The Link between Diabetes, Pancreatic Tumors, and miRNAs-New Players for Diagnosis and Therapy?

Despite significant progress in medicine, pancreatic cancer is one of the most tardily diagnosed cancer and is consequently associated with a poor prognosis and a low survival rate. The asymptomatic clinical picture and the lack of relevant diagnostic markers for the early stages of pancreatic cancer are believed to be the major constraints behind an accurate diagnosis of this disease. Furthermore, underlying mechanisms of pancreatic cancer development are still poorly recognized. It is well accepted that diabetes increases the risk of pancreatic cancer development, however the precise mechanisms are weakly investigated. Recent studies are focused on microRNAs as a causative factor of pancreatic cancer. This review aims to provide an overview of the current knowledge of pancreatic cancer and diabetes-associated microRNAs, and their potential in diagnosis and therapy. miR-96, miR-124, miR-21, and miR-10a were identified as promising biomarkers for early pancreatic cancer prediction. miR-26a, miR-101, and miR-200b carry therapeutic potential, as they not only regulate significant biological pathways, including the TGF-ß and PI3K/AKT, but their re-expression contributes to the improvement of the prognosis by reducing invasiveness or chemoresistance. In diabetes, there are also changes in the expression of microRNAs, such as in miR-145, miR-29c, and miR-143. These microRNAs are involved, among others, in insulin signaling, including IRS-1 and AKT (miR-145), glucose homeostasis (hsa-miR-21), and glucose reuptake and gluconeogenesis (miR-29c). Although, changes in the expression of the same microRNAs are observed in both pancreatic cancer and diabetes, they exert different molecular effects. For example, miR-181a is upregulated in both pancreatic cancer and diabetes mellitus, but in diabetes it contributes to insulin resistance, whereas in pancreatic cancer it promotes tumor cell migration, respectively. To conclude, dysregulated microRNAs in diabetes affect crucial cellular processes that are involved in pancreatic cancer development and progression.

Validation of the test for detecting SARS--CoV-2 antigens in the Polish population in patients with suspected SARS-CoV-2 infection.

In December 2019, the World Health Organization (WHO) reported that China had accumulated pneumonia of unclear etiology in Wuhan. According to WHO recommendations, in strictly defined situations, antigen tests can be implemented into the diagnostic algorithm to reduce the number of molecular tests performed and support the rapid identification and treatment of COVID-19 patients. According to WHO recommendations, the antigen test for diagnostic use should have a sensitivity of ≥ 80% and a specificity of ≥ 97% compared to molecular tests (NAAT). Based on the comparative analysis, the sensitivity and specificity of the SARS-CoV-2 Antigen ELISA test were determined concerning the RT-PCR reference method. The sensitivity of the SARS-CoV-2 Antigen ELISA was 100% (51/51) and the specificity was 98.84%. The obtained data demonstrate that the analyzed antigen test meets both the WHO and the Ministry of Health criteria.

Nucleoplasmin-like domain of FKBP39 from Drosophila melanogaster forms a tetramer with partly disordered tentacle-like C-terminal segments.

Nucleoplasmins are a nuclear chaperone family defined by the presence of a highly conserved N-terminal core domain. X-ray crystallographic studies of isolated nucleoplasmin core domains revealed a ß-propeller structure consisting of a set of five monomers that together form a stable pentamer. Recent studies on isolated N-terminal domains from Drosophila 39-kDa FK506-binding protein (FKBP39) and from other chromatin-associated proteins showed analogous, nucleoplasmin-like (NPL) pentameric structures. Here, we report that the NPL domain of the full-length FKBP39 does not form pentameric complexes. Multi-angle light scattering (MALS) and sedimentation equilibrium ultracentrifugation (SE AUC) analyses of the molecular mass of the full-length protein indicated that FKBP39 forms homotetrameric complexes. Molecular models reconstructed from small-angle X-ray scattering (SAXS) revealed that the NPL domain forms a stable, tetrameric core and that FK506-binding domains are linked to it by intrinsically disordered, flexible chains that form tentacle-like segments. Analyses of full-length FKBP39 and its isolated NPL domain suggested that the distal regions of the polypeptide chain influence and determine the quaternary conformation of the nucleoplasmin-like protein. These results provide new insights regarding the conserved structure of nucleoplasmin core domains and provide a potential explanation for the importance of the tetrameric structural organization of full-length nucleoplasmins.

Massive failure of TiNbN coating in surface engineered metal-on-metal hip arthroplasty: Retrieval analysis.

This article presents examination of a failed total hip replacement with surface engineered metal-on-metal (MoM) articulation. The implant was coated with a thin TiNbN film (Physical Vapor Deposition), and at retrieval 53 months after implantation the coating was abraded on weight-bearing part of the head and acetabular component. Scanning electron microscopy of bearing surfaces demonstrated multifocal crack formation, delamination of small film fragments, and formation of aggregates containing nanometer sized wear debris. We also observed coating damage in third body mechanism. Complex failure mechanism of TiNbN coating demonstrated in this study suggests insufficient bonding strength between the coating and substrate alloy and raise concerns regarding the use of such coatings in total hip arthroplasty with MoM bearing. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1043-1049, 2016.

Remodeling of bone tissue around the distal part of Zweymüller stem.

BACKGROUND: The Zweymüller stem is well-known in Europe and widely used for total hip replacement since 1980. Few authors have noted the presence of increased bone density below the tip of the stem; however, the underlying mechanism is still unknown. The aim of this study was to reveal factors influencing bone remodeling around the tip of the Zweymüller stem. MATERIAL AND METHODS: 102 consecutive patients (69 women and 33 men) who received a second generation Zweymüller type stem (123 prostheses) were included. Mean follow-up was 9.2 years (6 - 15 years). A Cortical Index (CI) was defined as the ratio between stem width and external cortical diameter in Gruen zones 3 and 5. RESULTS: Patients with a wide femoral canal and thin cortical bone (CI ≥0.4) demonstrated a positive correlation with the presence of increased bone density (IBD) below the stem (p<0.0001, r=0.6028). During follow-up, the mean Cortical Index decreased by 0.02 points and mean thickness of cortical bone in zone 3 and 5 increased by 2.0 millimeters. Cortical thickening was more pronounced in cases without IBD (1.5 vs. 2.4 mm, p=0.0172). CONCLUSIONS: 1. Thin cortical layers and a wide femoral canal (CI ≥0.4) can result in the presence of IBD below the stem. 2. IBDs probably appear due to mechanical stress transferred by the tip of stem to cancellous bone in Gruen zone 4. 3. Based on clinical symptoms, we conclude that the presence of IBD is not associated with increased aseptic loosening or stem instability.

Insight into the Unfolding Properties of Chd64, a Small, Single Domain Protein with a Globular Core and Disordered Tails.

Two major lipophilic hormones, 20-hydroxyecdysone (20E) and juvenile hormone (JH), govern insect development and growth. While the mode of action of 20E is well understood, some understanding of JH-dependent signalling has been attained only in the past few years, and the crosstalk of the two hormonal pathways remains unknown. Two proteins, the calponin-like Chd64 and immunophilin FKBP39 proteins, have recently been found to play pivotal roles in the formation of dynamic, multiprotein complex that cross-links these two signalling pathways. However, the molecular mechanism of the interaction remains unexplored. The aim of this work was to determine structural elements of Chd64 to provide an understanding of molecular basis of multiple interactions. We analysed Chd64 in two unrelated insect species, Drosophila melanogaster (DmChd64) and Tribolium castaneum (TcChd64). Using hydrogen-deuterium exchange mass spectrometry (HDX-MS), we showed that both Chd64 proteins have disordered tails that outflank the globular core. The folds of the globular cores of both Chd64 resemble the calponin homology (CH) domain previously resolved by crystallography. Monitoring the unfolding of DmChd64 and TcChd64 by far-ultraviolet (UV) circular dichroism (CD) spectroscopy, fluorescence spectroscopy and size-exclusion chromatography (SEC) revealed a highly complex process. Chd64 unfolds and forms of a molten globule (MG)-like intermediate state. Furthermore, our data indicate that in some conditions, Chd64 may exists in discrete structural forms, indicating that the protein is pliable and capable of easily acquiring different conformations. The plasticity of Chd64 and the existence of terminal intrinsically disordered regions (IDRs) may be crucial for multiple interactions with many partners.

Calponin-like Chd64 is partly disordered.

20-hydroxyecdysone (20E) and juvenile hormone (JH) signaling pathways interact to regulate insect development. Recently, two proteins, a calponin-like Chd64 and immunophilin FKBP39 have been found to play a pivotal role in the cross-talk between 20E and JH, although the molecular basis of interaction remains unknown. The aim of this work was to identify the structural features that would provide understanding of the role of Chd64 in multiple and dynamic complex that cross-links the signaling pathways. Here, we demonstrate the results of in silico and in vitro analyses of the structural organization of Chd64 from Drosophila melanogaster and its homologue from Tribolium castaneum. Computational analysis predicted the existence of disordered regions on the termini of both proteins, while the central region appeared to be globular, probably corresponding to the calponin homology (CH) domain. In vitro analyses of the hydrodynamic properties of the proteins from analytical size-exclusion chromatography and analytical ultracentrifugation revealed that DmChd64 and TcChd64 had an asymmetrical, elongated shape, which was further confirmed by small angle X-ray scattering (SAXS). The Kratky plot indicated disorderness in both Chd64 proteins, which could possibly be on the protein termini and which would give rise to specific hydrodynamic properties. Disordered tails are often involved in diverse interactions. Therefore, it is highly possible that there are intrinsically disordered regions (IDRs) on both termini of the Chd64 proteins that serve as platforms for multiple interaction with various partners and constitute the foundation for their regulatory function.

Debonding of porous coating of a threaded acetabular component: retrieval analysis.

This report presents a case of debonding of plasma sprayed porous titanium coating from a threaded acetabular component which caused aseptic loosening of the implant. Weight bearing after delamination caused abrasive damage of the acetabular shell, and particles of the coating embedded in the acetabular liner. Microscopic examination of periprosthetic tissues showed presence of metal particles and macrophage infiltration. Despite microscopic examination of the retrieved component the cause of debonding remains unclear.

30-year survival of a McKee-Farrar hip prosthesis--case report and microscopic analysis of bearing surface.

We report a case of a female patient using a McKee-Farrar prosthesis for 30 years, until revision surgery for aseptic loosening. Electron microscopy analysis of bearing surface of the retrieved implant was performed, and the results were presented in comparison with previously published papers.

[Assessment of the level of metal ions in the blood of patients after hip resurfacing--preliminary report]. / Ocena poziomu jonów metali we krwi pacjentów po endoprotezoplastyce powierzchniowej--doniesienie wstepne.

INTRODUCTION: Metal-on-metal bearings characterize lower wear than metal-poly, lower fracture risk than ceramics and they allow for the manufacturing of large diameter heads. The metal ion release from the bearings is the the major concern of these articulations. MATERIAL: The study group consisted of 16 patients who underwent hip resurfacing with Durom implant and had minimum 1 year follow-up period. Blood from the patients was collected 4 times: before the surgery, 2, 6 and 12 months postoperatively. METHODS: Clinical examination was done according to HHS, Radiographic image was used to measure the cup inclination, evaluation of chromium and cobalt ion blood levels was performed using graphite furnace atomic absorbtion spectrometry (GFAAS). RESULTS: The levels of cobalt and chromium increased postoperatively significantly to decrease slightly at 6 months. At 1 year cobalt levels increased to the similar level like at at 2 months. The chromium level decresed to the values as low as preoperatively. The mean cup inclination angle measured on X-rays was 48 degrees(range 39 degrees - 56 degrees). The mean HHS result was 89.86 (range 64.43 to 98.73). The mean activity level measured with UCLA scale was 6 (range 3-9). CONCLUSIONS: The metal ion blond levels increase sigficantly in the period 2-6 months following hip replacement with large diameter metal-on-metal articulation. In further examinations at 1 year post-op ion levels decrease.

[Early results of revision hip arthroplasty using modular Restoration stem]. / Wczesne wyniki rewizji endoprotezy stawu biodrowego za pomoca trzpienia modularnego Restoration.

UNLABELLED: There is an increasing number of hip joint arthroplasty procedures all over the world which are followed by revision surgery. The cases of severe bone loss and periprosthetic fractures revision of a stem can constitue a serious challenge even for an experienced orthopedic surgeon. MATERIAL: In the research material there are 18 patients 6-50 months after the stem of the hip prosthesis revision with Stryker Restoration modular stem. METHODS: Clinical evaluation according to HHS protocol, the quality of life measured with SF-36 form, and physical activity evaluated using UCLA score. The methods are also AP and X-Ray of both hips and lateral X-ray of revised hip with osteolysis around stem, stem subsidence, and difference in leg length evaluation, as well as the comparison of hip offsets. RESULTS: Mean HHS score was 78.6 pts, mean SF-36 based quality of life 50.5 pts, and the mean UCLA 4.72. Radiolucent zones around the stem were observed in several cases which were correlated with the stem subsidence. CONCLUSION: The clinical results in this study are similar to those from the literature, and slightly lower than of the patients after primary hip arthroplasty, particularly in function measuring subscales. The quality of life scores of our patients was significantly lower than reported by other authors in cases of hip revision arthroplasty. There was no case of aseptic loosening. Further observation of the patients considering osteolysis and its relation to stem subsidence is needed.

[Porous tantalum modular cups in revision hip arthroplasty]. / Zastosowanie modularnych komponentów z porowatego tantalu w endoprotezoplastyce rewizyjnej panewki stawu biodrowego.

INTRODUCTION: Modem indications for use of cemented or uncemented implants in revision hip arthroplasty are comparable. The use of bone cement provides predictable short term results, but the lack of osteointegration deteriorates its long term durability. Uncemented implants undergo osteointegration, but reduced contact with host bone may cause early loosening. Modular porous tantalum implants are highly osteointegrative, and the availability of bone stock augments increases the versatility of this system. MATERIAL AND METHODS: The study group consisted of 20 patients (21 hips) who underwent a revision hip arthroplasty using Trabecular Metal acetabular revision system. The follow-up period was between 7 and 31 months (average 20 months). All patients were evaluated with HHS and conventional radiography. RESULTS: The mean HHS increased form40.45 (range 18.74-56.65) preoperatively to 78.8 (56.5-96) at the last follow-up. No mechanical failures, nor septic complications were noted.

[Operative treatment of femoro-acetabular impingement in hip joint]. / Operacyjne leczenie konfliktu szyjkowo-panewkowego stawu biodrowego.

For many years early treatment of degenerative joint disease in hip joint included only conservative procedures or extraarticular surgery eg. pertrochanteric osteotomy, acetabular roof reconstruction. Discovery of femoro-acetabular impingement mechanism opened space for new advanced operative techniques. For the last few years these techniques are mastered using arthroscopic approach as well as open joint surgery. In this paper we are describing technique with osteotomy of the greater trochanter and joint luxation for open treatment of femoro-acetabular impingement.

[Reactions of bone tissue around the ABG II stem]. / Reakcje tkanki kostnej wokól trzpienia endoprotezy ABG II.

UNLABELLED: The uncemented total hip replacement became a standard in treatment of the severe hip osteoarthritis. Its long term efficiency is based on the correct osteointegration which depends on the adequate implantation. Material. The study group consisted of 49 patients (52 hips) following total hip replacement with ABG II stem and Trident PSL cup. The follow-up ranged between 6 months and 2 years. METHODS: In each case the Harris hip score was performed and high resolution x-rays were taken. On X-ray the fit and position of the stem, linear osteolysis around the stem and bone atrophy at the greater trochanter were evaluated. Results. The mean HHS at the last follow up was 90.4 (50-99). The mean angle of the stem position was 2.9 varus. The mean fit index was was 0.75. The significant correlation was found between the fit index and the varus stem position angle. The linear osteolysis surrounding the stemin the 1st Gruen zone was found in 70% of cases. The phenomenon of the linear radiolucenecy surrounded by linear densification was found in the 76% of cases. Bone atrophy at the greater trochanter was found in the 42% of cases. Conclusions. The use of ABG II stems provided very good clinical results. The stem has a tendency to a varus position, which seems to be connected with the use of the too small stems. Specific radiographic observations create a need of futher follow-up, but existed without the influence on the clinical results.

[Total knee replacement in joints with severe varus and bone deficiency]. / Endoprotezoplastyka stawu kolanowego ze znaczna szpotawoscia i deficytem kostnym.

INTRODUCTION: Total knee replacement in knees with severe valgus and defects of the medial tibial condyle are at higher risk complications than in knees with a correct axial allignement. MATERIAL AND METHODS: The study group included 10 patients (11 knees) with with severe valgus and defects of the medial tibial condyle in which TKR was performed. In 8 cases bone defects were filled with bone autograft in 3 cases defects were filled with metal augments. The mean follow-up was 37 months (26 months to 4 years). Clinical results were measured with the knee society score, the level of activity was evaluated with the UCLA score. Radiographic evaluation was based on radiograms taken preoperatively, postoperatively and at the follow-up examination. RESULTS: In All cases an improvement in clinical results was noted, the mean KSS result rised from 25.3 preoperatively to 87 postoperatively and the level of activity rised from 3.4 to 5.4 postoperatively. No signs of loosening were found in radiographic evaluation. CONCLUSIONS: TKR in joint with severe varus and medial tibial condyle defects creates a need for the reconstruction of defects. In lesser defects reconstruction with bone autografts is sufficient, in severe cases filling the defect with metal augments is needed. When indicitions are followed both methods provide good clinical results.

Total hip arthroplasty following Ganz periacetabular osteotomy. Cases study.

The Ganz periacetabular osteotomy (PAO) is currently the most popular hip-sparing procedure in adults with acetabular dysplasia. If this procedure fails and a total hip arthroplasty is necessary, spatial reorientation of the acetabulum alters the conditions of implanting the acetabular component of the prosthesis. In our study, we present two cases of total hip arthroplasty in patients who had undergone PAO.

[Current views on the pathogenesis of osteoarthritis]. / Wspólczesne poglady na patogeneze choroby zwyrodnieniowej stawów.

Degenerative joint disease is the most common joint pathology and the main cause of disability of elderly people in developed countries. It is caused by imbalance between degeneration and regeneration of articular cartilage accompanied by pathological changes of other joint structures. No generally recognizable description of the pathogenetic pathway of osteoarthritis (OA) exists so far, however recent studies have widened the knowledge of the underlying pathology. In this review views regarding the role of genetic and mechanical factors in OA pathogenesis were presented. The role of pro-inflammatory mediators such as cytokines (IL-1, TNF-alfa, IL-6), lipid mediators, NO, reactive oxygen species, were discussed. The contribution of adipokines (fat tissue derived hormones with cytokine activity) to the pathogenesis of degenerative joint disease was also described. The role of synovial membrane, articular cartilage, subchondral bone and such structures as osteophytes and infrapatellar fat pad in development of osteoarthritis were presented as well.

[Pedobarographic evaluation of the foot after Keller's procedure for Hallux valgus and Hallux rigidus]. / Ocena pedobarograficzna stopy po operacji palucha koslawego i sztywnego metoda Kellera.

Hallux valgus and hallux rigidus are common foot deformities. One of possible procedures is Keller's surgery. The purpose of this study is to evaluate the use of pedobarography for postoperative evaluation of the foot. Group. We examined 54 patients aged 48 to 82 (average 60.4) after surgical treatment of Hallux valgus (78 feet) or Hallux Rigidus (15 feet). Methods. Retrospective pedobarographic evaluation 1 to 11 years after surgery was performed using PEL-38 system. Clinical results. All patients had markedly increased pressure under the 2nd and 3rd metatarsal heads comparing to other forefoot regions. Only 17% of feet had distal dynamic transverse arch during stance phase of gait. There was severe impairment of function of the great toe in entire group. In 82.7% of feet there was no ground contact of the great toe in dynamic evaluation of the stance phase. Conclusion. Pedobarographic examination has good value in postoperative functional assessment of the foot. It's a valuable addition to physical and radiological examination.

Early acute phase response following total hip replacement.

BACKGROUND: The acute phase proteins are commonly known universal markers of the inflammatory process. The aim of the study was the evaluation of the acute phase response in the first 6 months THR. The secondary aim was to check if the type of hip replacement affects the acute phase response. MATERIAL AND METHODS: The study group consisted of 40 patients who underwent THA using uncemented (20) and cemented (20) endoprostheses. The concentrations of C-reactive protein, alpha-glycoprotein, and alpha-1-antichymotripsin, and microheterogeneity of AGP were evaluated. RESULTS: The blood levels of the acute phase proteins CRP, AGP, ACT rose significantly at 2 and 14 days after the surgery to return to preoperative values at 6 months after the surgery. The V3 variant of microheterogeneity of AGP, absent under normal conditions, and representative of acute inflammation, was found in a few patients preoperatively. In postoperative evaluations, it was found in the vast majority of the patients. CONCLUSIONS: The analysis of the profiles of the glycosylation of AGP shows that the presence of the acute inflammatory response immediately following total hip replacement, which later changes into persistent chronic inflammation, is more pronounced in patients receiving cemented endoprosthesis.

[Physical activity and quality of life following total uncemented hip replacement and hip resurfacing]. / Aktywnosc fizyczna i jakosc zycia po endoprotezoplastyce bezcementowej oraz kapoplastyce stawu biodrowego.

INTRODUCTION: The influence of physical activity on the survival of total hip replacement remains not fully recognized. It is unclear which activities are beneficient for patients following THR. MATERIAL: The study was conducted on group of 87 patients (94 hips) following uncemented THR with ABGII/Trident and 45 patients (51 hips) following hip resurfacing. The follow-up period was 6-30 months for THR group and 6-42 months for resurfacing group. METHODS: The patients answered a questionnaire based on WOMAC and SF-36 score, UCLA activity scale with additional questions concerning patients physical activity, working and place of living. RESULTS: In WOMAC, physical domains of SF-36 and UCLA activity score patients following hip resurfacing showed better results. The most preferred activity in both groups was exercise walking and biking. The last one was particularly preferred by patients living in rural areas. CONCLUSION: The vast majority of patients restricted their activity to disciplines with a safe range of hip weight bearing.