Comparative analysis of the bioaccumulation of bisphenol A in the blood serum and follicular fluid of women living in two areas with different environmental impacts.

Introduction: Bisphenol A (BPA) is a common contaminant widely used in many industrial sectors. Because of its wide use and dispersion, it can be accumulated in living human bodies through both oral assumption and nondietary routes. BPA exhibits hormone-like properties, falling under the class of endocrine disruptors; therefore, it can alter relevant physiological functions.

Development of a Potency Assay for Nous-209, a Multivalent Neoantigens-Based Genetic Cancer Vaccine.

Quality control testing of vaccines, including potency assessment, is critical to ensure equivalence of clinical lots. We developed a potency assay to support the clinical advancement of Nous-209, a cancer vaccine based on heterologous prime/boost administration of two multivalent viral vector products: GAd-209 and MVA-209. These consist of a mix of four Adeno (Great Ape Adenovirus; GAd) and four Modified Vaccinia Ankara (MVA) vectors respectively, each containing a different transgene encoding a synthetic polypeptide composed of antigenic peptide fragments joined one after the other.

Phase I Trial of Viral Vector-Based Personalized Vaccination Elicits Robust Neoantigen-Specific Antitumor T-Cell Responses.

Purpose: Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T-cell response to overcome tumor heterogeneity. NOUS-PEV is a vector-based personalized vaccine, expressing 60 nAgs and consists of priming with a nonhuman Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara. Here, we report data of a phase Ib trial of NOUS-PEV in combination with pembrolizumab in treatment-naïve patients with metastatic melanoma (NCT04990479).

Personalized Cancer Vaccines Go Viral: Viral Vectors in the Era of Personalized Immunotherapy of Cancer.

The aim of personalized cancer vaccines is to elicit potent and tumor-specific immune responses against neoantigens specific to each patient and to establish durable immunity, while minimizing the adverse events. Over recent years, there has been a renewed interest in personalized cancer vaccines, primarily due to the advancement of innovative technologies for the identification of neoantigens and novel vaccine delivery platforms. Here, we review the emerging field of personalized cancer vaccination, with a focus on the use of viral vectors as a vaccine platform.

MHC class II invariant chain-adjuvanted viral vectored vaccines enhances T cell responses in humans.

Strategies to enhance the induction of high magnitude T cell responses through vaccination are urgently needed. Major histocompatibility complex (MHC) class II-associated invariant chain (Ii) plays a critical role in antigen presentation, forming MHC class II peptide complexes for the generation of CD4 T cell responses. Preclinical studies evaluating the fusion of Ii to antigens encoded in vector delivery systems have shown that this strategy may enhance T cell immune responses to the encoded antigen.

Combined Raman and polarization sensitive holographic imaging for a multimodal label-free assessment of human sperm function.

Raman microspectroscopy (RM) and polarization sensitive digital holographic imaging (PSDHI) are valuable analytical tools in biological and medical research, allowing the detection of both biochemical and morphological variations of the sample without labels or long sample preparation. Here, using this multi-modal approach we analyze in vitro human sperm capacitation and the acrosome reaction induced by heparin. The multimodal microscopy provides morphofunctional information that can assess the sperms ability to respond to capacitation stimuli (sperm function).

Effects of impaction severity of treated palatally displaced canines on periodontal outcomes: a retrospective study.

Background: Even though periodontal health was suggested to be not related to the traction technique, some other variables might influence the esthetic outcome of palatally displaced canines (PDC) when aligned, such as the initial position and impaction rate of the canine before treatment. The purpose of the present study was therefore to evaluate the existing correlations between periodontal health outcome of PDC after their exposure and alignment and their initial position identified according to the different rates of impaction severity.

Materials And Methods: The final sample enrolled 293 PDC which satisfied inclusion and exclusion criteria.

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis: First-in-human trial of ChAd63-KH.

Background: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need.

Laparoscopic appendectomy: Hem-o-lok versus Endoloop in stump closure.

There are several techniques described to close the appendicular stump during laparoscopic appendectomy. The aim of this study was to investigate the safety and usefulness of the Hem-o-lok clip for the closure of appendicular stump, comparing these data with those concerning the endo-loop. We conducted a retrospective study that compared two groups of patients who underwent laparoscopic appendectomy from 2010 to 2015 at our institution.

The importance of the mesofascial interface in complete mesocolic excision.

Complete mesocolic excision (CME) with Central Vascular Ligation (CVL) is progressively gaining acceptance as the most updated surgical treatment in the multimodal management of colonic cancer. The concept is based on excision of the affected organ with its related primitive dorsal mesenterium as an intact package to maximize local clearance, and high tie ligation to boost regional control, translating the original concept of Total Mesorectal Excision proposed by Heald for rectal cancer. Aim of this review is to analyze the modern concept of the mesenteric organ, with particular regard to the interfaces between its single components and the importance of the meso-fascial interface as the correct plane of separation.

Laparoscopic complete mesocolic excision with central vascular ligation in 600 right total mesocolectomies: Safety, prognostic factors and oncologic outcome.

Background: To analyze our experience with laparoscopic right Mesocolectomy in right colonic cancers.

Methods: 600 consecutive patients were studied.

Results: Mortality was 0.

Combined brachial embolectomy and stent graft endovascular exclusion in the treatment of acute arm ischemia due to subclavian artery aneurysms thrombosis or distal embolization.

Aim: Purpose of this study is to report our results after simultaneous transbrachial embolectomy and endovascular aneurysm exclusion with stentgraft in the treatment of upper limb acute ischemia due to subclavian artery aneurysm thrombosis and embolization .

Methods: From January 2010 to December 2015, seven consecutive patients (6 men; mean age 71.5, range 44-85) underwent to emergent revascularization for upper limb ischemia due to thrombosis/embolization of SAA by means of brachial embolectomy and endovascular exclusion.

Anaphylactic Reaction during Implantation of Ovation Abdominal Stent Graft in Patients with Abdominal Aortic Aneurysm.

The Ovation Abdominal Stent Graft System is a trimodular endoprosthesis planned to overcome the limitations of currently available stent grafts, allowing complex iliac and femoral access and providing a proximal seal in challenge infrarenal neck morphology. The proximal sealing is achieved by means of a network of inflatable rings filled with low-viscosity radiopaque polyethylene glycol-based polymer during stent-graft deployment. The leakage of polymer outside the channel to fill the rings into the vascular system may induce an hypersensitivity reaction and anaphylactic shock.

"Ultra" E.R.A.S. in laparoscopic colectomy for cancer: discharge after the first flatus? A prospective, randomized trial.

Background: Enhanced Recovery After Surgery (E.R.A.

Laparoscopic complete mesocolic excision with central vascular ligation in right colon cancer: A comprehensive review.

Aim of the study is to comprehensively review the latest trends in laparoscopic complete mesocolic excision (CME) with central vascular ligation (CVL) for the multimodal management of right colon cancer. Historical and up-to-date anatomo-embryological concepts are analyzed in detail, focusing on the latest studies of the mesenteric organ, its dissection by mesofascial and retrofascial cleavage planes, and questioning the need for a new terminology in colonic resections. The rationale behind Laparoscopic CME with CVL is thoroughly investigated and explained.

Chronic hepatitis C viral infection subverts vaccine-induced T-cell immunity in humans.

Unlabelled: Adenoviral vectors encoding hepatitis C virus (HCV) nonstructural (NS) proteins induce multispecific, high-magnitude, durable CD4(+) and CD8(+) T-cell responses in healthy volunteers. We assessed the capacity of these vaccines to induce functional HCV-specific immune responses and determine T-cell cross-reactivity to endogenous virus in patients with chronic HCV infection. HCV genotype 1-infected patients were vaccinated using heterologous adenoviral vectors (ChAd3-NSmut and Ad6-NSmut) encoding HCV NS proteins in a dose escalation, prime-boost regimen, with and without concomitant pegylated interferon-α/ribavirin therapy.

Chimpanzee adenovirus- and MVA-vectored respiratory syncytial virus vaccine is safe and immunogenic in adults.

Respiratory syncytial virus (RSV) causes respiratory infection in annual epidemics, with infants and the elderly at particular risk of developing severe disease and death. However, despite its importance, no vaccine exists. The chimpanzee adenovirus, PanAd3-RSV, and modified vaccinia virus Ankara, MVA-RSV, are replication-defective viral vectors encoding the RSV fusion (F), nucleocapsid (N), and matrix (M2-1) proteins for the induction of humoral and cellular responses.

Mucosal delivery of a vectored RSV vaccine is safe and elicits protective immunity in rodents and nonhuman primates.

Respiratory Syncytial Virus (RSV) is a leading cause of severe respiratory disease in infants and the elderly. No vaccine is presently available to address this major unmet medical need. We generated a new genetic vaccine based on chimpanzee Adenovirus (PanAd3-RSV) and Modified Vaccinia Ankara RSV (MVA-RSV) encoding the F, N, and M2-1 proteins of RSV, for the induction of neutralizing antibodies and broad cellular immunity.

A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.

Background: The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak.

Methods: In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom.

Laparoscopic complete mesocolic excision with central vascular ligation in right colon cancer: Long-term oncologic outcome between mesocolic and non-mesocolic planes of surgery.

Aim: To analyze our experience in translating the concept of total mesorectal excision to "no-touch" complete removal of an intact mesocolonic envelope (complete mesocolic excision), along with central vascular ligation and apical node dissection, in the surgical treatment of right-sided colonic cancers, comparing "mesocolic" to less radical "non-mesocolic" planes of surgery in respect to quality of the surgical specimen and long-term oncologic outcome.

Method: A total of 115 patients with right-sided colonic cancers were retrospectively enrolled from 2008 to 2013 and operated on following the intent of minimally invasive complete mesocolic excision with central vascular ligation.

Results: Morbidity and mortality were 22.

A human vaccine strategy based on chimpanzee adenoviral and MVA vectors that primes, boosts, and sustains functional HCV-specific T cell memory.

A protective vaccine against hepatitis C virus (HCV) remains an unmet clinical need. HCV infects millions of people worldwide and is a leading cause of liver cirrhosis and hepatocellular cancer. Animal challenge experiments, immunogenetics studies, and assessment of host immunity during acute infection highlight the critical role that effective T cell immunity plays in viral control.

Stage I-IIIC right colonic cancer treated with complete mesocolic excision and central vascular ligation: quality of surgical specimen and long term oncologic outcome according to the plane of surgery.

Aim: Complete removal of mesocolon "as an envelope" (complete mesocolic excision, CME) with central vascular ligation and apical node dissection (CVL) in the surgical management of right sided colonic cancer is a novel technique focused on resection of the colon surrounded by its intact primitive dorsal mesentery containing the tumors and all the routes of initial cancerous diffusion; our aim was to evaluate quality of surgical specimens and the relative impact on long-term oncologic outcome when compared to less radical planes of surgery.

Methods: Data were collected in 159 staged I-IIIC right sided colon cancers operated on with the concept of CME and CVL, between 2008 and 2013.

Results: Morbidity and mortality were 37.

Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation.

Induction of antigen-specific CD8(+) T cells offers the prospect of immunization against many infectious diseases, but no subunit vaccine has induced CD8(+) T cells that correlate with efficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirus vector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequency T-cell responses (median >2400 SFC/10(6) peripheral blood mononuclear cells) to the liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protective efficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delays time to patency through substantial reduction of liver-stage parasite burden in five more (5/14, 36%), P=0.

Laparoscopic versus open total mesorectal excision for stage I-III mid and low rectal cancer: a retrospective 5 years analysis.

Introduction: Total mesorectal excision (TME) is the cornerstone of a correct surgical therapy for extraperitoneal rectal cancer. Aim of the study is to evaluate our 5 years experience confronting retrospectively laparoscopic (lap) TME in respect to its laparotomic (open) counterpart.

Patients And Methods: 30 patients were treated laparoscopically for stage I-III extraperitoneal rectal cancer and retrospectively compared to a homogeneous group, stratified for sex, age, comorbidities and stage of disease.