The Effects of Perceived Stress and Cortisol Concentration on Antiretroviral Adherence When Mediated by Psychological Flexibility Among Southern Black Men Living with HIV.

This pilot study investigates the correlation between psychological stress and antiretroviral therapy (ART) adherence and plasma HIV RNA (viral load) as mediated by psychological flexibility among Black men in the south. Data were collected from 48 HIV-positive, low income Black men. Results indicate a strong positive correlation between perceived stress and psychological inflexibility (adjusted for age and income rs = 0.67; p < 0.001), a negative correlation between psychological inflexibility and ART adherence (adjusted rs = - 0.32; p = 0.03), a negative correlation between perceived stress and ART adherence (adjusted rs = - 0.45; p = 0.006), and a negative correlation between ART adherence and viral load (adjusted rs = - 0.37; p = 0.04). Our findings suggest stress decreases adherence to ART and viral suppression among Black men living with HIV. However, psychological flexibility did not mediate the relationship between stress and treatment adherence. Hair cortisol concentrations were high (mean of 34.2 pg/mg), but uncorrelated with adherence.

Hyperviscosity Retinopathy Due to Waldenström Macroglobulinemia: A Case Report and Literature Review.

Purpose: This case report describes a case of hyperviscosity retinopathy secondary to the rare systemic hematologic malignant neoplasm Waldenström macroglobulinemia. Methods: Fundus photography, fluorescein angiography, optical coherence tomography (OCT), and OCT angiography were used as imaging modalities to characterize this pathology. Results: A 51-year-old man presented with hyperviscosity retinopathy and uniquely angiographically silent serous macular detachment. Over a 6-month period, he was treated with systemic and local therapies with little improvement in the hyperviscosity retinopathy, serous macular detachments, or visual acuity. Conclusions: Hyperviscosity retinopathy secondary to Waldenström macroglobulinemia presents a challenge to treating ophthalmologists given its rarity and the range of treatment responses described in the literature. Our patient's lack of response to antivascular endothelial growth factor and normal findings in OCT angiography and fluorescein angiography suggested the mechanism of subretinal fluid accumulation was not vascular endothelial growth factor mediated. Visual prognosis was guarded.

Nessys: A new set of tools for the automated detection of nuclei within intact tissues and dense 3D cultures.

Methods for measuring the properties of individual cells within their native 3D environment will enable a deeper understanding of embryonic development, tissue regeneration, and tumorigenesis. However, current methods for segmenting nuclei in 3D tissues are not designed for situations in which nuclei are densely packed, nonspherical, or heterogeneous in shape, size, or texture, all of which are true of many embryonic and adult tissue types as well as in many cases for cells differentiating in culture. Here, we overcome this bottleneck by devising a novel method based on labelling the nuclear envelope (NE) and automatically distinguishing individual nuclei using a tree-structured ridge-tracing method followed by shape ranking according to a trained classifier. The method is fast and makes it possible to process images that are larger than the computer's memory. We consistently obtain accurate segmentation rates of >90%, even for challenging images such as mid-gestation embryos or 3D cultures. We provide a 3D editor and inspector for the manual curation of the segmentation results as well as a program to assess the accuracy of the segmentation. We have also generated a live reporter of the NE that can be used to track live cells in 3 dimensions over time. We use this to monitor the history of cell interactions and occurrences of neighbour exchange within cultures of pluripotent cells during differentiation. We provide these tools in an open-access user-friendly format.

Transcriptionally dynamic progenitor populations organised around a stable niche drive axial patterning.

The elongating mouse anteroposterior axis is supplied by progenitors with distinct tissue fates. It is not known whether these progenitors confer anteroposterior pattern to the embryo. We have analysed the progenitor population transcriptomes in the mouse primitive streak and tail bud throughout axial elongation. Transcriptomic signatures distinguish three known progenitor types (neuromesodermal, lateral/paraxial mesoderm and notochord progenitors; NMPs, LPMPs and NotoPs). Both NMP and LPMP transcriptomes change extensively over time. In particular, NMPs upregulate Wnt, Fgf and Notch signalling components, and many Hox genes as progenitors transit from production of the trunk to the tail and expand in number. In contrast, the transcriptome of NotoPs is stable throughout axial elongation and they are required for normal axis elongation. These results suggest that NotoPs act as a progenitor niche whereas anteroposterior patterning originates within NMPs and LPMPs.

Direct Interactions Between Gli3, Wnt8b, and Fgfs Underlie Patterning of the Dorsal Telencephalon.

A key step in the development of the cerebral cortex is a patterning process, which subdivides the telencephalon into several molecularly distinct domains and is critical for cortical arealization. This process is dependent on a complex network of interactions between signaling molecules of the Fgf and Wnt gene families and the Gli3 transcription factor gene, but a better knowledge of the molecular basis of the interplay between these factors is required to gain a deeper understanding of the genetic circuitry underlying telencephalic patterning. Using DNA-binding and reporter gene assays, we here investigate the possibility that Gli3 and these signaling molecules interact by directly regulating each other's expression. We show that Fgf signaling is required for Wnt8b enhancer activity in the cortical hem, whereas Wnt/ß-catenin signaling represses Fgf17 forebrain enhancer activity. In contrast, Fgf and Wnt/ß-catenin signaling cooperate to regulate Gli3 expression. Taken together, these findings indicate that mutual interactions between Gli3, Wnt8b, and Fgf17 are crucial elements of the balance between these factors thereby conferring robustness to the patterning process. Hence, our study provides a framework for understanding the genetic circuitry underlying telencephalic patterning and how defects in this process can affect the formation of cortical areas.