Detailed clay mineralogy of the TriassicJurassic boundary section at Kendlbachgraben (Northern Calcareous Alps, Austria)

The Triassic-Jurassic boundary (TJB) is marked by one of the five largest Phanerozoic mass extinctions. To constrain existing models for TJB events, we obtained a stratigraphically highly resolved dataset from a marine section at Kendlbachgraben, Austria. The topmost Triassic Ko¨ssen Formation contains low to medium-charged smectite and vermiculite as alteration products of mafic-ultramafic minerals. The clay minerals in the boundary mudstone are kaolinite 5 illite + muscovite >> smectite > chlorite. Predominant kaolinite suggests humid climate and abundant terrigenous input. In the lowermost Jurassic, the clay mineral pattern changes to illite + muscovite >> kaolinite >> smectite, which reflects change to less humid and more moderate climate. The topmost Ko¨ssen Formation also contains clay spherules. Their composition, shape and size indicate that they are alteration products of airborne volcanic glass droplets solidified in the air, settled in the sea and altered rapidly with negligible transport in terrestrial or marine environments. Our data are consistent with sudden climatic change at the TJB, as a result of large-scale volcanic activity of the Central Atlantic Magmatic Province which produced distal airfall volcanic ash

Substance P induces gastric mucosal protection at supraspinal level via increasing the level of endomorphin-2 in rats.

The aim of the present study was to analyze the potential role of substance P (SP) in gastric mucosal defense and to clarify the receptors and mechanisms that may be involved in it. Gastric ulceration was induced by oral administration of acidified ethanol in male Wistar rats. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay. For analysis of gastric motor activity the rubber balloon method was used. We found that central (intracerebroventricular) injection of SP (9.3-74pmol) dose-dependently inhibited the formation of ethanol-induced ulcers, while intravenously injected SP (0.37-7.4nmol/kg) had no effect. The mucosal protective effect of SP was inhibited by pretreatment with neurokinin 1-, neurokinin 2-, neurokinin 3- and mu-opioid receptor antagonists, while delta- and kappa-opioid receptor antagonists had no effect. Endomorphin-2 antiserum also antagonized the SP-induced mucosal protection. In the gastroprotective dose range SP failed to influence the gastric motor activity. Inhibition of muscarinic cholinergic receptors, or the synthesis of nitric oxide or prostaglandins significantly reduced the effect of SP. In addition, centrally injected SP reversed the ethanol-induced reduction of gastric mucosal CGRP content. It can be concluded, that SP may induce gastric mucosal protection initiated centrally. Its protective effect is likely to be mediated by endomorphin-2, and vagal nerve may convey the centrally initiated protection to the periphery, where both prostaglandins, nitric oxide and CGRP are involved in mediating this effect

Antibiotic-induced release of small extracellular vesicles (exosomes) with surface-associated DNA

Recently, biological roles of extracellular vesicles (which include among others exosomes, microvesicles and apoptotic bodies) have attracted substantial attention in various fields of biomedicine. Here we investigated the impact of sustained exposure of cells to the fluoroquinolone antibiotic ciprofloxacin on the released extracellular vesicles. Ciprofloxacin is widely used in humans against bacterial infections as well as in cell cultures against Mycoplasma contamination. However, ciprofloxacin is an inducer of oxidative stress and mitochondrial dysfunction of mammalian cells. Unexpectedly, here we found that ciprofloxacin induced the release of both DNA (mitochondrial and chromosomal sequences) and DNA-binding proteins on the exofacial surfaces of small extracellular vesicles referred to in this paper as exosomes. Furthermore, a label-free optical biosensor analysis revealed DNA-dependent binding of exosomes to fibronectin. DNA release on the surface of exosomes was not affected any further by cellular activation or apoptosis induction. Our results reveal for the first time that prolonged low-dose ciprofloxacin exposure leads to the release of DNA associated with the external surface of exosomes

Anterior eye health recording.

AIMS: To survey eye care practitioners from around the world regarding their current practice for anterior eye health recording to inform guidelines on best practice. METHODS: The on-line survey examined the reported use of: word descriptions, sketching, grading scales or photographs; paper or computerised record cards and whether these were guided by proforma headings; grading scale choice, signs graded, level of precision, regional grading; and how much time eye care practitioners spent on average on anterior eye health recording. RESULTS: Eight hundred and nine eye care practitioners from across the world completed the survey. Word description (p<0.001), sketches (p=0.002) and grading scales (p<0.001) were used more for recording the anterior eye health of contact lens patients than other patients, but photography was used similarly (p=0.132). Of the respondents, 84.5% used a grading scale, 13.5% using two, with the original Efron (51.6%) and CCLRU/Brien-Holden-Vision-Institute (48.5%) being the most popular. The median features graded was 11 (range 1-23), frequency from 91.6% (bulbar hyperaemia) to 19.6% (endothelial blebs), with most practitioners grading to the nearest unit (47.4%) and just 14.7% to one decimal place. The average time taken to report anterior eye health was reported to be 6.8±5.7 min, with the maximum time available 14.0±11 min. CONCLUSIONS: Developed practice and research evidence allows best practice guidelines for anterior eye health recording to be recommended. It is recommended to: record which grading scale is used; always grade to one decimal place, record what you see live rather than based on how you intend to manage a condition; grade bulbar and limbal hyperaemia, limbal neovascularisation, conjunctival papillary redness and roughness (in white light to assess colouration with fluorescein instilled to aid visualisation of papillae/follicles), blepharitis, meibomian gland dysfunction and sketch staining (both corneal and conjunctival) at every visit. Record other anterior eye features only if they are remarkable, but indicate that the key tissue which have been examined

Látásjavító implantátumok látóhártya-degenerációkban = Vision restoration with implants in retinal degenerations

Az ideghártya fényérzékelő sejtjeinek maradandó károsodásával járó és vaksághoz vezető betegségek eddig gyógyíthatatlannak bizonyultak. Jelenleg a szembe ültethető retinaimplantátumok fejlesztése biztat leghamarabb a klinikai gyakorlatba is bevezethető eredménnyel e betegek számára. A közlemény célja az eltérő működési elv alapján csoportosított, különböző fejlesztési szakaszban levő implantátumokkal kapcsolatos kutatások ismertetése és jellemzőinek kiemelése, valamint a fejlesztések hazai vonatkozásainak bemutatása. Az összefoglaló a nemzetközi szakirodalomban megjelent publikációk áttekintésével és feldolgozásával, valamint személyes tapasztalatok alapján kíván áttekintést nyújtani a retina degeneratív betegségei esetén beültethető retinaimplantátumokról. Az elmúlt évek mikroelektronikai fejlesztései tették lehetővé, hogy a retina elpusztult fotoreceptorainak helyettesítése elektromos ingerléssel sikeresen megoldható legyen. Több egymástól mind felépítésében, mind egyéb tulajdonságaiban jelentősen eltérő implantátum fejlesztése folyik jelenleg is egymással párhuzamosan. Ezek közül két, az ideghártyával közvetlen kapcsolatban álló, a szemgolyóba ültethető rendszer emelkedik ki. Az ideghártya alá ültethető, subretinalis típusú implantátumokkal sikerült eddig a legfinomabb felbontást elérni. Az ideghártya felszínére rögzített implantátumnak ugyan csekélyebb a felbontása, de rövidebb műtétet igényel a beültetése. A retinaimplantátumok segítségével egyes ideghártya-betegségekben immár bizonyított, hogy látásszerű élmény váltható ki. A multicentrikus klinikai vizsgálatok lezárását követően néhány éven belül várható, hogy többfajta implantátumtípus is megjelenik a klinikai gyakorlatban. Orv. Hetil., 2011, 152, 537–545. | Up until now there has been no available treatment for diseases causing the permanent impairment of retinal photoreceptors. Currently the development of the retinal prostheses is the earliest to promise a result that can be implemented in the clinical treatment of these patients. Implants with different operating principles and in various stages of progress are presented in details, highlighting the characteristics, as well as the Hungarian aspects of the development. This survey intends to provide an overview on retinal prostheses, implantable in case of degenerative diseases of the retina, by reviewing and assessing the papers published in relevant journals and based on personal experience. Developments in microelectronics in recent years made it possible and proved to be feasible to replace the degenerated elements in the retina with electrical stimulation. Multiple comparable approaches are running simultaneously. Two types of these implants are directly stimulating the remaining living cells in the retina. Hitherto the finest resolution has been achieved with the subretinal implants. Although the epiretinal implant offer lower resolution, but requires shorter surgery for implantation. Retinal implants in certain retinal diseases are proved to be capable of generating vision-like experiences. A number of types of retinal implants can be expected to appear in clinical practice a few years after the successful conclusion of clinical trials. Orv. Hetil., 2011, 152, 537–545

PrImary decompressive Craniectomy in AneurySmal Subarachnoid hemOrrhage (PICASSO) trial: study protocol for a randomized controlled trial

BACKGROUND: Poor-grade aneurysmal subarachnoid hemorrhage (SAH) is associated with poor neurological outcome and high mortality. A major factor influencing morbidity and mortality is brain swelling in the acute phase. Decompressive craniectomy (DC) is currently used as an option in order to reduce intractably elevated intracranial pressure (ICP). However, execution and optimal timing of DC remain unclear. METHODS: PICASSO resembles a multicentric, prospective, 1:1 randomized standard treatment-controlled trial which analyzes whether primary DC (pDC) performed within 24 h combined with the best medical treatment in patients with poor-grade SAH reduces mortality and severe disability in comparison to best medical treatment alone and secondary craniectomy as ultima ratio therapy for elevated ICP. Consecutive patients presenting with poor-grade SAH, defined as grade 4–5 according to the World Federation of Neurosurgical Societies (WFNS), will be screened for eligibility. Two hundred sixteen patients will be randomized to receive either pDC additional to best medical treatment or best medical treatment alone. The primary outcome is the clinical outcome according to the modified Rankin Scale (mRS) at 12 months, which is dichotomized to favorable (mRS 0–4) and unfavorable (mRS 5–6). Secondary outcomes include morbidity and mortality, time to death, length of intensive care unit (ICU) stay and hospital stay, quality of life, rate of secondary DC due to intractably elevated ICP, effect of size of DC on outcome, use of duraplasty, and complications of DC. DISCUSSION: This multicenter trial aims to generate the first confirmatory data in a controlled randomized fashion that pDC improves the outcome in a clinically relevant endpoint in poor-grade SAH patients. TRIAL REGISTRATION: DRKS DRKS00017650. Registered on 09 June 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13063-022-06969-4

Personalized recurrence risk assessment following the birth of a child with a pathogenic de novo mutation

Following the diagnosis of a paediatric disorder caused by an apparently de novo mutation, a recurrence risk of 1–2% is frequently quoted due to the possibility of parental germline mosaicism; but for any specific couple, this figure is usually incorrect. We present a systematic approach to providing individualized recurrence risk. By combining locus-specific sequencing of multiple tissues to detect occult mosaicism with long-read sequencing to determine the parent-of-origin of the mutation, we show that we can stratify the majority of couples into one of seven discrete categories associated with substantially different risks to future offspring. Among 58 families with a single affected offspring (representing 59 de novo mutations in 49 genes), the recurrence risk for 35 (59%) was decreased below 0.1%, but increased owing to parental mixed mosaicism for 5 (9%)—that could be quantified in semen for paternal cases (recurrence risks of 5.6–12.1%). Implementation of this strategy offers the prospect of driving a major transformation in the practice of genetic counselling

Keratitis caused by the recently described new species Aspergillus brasiliensis: two case reports

<p>Abstract</p> <p>Introduction</p> <p>Human infections caused by <it>Aspergillus brasiliensis </it>have not yet been reported. We describe the first two known cases of fungal keratitis caused by <it>Aspergillus brasiliensis</it>.</p> <p>Case presentations</p> <p>A 49-year-old Indian Tamil woman agricultural worker came with pain and defective vision in the right eye for one month. Meanwhile, a 35-year-old Indian Tamil woman presented with a history of a corneal ulcer involving the left eye for 15 days. The fungal strains isolated from these two cases were originally suspected to belong to <it>Aspergillus </it>section <it>Nigri </it>based on macro- and micromorphological characteristics. Molecular identification revealed that both isolates represent <it>A. brasiliensis</it>.</p> <p>Conclusion</p> <p>The two <it>A. brasiliensis </it>strains examined in this study were part of six keratitis isolates from <it>Aspergillus </it>section <it>Nigri</it>, suggesting that this recently described species may be responsible for a significant proportion of corneal infections caused by black Aspergilli. The presented cases also indicate that significant differences may occur between the severities of keratitis caused by individual isolates of <it>A. brasiliensis</it>.</p

Bone marrow stromal cells attenuate sepsis via prostaglandin E2–dependent reprogramming of host macrophages to increase their interleukin-10 production

Sepsis causes over 200,000 deaths yearly in the US; better treatments are urgently needed. Administering bone marrow stromal cells (BMSCs—also known as mesenchymal stem cells) to mice before or shortly after inducing sepsis by cecal ligation and puncture reduced mortality and improved organ function. The beneficial effect of BMSCs was eliminated by macrophage depletion or pretreatment with antibodies specific for interleukin-10 (IL-10) or IL-10 receptor. Monocytes and/or macrophages from septic lungs made more IL-10 when prepared from mice treated with BMSCs versus untreated mice. Lipopolysaccharide (LPS)-stimulated macrophages produced more IL-10 when cultured with BMSCs, but this effect was eliminated if the BMSCs lacked the genes encoding Toll-like receptor 4, myeloid differentiation primary response gene-88, tumor necrosis factor (TNF) receptor-1a or cyclooxygenase-2. Our results suggest that BMSCs (activated by LPS or TNF-α) reprogram macrophages by releasing prostaglandin E2 that acts on the macrophages through the prostaglandin EP2 and EP4 receptors. Because BMSCs have been successfully given to humans and can easily be cultured and might be used without human leukocyte antigen matching, we suggest that cultured, banked human BMSCs may be effective in treating sepsis in high-risk patient groups