M dwarf G 9-40

Context. Despite being a prominent subset of the exoplanet population discovered in the past three decades, the nature and provenance of sub-Neptune-sized planets is still one of the open questions in exoplanet science. Aims. For planets orbiting bright stars, precisely measuring the orbital and planet parameters of the system is the best approach to distinguish between competing theories regarding their formation and evolution. Methods. We obtained 69 new radial velocity observations of the mid-M dwarf G 9-40 with the CARMENES instrument to measure for the first time the mass of its transiting sub-Neptune planet, G 9-40 b, discovered in data from the K2 mission. Results. Combined with new observations from the TESS mission during Sectors 44, 45, and 46, we are able to measure the radius of the planet to an uncertainty of 3.4% (R-b = 1.900 +/- 0.065 R-circle plus) and determine its mass with a precision of 16% (M-b = 4.00 +/- 0.63 M-circle plus). The resulting bulk density of the planet is inconsistent with a terrestrial composition and suggests the presence of either a water-rich core or a significant hydrogen-rich envelope. Conclusions. G 9-40 b is referred to as a keystone planet due to its location in period-radius space within the radius valley. Several theories offer explanations for the origin and properties of this population and this planet is a valuable target for testing the dependence of those models on stellar host mass. By virtue of its brightness and small size of the host, it joins L 98-59 d as one of the two best warm (T-eq similar to 400 K) sub-Neptunes for atmospheric characterization with JWST, which will probe cloud formation in sub-Neptune-sized planets and break the degeneracies of internal composition models

TOI-1268b: The youngest hot Saturn-mass transiting exoplanet

We report the discovery of TOI-1268b, a transiting Saturn-mass planet from the TESS space mission. With an age of less than 1 Gyr, derived from various age indicators, TOI-1268b is the youngest Saturn-mass planet known to date; it contributes to the small sample of well-characterised young planets. It has an orbital period of P = 8.1577080 \ub1 0.0000044 days, and transits an early K-dwarf star with a mass of M∗ = 0.96 \ub1 0.04 M+, a radius of R∗ = 0.92 \ub1 0.06 R+, an effective temperature of Teff = 5300 \ub1 100 K, and a metallicity of 0.36 \ub1 0.06 dex. By combining TESS photometry with high-resolution spectra acquired with the Tull spectrograph at the McDonald Observatory, and the high-resolution spectrographs at the Tautenburg and OndR ejov Observatories, we measured a planetary mass of Mp = 96.4 \ub1 8.3 Mp and a radius of Rp = 9.1 \ub1 0.6 Rp. TOI-1268 is an ideal system for studying the role of star-planet tidal interactions for non-inflated Saturn-mass planets. We used system parameters derived in this paper to constrain the planeta\u27s tidal quality factor to the range of 104.5-5.3. When compared with the sample of other non-inflated Saturn-mass planets, TOI-1268b is one of the best candidates for transmission spectroscopy studies

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Septins restrict inflammation and protect zebrafish larvae from Shigella infection

Shigella flexneri, a Gram-negative enteroinvasive pathogen, causes inflammatory destruction of the human intestinal epithelium. Infection by S. flexneri has been well-studied in vitro and is a paradigm for bacterial interactions with the host immune system. Recent work has revealed that components of the cytoskeleton have important functions in innate immunity and inflammation control. Septins, highly conserved cytoskeletal proteins, have emerged as key players in innate immunity to bacterial infection, yet septin function in vivo is poorly understood. Here, we use S. flexneri infection of zebrafish (Danio rerio) larvae to study in vivo the role of septins in inflammation and infection control. We found that depletion of Sept15 or Sept7b, zebrafish orthologs of human SEPT7, significantly increased host susceptibility to bacterial infection. Live-cell imaging of Sept15-depleted larvae revealed increasing bacterial burdens and a failure of neutrophils to control infection. Strikingly, Sept15-depleted larvae present significantly increased activity of Caspase-1 and more cell death upon S. flexneri infection. Dampening of the inflammatory response with anakinra, an antagonist of interleukin-1 receptor (IL-1R), counteracts Sept15 deficiency in vivo by protecting zebrafish from hyper-inflammation and S. flexneri infection. These findings highlight a new role for septins in host defence against bacterial infection, and suggest that septin dysfunction may be an underlying factor in cases of hyper-inflammation

Helicobacter pylori Counteracts the Apoptotic Action of Its VacA Toxin by Injecting the CagA Protein into Gastric Epithelial Cells

Infection with Helicobacter pylori is responsible for gastritis and gastroduodenal ulcers but is also a high risk factor for the development of gastric adenocarcinoma and lymphoma. The most pathogenic H. pylori strains (i.e., the so-called type I strains) associate the CagA virulence protein with an active VacA cytotoxin but the rationale for this association is unknown. CagA, directly injected by the bacterium into colonized epithelium via a type IV secretion system, leads to cellular morphological, anti-apoptotic and proinflammatory effects responsible in the long-term (years or decades) for ulcer and cancer. VacA, via pinocytosis and intracellular trafficking, induces epithelial cell apoptosis and vacuolation. Using human gastric epithelial cells in culture transfected with cDNA encoding for either the wild-type 38 kDa C-terminal signaling domain of CagA or its non-tyrosine-phosphorylatable mutant form, we found that, depending on tyrosine-phosphorylation by host kinases, CagA inhibited VacA-induced apoptosis by two complementary mechanisms. Tyrosine-phosphorylated CagA prevented pinocytosed VacA to reach its target intracellular compartments. Unphosphorylated CagA triggered an anti-apoptotic activity blocking VacA-induced apoptosis at the mitochondrial level without affecting the intracellular trafficking of the toxin. Assaying the level of apoptosis of gastric epithelial cells infected with wild-type CagA+/VacA+ H. pylori or isogenic mutants lacking of either CagA or VacA, we confirmed the results obtained in cells transfected with the CagA C-ter constructions showing that CagA antagonizes VacA-induced apoptosis. VacA toxin plays a role during H. pylori stomach colonization. However, once bacteria have colonized the gastric niche, the apoptotic action of VacA might be detrimental for the survival of H. pylori adherent to the mucosa. CagA association with VacA is thus a novel, highly ingenious microbial strategy to locally protect its ecological niche against a bacterial virulence factor, with however detrimental consequences for the human host

Co-Crystal Structures of Inhibitors with MRCKβ, a Key Regulator of Tumor Cell Invasion

MRCKα and MRCKβ (myotonic dystrophy kinase-related Cdc42-binding kinases) belong to a subfamily of Rho GTPase activated serine/threonine kinases within the AGC-family that regulate the actomyosin cytoskeleton. Reflecting their roles in myosin light chain (MLC) phosphorylation, MRCKα and MRCKβ influence cell shape and motility. We report further evidence for MRCKα and MRCKβ contributions to the invasion of cancer cells in 3-dimensional matrix invasion assays. In particular, our results indicate that the combined inhibition of MRCKα and MRCKβ together with inhibition of ROCK kinases results in significantly greater effects on reducing cancer cell invasion than blocking either MRCK or ROCK kinases alone. To probe the kinase ligand pocket, we screened 159 kinase inhibitors in an in vitro MRCKβ kinase assay and found 11 compounds that inhibited enzyme activity >80% at 3 µM. Further analysis of three hits, Y-27632, Fasudil and TPCA-1, revealed low micromolar IC50 values for MRCKα and MRCKβ. We also describe the crystal structure of MRCKβ in complex with inhibitors Fasudil and TPCA-1 bound to the active site of the kinase. These high-resolution structures reveal a highly conserved AGC kinase fold in a typical dimeric arrangement. The kinase domain is in an active conformation with a fully-ordered and correctly positioned αC helix and catalytic residues in a conformation competent for catalysis. Together, these results provide further validation for MRCK involvement in regulation of cancer cell invasion and present a valuable starting point for future structure-based drug discovery efforts

Macular thickness measurements in healthy Norwegian volunteers: an optical coherence tomography study

<p>Abstract</p> <p>Background</p> <p>Ethnic, intersubject, interoperator and intermachine differences in measured macular thickness seem to exist. Our purpose was to collect normative macular thickness data in Norwegians and to evaluate the association between macular thickness and age, gender, parity, and contraception status.</p> <p>Methods</p> <p>Retinal thickness was measured by Stratus Optical Coherence Tomography in healthy subjects. Mean macular thickness (MMT) was analyzed by repeated measures ANOVA with three dependent regional MMT-variables for interaction with age, gender, parity and oral contraception use. Exploratory correlation with age by the Pearson correlation test, both before and after stratification by gender was performed. Differences in MMT between older and younger subjects, between oral contraception users and non-users, as well as parous and nulliparous women were studied by post-hoc Student's t-tests.</p> <p>Results</p> <p>Central MMT in Norwegians was similar to values earlier reported in whites. MMT in central areas of 1 and 2.25 mm in diameter were higher in males than in females. In younger subjects (≤43 years) differences in MMT between genders were larger than in the mixed age group, whereas in older subjects (>43 years) the small differences did not reach the set significance level. No differences were found in minimal foveolar thickness (MMFT) between the genders in any age group.</p> <p>Mean foveal thickness (1 mm in diameter) was positively associated with age in females (r = 0.28, p = 0.03). MMFT was positively associated with age in all groups and reached significance both in females and in mixed gender group (r = 0.20, p = 0.041 and r = 0.26, p = 0.044 respectively).</p> <p>Mean foveal thickness and MMFT were significantly higher in parous than in nulliparous women, and age-adjusted ANOVA for MMFT revealed a borderline effect of parity.</p> <p>Conclusions</p> <p>Age and gender should be taken into consideration when establishing normal ranges for MMT in younger subjects. The gender difference in retinal thickness in young, but not older adults suggests a gonadal hormonal influence. The possible association between parity and retinal structure and its clinical relevance, should be studied further.</p