Cytomegalovirus antibodies in dried blood spots: a minimally invasive method for assessing stress, immune function, and aging

<p>Abstract</p> <p>Background</p> <p>Cytomegalovirus (CMV) is a prevalent herpesvirus with links to both stress and aging. This paper describes and validates a minimally invasive method for assessing antibodies against CMV in finger stick whole blood spot samples for use as an indirect marker of an aspect of cell-mediated immunity.</p> <p>Results</p> <p>Analysis of CMV in dried blood spot samples (DBS) was based on modifications of a commercially available protocol for quantifying CMV antibodies in serum or plasma. The method was evaluated through analysis of precision, reliability, linearity, and correlation between matched serum and DBS samples collected from 75 volunteers. Correlation between DBS and plasma values was linear and high (Pearson correlation <it>R </it>= .96), and precision, reliability, and linearity of the DBS assay were within acceptable ranges.</p> <p>Conclusions</p> <p>The validity of a DBS assay for CMV antibodies will enable its inclusion in population-based surveys and other studies collecting DBS samples in non-clinical settings, increasing scientific understanding of the interaction of social and biological stress and immune function.</p

Treatment Outcomes of Rathke's Cleft Cysts Managed with Marsupialization.

Objectives Rathke's cleft cysts (RCC) are benign cystic lesions of the sella resulting from incomplete obliteration of Rathke's cleft. Symptomatic lesions often require surgical decompression, which is often amenable to a transnasal, transsphenoidal (TNTS) approach. We report our experience with marsupialization of RCC and describe a novel technique to promote re-epithelization of the cyst cavity. Design Retrospective review. Setting Tertiary academic medical center. Participants Patients who underwent TNTS for RCC between 2007 and 2015. Main Outcome Measures Demographics, lesion characteristics, and reconstruction and treatment outcomes. Results In total, 52 patients were identified. The mean age was 41 ± 18 years. The mean RCC size was 13 ± 5 mm. Intraoperative cerebrospinal fluid (CSF) leak was encountered in 14 (27%) patients; all were repaired. There were six complications (12%) and no deaths. Mean follow-up was 20 ± 18 months, with five (10%) recurrences. RCC size was associated with intraoperative CSF leak (p = 0.04). In 12 patients, the marsupialized cyst cavity was lined with a free mucosal graft (FMG) to promote healing and re-epithelialization. Conclusions The TNTS approach is safe and effective in surgical decompression of RCC. Lining the exposed cyst cavity with an FMG is a simple intervention without added morbidity that may promote formation of an epithelialized tract. Level of Evidence Not applicable

Quality of Life before and after Endoscopic Pituitary Surgery as Measured by the Short-Form-36

Objectives/Hypotheses  To assess quality of life (QOL) after transnasal, endoscopic pituitary surgery using the 36-item short form (SF-36) instrument. Design  Retrospective review was used for this study. Setting  The study was conducted in a tertiary academic medical center. Participants  Patients who underwent endoscopic, transnasal, transsphenoidal surgery for pituitary adenomas between January 1, 2007 and July 1, 2016 and completed preoperative and postoperative SF-36 surveys. Main Outcome Measures  SF-36 survey data as measured by its eight domains (physical functioning, physical role functioning, emotional role functioning, energy/fatigue, emotional well-being, social functioning, pain, and general health). Results  There were 18 preoperative, 13 short-term (2 weeks or less after surgery) postoperative, and 14 longer term (&gt;2 weeks after surgery) postoperative surveys. There was no significant difference between preoperative and long-term postoperative SF-36 scores across domains ( p  &gt; 0.05). In comparing short-term postoperative and preoperative scores, tumor size was positively associated with emotional well-being ( p  = 0.049) and general health scores ( p  = 0.031), while visual changes preoperatively were positively associated with general health scores ( p  = 0.046). Compared with standard U.S. general population summary data, these patients scored lower preoperatively in all domains except for emotional role functioning and pain ( p  &lt; 0.05). Postoperatively, patients improved to baseline general population data scores with the exception of the physical role functioning domain ( p  &lt; 0.0001). Conclusion  Patients undergoing endoscopic, transnasal, transsphenoidal surgery for pituitary adenomas had lower QOL in six of eight domains preoperatively, but improved to baseline values on the long run after surgery in seven of eight domains. This suggests that minimally invasive pituitary surgery has a restorative role in general QOL as measured by the SF-36

Quality of Life before and after Endoscopic Pituitary Surgery as Measured by the Short-Form-36.

Objectives/Hypotheses  To assess quality of life (QOL) after transnasal, endoscopic pituitary surgery using the 36-item short form (SF-36) instrument. Design  Retrospective review was used for this study. Setting  The study was conducted in a tertiary academic medical center. Participants  Patients who underwent endoscopic, transnasal, transsphenoidal surgery for pituitary adenomas between January 1, 2007 and July 1, 2016 and completed preoperative and postoperative SF-36 surveys. Main Outcome Measures  SF-36 survey data as measured by its eight domains (physical functioning, physical role functioning, emotional role functioning, energy/fatigue, emotional well-being, social functioning, pain, and general health). Results  There were 18 preoperative, 13 short-term (2 weeks or less after surgery) postoperative, and 14 longer term (&gt;2 weeks after surgery) postoperative surveys. There was no significant difference between preoperative and long-term postoperative SF-36 scores across domains ( p  &gt; 0.05). In comparing short-term postoperative and preoperative scores, tumor size was positively associated with emotional well-being ( p  = 0.049) and general health scores ( p  = 0.031), while visual changes preoperatively were positively associated with general health scores ( p  = 0.046). Compared with standard U.S. general population summary data, these patients scored lower preoperatively in all domains except for emotional role functioning and pain ( p  &lt; 0.05). Postoperatively, patients improved to baseline general population data scores with the exception of the physical role functioning domain ( p  &lt; 0.0001). Conclusion  Patients undergoing endoscopic, transnasal, transsphenoidal surgery for pituitary adenomas had lower QOL in six of eight domains preoperatively, but improved to baseline values on the long run after surgery in seven of eight domains. This suggests that minimally invasive pituitary surgery has a restorative role in general QOL as measured by the SF-36

Quality of Life before and after Endoscopic Pituitary Surgery as Measured by the Short-Form-36

Objectives/Hypotheses  To assess quality of life (QOL) after transnasal, endoscopic pituitary surgery using the 36-item short form (SF-36) instrument. Design  Retrospective review was used for this study. Setting  The study was conducted in a tertiary academic medical center. Participants  Patients who underwent endoscopic, transnasal, transsphenoidal surgery for pituitary adenomas between January 1, 2007 and July 1, 2016 and completed preoperative and postoperative SF-36 surveys. Main Outcome Measures  SF-36 survey data as measured by its eight domains (physical functioning, physical role functioning, emotional role functioning, energy/fatigue, emotional well-being, social functioning, pain, and general health). Results  There were 18 preoperative, 13 short-term (2 weeks or less after surgery) postoperative, and 14 longer term (&gt;2 weeks after surgery) postoperative surveys. There was no significant difference between preoperative and long-term postoperative SF-36 scores across domains ( p  &gt; 0.05). In comparing short-term postoperative and preoperative scores, tumor size was positively associated with emotional well-being ( p  = 0.049) and general health scores ( p  = 0.031), while visual changes preoperatively were positively associated with general health scores ( p  = 0.046). Compared with standard U.S. general population summary data, these patients scored lower preoperatively in all domains except for emotional role functioning and pain ( p  &lt; 0.05). Postoperatively, patients improved to baseline general population data scores with the exception of the physical role functioning domain ( p  &lt; 0.0001). Conclusion  Patients undergoing endoscopic, transnasal, transsphenoidal surgery for pituitary adenomas had lower QOL in six of eight domains preoperatively, but improved to baseline values on the long run after surgery in seven of eight domains. This suggests that minimally invasive pituitary surgery has a restorative role in general QOL as measured by the SF-36

Microenvironment influences vascular differentiation of murine cardiovascular progenitor cells

We examined the effects of the microenvironment on vascular differentiation of murine cardiovascular progenitor cells (CPCs). We isolated CPCs and seeded them in culture exposed to the various extracellular matrix (ECM) proteins in both two-dimensional (2D) and 3D culture systems. To better understand the contribution of the microenvironment to vascular differentiation, we analyzed endothelial and smooth muscle cell differentiation at both day 7 and day 14. We found that laminin and vitronectin enhanced vascular endothelial cell differentiation while fibronectin enhanced vascular smooth muscle cell differentiation. We also observed that the effects of the 3D electrospun scaffolds were delayed and not noticeable until the later time point (day 14), which may be due to the amount of time necessary for the cells to migrate to the interior of the scaffold. The study characterized the contributions of both ECM proteins and the addition of a 3D culture system to continued vascular differentiation. Additionally, we demonstrated the capability bioengineer a CPC-derived vascular graft

Correction: Characterization and Therapeutic Potential of Induced Pluripotent Stem Cell-Derived Cardiovascular Progenitor Cells.

<div><h3>Background</h3><p>Cardiovascular progenitor cells (CPCs) have been identified within the developing mouse heart and differentiating pluripotent stem cells by intracellular transcription factors Nkx2.5 and Islet 1 (Isl1). Study of endogenous and induced pluripotent stem cell (iPSC)-derived CPCs has been limited due to the lack of specific cell surface markers to isolate them and conditions for their <em>in vitro</em> expansion that maintain their multipotency.</p> <h3>Methodology/Principal Findings</h3><p>We sought to identify specific cell surface markers that label endogenous embryonic CPCs and validated these markers in iPSC-derived Isl1⁺/Nkx2.5⁺ CPCs. We developed conditions that allow propagation and characterization of endogenous and iPSC-derived Isl1⁺/Nkx2.5⁺ CPCs and protocols for their clonal expansion <em>in vitro</em> and transplantation <em>in vivo</em>. Transcriptome analysis of CPCs from differentiating mouse embryonic stem cells identified a panel of surface markers. Comparison of these markers as well as previously described surface markers revealed the combination of Flt1⁺/Flt4⁺ best identified and facilitated enrichment for Isl1⁺/Nkx2.5⁺ CPCs from embryonic hearts and differentiating iPSCs. Endogenous mouse and iPSC-derived Flt1⁺/Flt4⁺ CPCs differentiated into all three cardiovascular lineages <em>in vitro</em>. Flt1⁺/Flt4⁺ CPCs transplanted into left ventricles demonstrated robust engraftment and differentiation into mature cardiomyocytes (CMs).</p> <h3>Conclusion/Significance</h3><p>The cell surface marker combination of Flt1 and Flt4 specifically identify and enrich for an endogenous and iPSC-derived Isl1⁺/Nkx2.5⁺ CPC with trilineage cardiovascular potential <em>in vitro</em> and robust ability for engraftment and differentiation into morphologically and electrophysiologically mature adult CMs <em>in vivo</em> post transplantation into adult hearts.</p> </div

Characterization and therapeutic potential of induced pluripotent stem cell-derived cardiovascular progenitor cells.

BackgroundCardiovascular progenitor cells (CPCs) have been identified within the developing mouse heart and differentiating pluripotent stem cells by intracellular transcription factors Nkx2.5 and Islet 1 (Isl1). Study of endogenous and induced pluripotent stem cell (iPSC)-derived CPCs has been limited due to the lack of specific cell surface markers to isolate them and conditions for their in vitro expansion that maintain their multipotency.Methodology/principal findingsWe sought to identify specific cell surface markers that label endogenous embryonic CPCs and validated these markers in iPSC-derived Isl1(+)/Nkx2.5(+) CPCs. We developed conditions that allow propagation and characterization of endogenous and iPSC-derived Isl1(+)/Nkx2.5(+) CPCs and protocols for their clonal expansion in vitro and transplantation in vivo. Transcriptome analysis of CPCs from differentiating mouse embryonic stem cells identified a panel of surface markers. Comparison of these markers as well as previously described surface markers revealed the combination of Flt1(+)/Flt4(+) best identified and facilitated enrichment for Isl1(+)/Nkx2.5(+) CPCs from embryonic hearts and differentiating iPSCs. Endogenous mouse and iPSC-derived Flt1(+)/Flt4(+) CPCs differentiated into all three cardiovascular lineages in vitro. Flt1(+)/Flt4(+) CPCs transplanted into left ventricles demonstrated robust engraftment and differentiation into mature cardiomyocytes (CMs).Conclusion/significanceThe cell surface marker combination of Flt1 and Flt4 specifically identify and enrich for an endogenous and iPSC-derived Isl1(+)/Nkx2.5(+) CPC with trilineage cardiovascular potential in vitro and robust ability for engraftment and differentiation into morphologically and electrophysiologically mature adult CMs in vivo post transplantation into adult hearts