Conversion of Danger Signals into Cytokine Signals by Hematopoietic Stem and Progenitor Cells for Regulation of Stress-Induced Hematopoiesis

During an infection, the body increases the output of mature immune cells to fight off the pathogen. Despite convincing evidence that hematopoietic stem and progenitor cells (HSPCs) can sense pathogens directly, how this contributes to hematopoietic cell output remains unknown. Here we have combined mouse models with a single cell proteomics platform to show that in response to toll-like receptor stimulation, short-term HSCs and multipotent progenitor cells produce copious amount of diverse cytokines through the NF-κB signaling. Interestingly, the cytokine production ability of HSPCs trumps mature immune cells in both magnitude and breadth. Among cytokines produced by HSPCs, IL-6 is a particularly important regulator of myeloid differentiation and HSPC proliferation in a paracrine manner and in mediating rapid myeloid cell recovery during neutropenia. This study has uncovered a novel property of HSPCs that enables them to convert danger signals into versatile cytokine signals for regulation of stress hematopoiesis

Central Retinal Artery Occlusion With Subsequent Central Retinal Vein Occlusion in Biopsy-Proven Giant Cell Arteritis

Central retinal artery occlusion with subsequent central retinal vein occlusion in the same eye is a rare entity. We present a 72-year-old man with biopsy-proven giant cell arteritis who developed bilateral arteritic anterior ischemic optic neuropathy and a left central retinal artery occlusion. Subsequently, he developed a left central retinal vein occlusion within 2 weeks of his initial vision loss. His vision did not improve with corticosteroids

An ultrastructural study of the pathology of the retinal pigment epithelium, Bruch\u27s membrane, and the choriocapillaris in the aged Fischer 344 rat.

PURPOSE: The neural retinal degeneration in the aging Fischer 344 (F344) rat has been previously characterized. Here we describe the ultrastructural changes that occur in the retinal pigment epithelium (RPE), Bruch\u27s membrane, and choriocapillaris in the periphery of the aged Fischer 344 rat. METHODS: F344 eyes from 24-month-old animals (n = 4 animals, 8 eyes) were fixed and embedded for ultrastructural study. Serial mid-sagittal sections were taken from the superior peripheral retinas within 300 microm of the ora serrata. Pathology within the RPE, Bruch\u27s membrane, and choriocapillaris was described. RESULTS: Progressive changes were seen in the RPE/Bruch\u27s/choriocapillaris complex, increasing anteriorly as the ora serrata was approached. Early pathology of the RPE included increased number of basal infoldings, increased number of phagolysosomes and lipofuscin deposits, attenuation, inclusion of vasculature, vesicle formation, and whirling extensions of the basement membrane into the cytoplasm. Bruch\u27s membrane showed spots of considerable thinning, but most prominent was the nodular thickening. The choriocapillaris was found to have severe endothelial degeneration and transformation to fibrous tissue in the most severely affected regions. Lipofuscin was also found in areas of degenerated choriocapillaris. CONCLUSIONS: Prior work focused on the neural retina, documented photoreceptor cell loss, and showed that Müller cell changes preceded that loss in the periphery of the F344 rat. It is now evident that the pathology in the RPE/Bruch\u27s membrane/choriocapillaris complex may also be a critical component of the overall degenerative process. A possible mechanism for the extensive peripheral retinal degeneration in the F344 is presented

Adaptive Optics Imaging With Histopathologic Correlation in Cancer-Associated Retinopathy

We describe the first report of in vivo adaptive optics imaging in cancer-associated retinopathy as correlated with histopathology

CARI: A model of assessment for educator preparation programs

This paper presents a model of assessment that fosters the development and maintenance of a culture of continuous improvement. Background consisting of a short discussion of accountability, the education standards movement, and a theoretical framework supporting the building of an assessment culture and a model is presented. Seven considerations for developing a model of assessment are presented. A four-phase plan for developing a culture of assessment is discussed. The connection between the considerations for developing a model of assessment, the four-phase plan for developing a culture of assessment and the development of the CARI (collect information, analyze data, report findings, and implement changes) model is woven throughout the document. Finally, a background on the research that supports the development of the CARI model and an example of how the model can be used is provided.Journal ArticleFinal article publishe

Esophageal Metastasis to the Iris Effectively Palliated Using Stereotactic Body Radiation Therapy and Adjuvant Intravitreal Chemotherapy: Case Report and Literature Review

We report a case of isolated iris metastasis from esophageal adenocarcinoma that was successfully managed with local application of stereotactic body radiation therapy (SBRT) and adjunctive intravitreal therapy. A 53-year-old man with locally advanced esophageal adenocarcinoma achieved a complete clinical and radiographic response after surgery and chemotherapy. Four months later, he developed headache and decreased vision and was diagnosed with metastasis to the iris by slit-lamp examination. The decrease in vision was secondary to cystoid macular edema. The metastatic tumor and the patient’s symptoms resolved after treatment with SBRT and intravitreal injections of bevacizumab and triamcinolone. We conclude that SBRT combined with intravitreal chemotherapy is an effective and well-tolerated palliative treatment for metastasis of esophageal adenocarcinoma to the iris

Mental status changes during elexacaftor/tezacaftor / ivacaftor therapy

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA, Trikafta) is the newest Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) modulator drug approved by the Food and Drug Administration. Post-marketing reports with earlier CFTR modulators suggest these medications can impact mood, and in clinical trials an adverse effect of headache was reported with all currently approved CFTR modulators. However, there are no other documented reports of mental status changes during clinical trials or in post-marketing reports with elexacaftor/tezacaftor/ivacaftor. In this case series, we describe 6 patients who reported mental fogginess or other mental status changes shortly after initiation of this drug. The mechanism of this patient-reported side effect is still unclear. All patients noticed a change within the first 3 months of therapy. The management differed in each case, with all four cystic fibrosis (CF) care teams utilizing a patient-centered decision-making approach to address this concern

Quantitative Comparison of Fundus Images by 2 Ultra-Widefield Fundus Cameras

To compare the relative number of retinal pixels and retinal area imaged using the Optos P200DTx (Optos PLC) and Zeiss Clarus 500 (Carl Zeiss Meditec AG) ultra-widefield (UWF) fundus cameras. Single-center retrospective cross-sectional analysis. Seventy-eight eyes of 46 patients. Eyes were imaged with Optos P200DTx, single-capture, and Zeiss Clarus 500, 2 capture montages when possible, UWF fundus cameras. Relative number of pixels encompassing all foveal-centered retinal quadrants were measured. Retinal area was measured with Zeiss Clarus 500 images that were registered to the Optos P200DTx images. Patients and technicians were asked for preferences between the machines. Imaging session times were recorded. Relative number of retinal pixels and retina area captured by each fundus camera. Optos P200DTx consistently captured more relative pixels compared with Zeiss Clarus 500: 510.4 versus 355.6 (P < 0.001) in total with a similarly statistically significant trend in all 4 quadrants (P < 0.001 for each). For area calculation, 70 of the 78 images achieved successful registration. Optos captured a larger total retinal area: 765.6 versus 566.5 mm2 (P < 0.001) with a similarly statistically significant trend in all 4 quadrants. In the subset of 52 of 70 registered and montaged Zeiss Clarus 500 images, similar results were found. For peripheral pathologic features, Optos P200DTx captured unique findings in 28 images, and Zeiss Clarus 500 captured unique findings 1 image (P < 0.001). Among the 48 imaging sessions in which technicians preferred Optos P200DTx for 28 sessions (58%) and Zeiss Clarus 500 for 20 (42%; P = 0.15). Among patients who responded with a preference, 24 preferred Optos P200DTx and 20 preferred Zeiss Clarus 500 (P = 0.52). Average imaging session time was 4.6 minutes (standard deviation, 3.0 minutes) for Optos P200DTx and 5.2 minutes (standard deviation, 3.0 minutes) for Zeiss Clarus 500 (P = 0.17). In the current study, the Optos P200DTx captured statistically significantly more retinal area in all 4 quadrants compared with the Zeiss Clarus 500. No statistically significant difference was found in patient or technician preference or image acquisition time between devices

This paper describes the Time Warp Operating System,

under development for three years at the Jet Propulsio

Fine-needle aspiration cytology of extra mammary metastatic lesions in the breast: A retrospective study of 36 cases diagnosed during 18 years

<b>Background:</b> Metastatic tumors in the breast require treatment according to origin and type of tumor. It is important to recognize these lesions in fine-needle aspiration cytology (FNAC) in order to avoid unnecessary mastectomy or non-relevant chemotherapy. The aim of this study was to evaluate the cytological features of metastatic tumors and possible criteria that could alert us as to the possibility of a metastasis from an extra mammary malignancy. <b> Methods: </b> The material included 36 confirmed or suspected metastases in the breast registered in the pathology files at Oslo University Hospital, Ulleval, during 1990-2007. There were a total of 6,325 cases of malignant breast FNAC, representing 30 men and 6,295 women. Smears were evaluated for the amount of material, presence or absence of myoepithelial cells, microcalcifications, mitoses and necrotic material. All carcinomas were graded. <b> Results: </b> There were seven men (7/30 = 23.3&#x0025;) and 29 women (29/6,295 = 0.46&#x0025;). The primary tumor was known in 22 cases (22/36 = 61.1&#x0025;). No other primary tumor was known and metastatic lesion was not initially suspected in 14 cases (14/36 = 38.9&#x0025;). The most common origin was lung (15/36 = 41.7&#x0025;). In five cases (5/36 = 13.9&#x0025;), the origin remained uncertain. <b> Conclusions: </b> Metastases from extra mammary sites are (relatively) common in males (23.3&#x0025;). In women, metastatic lesions are rare (0.46&#x0025;). A large proportion of them (88&#x0025;) are high-grade adenocarcinomas and poorly differentiated carcinomas that may resemble grade 3 ductal carcinomas. Unusual clinical and/or radiological presentation in combination with high-grade malignant cells should alert us to consider the possibility of a metastasis