Environmental factors favoring myopia development are still being studied and there is accumulating evidence for a significant role of nearwork. Recently, reading standard black-on-white text was ...found to activate the retinal OFF pathway and induce choroidal thinning, which is associated with myopia onset. Contrarily, reading white-on-black text led to thicker choroids, being protective against myopia. Respective effects on retinal processing are yet unknown. Here, we exploratively assessed the impact of contrast polarity on the retinal activity and possible interactions with eccentricity and refractive error. We recorded pattern electroretinograms in myopic and emmetropic adults while presenting a dead leaves stimulus (DLS), overlaid by masks of different size in ring or circle shape, either filled with uniform gray or text of inverted or standard contrast. In myopes, retinal responses for DLS with standard and inverted contrast were larger when the perifovea was stimulated (6-12 deg), however, including the fovea resulted in smaller amplitudes for inverted contrast than in emmetropes. The retina of emmetropes was more sensitive to inverted contrast than to standard and gray within 12 deg, but most sensitive for gray in the perifovea. This demonstrates that the refractive error influences the sensitivity to text contrast polarity, with a special role of the peripheral retina, which is in line with previous studies about blur sensitivity. Defining whether the differences derive from retinal processing or anatomical features of a myopic eye requires further investigation. Our approach might be a first step to explain how nearwork promotes the eye's elongation.
Presbyopia and myopia research shows a growing interest in ciliary muscle biometry using optical coherence tomography (OCT). Until now, segmentation of the ciliary muscle is often performed manually ...using either custom-developed programs or image processing software. Here we present a novel software for semi-automatic segmentation of the ciliary muscle. It provides direct import of OCT images in DICOM format, a standardized procedure for segmentation, image distortion correction, the export of anatomical ciliary muscle landmarks, like ciliary muscle apex and scleral spur, as well as a continuous thickness profile of the ciliary muscle as a novel way of analysis. All processing steps are stored as XML files, fostering documentation and reproducibility of research through the possibility of replicating the analysis. Additionally, CilOCT supports batch processing for the automated analysis of large numbers of images and the respective data export to tabulated text files based on the stored XML files. CilOCT was successfully applied in several studies and their results will be summarized in this paper.
This article examines the recent literary form of mash-up novels by comparing the German mash-up
Werther, der Werwolf
(2010) to its original
Die Leiden des jungen Werther
(1774) by Johann Wolfgang ...von Goethe. In both novels, the protagonist Werther is conceptualised as an antihero. In Goethe’s original, Werther’s existential failure is a result of his mental condition and inability to integrate into the bourgeois society; in the mash-up he fails because he struggles with his metamorphosis into a werewolf. In both cases, Werther’s obsessive love for a girl called Lotte aggravates the underlying conflict. This article aims to demonstrate the extent to which the antiheroic qualities of Goethe’s Werther are reflected in the mash-up character Werewolf-Werther, and to highlight to what extent the figure of the werewolf is an apt and contemporary metaphor for Werther’s story.
Biofeedback training has been used to access autonomically-controlled body functions through visual or acoustic signals to manage conditions like anxiety and hyperactivity. Here we examined the use ...of auditory biofeedback to improve accommodative responses to near visual stimuli in patients wearing single vision (SV) and multifocal soft contact lenses (MFCL). MFCLs are one evidence-based treatment shown to be effective in slowing myopia progression in children. However, previous research found that the positive addition relaxed accommodation at near, possibly reducing the therapeutic benefit. Accommodation accuracy was examined in 18 emmetropes and 19 myopes while wearing SVCLs and MFCLs (centre-distance). Short periods of auditory biofeedback training to improve the response (reduce the lag of accommodation) was performed and accommodation re-assessed while patients wore the SVCLs and MFCLs. Significantly larger accommodative lags were measured with MFCLs compared to SV. Biofeedback training effectively reduced the lag by ≥0.3D in individuals of both groups with SVCL and MFCL wear. The training was more effective in myopes wearing their habitual SVCLs. This study shows that accommodation can be changed with short biofeedback training independent of the refractive state. With this proof-of-concept, we hypothesize that biofeedback training in myopic children wearing MFCLs might improve the treatment effectiveness.
The APOBEC3 family of antiviral DNA cytosine deaminases is implicated as the second largest source of mutation in cancer. This mutational process may be a causal driver or inconsequential passenger ...to the overall tumor phenotype. We show that human APOBEC3A expression in murine colon and liver tissues increases tumorigenesis. All other APOBEC3 family members, including APOBEC3B, fail to promote liver tumor formation. Tumor DNA sequences from APOBEC3A-expressing animals display hallmark APOBEC signature mutations in TCA/T motifs. Bioinformatic comparisons of the observed APOBEC3A mutation signature in murine tumors, previously reported APOBEC3A and APOBEC3B mutation signatures in yeast, and reanalyzed APOBEC mutation signatures in human tumor datasets support cause-and-effect relationships for APOBEC3A-catalyzed deamination and mutagenesis in driving multiple human cancers.
Abstract
Late presentation to care and antiretroviral therapy (ART) initiation with advanced human immunodeficiency virus (HIV) disease are common in Latin America. We estimated the impact of these ...conditions on mortality in the region. We included adults enrolled during 2001–2014 at HIV care clinics. We estimated the adjusted attributable risk (AR) and population attributable fraction (PAF) for all-cause mortality of presentation to care with advanced HIV disease (advanced LP), ART initiation with advanced HIV disease, and not initiating ART. Advanced HIV disease was defined as CD4 of <200 cells/μL or acquired immune deficiency syndrome. AR and PAF were derived using marginal structural models. Of 9,229 patients, 56% presented with advanced HIV disease. ARs of death for advanced LP were 86%, 71%, and 58%, and PAFs were 78%, 58%, and 43% at 1, 5, and 10 years after enrollment. Among people without advanced LP, ARs of death for delaying ART were 39%, 32%, and 37% at 1, 5, and 10 years post-enrollment and PAFs were 20%, 14%, and 15%. Among people with advanced LP, ART decreased the hazard of death by 63% in the first year after enrollment, but 93% of these started ART; thus universal ART among them would reduce mortality by only 10%. Earlier presentation to care and earlier ART initiation would prevent most HIV deaths in Latin America.
Smoking is highly prevalent in people living with HIV/AIDS (PLHA), leading to detrimental effects in different tissues. We examined the effects of nicotine replacement therapy (NRT) on smoking ...cessation and vascular health. From December 2019 to October 2021, we prospectively enrolled PLHA who were actively smoking. The primary outcome was endothelial function measured by brachial artery flow-mediated dilatation (FMD). We evaluated the percent change in FMD compared to the baseline measure (Δ%FMD) to detect improvements among participants who quit smoking. To confirm the results, we used linear regression models to account for classical cardiovascular (CV) confounders. We included 117 participants with median age of 45.5 years (IQR= 36.4-54.8); 22 (20.4%) had hypertension, 9 (8.3%) had diabetes, almost half were smoking 20+ cigarettes/day (41.7%). After 12 weeks 30.76% participants quit smoking. Comparison of Δ%FMD change from baseline to week 12 showed that among participants adherent to therapy, there has been an increase in Δ%FMD when compared to those who relapsed (1.17% 0.29-2.98 vs -0.19% -1.95-0.91, p<0.001). After adjustment for CV factors, multiple linear regression showed that Δ%FMD in participants who quit smoking presented a 2.54 mean increase in comparison to those who continued smoking (p=0.007). In conclusion, this study provides evidence that a strategy of NRT and counseling is modestly effective for smoking cessation in PLHA and improves vascular health in a short period of time. This reinforces the importance of the widespread anti-tobacco programs in HIV clinics and the expected impact lowering the incidence of future cardiovascular events.
Anterior segment optical coherence tomography (AS-OCT), being non-invasive and well-tolerated, is the method of choice for an in vivo investigation of ciliary muscle morphology and function. The ...analysis requires the segmentation of the ciliary muscle, which is, when performed manually, both time-consuming and prone to examiner bias. Here, we present a convolutional neural network trained for the automatic segmentation of the ciliary muscle in AS-OCT images.
is based on the Freiburg U-net and was trained and validated using 1244 manually segmented OCT images from two previous studies. An accuracy of 97.5% for the validation dataset was achieved.
performance was evaluated by replicating the findings of a third study with 180 images as the test data. The replication demonstrated that
performed on par with two experienced examiners. The intersection-over-union index (0.84) of the ciliary muscle thickness profiles between
and an experienced examiner was the same as between the two examiners. The mean absolute error between the ciliary muscle thickness profiles of
and the two examiners (35.16 µm and 45.86 µm) was comparable to the one between the examiners (34.99 µm). A statistically significant effect of the segmentation type on the derived biometric parameters was found for the ciliary muscle area but not for the selective thickness reading ("perpendicular axis"). Both the inter-rater and the intra-rater reliability of
were good to excellent.
avoids time-consuming manual segmentation, thus enabling the analysis of large numbers of images of ample study cohorts while avoiding possible examiner biases.
is available as open-source.
Organotypic culture of human primary bronchial epithelial cells is a useful in vitro system to study normal biological processes and lung disease mechanisms, to develop new therapies, and to assess ...the biological perturbations induced by environmental pollutants. Herein, we investigate whether the perturbations induced by cigarette smoke (CS) and observed in the epithelium of smokers' airways are reproducible in this in vitro system (AIR-100 tissue), which has been shown to recapitulate most of the characteristics of the human bronchial epithelium. Human AIR-100 tissues were exposed to mainstream CS for 7, 14, 21, or 28 min at the air-liquid interface, and we investigated various biological endpoints e.g., gene expression and microRNA profiles, matrix metalloproteinase 1 (MMP-1) release at multiple postexposure time points (0.5, 2, 4, 24, 48 h). By performing a Gene Set Enrichment Analysis, we observed a significant enrichment of human smokers' bronchial epithelium gene signatures derived from different public transcriptomics datasets in CS-exposed AIR-100 tissue. Comparison of in vitro microRNA profiles with microRNA data from healthy smokers highlighted various highly translatable microRNAs associated with inflammation or with cell cycle processes that are known to be perturbed by CS in lung tissue. We also found a dose-dependent increase of MMP-1 release by AIR-100 tissue 48 h after CS exposure in agreement with the known effect of CS on this collagenase expression in smokers' tissues. In conclusion, a similar biological perturbation than the one observed in vivo in smokers' airway epithelium could be induced after a single CS exposure of a human organotypic bronchial epithelium-like tissue culture.
•Auditory biofeedback reduces accommodative lags for stimuli ≥2.5D.•Half of the experimental subjects reduced their lag of accommodation by ≥0.3D.•Some control subjects improved accuracy just by ...being aware of the accommodation task.
The purpose of this study was to investigate whether a reduction of the accommodative lag is possible by training the accuracy of accommodation using auditory biofeedback. Accommodation responses were measured in thirty-one young adults with myopia for dioptric target distances of 2.0, 2.5, and 3.0D using an eccentric infrared photorefractor. For the biofeedback training, subjects were randomly assigned to an experimental (n=15) or a control group (n=16). Subjects of the experimental group were provided with two tones while fixating a target, one tone was related to their accommodative response and the second to the target distance. Their task was to match these tones. The control group did not receive any auditory biofeedback. Two different training methods were applied, a continuous training of 200s, and ten consecutive sessions of 20s each. The training effects on the lag of accommodation (change Δ) were highly variable. Regarding the entire study group, the observed change in the accommodative lag was greater at closer distances, while no difference between the two training methods was revealed. Nevertheless, seven experimental subjects reduced their lag by ⩾0.3D (3.0D target distance: Δlong=−0.29±0.20D, Δshort=−0.24±0.21D). This reduction was also seen in two control subjects. Remeasurement revealed that the average training effect cannot be preserved over a period of 5–7days. The current investigation has shown that the accuracy of accommodation can be trained in some subjects using auditory biofeedback for target distances of 2.5D or closer.
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