Ablation of smooth muscle myosin heavy chain SM2 increases smooth muscle contractility and results in postnatal death in mice

The smooth muscle myosin heavy chains (SMHC) are motor proteins powering smooth muscle contraction. Alternate splicing of SHMC gene at the C-terminus produces SM1, and SM2 myosin isoforms; SM2 (200 kDa) contains a unique 9-amino-acid sequence at the carboxyl terminus, whereas SM1 (204 kDa) has a 43 amino acid non-helical tail region. To date the functional difference between C-terminal isoforms has not been established; therefore, we used an exon-specific gene targeting strategy and generated a mouse model specifically deficient in SM2. Deletion of exon-41 of the SMHC gene resulted in a complete loss of SM2 in homozygous (_SM2^-/-^_) mice, accompanied by a concomitant down-regulation of SM1 in bladders. While heterozygous (_SM2^+/-^_) mice appeared normal and fertile, _SM2^-/-^_ mice died within 30 days after birth. The peri-mortal _SM2^-/-^_ mice showed reduced body weight, distention of the bladder and alimentary tract, and end-stage hydronephrosis. Interestingly, strips from _SM2^-/-^_ bladders showed increased contraction to K^+^ depolarization or M3 receptor activation. These results suggest that SM2 myosin has a distinct functional role in smooth muscle, and the deficiency of SM2 increases smooth muscle contractility, and causes dysfunctions of smooth muscle organs, including the bladder that leads to the end-stage hydronephrosis and postnatal death

Plastron properties of a superhydrophobic surface

Most insects and spiders drown when submerged during flooding or tidal inundation, but some are able to survive and others can remain submerged indefinitely without harm. Many achieve this by natural adaptations to their surface morphology to trap films of air, creating plastrons which fix the water-vapor interface and provide an incompressible oxygen-carbon dioxide exchange surface. Here the authors demonstrate how the surface of an extremely water-repellent foam mimics this mechanism of underwater respiration and allows direct extraction of oxygen from aerated water. The biomimetic principle demonstrated can be applied to a wide variety of man-made superhydrophobic materials

Psychological and cognitive determinants of vision function in age-related macular degeneration.

OBJECTIVE: To investigate the effect of coping strategies, depression, physical health, and cognition on National Eye Institute Visual Function Questionnaire scores obtained at baseline in a sample of older patients with age-related macular degeneration (AMD) enrolled in the Improving Function in AMD Trial, a randomized controlled clinical trial that compares the efficacy of problem-solving therapy with that of supportive therapy to improve vision function in patients with AMD. METHODS: Baseline evaluation of 241 older outpatients with advanced AMD who were enrolled in a clinical trial testing the efficacy of a behavioral intervention to improve vision function. Vision function was characterized as an interval-scaled, latent variable of visual ability based on the near-vision subscale of the National Eye Institute Vision Function Questionnaire-25 plus Supplement. RESULTS: Visual ability was highly correlated with visual acuity. However, a multivariate model revealed that patient coping strategies and cognitive function contributed to their ability to perform near-vision activities independent of visual acuity. CONCLUSIONS: Patients with AMD vary in their coping strategies and cognitive function and in their visual acuity, and that variability determines patients\u27 self-report of vision function. Understanding patient coping mechanisms and cognition may help increase the precision of vision rating scales and suggest new interventions to improve vision function and quality of life in patients with AMD. Trial Registration clinicaltrials.gov Identifier: NCT00572039

Improving function in Age-Related Macular Degeneration: design and methods of a randomized clinical trial.

Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in older adults and impairs the ability to read, drive, and live independently and increases the risk for depression, falls, and earlier mortality. Although new medical treatments have improved AMD\u27s prognosis, vision-related disability remains a major public health problem. Improving Function in AMD (IF-AMD) is a two-group randomized, parallel design, controlled clinical trial that compares the efficacy of Problem-Solving Therapy (PST) with Supportive Therapy (ST) (an attention control treatment) to improve vision function in 240 patients with AMD. PST and ST therapists deliver 6 one-hour respective treatment sessions to subjects in their homes over 2 months. Outcomes are assessed masked to treatment assignment at 3 months (main trial endpoint) and 6 months (maintenance effects). The primary outcome is targeted vision function (TVF), which refers to specific vision-dependent functional goals that subjects highly value but find difficult to achieve. TVF is an innovative outcome measure in that it is targeted and tailored to individual subjects yet is measured in a standardized way. This paper describes the research methods, theoretical and clinical aspects of the study treatments, and the measures used to evaluate functional and psychiatric outcomes in this population

Improving Function in Age-related Macular Degeneration: A Randomized Clinical Trial.

PURPOSE: To compare the efficacy of problem-solving therapy (PST) with supportive therapy (ST) to improve targeted vision function (TVF) in age-related macular degeneration (AMD). DESIGN: Single-masked, attention-controlled, randomized clinical trial with outcome assessments at 3 months (main trial endpoint) and 6 months (maintenance effects). PARTICIPANTS: Patients with AMD (n = 241) attending retina practices. INTERVENTIONS: Whereas PST uses a structured problem-solving approach to reduce vision-related task difficulty, ST is a standardized attention-control treatment. MAIN OUTCOME MEASURES: We assessed TVF, the 25-item National Eye Institute Vision Function Questionnaire plus Supplement (NEI VFQ), the Activities Inventory (AI), and vision-related quality of life (QoL). RESULTS: There were no between-group differences in TVF scores at 3 (P = 0.47) or 6 (P = 0.62) months. For PST subjects, mean ± standard deviation TVF scores improved from 2.71±0.52 at baseline to 2.18±0.88 at 3 months (P = 0.001) and were 2.18±0.95 at 6 months (change from 3 to 6 months, P = 0.74). For ST subjects, TVF scores improved from 2.73±0.52 at baseline to 2.14±0.96 at 3 months (P = 0.001) and were 2.15±0.96 at 6 months (change from 3 to 6 months, P = 0.85). Similar proportions of PST and ST subjects had less difficulty performing a TVF goal at 3 months (77.4% vs 78.6%, respectively; P = 0.83) and 6 months (76.2% vs 79.1%, respectively; P = 0.61). There were no changes in the NEI VFQ or AI. Vision-related QoL improved for PST relative to ST subjects at 3 months (F(4, 192) = 2.46; P = 0.05) and at 6 months (F(4, 178) = 2.55; P = 0.05). The PST subjects also developed more adaptive coping strategies than ST subjects. CONCLUSIONS: We found that PST was not superior to ST at improving vision function in patients with AMD, but that PST improved their vision-related QoL. Despite the benefits of anti-vascular endothelial growth factor treatments, AMD remains associated with disability, depression, and diminished QoL. This clinical reality necessitates new rehabilitative interventions to improve the vision function and QoL of older persons with AMD. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article

Low Vision Depression Prevention Trial in Age-Related Macular Degeneration: A Randomized Clinical Trial.

PURPOSE: To compare the efficacy of behavior activation (BA) + low vision rehabilitation (LVR) with supportive therapy (ST) + LVR to prevent depressive disorders in patients with age-related macular degeneration (AMD). DESIGN: Single-masked, attention-controlled, randomized, clinical trial with outcome assessment at 4 months. PARTICIPANTS: Patients with AMD and subsyndromal depressive symptoms attending retina practices (n = 188). INTERVENTIONS: Before randomization, all subjects had 2 outpatient LVR visits, and were then randomized to in-home BA+LVR or ST+LVR. Behavior activation is a structured behavioral treatment that aims to increase adaptive behaviors and achieve valued goals. Supportive therapy is a nondirective, psychological treatment that provides emotional support and controls for attention. MAIN OUTCOME MEASURES: The Diagnostic and Statistical Manual IV defined depressive disorder based on the Patient Health Questionnaire-9 (primary outcome), Activities Inventory, National Eye Institute Vision Function Questionnaire-25 plus Supplement (NEI-VFQ), and NEI-VFQ quality of life (secondary outcomes). RESULTS: At 4 months, 11 BA+LVR subjects (12.6%) and 18 ST+LVR subjects (23.4%) developed a depressive disorder (relative risk [RR], 0.54; 95% CI, 0.27-1.06; P = 0.067). In planned adjusted analyses the RR was 0.51 (95% CI, 0.27-0.98; P = 0.04). A mediational analysis suggested that BA+LVR prevented depression to the extent that it enabled subjects to remain socially engaged. In addition, BA+LVR was associated with greater improvements in functional vision than ST+LVR, although there was no significant between-group difference. There was no significant change or between-group difference in quality of life. CONCLUSIONS: An integrated mental health and low vision intervention halved the incidence of depressive disorders relative to standard outpatient LVR in patients with AMD. As the population ages, the number of persons with AMD and the adverse effects of comorbid depression will increase. Promoting interactions between ophthalmology, optometry, rehabilitation, psychiatry, and behavioral psychology may prevent depression in this population

Emphasis on Carbohydrates May Negatively Influence Dietary Patterns in Youth With Type 1 Diabetes

This is an uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Association, publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes Care in print and online a

Semantic Segmentation of Histopathological Slides for the Classification of Cutaneous Lymphoma and Eczema

Mycosis fungoides (MF) is a rare, potentially life threatening skin disease, which in early stages clinically and histologically strongly resembles Eczema, a very common and benign skin condition. In order to increase the survival rate, one needs to provide the appropriate treatment early on. To this end, one crucial step for specialists is the evaluation of histopathological slides (glass slides), or Whole Slide Images (WSI), of the patients' skin tissue. We introduce a deep learning aided diagnostics tool that brings a two-fold value to the decision process of pathologists. First, our algorithm accurately segments WSI into regions that are relevant for an accurate diagnosis, achieving a Mean-IoU of 69% and a Matthews Correlation score of 83% on a novel dataset. Additionally, we also show that our model is competitive with the state of the art on a reference dataset. Second, using the segmentation map and the original image, we are able to predict if a patient has MF or Eczema. We created two models that can be applied in different stages of the diagnostic pipeline, potentially eliminating life-threatening mistakes. The classification outcome is considerably more interpretable than using only the WSI as the input, since it is also based on the segmentation map. Our segmentation model, which we call EU-Net, extends a classical U-Net with an EfficientNet-B7 encoder which was pre-trained on the Imagenet dataset.Comment: Submitted to https://link.springer.com/chapter/10.1007/978-3-030-52791-4_