The dendritic cell receptor DNGR-1 controls endocytic handling of necrotic cell antigens to favor cross-priming of CTLs in virus-infected mice

DNGR-1 (CLEC9A) is a receptor for necrotic cells required by DCs to cross-prime CTLs against dead cell antigens in mice. It is currently unknown how DNGR-1 couples dead cell recognition to cross-priming. Here we found that DNGR-1 did not mediate DC activation by dead cells but rather diverted necrotic cell cargo into a recycling endosomal compartment, favoring cross-presentation to CD8(+) T cells. DNGR-1 regulated cross-priming in non-infectious settings such as immunization with antigen-bearing dead cells, as well as in highly immunogenic situations such as infection with herpes simplex virus type 1. Together, these results suggest that DNGR-1 is a dedicated receptor for cross-presentation of cell-associated antigens. Our work thus underscores the importance of cross-priming in immunity and indicates that antigenicity and adjuvanticity can be decoded by distinct innate immune receptors. The identification of specialized receptors that regulate antigenicity of virus-infected cells reveals determinants of antiviral immunity that might underlie the human response to infection and vaccination.     

Crowdsourcing for research data collection in rosacea

Several medical crowdsourcing sites are available to patients online, but few studies in the literature have compared crowdsourced data to clinical trials. Herein, we compare data from rosacea patients from a major medical crowdsourcing site with those from randomized controlled trials.     

Noncompaction cardiomyopathy: A new mechanism for mitral regurgitation with distinct clinical,echocardiographic features and pathological correlations

Noncompaction cardiomyopathy (NCCM) is a primary, genetic cardiomyopathy with variable clinical manifestations that include mitral regurgitation (MR).

Methods

This study comprised patients diagnosed with NCCM and MR in two cardiac centers (King Abdul-Aziz Cardiac Center, Riyadh, Kingdom of Saudi Arabia and Sudan Heart Institute, Khartoum, Sudan), and seen in the period between 2002 and 2013. The study describes follow up, clinical, echocardiographic, and histopathological findings.

Results

Nineteen cases (85% females) were identified. Ten percent of the cases had relapses and remissions of heart failure. Echocardiographic features included leaflet retraction in all patients, characteristic malcoaptation, and a zigzag deformity of anterior leaflet in 57% of patients. Ruptured chordae were found in 15% of the patients. One patient had pathological examination of the mitral valve which showed myxomatous degeneration, and sclerotic and calcific changes.

Conclusion

We describe and discuss a new mechanism for MR caused by NCCM with identifiable clinical and echocardiographic features, and pathological correlations.     

Hodgkin Lymphoma in Childhood: Clinicopathological features and therapy outcome at 2 Centers From a Developing Country

Hodgkin lymphoma (HL) accounts for 5% to 6% of all childhood cancer. It displays characteristic epidemiological, clinical, and pathological features according to various geographic areas. We aimed to assess the epidemiological aspects, clinicopathological features, and treatment outcome of pediatric HL treated at 2 Egyptian centers: Zagazig University Pediatric Oncology Unit and Benha Special Hospital Pediatric Oncology Unit.We carried a cross-sectional retrospective study by reviewing medical records for all patients admitted with the diagnosis of HL over 8 years in 2 oncology units during the period from January 2004 to January 2012.Age of the patients at presentation ranged from 3 to 14 years (median 6 years) and male: female ratio 1.7:1. Lymphadenopathy was the most common presentation (96.6%). Mixed cellularity subtype was dominant (50.8%), followed by nodular sclerosis (28.9%), lymphocyte-rich (18.6%) with lymphocyte depletion being the least dominant (1.7%). More than half of patients (55.9 %) had advanced disease (Ann Arbor stage III/IV disease). The duration of follow-up ranged from 5 to 87 months (mean 39.8 ± 24.1 months). The 5-year overall survival and event-free survival for patients were 96.6% and 84.7% respectively.In Egypt, HL occurs in young age group, with a higher incidence of mixed cellularity subtype and advanced disease. None of the clinical, epidemiological, or pathological characteristics had a significant association with the overall survival. The outcomes of HL in our 2 centers were satisfactory approaching the international percentage.     

Crimean-Congo hemorrhagic fever virus infection triggers the upregulation of the Wnt signaling pathway inhibitor genes

Virus Genes - Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic agent. Thus far, vaccines and specific antiviral therapies are not available against the threat of infection. Our...     

Value and risk of laparoscopic surgery in hemophiliacs—experiences from a tertiary referral center for hemorrhagic diatheses

Purpose

Laparoscopic surgery (LS) is gaining popularity worldwide because of benefits like faster recovery, earlier hospital discharge, and better cosmetic results. In hemophiliacs, surgery in general harbors an increased risk for severe complications. Whether LS or conventional surgery (CS) should be recommended in these patients is controversial and therefore the issue of our present study.

Methods

We performed a retrospective matched-pair analysis including laparoscopically operated non-hemophiliacs (LONH), laparoscopically operated hemophiliacs (LOH), and conventionally operated hemophiliacs (COH) concerning duration of surgery, drainages, hospital stay, complications, factor use (VIII, IX, and X), and blood values. Mann-Whitney U test was used (significance level P?=?0.05).

Results

No significant differences were found in duration of surgery and drains in laparoscopically or conventionally operated hemophiliacs versus matched pairs. Complication rate did not differ among the different groups. Concerning the total duration of hospital stay (t-DHOS) and the postoperative duration of hospital stay (p-DHOS), there was no statistical difference between LOH versus matched LONH. However, in COH versus matched LOH, a longer time was required for preparation and recovery (t-DHOS, P?=?0.04; p-DHOS, P?<?0.001). Also, the median factor supply perioperatively including the day of surgery did not differ between laparoscopically versus conventionally operated hemophiliacs.

Conclusions

Our study underscores the safety and benefits of laparoscopic procedures in hemophiliacs by showing a significantly shorter hospital stay for these patients resulting in reduced therapeutic costs and a faster mobilization. Still, the surgical and perioperative management of hemophiliacs continues to be a challenge requiring an experienced interdisciplinary team.     

Hydrogen sulphide and tempol treatments improve the blood pressure and renal excretory responses in spontaneously hypertensive rats

Oxidative stress and suppressed H₂S production lead to increased renal vascular resistance, disturbed glomerular hemodynamics, and abnormal renal sodium and water handling, contribute to the pathogenesis and maintenance of essential hypertension in man and the spontaneously hypertensive rat. This study investigated the impact of H₂S and tempol alone and in combination on blood pressure and renal hemodynamics and excretory functions in the SHR. Groups of WKY rats or SHR (n?=?6) were treated for 4?weeks either as controls or received NaHS (SHR?+?NaHS), tempol (SHR?+?Tempol), or NaHS plus tempol (SHR?+?NaHS?+?Tempol). Metabolic studies were performed on days 0, 14, and 28, thereafter animals were anaesthetized to measure renal hemodynamics and plasma oxidative and antioxidant markers. SHR control rats had higher mean arterial blood pressure (140.0?±?2 vs. 100.0?±?3?mmHg), lower plasma and urinary H₂S, creatinine clearance, urine flow rate and urinary sodium excretion, and oxidative stress compared to WKY (all p?p?2S and tempol together resulted in greater reductions in blood pressure and normalization of kidney function compared with either compound alone.     

Gastrogastric Fistulae Following Gastric Bypass Surgery—Clinical Recognition and Treatment

There have been many recent advances and observations regarding colorectal cancer (CRC) screening. New CRC surveillance guidelines have been published to help endoscopists with the management of important clinical issues such as serrated polyps. There have been several important large studies examining the impact of endoscopic process measures such as bowel prep, withdrawal time, and adenoma detection rate on CRC screening. In addition, there have been technical advances in CT colonography including the development of exams that do not require a bowel preparation. Other new technology such as colon capsule endoscopy may aid endoscopists in the challenge of completing the evaluation of the colon in those patients with an incomplete colonoscopy. Finally, there have been large studies which examine the performance characteristics of the so-called non-invasive CRC screening tests such as fecal immunochemical test (FIT) and fecal DNA.