Do biometric parameters improve the quality of optic nerve head measurements with spectral domain optical coherence tomography?

BACKGROUND: Spectral domain optical coherence tomography (SD-OCT) is a widely applied non-invasive technique for evaluating optic nerve head parameters. The aim of this study was to evaluate the impact of biometric parameters such as the spherical equivalent (SE) and the anterior corneal curvature (ACC) on the peripapillary retinal nerve fiber layer (pRNFL), Bruch's membrane opening (BMO), and the minimum rim width (MRW) measurements performed by spectral domain optical coherence tomography (SD-OCT) in glaucomatous and healthy eyes. METHODS: In this cross-sectional, case-control prospective pilot study, the glaucoma group consisted of 50 patients with previously diagnosed and treated glaucoma and one healthy group of 50 subjects. Two consecutive examinations of pRNFL, BMO, and MRW with SD-OCT for every patient were performed without ACC and objective refraction (imaging 1) and with them (imaging 2). RESULTS: The interclass correlation coefficient (ICC) reflected high agreement between imaging 1 and imaging 2 in both groups. The ICC in the glaucoma and healthy groups for pRNFL (0.99 vs. 0.98), BMO (0.95 vs. 0.97), and MRW (1.0 vs. 1.0) was comparable. CONCLUSIONS: Our preliminary data from a small number of eyes showed that the measurements of pRNFL, MRW, and BMO reflected high agreement between both imaging techniques with ACC and objective refraction and without these parameters in subjects with a refractive error up to ± 6.0 diopters. Further studies with participants with higher refractive error are necessary to evaluate the impact of biometric parameters such as SE and ACC on measurements with SD-OCT.

SARS-CoV-2 in first trimester pregnancy: a cohort study.

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) in first trimester pregnancy have an impact on the fetal development as measured by nuchal translucency thickness and pregnancy loss? SUMMARY ANSWER: Nuchal translucency thickness at the first trimester scan was not significantly different in pregnant women with versus without SARS-CoV-2 infection in early pregnancy and there was no significantly increased risk of pregnancy loss in women with SARS-CoV-2 infection in the first trimester. WHAT IS KNOWN ALREADY: Pregnant women are more vulnerable to viral infections. Previous coronavirus epidemics have been associated with increased maternal morbidity, mortality and adverse obstetric outcomes. Currently, no evidence exists regarding possible effects of SARS-CoV-2 in first trimester pregnancies. STUDY DESIGN, SIZE, DURATION: Cohort study of 1019 women with a double test taken between 17 February and 23 April 2020, as a part of the combined first trimester risk assessment, and 36 women with a first trimester pregnancy loss between 14 April and 21 May 2020, prior to the double test. The study period was during the first SARS-CoV-2 epidemic wave in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cohort 1 included pregnant women with a double test taken within the study period. The excess serum from each double test was analyzed for SARS-CoV-2 antibodies. Results were correlated to the nuchal translucency thickness and the number of pregnancy losses before or at the time of the first trimester scan. Cohort 2 included women with a pregnancy loss before the gestational age for double test sample. Serum from a blood test taken the day the pregnancy loss was identified was analyzed for SARS-CoV-2 antibodies. The study was conducted at a public university hospital serving ∼12% of pregnant women and births in Denmark. All participants in the study provided written informed consent. MAIN RESULTS AND THE ROLE OF CHANCE: Eighteen (1.8%) women had SARS-CoV-2 antibodies in the serum from the double test suggestive of SARS-CoV-2 infection in early pregnancy. There was no significant difference in nuchal translucency thickness for women testing positive for previous SARS-CoV-2 infection (n = 16) versus negative (n = 966) (P = 0.62). There was no significantly increased risk of pregnancy loss for women with antibodies (n = 1) (OR 3.4, 0.08-24.3 95% CI, P = 0.27). None of the women had been hospitalized due to SARS-CoV-2 infection. None of the women with pregnancy loss prior to the double test (Cohort 2) had SARS-CoV-2 antibodies. LIMITATIONS, REASONS FOR CAUTION: These results may only apply to similar populations and to patients who do not require hospitalization due to SARS-CoV-2 infection. A limitation of the study is that only 1.8% of the study population had SARS-CoV-2 antibodies suggestive of previous infection. WIDER IMPLICATION OF THE FINDINGS: Maternal SARS-CoV-2 infection had no effect on the nuchal translucency thickness and there was no significantly increased risk of pregnancy loss for women with SARS-CoV-2 infection in first trimester pregnancy. Evidence concerning COVID-19 in pregnancy is still limited. These data indicate that infection with SARS-CoV-2 in not hospitalized women does not pose a significant threat in first trimester pregnancies. Follow-up studies are needed to establish any risk to a fetus exposed to maternal SARS-CoV-2 infection. STUDY FUNDING/COMPETING INTEREST(S): Prof. H.S.N. and colleagues received a grant from the Danish Ministry of Research and Education for research of COVID-19 among pregnant women. The Danish government was not involved in the study design, data collection, analysis, interpretation of data, writing of the report or decision to submit the paper for publication. A.I., J.O.-L., J.B.-R., D.M.S., J.E.-F. and E.R.H. received funding from a Novo Nordisk Foundation (NNF) Young Investigator Grant (NNF15OC0016662) and a Danish National Science Foundation Center Grant (6110-00344B). A.I. received a Novo Scholarship. J.O.-L. is funded by an NNF Pregraduate Fellowship (NNF19OC0058982). D.W. is funded by the NNF (NNF18SA0034956, NNF14CC0001, NNF17OC0027594). A.M.K. is funded by a grant from the Rigshospitalet's research fund. H.S.N. has received speaker's fees from Ferring Pharmaceuticals, Merck Denmark A/S and Ibsa Nordic (outside the submitted work). N.l.C.F. has received a grant from Gedeon Richter (outside the submitted work). A.M.K. has received speaker's fee from Merck (outside the submitted work). The other authors did not report any potential conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

A distinctive epigenetic ageing profile in human granulosa cells.

STUDY QUESTION: Does women's age affect the DNA methylation (DNAm) profile differently in mural granulosa cells (MGCs) from other somatic cells? SUMMARY ANSWER: Accumulation of epimutations by age and a higher number of age-related differentially methylated regions (DMR) in MGCs were found compared to leukocytes from the same woman, suggesting that the MGCs have a distinctive epigenetic profile. WHAT IS KNOWN ALREADY: The mechanisms underlying the decline in women's fertility from the mid-30s remain to be fully elucidated. The DNAm age of many healthy tissues changes predictably with and follows chronological age, but DNAm age in some reproductive tissues has been shown to depart from chronological age (older: endometrium; younger: cumulus cells, spermatozoa). STUDY DESIGN, SIZE, DURATION: This study is a multicenter cohort study based on retrospective analysis of prospectively collected data and material derived from healthy women undergoing IVF or ICSI treatment following ovarian stimulation with antagonist protocol. One hundred and nineteen women were included from September 2016 to June 2018 from four clinics in Denmark and Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS: Blood samples were obtained from 118 healthy women with varying ovarian reserve status. MGCs were collected from 63 of the 119 women by isolation from pooled follicles immediately after oocyte retrieval. DNA from leukocytes and MGCs was extracted and analysed with a genome-wide methylation array. Data from the methylation array were processed using the ENmix package. Subsequently, DNAm age was calculated using established and tailored age predictors and DMRs were analysed with the DMRcate package. MAIN RESULTS AND ROLE OF CHANCE: Using established age predictors, DNAm age in MGCs was found to be considerable younger and constant (average: 2.7 years) compared to chronological age (average: 33.9 years). A Granulosa Cell clock able to predict the age of both MGCs (average: 32.4 years) and leukocytes (average: 38.8 years) was successfully developed. MGCs differed from leukocytes in having a higher number of epimutations (P = 0.003) but predicted telomere lengths unaffected by age (Pearson's correlation coefficient = -0.1, P = 0.47). DMRs associated with age (age-DMRs) were identified in MGCs (n = 335) and in leukocytes (n = 1) with a significant enrichment in MGCs for genes involved in RNA processing (45 genes, P = 3.96 × 10-08) and gene expression (152 genes, P = 2.3 × 10-06). The top age-DMRs included the metastable epiallele VTRNA2-1, the DNAm regulator ZFP57 and the anti-Müllerian hormone (AMH) gene. The apparent discordance between different epigenetic measures of age in MGCs suggests that they reflect difference stages in the MGC life cycle. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: No gene expression data were available to associate with the epigenetic findings. The MGCs are collected during ovarian stimulation, which may influence DNAm; however, no correlation between FSH dose and number of epimutations was found. WIDER IMPLICATIONS OF THE FINDINGS: Our findings underline that the somatic compartment of the follicle follows a different methylation trajectory with age than other somatic cells. The higher number of epimutations and age-DMRs in MGCs suggest that their function is affected by age. STUDY FUNDING/COMPETING INTEREST(S): This project is part of ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS, the Danish National Research Foundation and the European Research Council. The authors declare no conflict of interest.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

[Recommendations for the perioperative use of dipyrone : Expert recommendation of the working group on acute pain of the German Pain Society, the scientific working group on pain medicine of the German Society for Anesthesiology and Intensive Care Medicine and the surgical working group on acute pain of the German Society for Surgery with participation of representatives of the Drug Commission of the German Medical Association]. / Empfehlungen zur perioperativen Anwendung von Metamizol : Expertenempfehlung des Arbeitskreises Akutschmerz der Deutschen Schmerzgesellschaft, des Wissenschaftlichen Arbeitskreises Schmerzmedizin der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin und der Chirurgischen Arbeitsgemeinschaft Akutschmerz der Deutschen Gesellschaft für Chirurgie unter Beteiligung von Vertretern der Arzneimittelkommission der deutschen Ärzteschaft.

BACKGROUND: Dipyrone (metamizole) is widely used for perioperative pain management in countries where it is marketed; however, uncertainty exists concerning the safe use of this drug, specifically considering the rare adverse event of an agranulocytosis. METHODS: As evidence from published studies was lacking, an expert panel developed recommendations for the perioperative use of dipyrone. After a formal, structured consensus process, the recommendations were approved by the involved medical societies. RESULTS: The panel agreed that blood cell counts shall not be standard for short-term perioperative use in patients unless they are at risk for neutropenia. The medical staff shall be aware of the symptoms and course of action when agranulocytosis is suspected. Patients shall be informed about the risks and benefits of dipyrone and about potential alternatives. The expert group concluded that dipyrone has a relatively positive risk-benefit ratio compared to other nonopioid analgesics. The group strongly recommended educating patients about the symptoms of agranulocytosis if they have received dipyrone over several days and/or treatment is to be continued after discharge, because agranulocytosis can occur several days after discontinuation of metamizole. Further recommendations refer to the information of the physician taking over the patient's care after discharge and the avoidance of re-exposure in patients having previously suffered from dipyrone-induced agranulocytosis. CONCLUSION: The group's recommendations shall be communicated in order to raise medical staff's and patients' awareness of the appropriate use of dipyrone in the perioperative period.

Disseminated histoplasmosis and AIDS: a prospective and multicentre study to evaluate the performance of different diagnostic tests.

The burden of histoplasmosis has been poorly documented in most of the endemic areas for the disease, including Brazil. Also, modern non-culture-based diagnostic tests are often non-available in these regions. This was a prospective cohort study in HIV-infected patients with suspected disseminated disease evaluated with different diagnostic tests. Patients were enrolled in three referral medical centres in Porto Alegre, Brazil. Among 78 evaluated patients, disseminated histoplasmosis was confirmed in eight individuals (10.3%) by the means of classical (culture/histopathology) tests. Antigen detection in the urine was found to be more sensitive: IMMY® ALPHA ELISA detected 13 positive cases (16.7%) and the in-house ELISA test developed by the Centers for Disease Prevention and Control (CDC) detected 14 (17.9%). IMMY® and CDC tests provided concordant results in 96.2% of cases. This is the first study to compare the performance of the in-house CDC ELISA test with the IMMY® commercial test for the diagnosis of histoplasmosis, and a high degree of concordance was observed. The study revealed that H. capsulatum is an important agent of disseminated disease in AIDS patients in Brazil, reinforcing the importance of making available modern diagnostic tests as well as safer antifungal agents for the treatment of histoplasmosis.

[Prevalence of hearing loss in Northern and Southern Germany. German version]. / Prävalenz von Schwerhörigkeit in Nord- und Süddeutschland.

BACKGROUND: The HÖRSTAT study conducted in Northwest Germany yielded hearing impairment in approximately 16% of adults according to the World Health Organization (WHO) criterion. However, the robustness of extrapolations on a national level might be questioned, as the epidemiological data were collected on a regional level. METHODS: Independently from HÖRSTAT, the "Hearing in Germany" study examined adult hearing in Aalen, a town located in Southwest Germany. Both cross-sectional studies were based on stratified random samples from the general population. Pure-tone average at 0.5, 1, 2, and 4 kHz (PTA4), the prevalence of hearing impairment (WHO criterion: PTA4 in the better ear >25 dB HL), and hearing aid provision were compared. Data from the Aalen study and HÖRSTAT were pooled (n = 3105) to extrapolate the prevalence and degree of hearing impairment for the years 2015, 2020, and 2025. RESULTS: Both studies show very similar results for PTA4. Weighted for official population statistics, the prevalence of hearing impairment according to the WHO criterion is 16.2% among adults, affecting 11.1 million persons in Germany. Due to demographic changes, the prevalence is expected to increase in the medium term by around 1% per 5­year period. With a similar degree of hearing loss, hearing aid provision differs from place to place. CONCLUSION: Adjusted for gender and age to the European Standard Population (ESP), the prevalence of hearing impairment observed both in HÖRSTAT and the Aalen sample is considerably lower than reported for international studies. Since the analysis refers to cross-sectional data only, possible cohort effects are not considered in the prevalence projection.

Prevalence of hearing loss in Northern and Southern Germany.

BACKGROUND: The HÖRSTAT study conducted in Northwest Germany found hearing impairment in approximately 16% of adults when applying the World Health Organization (WHO) criterion. However, the robustness of extrapolations to a national level might be questioned, as the epidemiological data were collected on a regional level. METHODS: Independently from HÖRSTAT, the "Hearing in Germany" study examined adult hearing in Aalen, a town located in Southwest Germany. Both cross-sectional studies were based on stratified random samples from the general population. The average pure-tone threshold shift at 0.5, 1, 2, and 4 kHz (PTA4), the prevalence of hearing impairment (WHO criterion: PTA4 in the better ear >25), and hearing aid uptake were compared. Data from the Aalen and HÖRSTAT studies were pooled (n = 3105) to extrapolate to the prevalence and the degree of hearing impairment for the years 2015, 2020, and 2025. RESULTS: Both studies yielded very similar results for PTA4. Weighted for official population statistics, the prevalence of hearing impairment according to the WHO criterion is 16.2% in adults, thus affecting 11.1 million persons in Germany. Owing to demographic changes, the prevalence is expected to increase in the medium term by around 1% per 5­year period. With a similar degree of hearing loss, hearing aid provision differs from place to place. CONCLUSION: When adjusted for gender and age to the European Standard Population, the prevalence of hearing impairment observed both in HÖRSTAT and the Aalen sample is considerably lower than reported for international studies. Since the analysis refers to cross-sectional data only, possible cohort effects are not considered in the prevalence projection.

Demonstration of Confined Electron Gas and Steep-Slope Behavior in Delta-Doped GaAs-AlGaAs Core-Shell Nanowire Transistors.

Strong surface and impurity scattering in III-V semiconductor-based nanowires (NW) degrade the performance of electronic devices, requiring refined concepts for controlling charge carrier conductivity. Here, we demonstrate remote Si delta (δ)-doping of radial GaAs-AlGaAs core-shell NWs that unambiguously exhibit a strongly confined electron gas with enhanced low-temperature field-effect mobilities up to 5 × 10(3) cm(2) V(-1) s(-1). The spatial separation between the high-mobility free electron gas at the NW core-shell interface and the Si dopants in the shell is directly verified by atom probe tomographic (APT) analysis, band-profile calculations, and transport characterization in advanced field-effect transistor (FET) geometries, demonstrating powerful control over the free electron gas density and conductivity. Multigated NW-FETs allow us to spatially resolve channel width- and crystal phase-dependent variations in electron gas density and mobility along single NW-FETs. Notably, dc output and transfer characteristics of these n-type depletion mode NW-FETs reveal excellent drain current saturation and record low subthreshold slopes of 70 mV/dec at on/off ratios >10(4)-10(5) at room temperature.

ANO1 (TMEM16A) in pancreatic ductal adenocarcinoma (PDAC).

Pancreatic ductal adenocarcinoma (PDAC) has one of the worst survival rates of all cancers. ANO1 (TMEM16A) is a recently identified Ca(2+)-activated Cl(-) channel (CaCC) that is upregulated in several tumors. Although ANO1 was subject to extensive studies in the recent years, its pathophysiological function has only been poorly understood. The aim of the present study is to establish the significance of ANO1 in PDAC behavior and demarcate its roles in PDAC from those of the volume-regulated anion channel (VRAC). We performed qPCR and Western blot measurements on different PDAC cell lines (Panc-1, Mia PaCa 2, Capan-1, AsPC-1, BxPC-3) and compared the results to those obtained in a human pancreatic ductal epithelium (HPDE) cell line. All cancer cell lines showed an upregulation of ANO1 on mRNA and protein levels. Whole-cell patch-clamp recordings identified large Ca(2+) and voltage-dependent Cl(-) currents in PDAC cells. Using siRNA knockdown of ANO1 and three ANO1 inhibitors (T16Ainh-A01, CaCCinh-A01, and NS3728), we found that ANO1 is the main constituent of CaCC current in PDAC cells. We further characterized these three inhibitors and found that they had unspecific effects on the free intracellular calcium concentration. Functional studies on PDAC behavior showed that surprisingly inhibition of ANO1 did not influence cellular proliferation. On the other hand, we found ANO1 channel to be pivotal in PDAC cell migration as assessed in wound healing experiments.

Peripapillary Choroidal Thickness and Choroidal Area in Glaucoma, Ocular Hypertension and Healthy Subjects by SD-OCT.

BACKGROUND: The exact pathogenesis of open angle glaucoma and ocular hypertension remains unclear. Hemodynamic influences are discussed as potential risk factors and the choroid may play an important role in the pathogenesis of open angle glaucoma or ocular hypertension. The current study investigates peripapillary choroidal thickness and choroidal area in patients with open angle glaucoma, subjects with ocular hypertension and healthy subjects using spectral-domain OCT. It furthermore assesses the association between peripapillary choroidal thickness and age, central corneal thickness, refractive error and intraocular pressure. PATIENTS AND METHODS: Prospectively recorded data of 213 eyes of 177 open angle glaucoma patients, 73 eyes of 50 subjects with ocular hypertension and 152 eyes of 116 healthy control subjects were analyzed by fitting a linear mixed model including age and disease. RESULTS: Peripapillary choroidal thickness was thinnest in glaucoma patients (125 µm), followed by healthy subjects (127 µm) and ocular hypertensive subjects (135 µm). A marginally significant difference was present between ocular hypertension and glaucoma (p=0.059). Thickest choroids were found superiorly and thinnest choroids inferiorly. Choroidal area was highest in the supero-nasal and lowest in the infero-temporal sectors. Choroidal thickness decreased with age, no significant correlation was evident between peripapillary choroidal thickness and refractive error or intraocular pressure. Peripapillary choroidal thickness and central corneal thickness are significantly negative correlated in healthy subjects. CONCLUSIONS: There is a trend towards thicker choroids in ocular hypertensive subjects compared to healthy subjects or glaucoma patients. Thickest choroids are found superiorly, thinnest inferiorly. Interestingly, choroidal area is thinnest in the temporal-inferior sector, one of the regions where glaucomatous damage tends to start.

Anoctamin 6 differs from VRAC and VSOAC but is involved in apoptosis and supports volume regulation in the presence of Ca2+.

Anoctamin 6 (ANO6), also known as TMEM16F, has been shown to be a calcium-activated anion channel with delayed calcium activation. The cellular function of ANO6 is under debate, and different groups have come to different conclusions about ANO6's physiological role. Although it is now quite well established that ANO6 is distinct from the volume-regulated anion channel, it is still unclear whether ANO6 or other anoctamins can be activated by cell swelling. In this study, we suggest that ANO1, ANO6, and ANO10 do not contribute to the volume-activated current in ANO-overexpressing HEK293 cells. Furthermore, knock-down of ANO6 in Ehrlich ascites tumor cells (EATC) and Ehrlich-Lettre ascites (ELA) did not decrease but instead significantly increased swelling-activated membrane currents. Knock-down of ANO6 in EATC did not reduce regulatory volume decrease (RVD) in the absence of extracellular calcium, whereas it significantly reduced RVD in the presence of calcium. Interestingly, we found that knock-down of ANO6 in ELA cells resulted in a decrease in cisplatin-induced caspase-3 activity, confirming earlier findings that ANO6 is involved in apoptosis. Finally, knock-down of ANO1 and ANO6 did not affect the volume-sensitive release of taurine in ELA cells. Thus, our data provide evidence that ANO6 cannot be activated directly by cell swelling unless Ca(2+) is present. We also conclude that ANO6 carries a current during RVD, provided extracellular calcium is present. Thus, swelling activation of ANO6 requires the presence of free calcium.

[ChatGPT and the German board examination for ophthalmology: an evaluation]. / ChatGPT und die deutsche Facharztprüfung für Augenheilkunde: eine Evaluierung.

PURPOSE: In recent years artificial intelligence (AI), as a new segment of computer science, has also become increasingly more important in medicine. The aim of this project was to investigate whether the current version of ChatGPT (ChatGPT 4.0) is able to answer open questions that could be asked in the context of a German board examination in ophthalmology. METHODS: After excluding image-based questions, 10 questions from 15 different chapters/topics were selected from the textbook 1000 questions in ophthalmology (1000 Fragen Augenheilkunde 2nd edition, 2014). ChatGPT was instructed by means of a so-called prompt to assume the role of a board certified ophthalmologist and to concentrate on the essentials when answering. A human expert with considerable expertise in the respective topic, evaluated the answers regarding their correctness, relevance and internal coherence. Additionally, the overall performance was rated by school grades and assessed whether the answers would have been sufficient to pass the ophthalmology board examination. RESULTS: The ChatGPT would have passed the board examination in 12 out of 15 topics. The overall performance, however, was limited with only 53.3% completely correct answers. While the correctness of the results in the different topics was highly variable (uveitis and lens/cataract 100%; optics and refraction 20%), the answers always had a high thematic fit (70%) and internal coherence (71%). CONCLUSION: The fact that ChatGPT 4.0 would have passed the specialist examination in 12 out of 15 topics is remarkable considering the fact that this AI was not specifically trained for medical questions; however, there is a considerable performance variability between the topics, with some serious shortcomings that currently rule out its safe use in clinical practice.

The role of TMEM16A (ANO1) and TMEM16F (ANO6) in cell migration.

Members of the TMEM16 family have recently been described as Ca(2+)-activated Cl(-) channels. They have been implicated in cancer and appear to be associated with poor patient prognosis. Here, we investigate the role of TMEM16 channels in cell migration, which is largely unknown. We focused on TMEM16A and TMEM16F channels that have the highest expression of TMEM16 channels in Ehrlich Lettre ascites (ELA) cells. Due to the lack of specific pharmacological modulators, we employed a miRNA approach and stably knocked down the expression of TMEM16A and TMEM16F channels, respectively. Migration analysis shows that TMEM16A KD clones are affected in their directional migration, whereas TMEM16F KD clones show a 40 % reduced rate of cell migration. Moreover, TMEM16A KD clones have a smaller projected cell area, and they are rounder than TMEM16F KD clones. The morphological changes are linearly correlated with the directionality of cells. TMEM16A and TMEM16F, thus, have an important function in cell migration-TMEM16A in directional migration, TMEM16F in determination of the speed of migration. We conclude that TMEM16A and TMEM16F channels have a distinct impact on the steering and motor mechanisms of migrating ELA cells.

Intratumoral heterogeneity after targeted therapy in murine cancer models with differing degrees of malignancy.

INTRODUCTION: Conventional morphologic and volumetric assessment of treatment response is not suitable for adequately assessing responses to targeted cancer therapy. The aim of this study was to evaluate changes in tumor composition after targeted therapy in murine models of breast cancer with differing degrees of malignancy via non-invasive magnetic resonance imaging (MRI). MATERIALS AND METHODS: Mice bearing highly malignant 4T1 tumors or low malignant 67NR tumors were treated with either a combination of two immune checkpoint inhibitors (ICI, anti-PD1 and anti-CTLA-4) or the multi-tyrosine kinase inhibitor sorafenib, following experiments with macrophage-depleting clodronate-loaded liposomes and vessel-stabilizing angiopoietin-1. Mice were imaged on a 9.4 T small animal MRI system with a multiparametric (mp) protocol, comprising T1 and T2 mapping and diffusion-weighted imaging. Tumors were analyzed ex vivo with histology. RESULTS AND DISCUSSIONS: All treatments led to an increase in non-viable areas, but therapy-induced intratumoral changes differed between the two tumor models and the different targeted treatments. While ICI treatment led to intratumoral hemorrhage, sorafenib treatment mainly induced intratumoral necrosis. Treated 4T1 tumors showed increasing and extensive areas of necrosis, in comparison to 67NR tumors with only small, but also increasing, necrotic areas. After either of the applied treatments, intratumoral heterogeneity, was increased in both tumor models, and confirmed ex vivo by histology. Apparent diffusion coefficient with subsequent histogram analysis proved to be the most sensitive MRI sequence. In conclusion, mp MRI enables to assess dedicated therapy-related intratumoral changes and may serve as a biomarker for treatment response assessment.

Left atrial appendage volume is an independent predictor of atrial arrhythmia recurrence following cryoballoon pulmonary vein isolation in persistent atrial fibrillation.

Purpose: Pulmonary vein isolation (PVI) is the cornerstone of atrial fibrillation (AF) ablation in persistent AF (persAF), and cryoballoon PVI emerged as an initial ablation strategy. Symptomatic atrial arrhythmia recurrence following successful PVI in persAF is observed more frequently than in paroxysmal AF. Predictors for arrhythmia recurrence following cryoballoon PVI for persAF are not well described, and the role of left atrial appendage (LAA) anatomy is uncertain. Methods: Patients with symptomatic persAF and pre-procedural cardiac computed tomography angiography (CCTA) images undergoing initial second-generation cryoballoon (CBG2) were enrolled. Left atrial (LA), pulmonary vein (PV) and LAA anatomical data were assessed. Clinical outcome and predictors for atrial arrhythmia recurrence were evaluated by univariate and multivariate regression analysis. Results: From May 2012 to September 2016, 488 consecutive persAF patients underwent CBG2-PVI. CCTA with sufficient quality for measurements was available in 196 (60.4%) patients. Mean age was 65.7 ± 9.5 years. Freedom from arrhythmia was 58.2% after a median follow-up of 19 (13; 29) months. No major complications occurred. Independent predictors for arrhythmia recurrence were LAA volume (HR 1.082; 95% CI, 1.032 to 1.134; p = 0.001) and mitral regurgitation ≥ grade 2 (HR, 2.49; 95% CI 1.207 to 5.126; p = 0.013). LA volumes ≥110.35 ml [sensitivity: 0.81, specificity: 0.40, area under the curve (AUC) = 0.62] and LAA volumes ≥9.75 ml (sensitivity: 0.56, specificity 0.70, AUC = 0.64) were associated with recurrence. LAA-morphology, classified as chicken-wing (21.9%), windsock (52.6%), cactus (10.2%) and cauliflower (15.3%), did not predict outcome (log-rank, p = 0.832). Conclusion: LAA volume and mitral regurgitation were independent predictors for arrhythmia recurrence following cryoballoon ablation in persAF. LA volume was less predictive and correlated with LAA volume. LAA morphology did not predict the clinical outcome. To improve outcomes in persAF ablation, further studies should focus on treatment strategies for persAF patients with large LAA and mitral regurgitation.

On the role of TRPC1 in control of Ca2+ influx, cell volume, and cell cycle.

Ca(+) signaling plays a crucial role in control of cell cycle progression, but the understanding of the dynamics of Ca(2+) influx and release of Ca(2+) from intracellular stores during the cell cycle is far from complete. The aim of the present study was to investigate the role of the free extracellular Ca(2+) concentration ([Ca(2+)](o)) in cell proliferation, the pattern of changes in the free intracellular Ca(2+) concentration ([Ca(2+)](i)) during cell cycle progression, and the role of the transient receptor potential (TRP)C1 in these changes as well as in cell cycle progression and cell volume regulation. In Ehrlich Lettré Ascites (ELA) cells, [Ca(2+)](i) decreased significantly, and the thapsigargin-releasable Ca(2+) pool in the intracellular stores increased in G(1) as compared with G(0). Store-depletion-operated Ca(2+) entry (SOCE) and TRPC1 protein expression level were both higher in G(1) than in G(0) and S phase, in parallel with a more effective volume regulation after swelling [regulatory volume decrease (RVD)] in G(1) as compared with S phase. Furthermore, reduction of [Ca(2+)](o), as well as two unspecific SOCE inhibitors, 2-APB (2-aminoethyldiphenyl borinate) and SKF96365 (1-(ß-[3-(4-methoxy-phenyl)propoxyl-4-methoxyphenethyl)1H-imidazole-hydrochloride), inhibited ELA cell proliferation. Finally, Madin-Darby canine kidney cells in which TRPC1 was stably silenced [TRPC1 knockdown (TRPC1-KD) MDCK] exhibited reduced SOCE, slower RVD, and reduced cell proliferation compared with mock controls. In conclusion, in ELA cells, SOCE and TRPC1 both seem to be upregulated in G(1) as compared with S phase, concomitant with an increased rate of RVD. Furthermore, TRPC1-KD MDCK cells exhibit decreased SOCE, decreased RVD, and decreased proliferation, suggesting that, at least in certain cell types, TRPC1 is regulated during cell cycle progression and is involved in SOCE, RVD, and cell proliferation.

Path entanglement of continuous-variable quantum microwaves.

Path entanglement constitutes an essential resource in quantum information and communication protocols. Here, we demonstrate frequency-degenerate entanglement between continuous-variable quantum microwaves propagating along two spatially separated paths. We combine a squeezed and a vacuum state using a microwave beam splitter. Via correlation measurements, we detect and quantify the path entanglement contained in the beam splitter output state. Our experiments open the avenue to quantum teleportation, quantum communication, or quantum radar with continuous variables at microwave frequencies.

Cryoballoon in atrial fibrillation ablation.

Encouraging results of ablation therapy in patients with paroxysmal atrial fibrillation (AF) have prompted changes in professional practice guidelines. The most recent European guidelines have suggested that ablation might be offered as first-line therapy in selected patients. Cryoballoon ablation is a promising technology in interventional AF therapy. Two different sizes of the cryoballoon are currently available: a smaller (23 mm) and a larger (28 mm) balloon relative to the ostial diameter of the pulmonary veins. New tools, the circular mapping catheter and the use of intracardiac echocardiography, provide important periprocedural information. A meta-analysis of previous studies revealed outcome data with an AF-free survival rate of 72.83% at the 1-year follow-up in paroxysmal AF patients undergoing cryoballoon ablation. The most frequent, but reversible complication is phrenic nerve palsy with reported incidences up to 10%. All efforts must be taken to overcome this limitation, since the overall major complication rate tends to be lower in cryoballoon compared to radiofrequency ablation. In persistent AF, reported results in cryoballoon ablation had a limited success rate below 50% after a single procedure. A double balloon approach using both cryoballoon sizes might overcome some of the limitations in persistent AF. Prospective data and randomized studies are required. This article outlines the current status of cryoballoon technology in AF ablation therapy.

[Optical coherence tomography (OCT) in glaucoma diagnostics]. / Stellenwert der optischen Kohärenztomografie (OCT) für die Glaukomdiagnostik.

Optical coherence tomography (OCT) provides high resolution objective and quantitative measurements of the optic disc parameters and RNFL thickness and has been widely used for detection of glaucomatous damage and disease progression. The recent introduction of spectral domain (SD)-OCT technology, also known as Fourier domain (FD)-OCT offers significant advantages over the previous time domain (TD)-OCT, allowing 3 D imaging of the retina and optic disc with ultra-high acquisition speed and ultra-high resolution. The higher resolution of (SD)-OCT offers enhanced visualisation and improved segmentation of the retinal layers, providing a higher accuracy in identification of subtle changes of the optic disc and RNFL thinning associated with glaucoma.