A universal method for determining the detergent effect of surfactants.

Surfactants are indispensable in industrial applications today due to their wetting, emulsifying, dispersing, cleansing, and detergent properties. The use of surfactants extends from the cosmetic industry to the petroleum industry and beyond. Their characteristics and effectiveness can be assessed through various standardized tests, and based on these methods, their applications can be determined. However, there is a lack of a universally applicable testing method for one crucial and complex property: the detergent effect. The detergent effect refers to the removal of unwanted contaminants from a solid surface. However, cleaning is not solely attributed to the surfactant but to the appropriate combination of various factors, whose synergistic effect reduces surface contamination. The most significant factors influencing detergent effect include the characteristics and nature of the contaminants, properties of the cleaning solution (surfactant concentration and composition, water hardness, enzymes, etc.), temperature, washing time, and hydrodynamic conditions. Additionally, the presence of electrolytes, pH of the cleaning solution, and detergent foaming properties may also play important roles. Our goal was to develop a detergent effect testing methodology that is not specific to any particular application domain but offers a straightforward and easy-to-implement solution for comparing the detergent effect of various types of surfactants.•The study presents a method for determining detergent effect of surfactants.•The method is universal and suitable for the evaluation of any type of surfactant.•The method is low-cost and easy to perform.

An improved method for determining the water number for surfactants.

Surfactants have a significant role in everyday life and various industries. Their amphipathic nature significantly influences their properties, functions, and applicability. The ratio of water and oil solubility is characterized by the HLB value (hydrophilic-lipophilic balance) or the closely related water number. A determination of the water number of surfactants represents the amount of water that a surfactant can incorporate into a microemulsion. The results of measuring the water number provide information about the hydrophilic properties of the surfactant in question. Understanding the water number helps determine the applicability of surfactants. From the water number of surfactants, conclusions can be drawn about the HLB value of the particular surfactant, providing further insights into its properties. Although a well-established method for determining water number has long been available, it has been revealed that many of the auxiliary substances and chemicals used in this process have severe health-damaging effects, leading to their discontinuation in routine laboratory use. Our goal was to find a solvent combination that would be suitable for the water number determination method. Additionally, we aimed to investigate solvents that are environmentally and human-biologically less harmful, easily and affordably obtainable.•The study presents a method for determining the water number of surfactants.•The method is straightforward to execute and free from harmful solvents.•By improving the method, we enhanced the reliability of the examination.

A glycolytic metabolite bypasses "two-hit" tumor suppression by BRCA2.

Knudson's "two-hit" paradigm posits that carcinogenesis requires inactivation of both copies of an autosomal tumor suppressor gene. Here, we report that the glycolytic metabolite methylglyoxal (MGO) transiently bypasses Knudson's paradigm by inactivating the breast cancer suppressor protein BRCA2 to elicit a cancer-associated, mutational single-base substitution (SBS) signature in nonmalignant mammary cells or patient-derived organoids. Germline monoallelic BRCA2 mutations predispose to these changes. An analogous SBS signature, again without biallelic BRCA2 inactivation, accompanies MGO accumulation and DNA damage in Kras-driven, Brca2-mutant murine pancreatic cancers and human breast cancers. MGO triggers BRCA2 proteolysis, temporarily disabling BRCA2's tumor suppressive functions in DNA repair and replication, causing functional haploinsufficiency. Intermittent MGO exposure incites episodic SBS mutations without permanent BRCA2 inactivation. Thus, a metabolic mechanism wherein MGO-induced BRCA2 haploinsufficiency transiently bypasses Knudson's two-hit requirement could link glycolysis activation by oncogenes, metabolic disorders, or dietary challenges to mutational signatures implicated in cancer evolution.

Investigation of Vegetable Oils and Their Derivatives for the Synthesis of Extreme Pressure Additives.

The harmful effects of wear can be reduced through proper lubrication of the frictional parts. When exposed to excessive loads, the lubricant film is displaced from the surfaces, and even the adhesive lubricant layer may rupture. Additives known as Extreme Pressure (EP) are frequently incorporated into lubricants to minimise wear and avert seizures under high temperature and pressure. Mechanistically, these additives generate a film on the surface through chemisorption. These additives are extensively applied in various lubricants, with the largest quantities being employed in metalworking fluids and lubricating greases. Sulfurized vegetable oils and their derivates can be used as EP additives for lubricants. To conduct the investigations, sulfurized additives were synthesized using different vegetable-based oils and fatty acid esters, and alpha-olefins. In this study, the Four-ball test results were compared to gain a more accurate comprehension of how various raw-material-based additives influence wear and friction. The goal was to select raw materials that could be used with favorable results for the production of EP additives. The objective was to achieve a minimum Four-ball weld load parameter of 2000 N. The experiments revealed that the functional impacts of the synthesized samples are dependent on the type of raw materials employed. Based on the experimental data and the stated criteria, the examined raw materials were found to be suitable for the synthesis of EP additives.

Genetic Etiology of Nonsyndromic Hearing Loss in Hungarian Patients.

Hearing loss is the most prevalent sensory disorder worldwide. The majority of congenital nonsyndromic hearing loss (NSHL) cases are caused by hereditary factors. Previously, the majority of NSHL studies focused on the GJB2 gene; however, with the availability of next-generation sequencing (NGS) methods, the number of novel variants associated with NSHL has increased. The purpose of this study was to design effective genetic screening for a Hungarian population based on a pilot study with 139 NSHL patients. A stepwise, comprehensive genetic approach was developed, including bidirectional capillary sequencing, multiplex ligation-dependent probe amplification (MLPA), and an NGS panel of 108 hearing loss genes. With our results, a genetic diagnosis was possible for 92 patients. Sanger sequencing and MLPA identified the genetic background of 50% of these diagnosed cases, and the NGS panel identified another 16%. The vast majority (92%) of the diagnosed cases showed autosomal recessive inheritance and 76% were attributed to GJB2. The implementation of this stepwise analysis markedly increased our diagnostic yield and proved to be cost-effective as well.

Attenuated transcriptional response to pro-inflammatory cytokines in schizophrenia hiPSC-derived neural progenitor cells.

Maternal immune activation (MIA) during prenatal development is an environmental risk factor for psychiatric disorders including schizophrenia (SZ). Converging lines of evidence from human and animal model studies suggest that elevated cytokine levels in the maternal and fetal compartments are an important indication of the mechanisms driving this association. However, there is variability in susceptibility to the psychiatric risk conferred by MIA, likely influenced by genetic factors. How MIA interacts with a genetic profile susceptible to SZ is challenging to test in animal models. To address this gap, we examined whether differential gene expression responses occur in forebrain-lineage neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (hiPSC) generated from three individuals with a diagnosis of schizophrenia and three healthy controls. Following acute (24 h) treatment with either interferon-gamma (IFNγ; 25 ng/µl) or interleukin (IL)-1ß (10 ng/µl), we identified, by RNA sequencing, 3380 differentially expressed genes (DEGs) in the IFNγ-treated control lines (compared to untreated controls), and 1980 DEGs in IFNγ-treated SZ lines (compared to untreated SZ lines). Out of 4137 genes that responded significantly to IFNγ across all lines, 1223 were common to both SZ and control lines. The 2914 genes that appeared to respond differentially to IFNγ treatment in SZ lines were subjected to a further test of significance (multiple testing correction applied to the interaction effect between IFNγ treatment and SZ diagnosis), yielding 359 genes that passed the significance threshold. There were no differentially expressed genes in the IL-1ß-treatment conditions after Benjamini-Hochberg correction. Gene set enrichment analysis however showed that IL-1ß impacts immune function and neuronal differentiation. Overall, our data suggest that a) SZ NPCs show an attenuated transcriptional response to IFNγ treatment compared to controls; b) Due to low IL-1ß receptor expression in NPCs, NPC cultures appear to be less responsive to IL-1ß than IFNγ; and c) the genes differentially regulated in SZ lines - in the face of a cytokine challenge - are primarily associated with mitochondrial, "loss-of-function", pre- and post-synaptic gene sets. Our findings particularly highlight the role of early synaptic development in the association between maternal immune activation and schizophrenia risk.

Cell line specific alterations in genes associated with dopamine metabolism and signaling in midbrain dopaminergic neurons derived from 22q11.2 deletion carriers with elevated dopamine synthesis capacity.

Microdeletions at the 22q11.2 locus are associated with increased risk for schizophrenia. Recent work has demonstrated that antipsychotic naïve 22q11.2 carriers display elevated levels of dopamine synthesis capacity (DSC) as assessed by 18F-DOPA PET imaging. While this is consistent with a role for abnormal dopamine function in schizophrenia, it is unclear what molecular changes may be associated with this neuro-imaging endophenotype, and moreover, if these alterations occur independently of clinical presentation. We therefore conducted a pilot study in which we generated human induced pluripotent stem cells (hiPSCs) from two 22q11.2 deletion carriers with elevated DSC in vivo, but distinct clinical presentations. From these and neurotypical control lines we were able to robustly generate midbrain dopaminergic neurons (mDA-neurons). We then assessed whether genes associated with dopamine synthesis, metabolism or signaling show altered expression between genotypes and further between the 22q11.2 deletion lines. Our data showed alterations in expression of genes associated with dopamine metabolism and signaling that differed between the two 22q11.2 hiPSC lines with distinct clinical presentations. This reinforces the importance of considering clinical, genetic and molecular information, when possible, when choosing which donors to generate hiPSCs from, to carry out mechanistic studies.

A new method of preoperative assessment of correct electrode array alignment based on post-operative measurements in a cochlear implanted cohort.

PURPOSE: During cochlear implantation surgery, a range of complications may occur such as tip fold-over. We recently developed a method to estimate the insertion orientation of the electrode array. The aim of the study was to determine the optimal angle of orientation in a cohort of cochlear implanted patients. METHODS: On eighty-five CT scans (80 uncomplicated insertions and 5 cases with tip fold-over), location of the electrode array's Insertion Guide (IG), Orientation marker (OM) and two easily identifiable landmarks (the round window (RW) and the incus short process (ISP)) were manually marked. The angle enclosed by ISP-RW line and the Cochlear™ Slim Modiolar electrode array's OM line determined the electrode array insertion angle. RESULTS: The average insertion angle was 45.0-47.2° ± 10.4-12° SD and was validated with 98% confidence interval. Based on the measurements obtained, patients' sex and age had no impact on the size of this angle. Although the angles of the tip fold-over cases (44.9°, 46.9°, 34.2°, 54.3°, 55.9°) fell within this average range, the further it diverted from the average it increased the likelihood for tip fold-over. CONCLUSION: Electrode array insertion in the individually calculated angle relative to the visible incus short process provides a useful guide for the surgeon when aiming for the optimal angle, and potentially enhances good surgical outcomes. Our results show that factors other than the orientation angle may additionally contribute to failures in implantation when the Slim Modiolar electrode is used.

Optical Microscopy Systems for the Detection of Unlabeled Nanoparticles.

Label-free detection of nanoparticles is essential for a thorough evaluation of their cellular effects. In particular, nanoparticles intended for medical applications must be carefully analyzed in terms of their interactions with cells, tissues, and organs. Since the labeling causes a strong change in the physicochemical properties and thus also alters the interactions of the particles with the surrounding tissue, the use of fluorescently labeled particles is inadequate to characterize the effects of unlabeled particles. Further, labeling may affect cellular uptake and biocompatibility of nanoparticles. Thus, label-free techniques have been recently developed and implemented to ensure a reliable characterization of nanoparticles. This review provides an overview of frequently used label-free visualization techniques and highlights recent studies on the development and usage of microscopy systems based on reflectance, darkfield, differential interference contrast, optical coherence, photothermal, holographic, photoacoustic, total internal reflection, surface plasmon resonance, Rayleigh light scattering, hyperspectral and reflectance structured illumination imaging. Using these imaging modalities, there is a strong enhancement in the reliability of experiments concerning cellular uptake and biocompatibility of nanoparticles, which is crucial for preclinical evaluations and future medical applications.

Biocompatible poly(ethylene succinate) polyester with molecular weight dependent drug release properties.

In the present study, we demonstrate that well-known molecular weight-dependent solubility properties of a polymer can also be used in the field of controlled drug delivery. To prove this, poly(ethylene succinate) (PES) polyesters with polycondensation time regulated molecular weights were synthesized via catalyst-free direct polymerization in an equimolar ratio of ethylene glycol and succinic acid monomers at 185 °C. DSC and contact angle measurements revealed that increasing the molecular weight (Mw, 4.3-5.05 kDa) through the polymerization time (40-80 min) increased the thermal stability (Tm= ∼61-80 °C) and slightly the hydrophobicity (Θw= ∼27-41°) of the obtained aliphatic polyester. Next, this biodegradable polymer was used for the encapsulation of Ca2+ channel blocker Nimodipine (NIMO) to overcome the poor water solubility and enhance the bioavailability of the drug. The drug/ polymer compatibility was proved by the means of solubility (δ) and Flory-Huggins interaction (miscibility) parameters (χ). The nanoprecipitation encapsulation of NIMO into PES with increasing Mw resulted in the formation of spherical 270 ± 103 nm NIMO-loaded PES nanoparticles (NPs). Furthermore, based on the XRD measurements, the encapsulated form of NIMO-loaded PES NPs showed lower drug crystallinity, which enhanced not only the water solubility but even the water stability of the NIMO in an aqueous medium. The in-vitro drug release experiments demonstrated that the release of NIMO drug could be accelerated or even prolonged by the molecular weights of PES as well. Due to the low crystallinity of PES polyester and low particle size of the encapsulated NIMO drug led to enhance solubility and releasing process of NIMO from PES with lower Mw (4.3 kDa and 4.5 kDa) compared to pure crystalline NIMO. However, further increasing the molecular weight (5.05 kDa) was already reduced the amount of drug release that provides the prolonged therapeutic effect and enhances the bioavailability of the NIMO drug.

Pediatric morphometric study to guide the optimized implantation of the Osia® 2 implant system.

PURPOSE: Continuous technological advances result in the availability of new bone conduction hearing implants, of which their suitability for pediatric patients is of major concern. The CochlearTMOsia® 2 is a new active osseointegrated steady-state implant system that uses digital piezoelectric stimulation to treat hearing loss. The implant in the United States was approved for patients aged 12 years and above, whereas the CE mark is independent of age, the only requirement is body weight of at least 7 kg. Therefore, further clinical studies are required to assess device characteristics in younger patients. The aim of our study was to perform a morphometric study among 5-12-year-old children, and to develop a surgical protocol for Osia 2 system implantation based on these findings. METHODS: We examined retrospectively cranial CT scans of 5-12-year-old patients from our clinical database. We measured the bone and soft-tissue thickness in the region of interest, and the position of the sigmoid sinus. 3D printed temporal bones were also used for planning. RESULTS: Soft-tissue thickness varied between 3.2 ± 0.5 mm and 3.6 ± 0.6 mm and bone thickness varied between 3.5 ± 1.1 mm and 4.7 ± 0.3 mm. The sigmoid sinus was located 1.3 ± 0.2 cm posterior to the ear canal, and the anterior distance was 4.8 ± 0.9 to 7.1 ± 1.1 mm. CONCLUSIONS: Our morphometric studies showed that patients aged 5-12 have different anatomical dimensions compared to adults, but that implantation of the Osia 2 system is feasible in these patients using an altered implant positioning recommended by our data. The Cochlear™ Osia® 2 is, therefore, an option for hearing rehabilitation in younger pediatrics.

The Effect of Molecular Weight on the Solubility Properties of Biocompatible Poly(ethylene succinate) Polyester.

Poly(ethylene succinate) (PES) is one of the most promising biodegradable and biocompatible polyesters and is widely used in different biomedical applications. However, little information is available on its solubility and precipitation properties, despite that these solution behavior properties affect its applicability. In order to systematically study these effects, biodegradable and biocompatible poly(ethylene succinate) (PES) was synthesized using ethylene glycol and succinic acid monomers with an equimolar ratio. Despite the optimized reaction temperature (T = 185 °C) of the direct condensation polymerization, relatively low molecular mass values were achieved without using a catalyst, and the Mn was adjustable with the reaction time (40-100 min) in the range of ~850 and ~1300 Da. The obtained crude products were purified by precipitation from THF ("good" solvent) with excess of methanol ("bad" solvent). The solvents for PES oligomers purification were chosen according to the calculated values of solubility parameters by different approaches (Fedors, Hoy and Hoftyzer-van Krevelen). The theta-solvent composition of the PES solution was 0.3 v/v% water and 0.7 v/v% DMSO in this binary mixture. These measurements were also allowed to determine important parameters such as the coefficients A (=0.67) and B (=3.69 × 104) from the Schulz equation, or the Kη (=8.22 × 10-2) and α (=0.52) constants from the Kuhn-Mark-Houwink equation. Hopefully, the prepared PES with different molecular weights is a promising candidate for biomedical applications and the reported data and constants are useful for other researchers who work with this promising polyester.

Detection of "tip fold-over" of the cochlear implant electrode array with transimpedance matrix (TIM) measurement / Az elektródasor visszatekeredésének kimutatása transzimpedanciamátrix (TIM)-vizsgálattal cochlearis implantátumban.

Összefoglaló. Bevezetés: Az elmúlt években a cochlearis implantátum a súlyos halláskárosodás vagy a teljes siketség rutinszeru és hatékony kezelési eszközévé vált. Korunk egyik leggyakrabban használt és leghatékonyabb újítása a cochlearis implantációban a perimodiolaris vékony elektródasorok alkalmazása. A cochlea középtengelyét, a modiolust szorosan ölelo atraumatikus elektródasor igen meggyozo eredménnyel bizonyítja népszeruségét, mind az elektrofiziológiai mérések során, mind az akusztikus hallás megorzése terén nyújtott teljesítményével. Ugyanakkor igen kevés publikáció írja le az elektródasor nem megfelelo helyzetének elofordulási gyakoriságát, pontosabban a visszatekeredését a csúcsi szakaszon. Célkituzés: Tanulmányunk célja olyan szoftveres technika, a transzimpedancia-mátrix (TIM) beillesztése a rutin intraoperatív elektrofiziológiai mérési metodikák közé, amely képes objektív diagnosztikai lehetoséget biztosítani ahhoz, hogy korán felismerhessük a cochlearis implantátum elektródasorán keletkezett hurkot. Módszer: Hároméves kisgyermek kétoldali cochlearis implantációját követoen, posztoperatív röntgenfelvételen a bal oldalon az elektródasor megfelelo pozíciója figyelheto meg, míg a jobb oldalon az intracochlearis elektródasor végének visszatekeredése igazolódott. Képalkotó vizsgálatot követoen elektrofiziológiai metódusként TIM-vizsgálatot végeztünk. Az eljárás során a méroeszköz a kijelölt stimuláló elektródákon 1 V nagyságrendu feszültséget közöl állandó áramerosség mellett a cochlea közel eso struktúrái felé. Méroelektródák segítségével regisztráljuk a szöveteken mérheto feszültséget, majd transzimpedancia-mátrixszá alakítjuk a mért értékeket. Eredmények: Az elektródasor visszatekeredése, amelyet korábban radiológiai vizsgálattal igazoltunk, az objektív elektrofiziológiai mérések segítségével is jól azonosítható, és a vizsgálatok szoros párhuzamot mutatnak. Következtetés: Az elektródák helyzetének megjelenítésére szolgáló standard radiológiai képalkotási technikák kiegészíthetok, illetve kiválthatók egyszeruen elvégezheto, hatékony, objektív elektrofiziológiai vizsgálatokkal. Intraoperatíven, még a sebzárás elott kimutatható, ha az elektródasor nem megfelelo helyzetbe került, így csökkenthetjük a radiológiai vizsgálatokkal járó sugárterhelés és annak finanszírozási problémáját. Orv Hetil. 2021; 162(25): 988-996. INTRODUCTION: In recent years, the cochlear implant has become a routine and effective treatment tool for severe hearing loss and total deafness. One of the commonly used and effective innovations of our time in cochlear implantation is the perimodiolar thin electrode array. The atraumatic electrode array, which closely embraces the central axis of the cochlea (modiolus), has served its popularity with very convincing results, with its performance in both electrophysiological measurements and acoustic hearing preservation. However, very few publications describe the frequency of improper positioning of the electrode array, which is known as 'tip fold-over'. OBJECTIVE: The aim of our study is to incorporate a software technique, the transimpedance matrix (TIM), into routine intraoperative electrophysiological measurement methodologies to provide a potential objective diagnostic opportunity for early detection of tip fold-over of the electrode array. METHOD: Following bilateral cochlear implantation of a three-year-old child, postoperative radiography showed the correct position of the electrode array on the left side, while tip fold-over of the intracochlear electrode array was detected on the right side. Following imaging, a TIM study was performed as an electrophysiological method. During the procedure, the measuring device transmits a voltage of the order of 1 V to the nearby structures of the cochlea at a constant current at the designated stimulus electrodes. Measuring electrodes were used to register the voltage measured on the tissues, and then converted into a TIM. RESULTS: Electrode tip fold-over was previously diagnosed by radiological examination, while it can also be diagnosed by objective electrophysiological measurements now, and these two tests correlate well. CONCLUSION: Standard radiological imaging techniques for electrode positioning can be supplemented or replaced by easy-to-perform, effective objective electrophysiological studies. Tip fold-over can be detected intraoperatively, even before wound closure, if the electrode array is in the wrong position, thus reducing the radiation exposure associated with radiological examinations as well as reducing relevant costs. Orv Hetil. 2021; 162(25): 988-996.

A novel intraoperative imaging tool to follow the cochlear implant electrode array insertion dynamics / Új mutéti képalkotó lehetoség a belsofül-implantátum elektródasorának dinamikus helyzetmeghatározására.

Összefoglaló. Bevezetés: A cochlearis implantátum egy mutétileg behelyezett elektromos eszköz, amely az akusztikus hanghullámokat elektromos jelekké alakítja, közvetlenül a hallóideget stimulálja, így segíti a súlyos fokú hallássérüléssel vagy teljes hallásvesztéssel élok életét. Cochlearis implantációt követoen a legjobb rehabilitációs eredmény elérésének technikai feltétele többek között az esetre szabott elektródaválasztás és az elektródasor teljes, kontrollált, szövodménymentes bejuttatása a scala tympaniba, miközben a cochlea belso struktúrája a leheto legkisebb mértékben sérül. A rutin intraoperatív elektrofiziológiai tesztek fontos információt adnak a készülék muködoképességérol és a hallóideg stimulációjáról, azonban nem hagyatkozhatunk rájuk az elektródasor cochleán belüli helyzetének igazolásában. Mivel elofordulhat, hogy a rendelkezésre álló elektrofiziológiai vizsgálatok eredménye megfelelo, és mégis rendellenes helyzetbe kerül az elektróda, az arany standardot a képalkotó vizsgálatok jelentik. Módszer: Közleményünkben egy modern, hibrid muto által nyújtott technológiai háttér új alkalmazási területét mutatjuk be. Szimultán kétoldali cochlearis implantációt végeztünk Cochlear Nucleus Slim Modiolar típusú perimodiolaris elektródasorral, a belso fül fejlodési rendellenességével rendelkezo betegen. Az intraoperatív képalkotást Siemens Artis pheno C-karos robot digitális szubtrakciós angiográfiás rendszer biztosította valós ideju átvilágító és volumentomográfiás funkcióval. Eredmények: Az intraoperatív képalkotás által dinamikusan követheto az elektródasor bevezetésének folyamata, ellenorizheto az elektródasor statikus helyzete, így kiváltható a rutinnak számító posztoperatív képalkotó vizsgálat. A rendellenes helyzetbe kerülo elektródasor pozíciója egy ülésben korrigálható, az újból bevezetheto, így elkerülheto az újabb altatással járó, bizonytalan kimenetelu revíziós mutét. Következtetés: A hibrid muto jól kontrollált, minimálisan invazív eljárások elvégzését biztosítja. Különösen a hallószerv fejlodési rendellenessége vagy egyéb, az elektródának a cochleába vezetését nehezíto rendellenesség esetén javasolt a mutoi képalkotó diagnosztika. Orv Hetil. 2021; 162(22): 878-883. INTRODUCTION: The cochlear implant is a surgically inserted electrical device that converts acoustic sound waves into electrical signals to stimulate the cochlear nerve, thus helps the rehabilitation of people with severe to total hearing loss. One of the most important technical conditions for achieving the best rehabilitation result after cochlear implantation is the personalized choice of electrodes. Additionally, it is vital that there is a complete, controlled, uncomplicated delivery of the electrode array to the scala tympani while minimizing damage to the inner structures of the cochlea. Routine electrophysiological tests provide important information about device functionality and auditory nerve stimulation. However, they probably do not show an abnormal position of the electrode array within the cochlea. Thus, imaging studies remain the gold standard. METHOD: In our paper, we present a novel application field of the modern technological background provided by a hybrid operating room. Simultaneous bilateral cochlear implantation was performed with cochlear implants with perimodiolar electrode array (Nucleus Slim Modiolar) in a patient with cochlear malformation. Intraoperative imaging was provided by a Siemens Artis pheno C-arm robot digital subtraction angiography system with real-time fluoroscopy and volume tomography function. RESULTS: Intraoperative imaging ensures dynamic follow-up of the introduction and static determination of the position of the electrode array and replaces routine postoperative imaging. If the electrode array was inserted in an abnormal position, the revision can be performed in the same sitting. Also, the revision surgery with a potential risk of uncertain outcome, alongside additional anaesthesia, can be prevented. CONCLUSION: The hybrid operating room ensures that well-controlled, minimally invasive procedures are performed. Intraoperative imaging can be imperative in malformed cochleae and conditions that may complicate electrode insertion. Orv Hetil. 2021; 162(22): 878-883.

Application field of VOXEL-MAN Tempo 3D virtual reality simulator in surgery of pars petrosa of temporal bone / A VOXEL-MAN Tempo 3D virtuálisvalóság-szimulátor alkalmazása a sziklacsont sebészetében.

Összefoglaló. Bevezetés: Az emberi sziklacsont a halántékcsont része, egy bonyolult és változatos anatómiai felépítésu struktúra. A sziklacsonton végzett beavatkozások elott, a mutéti szövodmények megelozése érdekében, nélkülözhetetlen a biztos anatómiai tudás és kézügyesség megszerzése, valamint az egyes mutéti lépések és mozdulatok begyakorlása. A VOXEL-MAN Tempo 3D fül-orr-gégészeti szimulátor a virtuális valóság és a robotika alkalmazásával nyújt gyakorlási lehetoséget. Célkituzés: A Szegedi Tudományegyetem 2019-ben VOXEL-MAN fül-orr-gégészeti szimulátort helyezett üzembe az Orvosi Készségfejlesztési Központban. A cikk fül-orr-gégész szakorvos szerzoi a VOXEL-MAN Tempo szimulátor megismerését követoen bemutatják a készüléket, és megfogalmazzák a szimulátorral végzett beavatkozásokkal szemben támasztott igényüket. Módszer: A szerzok a megfogalmazott szempontoknak megfeleloen értékelik a VOXEL-MAN Tempo szimulátort, és meghatározzák, milyen szerepet szánnak neki a gyakorlati képzésben. Eredmények: A szimulátor virtuálisan, mégis valósághuen mutatja meg a sziklacsont anatómiai viszonyait, a fontos anatómiai struktúrák valós térbeli elhelyezkedését és egymástól, illetve a sebészi eszköztol mért távolságát. A rendszer lehetové teszi a fülmutétek valósághu elvégzését (kétkezes csontmunka fúróval és szívóval, vérzés szimulálása) taktilis visszacsatolással. Az egy- vagy kétkezes feladatokkal fejleszthetjük a sebészi készségeket. A fülmutétek csontmunkája reprodukálható módon elvégezheto valódi beteg halántékcsontjáról készített rutin, nagy felbontású komputertomográfiás vizsgálat anyagából. Következtetés: Tapasztalataink alapján a szimulátor kiválóan alkalmas az egyes mutéti lépesek begyakorlására. A jövoben fontos szerepet szánunk a virtuális rendszernek a fül-orr-gégészeti graduális és a fülsebészeti posztgraduális képzésben. Orv Hetil. 2021; 162(16): 623-628. INTRODUCTION: The pars petrosa of the human temporal bone is a structure of complex and diverse anatomy. Prior to surgical interventions, in order to prevent surgical complications, it is essential to acquire sound anatomical knowledge and dexterity as well as to practice each surgical step and movement. The VOXEL-MAN Tempo 3D simulator uses virtual reality and robotics to provide an opportunity to practice. OBJECTIVE: In 2019, the University of Szeged installed a VOXEL-MAN Virtual Reality simulator at the Medical Skills Development Center. After learning about the VOXEL-MAN Tempo simulator, the authors present the device and articulate their need for interventions with the simulator. METHOD: The VOXEL-MAN Tempo simulator is evaluated according to the formulated criteria and the role assigned to it in the practical training is determined. RESULTS: The simulator shows the anatomical structure of the temporal bone virtually, yet realistically, the real spatial location of the important anatomical structures and their distance from each other and from the surgical instrument. The system allows ear surgery to be performed realistically (two-handed bone work with a drill and suction) with tactile (vibration) and visual (bleeding) feedback. One can improve surgical skills with one- or two-handed tasks. Bone work in ear surgeries can be performed in a reproducible manner from routine, high-resolution computer tomography of the temporal bone of a real patient. CONCLUSION: With reference to our experience, the simulator is excellent for practicing each surgical step. In the future, we intend to use this virtual system in undergraduate and postgraduate training in otolaryngology. Orv Hetil. 2021; 162(16): 623-628.

Atypical Neurogenesis in Induced Pluripotent Stem Cells From Autistic Individuals.

BACKGROUND: Autism is a heterogeneous collection of disorders with a complex molecular underpinning. Evidence from postmortem brain studies have indicated that early prenatal development may be altered in autism. Induced pluripotent stem cells (iPSCs) generated from individuals with autism with macrocephaly also indicate prenatal development as a critical period for this condition. But little is known about early altered cellular events during prenatal stages in autism. METHODS: iPSCs were generated from 9 unrelated individuals with autism without macrocephaly and with heterogeneous genetic backgrounds, and 6 typically developing control individuals. iPSCs were differentiated toward either cortical or midbrain fates. Gene expression and high throughput cellular phenotyping was used to characterize iPSCs at different stages of differentiation. RESULTS: A subset of autism-iPSC cortical neurons were RNA-sequenced to reveal autism-specific signatures similar to postmortem brain studies, indicating a potential common biological mechanism. Autism-iPSCs differentiated toward a cortical fate displayed impairments in the ability to self-form into neural rosettes. In addition, autism-iPSCs demonstrated significant differences in rate of cell type assignment of cortical precursors and dorsal and ventral forebrain precursors. These cellular phenotypes occurred in the absence of alterations in cell proliferation during cortical differentiation, differing from previous studies. Acquisition of cell fate during midbrain differentiation was not different between control- and autism-iPSCs. CONCLUSIONS: Taken together, our data indicate that autism-iPSCs diverge from control-iPSCs at a cellular level during early stage of neurodevelopment. This suggests that unique developmental differences associated with autism may be established at early prenatal stages.

Interferon-γ signaling in human iPSC-derived neurons recapitulates neurodevelopmental disorder phenotypes.

Maternal immune activation increases the risk of neurodevelopmental disorders. Elevated cytokines, such as interferon-γ (IFN-γ), in offspring's brains play a central role. IFN-γ activates an antiviral cellular state, limiting viral entry and replication. Moreover, IFN-γ is implicated in brain development. We tested the hypothesis that IFN-γ signaling contributes to molecular and cellular phenotypes associated with neurodevelopmental disorders. Transient IFN-γ treatment of neural progenitors derived from human induced pluripotent stem cells increased neurite outgrowth. RNA sequencing analysis revealed that major histocompatibility complex class I (MHCI) genes were persistently up-regulated through neuronal differentiation-an effect that was mediated by IFN-γ-induced promyelocytic leukemia protein (PML) nuclear bodies. Critically, IFN-γ-induced neurite outgrowth required both PML and MHCI. We also found evidence that IFN-γ disproportionately altered the expression of genes associated with schizophrenia and autism, suggesting convergence between genetic and environmental risk factors. Together, these data implicate IFN-γ signaling in neurodevelopmental disorder etiology.

Spin-controlled generation of indistinguishable and distinguishable photons from silicon vacancy centres in silicon carbide.

Quantum systems combining indistinguishable photon generation and spin-based quantum information processing are essential for remote quantum applications and networking. However, identification of suitable systems in scalable platforms remains a challenge. Here, we investigate the silicon vacancy centre in silicon carbide and demonstrate controlled emission of indistinguishable and distinguishable photons via coherent spin manipulation. Using strong off-resonant excitation and collecting zero-phonon line photons, we show a two-photon interference contrast close to 90% in Hong-Ou-Mandel type experiments. Further, we exploit the system's intimate spin-photon relation to spin-control the colour and indistinguishability of consecutively emitted photons. Our results provide a deep insight into the system's spin-phonon-photon physics and underline the potential of the industrially compatible silicon carbide platform for measurement-based entanglement distribution and photonic cluster state generation. Additional coupling to quantum registers based on individual nuclear spins would further allow for high-level network-relevant quantum information processing, such as error correction and entanglement purification.