333 research outputs found
RC BEAMS SHEAR-STRENGTHENED WITH FABRIC-REINFORCED-CEMENTITIOUS-MATRIX (FRCM) COMPOSITE
The interest in retrofit/rehabilitation of existing concrete structures has increased due to degradation and/or introduction of more stringent design requirements. Among the externally-bonded strengthening systems fiber-reinforced polymers is the most widely known technology. Despite its effectiveness as a material system, the presence of an organic binder has some drawbacks that could be addressed by using in its place a cementitious binder as in fabric- reinforced cementitious matrix (FRCM) systems. The pur- pose of this paper is to evaluate the behavior of reinforced concrete (RC) beams strengthened in shear with U-wraps made of FRCM. An extensive experimental program was undertaken in order to understand and characterize this composite when used as a strengthening system. The labo- ratory results demonstrate the technical viability of FRCM for shear strengthening of RC beams. Based on the experi- mental and analytical results, FRCM increases shear strength but not proportionally to the number of fabric plies installed. On the other hand, FRCM failure modes are related with a high consistency to the amount of external reinforcement applied. Design considerations based on the algorithms proposed by ACI guidelines are also provided
ADAM10 Localization in Temporomandibular Joint Disk with Internal Derangement: An Ex Vivo Immunohistochemical Study
The purpose of this study was to determine the presence of ADAM10 in temporomandibular joint disk with internal derangement. Twenty-five paraffin blocks of displaced temporomandibular joint (TMJ) disk specimens from earlier investigations were retrieved from the archives of the University of Catania. Of these 16 had been removed from females and 9 from males; 11 with anterior disk displacement with reduction (ADDwR) and 14 with anterior disk displacement without reduction (ADDwoR). The sections were dehydrated, embedded in paraffin and cut. Then they were incubated in 0.3% H2O2/methanol and half of sections from each sample were incubated in diluted rabbit polyclonal anti-ADAM10 antibody. Then biotinylated anti-mouse/anti-rabbit IgG was applied to the sections, followed by avidin–biotin–perioxidase complex. The results were analyzed and the results were that ADAM10 was overexpressed in the posterior band of sections from patients with ADDwR compared to the other bands of both ADDwR and ADDwoR sections. Overexpression correlated with severe histopathological degeneration. We believe these results have the potential to provide insights into the pathogenesis of TMJ disk degeneration and to help design new therapeutic approaches targeting the proteolytic events that lead to tissue degeneration. Early therapeutic block of ADAM10 activity could succeed in limiting aggrecan-rich matrix breakdown without affecting normal physiology
Management of patients with a failed kidney transplant: what should we do?
Abstract
The number of kidney transplant recipients returning to dialysis after graft failure is steadily increasing over time. Patients with a failed kidney transplant have been shown to have a significant increase in mortality compared with patients with a functioning graft or patients initiating dialysis for the first time. Moreover, the risk for infectious complications, cardiovascular disease and malignancy is greater than in the dialysis population due to the frequent maintenance of low-dose immunosuppression, which is required to reduce the risk of allosensitization, particularly in patients with the prospect of retransplantation from a living donor. The management of these patients present several controversial opinions and clinical guidelines are lacking. This article aims to review the leading evidence on the main issues in the management of patients with failed transplant, including the ideal timing and modality of dialysis reinitiation, the indications for an allograft nephrectomy or the correct management of immunosuppression during graft failure. In summary, retransplantation is a feasible option that should be considered in patients with graft failure and may help to minimize the morbidity and mortality risk associated with dialysis reinitiation
Immunohistochemical evaluation of vitamin D receptor (VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms
ObjectiveVitamin D receptor (VDR) mediates vitamin D activity. We examined whether VDR expression in excised melanoma
tissues is associated with VDR gene (VDR) polymorphisms.
MethodsWe evaluated VDR protein expression (by monoclonal antibody immunostaining), melanoma characteristics, and
carriage of VDR-FokI-rs2228570 (C>T), VDR-BsmI-rs1544410 (G>A), VDR-ApaI-rs7975232 (T>G), and VDR-TaqI-rs731236
(T>C) polymorphisms (by restriction fragment length polymorphism). Absence or presence of restriction site was denoted by a
capital or lower letter, respectively: \u201cF\u201d and \u201cf\u201d for FokI, \u201cB\u201d and \u201cb\u201d for BsmI, \u201cA\u201d and \u201ca\u201d for ApaI, and \u201cT\u201d and \u201ct\u201d for TaqI
endonuclease. Seventy-four Italian cutaneous primary melanomas (52.1\ub112.7 years old) were studied; 51.4% were Stage I, 21.6%
Stage II, 13.5% Stage III, and 13.5% Stage IV melanomas. VDR expression was categorized as follows: 100% positive vs. <100%;
over the median 20% (high VDR expression) vs. 6420% (low VDR expression); absence versus presence of VDR-expressing cells.
ResultsStage I melanomas, Breslow thickness of <1.00 mm, level II Clark invasion, Aa heterozygous genotype, and AaTT
combined genotype were more frequent in melanomas with high versus low VDR expression. Combined genotypes BbAA, bbAa,
AATt, BbAATt, and bbAaTT were more frequent in 100% versus <100% VDR-expressing cells. Combined genotype AATT was
more frequent in melanomas lacking VDR expression (odds ratio=14.5; P=0.025). VDR expression was not associated with
metastasis, ulceration, mitosis >1, regression, tumor-infiltrating lymphocytes, tumoral infiltration of vascular tissues, additional
skin and non-skin cancers, and melanoma familiarity.
ConclusionsWe highlighted that VDR polymorphisms can affect VDR expression in excised melanoma cells. Low VDR expression
in AATT carriers is a new finding that merits further study. VDR expression possibly poses implications for vitamin D
supplementation against melanoma. VDR expression and VDR genotype may become precise medicinal tools for melanoma in the
future
Monitoring Creep Damage and Microstructure Evolution in Concrete Using Nonlinear Rayleigh Waves
This paper uses nonlinear ultrasonic measurements to monitor creep-induced microstructural changes in concrete. A new NDE approach that enables the in-situ monitoring of the damage state in concrete is developed in which the second harmonic generation (SHG) technique using nonlinear Rayleigh surface waves is adapted to a cylindrical specimen. This cylindrical specimen is under a uniaxial compressive load (70% of the ultimate strength). The acoustic nonlinearity parameter, β is measured as a function of creep time. The following conclusions are drawn from the experiments: (1) the results suggest that the proposed NLU technique based on the SHG theory (β) is feasible in concrete and this approach shows the expected trends in the behavior of the fundamental and second harmonic amplitudes with respect to propagation distance; (2) the measured nonlinearity parameter, β is highly sensitive to creep- induced changes in the microstructure; and (3) unlike conventional strain based creep monitoring methods, the nonlinearity parameter, β gives a clear indication of the secondary stage of creep. Consequently, it is demonstrated that the time-dependent creep damage in concrete can be monitored with the proposed SHG method. These results can be used to study the microstructure behavior of concrete under creep through a mechanistic model and illustrate the potential of SHG for the in situ monitoring of creep in concrete structures
Para- and perirenal ultrasonographic fat thickness is associated with 24-hours mean diastolic blood pressure levels in overweight and obese subjects
BACKGROUND:
Renal sinus fat (RSF) has been recognized as a risk factor for arterial hypertension. This study was addressed to examine whether also para- and perirenal fat accumulation is associated to higher 24-h mean systolic (SBP) and/or diastolic blood pressure (DBP) levels in overweight and obese subjects.
METHODS:
A cohort of 42 overweight and obese patients, 29 women and 13 men, aged 25-55 years, not treated with any kind of drug, was examined. Body mass index (BMI), waist circumference (WC), fasting insulin and glucose serum levels, insulin resistance (assessed by using the homeostasis model assessment [HOMAIR]), and 24-h aldosterone urine levels were measured. Ambulatory blood pressure monitoring (ABPM) was measured with 15 min intervals from 7.0 a.m. to 11.0 a.m. and with 30 min intervals from 23.0 to 7.0 for consecutive 24 h, starting from 8:30 AM. Measurement of para- and perirenal fat thickness was performed by ultrasounds by a duplex Doppler apparatus.
RESULTS:
Para- and perirenal ultrasonographic fat thickness (PUFT) was significantly and positively correlated with WC (p < 0.01), insulin (p < 0.01), HOMAIR (p < 0.01), and 24-h mean DBP levels (p < 0.05). 24-h mean DBP was also significantly and positively correlated with 24-h aldosterone urine concentrations (p < 0.001). A multivariate analysis by multiple linear regression was performed; the final model showed that the association of 24-h mean DBP as dependent variable with PUFT (multiple R = 0.34; p = 0.026) and daily aldosterone production (multiple R = 0.59; p = 0.001) was independent of other anthropometric, hormone and metabolic parameters.
DISCUSSION AND CONCLUSIONS:
This study shows a positive independent association between PUFT and mean 24-h diastolic blood pressure levels in overweight and obese subjects, suggesting a possible direct role of PUFT in increasing daily diastolic blood pressure
Recurrence of immunoglobulin A nephropathy after kidney transplantation: a narrative review on incidence, risk factors, pathophysiology and management of immunosuppressive therapy
Abstract
Glomerulonephritis (GN) is the underlying cause of end-stage renal failure in 30–50% of kidney transplant recipients. It represents the primary cause of end-stage renal disease for 25% of the dialysis population and 45% of the transplant population. For patients with GN requiring renal replacement therapy, kidney transplantation is associated with superior outcomes compared with dialysis. Recurrent GN was previously considered to be a minor contributor to graft loss, but with the prolongation of graft survival, the effect of recurrent disease on graft outcome assumes increasing importance. Thus the extent of recurrence of original kidney disease after kidney transplantation has been underestimated for several reasons. This review aims to provide updated knowledge on one particular recurrent renal disease after kidney transplantation, immunoglobulin A nephropathy (IgAN). IgAN is one of the most common GNs worldwide. The pathogenesis of IgAN is complex and remains incompletely understood. Evidence to date is most supportive of a several hit hypothesis. Biopsy is mandatory not only to diagnose the disease in the native kidney, but also to identify and characterize graft recurrence of IgAN in the kidney graft. The optimal therapy for IgAN recurrence in the renal graft is unknown. Supportive therapy aiming to reduce proteinuria and control hypertension is the mainstream, with corticosteroids and immunosuppressive treatment tailored for certain subgroups of patients experiencing a rapidly progressive course of the disease with active lesions on renal biopsy and considering safety issues related to infectious complications
The Italian experience of the national registry of renal biopsies
The Italian experience of the national registry of renal biopsies.BackgroundAlthough several registries collecting data of patients with kidney diseases exist, there are only a few registries which specifically collect data relating to renal biopsy; one such registry is the Italian Registry of Renal Biopsies (IRRB). The aim of this study was to report on the relative frequency of nephropathies according to gender, age at time of biopsy, clinical presentation and renal function, based on the histologic diagnosis during the years 1996 to 2000.MethodsWe evaluated data relating to 14607 renal biopsies, provided by 128 renal units in Italy. Data entry was performed by using the Internet-based database directly (URL http://www.irrb.net). Clinical presentation was defined as urinary abnormalities (UA), nephrotic syndrome (NS), acute nephritic syndrome (ANS). Renal diseases were divided in four major categories: (1) primary glomerulonephritides (GN); (2) secondary GN; (3) tubulointerstitial nephropathies (TIN); and (4) vascular nephropathies (VN).ResultsPrimary GN, TIN, and VN were more frequent in males compared to females while secondary GN was more frequent in females. Diseases whose frequency was higher in males were IgA nephropathy (IgAN), benign nephroangiosclerosis (BNA), and acute tubular necrosis (ATN). A significantly higher frequency of immune-mediated secondary GN, as well as primary GN, including minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and mesangiocapillary GN (MCGN), was shown in females. Primary and secondary GN, TIN, and VN were more frequent in the range 15 to 65 years of age. At the time of biopsy 77% of primary GN and 61% of secondary GN presented with normal renal function. Acute renal failure (ACR) was more present in TIN (52%), while chronic renal failure (CRF) was more frequent in VN (47%).ConclusionWe believe collection of data relating to renal biopsies in a national registry is a useful tool for nephrologists in that it meets one of the current challenges facing the clinical research enterprise. The availability of these data will allow epidemiologic studies in health care to answer the several open questions in both prevention and treatment of renal diseases
Identification and monitoring of Copy Number Variants (CNV) in monoclonal gammopathy
Monoclonal gammopathy of undetermined significance (MGUS) represents the pre-clinical stage of Multiple Myeloma (MM) with the 5% of MGUS progresses to MM. Although the progression from MGUS to MM has not been completely characterized, it is possible to monitor the DNA modifications of patients diagnosed with MGUS to detect early specific genomic abnormalities, including copy number variations (CNV). The CNVs of chromosome 1q and chromosome 13q are associated with a worse prognosis in MM.In the present study, we showed that it is possible to monitor the 1q21 gain and 13q deletion frequencies in gDNA using digital PCR. The CNV analysis of three cell lines with a well-characterized cytogenetic profile were compared with measures performed by a real-time PCR approach and with a digital PCR approach. Then, we analyzed CNVs in CD138+ plasma cells isolated from bone marrow of MGUS and MM patients.Our results show that digital PCR and targeted DNA monitoring represent a specific and accurate technique for the early detection of specific genomic abnormalities both in MM and in MGUS patients.Our results could represent a remarkable advancement in MM and MGUS diagnosis and in CNV analysis for the evaluation of the risk of progression from MGUS to MM
Extracellular Vesicles Derived from Endothelial Progenitor Cells Protect Human Glomerular Endothelial Cells and Podocytes from Complement- and Cytokine-Mediated Injury
Glomerulonephritis are renal inflammatory processes characterized by increased permeability of the Glomerular Filtration Barrier (GFB) with consequent hematuria and proteinuria. Glomerular endothelial cells (GEC) and podocytes are part of the GFB and contribute to the maintenance of its structural and functional integrity through the release of paracrine mediators. Activation of the complement cascade and pro-inflammatory cytokines (CK) such as Tumor Necrosis Factor α (TNF-α) and Interleukin-6 (IL-6) can alter GFB function, causing acute glomerular injury and progression toward chronic kidney disease. Endothelial Progenitor Cells (EPC) are bone-marrow-derived hematopoietic stem cells circulating in peripheral blood and able to induce angiogenesis and to repair injured endothelium by releasing paracrine mediators including Extracellular Vesicles (EVs), microparticles involved in intercellular communication by transferring proteins, lipids, and genetic material (mRNA, microRNA, lncRNA) to target cells. We have previously demonstrated that EPC-derived EVs activate an angiogenic program in quiescent endothelial cells and renoprotection in different experimental models. The aim of the present study was to evaluate in vitro the protective effect of EPC-derived EVs on GECs and podocytes cultured in detrimental conditions with CKs (TNF-α/IL-6) and the complement protein C5a. EVs were internalized in both GECs and podocytes mainly through a L-selectin-based mechanism. In GECs, EVs enhanced the formation of capillary-like structures and cell migration by modulating gene expression and inducing the release of growth factors such as VEGF-A and HGF. In the presence of CKs, and C5a, EPC-derived EVs protected GECs from apoptosis by decreasing oxidative stress and prevented leukocyte adhesion by inhibiting the expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin). On podocytes, EVs inhibited apoptosis and prevented nephrin shedding induced by CKs and C5a. In a co-culture model of GECs/podocytes that mimicked GFB, EPC-derived EVs protected cell function and permeselectivity from inflammatory-mediated damage. Moreover, RNase pre-treatment of EVs abrogated their protective effects, suggesting the crucial role of RNA transfer from EVs to damaged glomerular cells. In conclusion, EPC-derived EVs preserved GFB integrity from complement- and cytokine-induced damage, suggesting their potential role as therapeutic agents for drug-resistant glomerulonephritis
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