Over the past four decades, the number of people with Type 1 Diabetes (T1D) has increased by 4% per year, making it an important public health challenge. Currently, no curative therapy exists for T1D and the only available treatment is insulin replacement. HLA-DQ8 has been shown to present antigenic islet peptides driving the activation of CD4+ T-cells in T1D patients. Specifically, the insulin peptide InsB9-23 activates self-reactive CD4+ T-cells, causing pancreatic beta cell destruction. The aim of the current study was to identify retro-inverso-d-amino acid based peptides (RI-D-peptides) that can suppress T-cell activation by blocking the presentation of InsB9-23 peptide within HLA-DQ8 pocket. We identified a RI-D-peptide (RI-EXT) that inhibited InsB9-23 binding to recombinant HLA-DQ8 molecule, as well as its binding to DQ8 expressed on human B-cells. RI-EXT prevented T-cell activation in a cellular antigen presentation assay containing human DQ8 cells loaded with InsB9-23 peptide and murine T-cells expressing a human T-cell receptor specific for the InsB9-23-DQ8 complex. Moreover, RI-EXT blocked T-cell activation by InsB9-23 in a humanized DQ8 mice both ex vivo and in vivo, as shown by decreased production of IL-2 and IFN-γ and reduced lymphocyte proliferation. Interestingly, RI-EXT also blocked lymphocyte activation and proliferation by InsB9-23 in PBMCs isolated from recent onset DQ8-T1D patients. In summary, we discovered a RI-D-peptide that blocks InsB9-23 binding to HLA-DQ8 and its presentation to T-cells in T1D. These findings set the stage for using our approach as a novel therapy for patients with T1D and potentially other autoimmune diseases.
TNM-8 staging separates oropharyngeal squamous cell carcinomas (OPSCC) into human papillomavirus (HPV)-mediated and -unrelated OPSCC based on p16INK4a overexpression (p16+), as surrogate marker for HPV. However, OPSCC is histologically and clinically heterogenous including tonsillar and base of tongue squamous cell carcinomas (TSCC and BOTSCC respectively), and carcinomas of soft palate and walls (otherOPSCC). The significance of HPV is established in TSCC/BOTSCC, while its role in otherOPSCC is unclear, which is not considered in TNM-8. Here, p16+ was therefore evaluated in relation to overall survival (OS) and tumor stage per OPSCC subsite.
All 932 patients, treated with curative intent in Stockholm 2000-2016 with OPSCC, previously analyzed for p16 expression, were included. Clinical data, including stage and OS, was collected retrospectively.
Patients with p16+ otherOPSCC had significantly poorer OS compared to patients with p16+ TSCC/BOTSCC (p=0.005) and their survival was similar to that of patients with p16-otherOPSCC/TSCC/BOTSCC. Moreover, patients with TNM-8 stage I-II and p16+ otherOPSCC had a significant poorer OS compared to patients with p16+ TSCC/BOTSCC and similar stage (p=0.02). Lastly, patients with otherOPSCC and low TNM-7 stage had a significant better OS, as compared to those with a high stage (p=0.019) while no hazard discrimination was observed with TNM-7 in TSCC/BOTSCC.
Our results indicate a risk of misclassification of patients with otherOPSCC and low TNM-8 stage. CA-074 Me mw We suggest that p16 should only be evaluated in TSCC/BOTSCC and that patients with otherOPSCC should all be staged as patients with HPV-unrelated (p16-) OPSCC.
Our results indicate a risk of misclassification of patients with otherOPSCC and low TNM-8 stage. We suggest that p16 should only be evaluated in TSCC/BOTSCC and that patients with otherOPSCC should all be staged as patients with HPV-unrelated (p16-) OPSCC.
The Endonasal Endoscopic Transsphenoidal Surgery (EETS) is a minimally invasive procedure to approach and remove pituitary tumors and other sellar lesions. The process causes less pain, faster recovery, and provides further minimal invasive access in critical cases. However, a slight deviation of tools from the target area can be fatal to the patients. The aim of this study is to design and develop a prototype robot to demonstrate neurosurgical robot-assisted EET approach.
The effectiveness of a prototype robot in executing a minimally invasive EET surgery was studied in 6 cadavers. The robot was associated with a multi-information integrated technique for surgery including QR code tracking. The robot was controlled and driven by the neurosurgeon.
The standard procedure of EET was followed and the robot carried out the first stage of EET under the supervision of neurosurgeon. Finally, the sellar was reached by the neurosurgeon. The result was determined by qualitative analysis and was confirmed by the neurosurgeon. The time for the entire EET surgical procedure showed marked reduction compared to the traditional EET approach.
The robot design was found to be technically feasible and hence can be used for assisting the EET procedure. The robot used was able to assist the neurosurgeon correctly to approach the sinus.
The robot design was found to be technically feasible and hence can be used for assisting the EET procedure. The robot used was able to assist the neurosurgeon correctly to approach the sinus.
A high incidence of delayed gastric emptying (DGE) is observed in patients undergoing pylorus-preserving pancreaticoduodenectomy (PpPD). However, DGE incidence after pancreaticoduodenectomy varied because of heterogeneity in surgical techniques, number of surgeons, and DGE definition. This study aimed to evaluate the difference in the incidence of DGE following PpPD and pylorus-resecting pancreaticoduodenectomy (PrPD) and to analyze the risk factor of DGE by a single surgeon to determine whether pylorus preservation was the main factor of DGE.
This retrospective study included 115 patients who underwent PpPD (with pylorus ring preservation) and PrPD (without pylorus ring preservation) with laparotomy by a single surgeon at a tertiary center.
The overall incidence of DGE was 23.1%. For comparison, 20 patients (39.2%) in the PpPD group and 5 patients (8.8%) in the PrPD group had DGE, showing a significant difference (p<0.001). On univariate analysis, hypertension, PpPD, operation time, intraoperative bleeding, packed red blood cell transfusion ≥500mL, and clinically relevant postoperative pancreatic fistula were associated with DGE.CA-074 Me mw
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