Molecular Mechanisms Responsible for the Antiinflammatory and Protective Effect of HDL on the Endothelium

In addition to their role in reverse cholesterol transport, high-density lipoproteins (HDL) exert several beneficial effects, including the prevention and correction of endothelial dysfunction. HDL promote endothelium proliferation and diminish endothelial apoptosis; they play a key role in vasorelaxation by increasing the release of nitric oxide and prostacyclin through the induction of the expression and the activity of endothelial nitric oxide synthase and the coupling of cyclooxygenase 2 and prostacyclin synthase. In addition, HDL affect coagulation, fibrynolisis, platelet adhesion, adhesion molecules, and protease expression, and they exert antioxidant activity. These effects are achieved at the gene expression level and are dependent on the activation of several intracellular signaling pathways, including PI3K/Akt, ERK1/2, PKC, and p38MAPK. The complexity of the signaling pathways modulated by HDL reflects the different effects of the components of this class of lipoproteins such as apolipoproteins or lipids on endothelial cell gene expression and the subsequent modulation of endothelial function observed. The in vivo relevance of these findings to endothelial recovery during physiological or pathological conditions remains to be addressed; nevertheless, the results of clinical studies with synthetic HDL, ApoA-I mimetics, and drugs that are becoming available that selectively affect HDL plasma levels and biological functions support the importance of the correction of endothelial function by HDL

Class II Phosphoinositide 3-Kinases Contribute to Endothelial Cells Morphogenesis

PMCID: PMC3539993This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Social contacts and loneliness in people with psychotic and mood disorders

Background Social relations can be measured through: a) objective indicators, i.e. the number of social contacts in a given time interval or b) subjective indicators, i.e. feelings of loneliness. Comparing subjective and objective indicators in patients with psychotic and mood disorders may help to understand whether diagnosis-specific interventions should be designed for increasing their social relations. In this study we assessed social contacts outside home, work environments and mental health services, which may be increased by these interventions. We also explored feelings of loneliness which could influence readiness of patients to participate in interventions. Methods 100 patients in outpatient mental health care were asked to: a) list their social contacts; b) report their feelings of loneliness on a validated five point Likert scale. Multiple logistic regression models were used to test associations of diagnostic categories with: a) having more than one social contact in the previous week; b) reporting at least moderate feelings of loneliness. Results Patients had on average 1.7 (SD = 1.7) social contacts in the previous week (median = 1.0); 77 patients reported at least moderate feelings of loneliness. Patients with psychotic disorders (n = 30) showed a statistical trend towards having just one or no contacts in the week before the assessment (Odds ratio, OR = 2.246, p =.087). Patients with mood disorders were more likely to report at least moderate feelings of loneliness (OR = 2.798; p <.05). Conclusions Patients with psychotic disorders, compared to those with mood disorders, may be less likely to report feeling lonely although they tend to have less social contacts. Strategies to enhance social relations of people with psychotic disorders may include approaches to increase patients' drive to establish new social contacts and to emotionally support them in this process

The ETS factor ESE3/EHF represses IL-6 preventing STAT3 activation and expansion of the prostate cancer stem-like compartment.

Metastatic prostate cancer represents a yet unsolved clinical problem due to the high frequency of relapse and treatment resistance. Understanding the pathways that lead to prostate cancer progression is an important task to prevent this deadly disease. The ETS transcription factor ESE3/EHF has an important role in differentiation of human prostate epithelial cells. Loss of ESE3/EHF in prostate epithelial cells determines transformation, epithelial-to-mesenchymal transition (EMT) and acquisition of stem-like properties. In this study we identify IL-6 as a direct target of ESE3/EHF that is activated in prostate epithelial cells upon loss of ESE3/EHF. ESE3/EHF and IL-6 were significantly inversely correlated in prostate tumors. Chromatin immunoprecipitation confirmed binding of ESE3/EHF to a novel ETS binding site in the IL-6 gene promoter. Inhibition of IL-6 reverted transformation and stem-like phenotype in tumorigenic ESE3/EHF knockdown prostate epithelial cell models. Conversely, IL-6 stimulation induced malignant phenotypes, stem-like behavior and STAT3 activation. Increased level of IL-6 was observed in prostatospheres compared with adherent bulk cancer cells and this was associated with stronger activation of STAT3. Human prostate tumors with IL-6 elevation and loss of ESE3/EHF were associated with STAT3 activation and displayed upregulation of genes related to cell adhesion, cancer stem-like and metastatic spread. Pharmacological inhibition of IL-6/STAT3 activation by a JAK inhibitor restrained cancer stem cell growth in vitro and inhibited self-renewal in vivo. This study identifies a novel connection between the transcription factor ESE3/EHF and the IL-6/JAK/STAT3 pathway and suggests that targeting this axis might be preferentially beneficial in tumors with loss of ESE3/EHF

Community next steps for making globally unique identifiers work for biocollections data

Biodiversity data is being digitized and made available online at a rapidly increasing rate but current practices typically do not preserve linkages between these data, which impedes interoperation, provenance tracking, and assembly of larger datasets. For data associated with biocollections, the biodiversity community has long recognized that an essential part of establishing and preserving linkages is to apply globally unique identifiers at the point when data are generated in the field and to persist these identifiers downstream, but this is seldom implemented in practice. There has neither been coalescence towards one single identifier solution (as in some other domains), nor even a set of recommended best practices and standards to support multiple identifier schemes sharing consistent responses. In order to further progress towards a broader community consensus, a group of biocollections and informatics experts assembled in Stockholm in October 2014 to discuss community next steps to overcome current roadblocks. The workshop participants divided into four groups focusing on: identifier practice in current field biocollections; identifier application for legacy biocollections; identifiers as applied to biodiversity data records as they are published and made available in semantically marked-up publications; and cross-cutting identifier solutions that bridge across these domains. The main outcome was consensus on key issues, including recognition of differences between legacy and new biocollections processes, the need for identifier metadata profiles that can report information on identifier persistence missions, and the unambiguous indication of the type of object associated with the identifier. Current identifier characteristics are also summarized, and an overview of available schemes and practices is provided

asociacion entre angioma cavernoso y glioma cerebral reporte de dos casos y revision de la literatura acerca de los llamados angiogliomas

La asociacion entre las malformaciones vasculares y los gliomas cerebrales es inusual. Mientras que la asociacion entre angioma cavernoso con lesiones gliomatosas es aun mas rara, es por esto considerado por algunos autores como una entidad patologica particular llamada angioglioma. Los autores reportan dos casos de asociacion de un angioma cavernoso con una ganglioglioma y un oligodendroglioma, respectivamente. Ademas se realizo una revision de la literatura sobre los llamados angiogliomas. En opinion de los autores, la entidad de los angiogliomas se presenta dentro de un espectro general de neoplasias angiomatosas, que incluyen tumores cerebrales, en su mayoria gliomas de bajo grado, asociados a su vez, con un componente vascular importante

Familial hypercholesterolemia: The Italian Atherosclerosis Society Network (LIPIGEN)

Primary dyslipidemias are a heterogeneous group of disorders characterized by abnormal levels of circulating lipoproteins. Among them, familial hypercholesterolemia is the most common lipid disorder that predisposes for premature cardiovascular disease. We set up an Italian nationwide network aimed at facilitating the clinical and genetic diagnosis of genetic dyslipidemias named LIPIGEN (LIpid TransPort Disorders Italian GEnetic Network)

Obturator prosthesis rehabilitation after maxillectomy: Functional and aesthetical analysis in 25 patients

The number of patients undergoing a surgical resection of the maxilla for oncological reasons is constantly increasing, the most common complication of which remains the communication between oral and nasal cavities. On the basis of data arising from the literature regarding the treatment options of maxillary oncological post-surgical defects, obturator prosthesis remains the most used worldwide. We studied 25 patients (with at least 1-year follow up) rehabilitated by obturator prosthesis after maxillary resection leading to oro-nasal communication, providing data on the objective/subjective evaluation of such rehabilitation and mastication performance measured by a two-color chewing gum test. The type of defect was classified according to the classification system proposed by Aramany. Among the patients in our study, 72% rated a higher score for either stability and retention than for aesthetic appearance, as confirmed by the Kapur score rated by clinicians. The two-color chewing gum test shows similar results as only one patient had insufficient chewing function. Interestingly, we found no correlation between the masticatory function and residual denture, confirming that the maxillary obturator remains a predictable solution in such patients regardless of the anatomical alterations following surgery

Cranio-Mandibular Disorders after Whiplash Injury: A Mono-Institutional Clinical Study on 31 Patients

Background: Whiplash is a consequence of traumatic injuries, mostly related to road accidents, with variable clinical manifestations, also known as Whiplash Associated Disorders, such as neck, head and temporo-cranio-mandibular pain. Methods: The current study aims to evaluate the onset and evolution of temporomandibular joint pain in people with whiplash in a study group treated with the use of Zimmer Collars (adjustable rigid cervical collars for neck immobilization), as compared to a control group. This prospective study included 31 patients followed by the Dental Prosthesis Department of the University of Bari “Aldo Moro”: 20 patients with whiplash (age range: 20–39 years) treated with Zimmer collars and 11 patients with whiplash (age range: 20–33 years) who were not. Immediately after the whiplash occurred, a visual analogue scale (VAS) was used to describe the intensity of pain and to complete the chart of the European Academy of Craniomandibular Disorders. Five out of twenty patients, already treated with a Zimmer collar, wore an occlusal splint as well because of persistent pain reported at the 28-day and 60-day follow-up and were supported by pharmacological therapy with analgesics (paracetamol) and muscle relaxants (thiocolchicoside). Results: During the last follow-up (at six months), three out of five patients displayed a residual VAS score of 3, 4, and 5, respectively, while the remaining two displayed a VAS of 0. In the control group, four out of eleven patients needed to wear an occlusal splint but without muscle relaxants and analgesics pharmacological therapy; these four corresponded to the patients showing a residual painful symptomatology, with VAS reaching value of 2, and also were the oldest patients of the group. Data regarding VAS values and Zimmer collar use, both at the first visit and six months later, were statistically analyzed. Conclusion: Our prospective study highlights how whiplash-associated acute disorders are often self-limiting over a period of few months, thus reducing the possibility of symptom chronicity; the latter seems to be strictly related to lesion severity, pre-existence of a craniomandibular dysfunction and patient age, but appears to be independent from Zimmer collar use, as statistically confirmed