Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall

Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF(-/-), hTF-Tg+, or "low-TF") demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes.     

The perception of respiratory work and effort can be independent of the perception of air hunger

Dyspnea in patients could arise from both an urge to breathe and increased effort of breathing. Two qualitatively different sensations, "air hunger" and "respiratory work and effort," arising from different afferent sources are hypothesized. In the laboratory, breathing below the spontaneous level may produce an uncomfortable sensation of air hunger, and breathing above it a sensation of work or effort. Measurement of a single sensory dimension cannot distinguish these as separate sensations; we therefore measured two sensory dimensions and attempted to vary them independently. In five normal subjects we obtained simultaneous ratings of air hunger and of work and effort while independently varying PCO(2) or the level of targeted voluntary breathing. We found a difference in response to the two stimulus dimensions: air hunger ratings changed more steeply when PCO(2) was altered and ventilation was constant; work or effort ratings changed more steeply when ventilation was altered and PCO(2) was constant. We conclude that "air hunger" is qualitatively different from "work and effort" and arises from different afferent sources.     

Single-port laparoscopic treatment of small bowel obstruction

Background

The aim of this study was to report our initial experience with single-port laparoscopic surgery (SPLS) for small bowel obstruction (SBO).

Methods

Between October 2009 and April 2013, 36 patients underwent SPLS for SBO. SPLS was performed transumbilically. Patient demographics and operative and postoperative outcomes were analyzed.

Results

SPLS for SBO was successful in 35 patients. In 1 patient, a conversion to laparotomy was required. The median incision length, operative time, and postoperative length of stay were 2.3 cm (range, 1.5 to 5.0 cm), 115 min (range, 30 to 250 min), and 8 days (range, 3 to 26 days), respectively. The median time to resume oral intake was 3 days (range, 1 to 16 days). The intra- and postoperative complication rates were 6% and 11%, respectively.

Conclusion

SPLS was a safe and feasible therapeutic approach for SBO and may also be an excellent diagnostic tool when performed by an experienced SPLS surgeon in selected patients.     

Clinical characteristics and cytokine biomarkers in patients with chronic graft-vs-host disease persisting seven or more years after diagnosis

Chronic graft-versus-host disease (cGVHD) is the leading late complication after allogeneic hematopoietic stem cell transplantation (HSCT). Many patients receive multiple lines of systemic therapy until cGVHD resolves, but about 15% remain on systemic treatment for more than 7 years after cGVHD diagnosis. This study describes the clinical and biological factors of patients who present with cGVHD persisting for ≥7 years (persistent cGVHD). Patients with persistent cGVHD (n = 38) and those with cGVHD for <1 year (early cGVHD) (n = 83) were enrolled in a prospective cross-sectional natural history study. Patients in the persistent cGVHD group were a median of 10.2 years from cGVHD diagnosis (range 7-27 years). Fifty-eight percent of persistent cGVHD patients (22/38) were receiving systemic immunosuppression, compared to 88% (73/83) in the early cGVHD group. In multivariable analysis, bone marrow (BM) stem cell source, presence of ENA autoantibodies, higher NIH lung score, higher platelet counts, and higher IgA levels were significantly associated with persistent cGVHD. A high sensitivity panel of serum biomarkers including seven cytokines diagnostic for cGVHD was analyzed and showed significantly lower levels of BAFF and CXCL10 in patients with persistent cGVHD. In conclusion, standardly accepted clinical measures of disease severity may not accurately reflect disease activity in patients with persistent cGVHD. However, many patients with persistent cGVHD are still receiving systemic immunosuppression despite lacking evidence of disease activity. Development of reliable clinical biomarkers of cGVHD activity may help guide future systemic treatments.     

Enhancement of antigen-specific CD8 T cell responses by co-delivery of Fc-fused CXCL11

Chemokines have been known to play an important role in eliciting adaptive immune responses by, selectively attracting the innate cellular components to the site of antigen presentation. In this study, we demonstrated that all three CXCR3 ligands, CXCL9, CXCL10, and CXCL11, could act as a strong, genetic adjuvant. Among them, CXCL11 increased vaccine antigen-specific CD8 T cells, including, several cytokine secretions (IFN-γ and TNF-α) to a greater degree than the other two CXCR3 ligands. Fc-fusion of CXCL11 (CXCL11-Fc) induced similar but slightly higher CD8 T cell response, which, appeared to be antigen- (ovalbumin (OVA) vs. human papillomavirus 16 (HPV16) E7) and vaccine, type- (adenovirus vs. DNA vaccine) independent. In addition, the adjuvant effect of CXCL11-Fc was, further confirmed by suppressing tumor growth and extension of survival rates in a therapeutic tumor, model, which was correlated with enhanced antigen-specific CD8 T cell responses. Interestingly, the, enhanced antigen-specific CD8 T cell responses by co-delivery of CXCL11-Fc were associated with CD8, T cell proliferation, followed by increased total and effector memory T cell frequencies. Taken together, our findings provide a novel role of CXCL11 as a strong genetic adjuvant which might be used to, increase antigen-specific CD8 T cell immunity elicited by vaccination.     

Synthesis of Stretchable,Environmentally Stable,Conducting Polymer PEDOT Using a Modified Acid Template Random Copolymer

Although poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has good electrical conductivity and high transparency in most applications, its usage in stretchable applications is limited because of its rigidity, reduced conductivity after elongation, and poor environmental stability. This study addresses these issues by incorporating the soft and relatively hydrophobic moiety poly(ethylene glycol) methacrylate (PEGMA). By incorporating PEGMA randomly in the rigid PSS chain, a soft and hydrophobic copolymer P(SS‐co‐PEGMA) is obtained. The conducting P(SS‐co‐PEGMA)‐based polymer‐coated PET film exhibits good resistance even after 400% elongation. In addition, PEDOT:P(SS‐co‐PEGMA) has better environmental stability than PEDOT:PSS because of the presence of the relatively hydrophobic PEGMA moiety in the chain. Moreover, the potential applicability of the synthesized flexible and stretchable electronic material as a stretchable matrix is established, which includes inorganic conductors (AgNW). When this material is stretched, it can be applied as a conductive interconnector to maintain the electrical pathway, instead of the other insulating matrices.     

Clinical and genetic features of four patients with Pearson syndrome: An observational study

Pearson syndrome (PS) is a multisystem mitochondrial cytopathy arising from deletions in mitochondrial DNA. Pearson syndrome is a sporadic disease that affects the hematopoietic system, pancreas, eyes, liver, and heart and the prognosis is poor. Causes of morbidity include metabolic crisis, bone marrow dysfunction, sepsis, and liver failure in early infancy or childhood. Early diagnosis may minimize complications, but suspicion of the disease is difficult and only mitochondrial DNA gene testing can identify mutations. There is no specific treatment for PS, which remains supportive care according to symptoms; however, hematopoietic stem cell transplantation may be considered in cases of bone marrow failure.We herein describe the clinical and genetic characteristics of four patients with PS. One patient presented with hypoglycemia, two developed pancytopenia, and the final patient had hypoglycemia and acute hepatitis as the primary manifestation. All patients had lactic acidosis. Additionally, all patients showed a variety of clinical features including coagulation disorder, pancreatic, adrenal, and renal tubular insufficiencies. Two patients with pancytopenia died in their early childhood. Our experience expands the phenotypic spectrum associated with PS and its clinical understanding.