Temporal reduction of LATS kinases in the early preimplantation embryo prevents ICM lineage differentiation

Cellular localization of the Yes-associated protein (YAP) is dependent on large tumor suppressor (LATS) kinase activity and initiates lineage specification in the preimplantation embryo. We temporally reduced LATS activity to disrupt this early event, allowing its reactivation at later stages. This interference resulted in an irreversible lineage misspecification and aberrant polarization of the inner cell mass (ICM). Complementation experiments revealed that neither epiblast nor primitive endoderm can be established from these ICMs. We therefore conclude that precisely timed YAP localization in early morulae is essential to prevent trophectoderm marker expression in, and lineage specification of, the ICM.     

Pre-discharge and early post-discharge management of patients hospitalized for acute heart failure: A scientific statement by the Heart Failure Association of the ESC

Acute heart failure is a major cause of urgent hospitalizations. These are followed by marked increases in death and rehospitalization rates, which then decline exponentially though they remain higher than in patients without a recent hospitalization. Therefore, optimal management of patients with acute heart failure before discharge and in the early post-discharge phase is critical. First, it may prevent rehospitalizations through the early detection and effective treatment of residual or recurrent congestion, the main manifestation of decompensation. Second, initiation at pre-discharge and titration to target doses in the early post-discharge period, of guideline-directed medical therapy may improve both short- and long-term outcomes. Third, in chronic heart failure, medical treatment is often left unchanged, so the acute heart failure hospitalization presents an opportunity for implementation of therapy. The aim of this scientific statement by the Heart Failure Association of the European Society of Cardiology is to summarize recent findings that have implications for clinical management both in the pre-discharge and the early post-discharge phase after a hospitalization for acute heart failure.     

Large complex odontoma of the left maxillary sinus

Odontomas as a group are the most common odontogenic neoplasms. They are mixed lesions containing fully formatted dental tissues, both epithelial and mesenchymal, and are usually found during a routine radiographic examination or as a factor in noneruption. Odontomas can be divided into two types: the complex and the compound odontoma. Both types are composed of enamel, dentin, cementum and pulp tissues, but in complex odontomas the tissues are arranged in a haphazard fashion with no discernible dental structures, whereas in compound odontomas the dental tissues exist in a more regular pattern so that the lesion consists of tooth-like structures. We report a case of a 23-year-old man with a large complex odontoma involving the left maxilla and maxillary sinus with clinical, radiographic and histological findings. Because of the size of the mass and its clinical course, benign neoplasms were considered in the differential diagnosis. Surgery was the treatment of choice, and recurrence of the lesion is not expected.     

Management of Smell Dysfunction

Olfaction is an essential chemosensory system in the living world. Although less appreciated in humans, smell impairment significantly affects many aspects of quality of life. Smell disorders may be caused by an impaired nasal airway or by lesions in the olfactory system, leading to reduced or distorted smell perception. The most common causes of smell disorders are aging, upper respiratory tract infection, sinonasal disease, and head trauma. Recovery is rarely complete. Counseling is important in progressive or severe smell loss. In patients with distorted smell perception, antidepressant medication is sometimes necessary. Best response to treatment is achieved for nasal obstruction and sinonasal inflammatory disease. Treatment of olfactory impairment caused by sinonasal disease includes medication with topical and systemic steroids, or surgery for refractory cases. Although there are reports that surgical resection of olfactory neurons may lead to reinnervation and recovery of smell, adequate treatment of the smell loss remains an unmet need.     

A case of postpartum eosinophilic gastroenteritis and review of the literature

Eosinophilic gastroenteritis (EG) is a rare disease of unknown etiology that can involve any area of the gastrointestinal (GI) tract. It can be classified into three major types: predominantly mucosal, muscularis, or subserosal form. Diagnosis of EG is confirmed after the exclusion of other disorders having similar features, such as parasitic infection, carcinoma, allergy, and autoimmune conditions such as Churg-Strauss disease. Correct diagnosis hinges on the presence of eosinophilic infiltration of one or more areas of the GI tract, without extraintestinal involvement. We present the case of a 30-year-old female with symptoms of EG 26 days after delivery. After corticosteroid and montelukast treatment for 2 weeks, all symptoms and objective clinical findings disappeared. Although numerous cases of this disorder have been described, to our knowledge this is the first case of postpartum EG. This case highlights the need to include this entity in the differential diagnosis of postpartum GI disorders.     

The Influence of Etiologic Factors on Clinical Outcome in Patients with Peptic Ulcer Bleeding

Background

Peptic ulcer bleeding remains an important cause of morbidity and mortality.

Aim

The aim of this study was to evaluate the prevalence of non-steroidal anti-inflammatory drugs (NSAID) use, Helicobacter pylori infection and non-H. pylori?Cnon-NSAIDs causes of peptic ulcer bleeding and to identify the predictive factors influencing the rebleeding rate and in-hospital mortality in patients with bleeding peptic ulcer.

Methods

A total of 1,530 patients with endoscopically confirmed peptic ulcer bleeding were evaluated consecutively between January 2005 and December 2009. The 30-day mortality and clinical outcome were related to patient??s demographic data, endoscopic and clinical characteristics.

Results

The age-standardized 1-year cumulative incidence for peptic ulcer bleeding was 40.4 cases/100,000 people. The proportion of patients over 65?years increased from 45.7?% in 2005 to 61.4?% in 2009 (p?=?0.007). Overall 30-day mortality rate was 4.6?%, not significantly different for conservatively and surgically treated patients (4.9 vs. 4.1?%, p?=?0.87). Mortality was significantly higher in patients over 65?years of age and those with in-hospital bleeding recurrence. Patients with non-H. pylori?Cnon-NSAID idiopathic ulcers had significantly higher 30-day mortality rate than those with H. pylori ulcers and NSAID?CH. pylori ulcers (7.1 vs. 0 vs. 0.8?%, p?=?0.001 and p?=?0.007, respectively). There was no statistically significant difference between patients with NSAID ulcers and non-H. pylori?Cnon-NSAID idiopathic ulcers in terms of 30-day mortality rate (5.3 vs. 7.1?%, p?=?0.445).

Conclusion

The incidence of peptic ulcer bleeding has not changed over a 5-year observational period. The overall 30-day mortality was positively correlated to older age, underlying comorbid illnesses, in-hospital bleeding recurrence and the absence of H. pylori infection.     

HIV-1 infection–induced apoptotic microparticles inhibit human DCs via CD44

Acute HIV-1 infection results in dysregulated immunity, which contributes to poor control of viral infection. DCs are key regulators of both adaptive and innate immune responses needed for controlling HIV-1, and we surmised that factors elicited during acute HIV-1 infection might impede DC function. We derived immature DCs from healthy donor peripheral blood monocytes and treated them with plasma from uninfected control donors and donors with acute HIV-1 infections. We found that the plasma from patients with HIV specifically inhibited DC function. This suppression was mediated by elevated apoptotic microparticles derived from dying cells during acute HIV-1 infection. Apoptotic microparticles bound to and inhibited DCs through the hyaluronate receptor CD44. These data suggest that targeting this CD44-mediated inhibition by apoptotic microparticles could be a novel strategy to potentiate DC activation of HIV-specific immunity.