Transitional cell carcinoma (TCC) is the most common type of bladder cancer. Emerging evidence has suggested that the capability of a tumor to grow and propagate is dependent on a small subset of ...cells, the cancer stem‐like cells (CSCs) or tumor initiating cells. We report on the isolation and biological characterization of putative bladder CSC populations from primary TCCs. Isolated cells were induced to proliferate in stem cell culture conditions (serum‐free medium containing mitogenic growth factors). The proliferating cells formed spheroids (urospheres) and their abilities for extensive proliferation and self‐renewal were assayed. Their positivity for several stem cell markers (CD133, Oct‐3/4, nestin, and cytokeratins) was also assessed by immunofluorescence tests and they could have the potential to differentiate in the presence of serum. In stem cell culture conditions they gradually showed loss of proliferation, adherence to the substrate, and morphological changes, which might reflect their progressive acquisition of differentiative capacity and loss of self‐renewal ability. To evaluate if effective cell selection occurred after isolation, conventional cytogenetic studies on fresh chromosome spreads immediately after isolation and after culture were carried out. In addition, a molecular cytogenetic study by UroVysion assay was carried out on paraffin‐embedded tissue sections and on fresh and after culture nuclei preparations. The data collected indicated important karyotype changes and a positive selection for hypo‐ or near‐diploid cells, losing the complexity present in fresh tumors. (Cancer Sci 2009)
In end-stage chronic kidney disease, the option of organ transplantation is limited because of the scarce availability of kidneys. The combination of stem cell research, regenerative medicine, and ...tissue engineering seems a promising approach to produce new transplantable kidneys. Currently, the possibility to repopulate naturally obtained scaffolds with cells of different sources is advancing. Our aim was to test, for the first time, whether the nephrosphere (NS) cells, composed by renal stem/progenitor-like cells, were able to repopulate different nephron portions of renal extracellular matrix scaffolds obtained after decellularization of human renal tissue slices. Our decellularization protocol enabled us to obtain a completely acellular renal scaffold while maintaining the extracellular matrix structure and composition in terms of collagen IV, laminin, and fibronectin. NS cells, cultured on decellularized renal scaffolds with basal medium, differentiated into proximal and distal tubules as well as endothelium, as highlighted by histology and by the specific expression of epithelial cytokeratin 8.18, proximal tubular CD10, distal tubular cytokeratin 7, and endothelial von Willebrand factor markers. Endothelial medium promoted the differentiation toward the endothelium, whereas epithelial medium promoted the differentiation toward the epithelium. NS cells seem to be a good tool for scaffold repopulation, paving the way for experimental investigations focused on whole-kidney reconstruction.
Background & Aims
In the direct‐acting antiviral era, treatment of genotype‐3 HCV (HCV‐GT3) is still challenging. Real‐life comparisons between recommended regimens, sofosbuvir (SOF)+daclatasvir ...(DAC), SOF/velpatasvir (VEL), glecaprevir/pibrentasvir (GLE/PIB), are scarce. We aimed at filling this data gap.
Methods
Sustained virological response 12 weeks after treatment completion (SVR12) was assessed for all HCV‐GT3 patients consecutively treated within the Lombardia web‐based Navigatore HCV‐Network; differences in SVR12 across regimens were evaluated by logistic regression.
Results
Of the 2082 subjects with HCV‐GT3, 1544 were evaluable for comparisons between regimens: SOF + DAC (1023, 66.2%), SOF/VEL (369, 23.9%), GLE/PIB (152, 9.8%). Patients treated with former regimens were more frequently male, cirrhotic, HIV‐positive, pretreated, used ribavirin in their regimen, and had lower baseline HCV‐RNA. SVR12 was similar across groups: 94.8% in SOF + DAC, 97.6% in SOF/VEL, 96.7% in GLE/PIB (P = .065). At univariate analysis, SVR12 was associated with female gender (97.9% vs 94.8%, P = .007) and lower median pretreatment Log10HCV‐RNA (5.87 vs 6.20, P = .001). At multivariate logistic regression analysis, treatment with SOF/VEL was associated with a higher likelihood of SVR12 than SOF + DAC, but only in the absence of ribavirin (98% vs 90.3%). Female gender and lower pretreatment HCV‐RNA were independently associated with SVR12.
Conclusions
In a large real‐life setting of HCV‐GT3‐infected patients with a high proportion of cirrhosis, the success rate was remarkable. The slight advantage of SOF/VEL on SOF + DAC was significant only without ribavirin. The current prescription shift towards novel regimens (ie SOF/VEL and GLE/PIB) in easier‐to‐treat patients allows ribavirin‐free and shorter schedules without mining SVR12 in this <<difficult‐to‐treat>> genotype.
Objectives
Parvovirus B19 (B19V) infection in pregnancy is generally asymptomatic, but in about 3% it can cause complications, including miscarriage, severe foetal anaemia and foetal hydrops. The ...seroprevalence in pregnancy ranges from 20% to 82% in Africa, but there are no data for Benin. We therefore retrospectively assessed the seroprevalence of B19V in pregnant women attending the Saint Jean de Dieu Hospital in Tanguiéta, a rural district of Atacora, in northern Benin.
Methods
We searched for anti‐B19V immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies in 227 sequential sera from as many women (mean age 26.3 years, range: 16–41) of whom 30 were in the first trimester, 66 in the second and 131 in the third. Samples that tested positive for IgM were analysed with an immunoblot test and the viral genome (DNA‐B19V) was searched for using a polymerase chain reaction.
Results
Of the 227 women, 153 (67.4%) were positive for IgG anti‐B19V, 7 (3.1%) for IgM and 73 (32.2%) were non‐immune. Six IgM‐positive women were also IgG positive. The difference in IgG seroprevalence between trimesters or ages was not statistically significant. Of the seven IgM‐positive samples, three were confirmed positive by immunoblot (of which two were DNA‐B19V positive), three were indeterminate (DNA‐B19V negative) and one was negative (DNA‐B19V negative). Of the three women with confirmed positive IgM, two were in the third trimester and one in the second trimester of pregnancy.
Conclusions
The seroprevalence of anti‐B19V IgG among pregnant women in Benin is high and in line with those reported in some African countries. IgM seroprevalence is also similar to that described in some African countries in non‐epidemic periods. The low viral load observed depicts non‐acute infections, but it is difficult to establish the precise time of the infection, especially for women tested in the second or third trimester of pregnancy, when the observed viremia could be a sign of an acute infection that occurred in the previous trimester. Consequently, clinical follow‐up and further investigations to highlight possible foetal consequences are indicated.
Human clear cell renal cell carcinoma (ccRCC) is therapy resistant; therefore, it is worthwhile studying in depth the molecular aspects of its progression. In ccRCC the biallelic inactivation of the ...VHL gene leads to stabilization of hypoxia-inducible factors (HIFs). Among the targets of HIF-1α transcriptional activity is the LOX gene, which codes for the inactive proenzyme (Pro-Lox) from which, after extracellular secretion and proteolysis, derives the active enzyme (Lox) and the propeptide (Lox-PP). By increasing stiffness of extracellular matrix by collagen crosslinking, Lox promotes tumor progression and metastasis. Lox and Lox-PP can reenter the cells where Lox promotes cell proliferation and invasion, whereas Lox-PP acts as tumor suppressor because of its Ras recision and apoptotic activity. Few data are available concerning LOX in ccRCC. Using an in vitro model of ccRCC primary cell cultures, we performed, for the first time in ccRCC, a detailed study of endogenous LOX and investigated the transcriptomic profile. We found that endogenous LOX is overexpressed in ccRCC, is involved in a positive-regulative loop with HIF-1α, and has a major action on ccRCC progression through cellular adhesion, migration, and collagen matrix stiffness increment; however, the oncosuppressive action of Lox-PP was not found to prevail. These findings may suggest translational approaches for new therapeutic strategies in ccRCC.
Aim
To evaluate the integration of implants installed using a surgical guide in augmented sites with autologous bone or deproteinized bovine bone mineral (DBBM) blocks, concomitantly with a collagen ...membrane.
Material and methods
Mandibular molars were extracted bilaterally in six Labrador dogs, the buccal bony wall was removed, and a box‐shaped defect was created. After 3 months, flaps were elevated, a bony graft was harvested from the ascending ramus, and secured to the lateral wall of the defect by means of screws. In the left mandibular side, a DBBM block was fixed into the defect. A resorbable membrane was applied at both sides, and the flaps were sutured. After 3 months, flaps were elevated, and a customized device was used as surgical guide to prepare the recipient sites in the interface between grafts and parent bone. One implant was installed in each side of the mandible. After 3 months, biopsies were harvested, and ground sections were prepared for histologic evaluation.
Results
One autologous bone block graft was lost before implant installation. The width of the alveolar crest at the test sites (DBBM) was 5.4 ± 1.2 mm before, 9.4 ± 1.2 mm immediately after grafting, and 9.3 ± 1 mm at implant installation. At the control sites (autologous bone), the corresponding values were: 5.2 ± 1, 9 ± 1.2, and 8.7 ± 0.9 mm, respectively. All implants installed were available for histologic evaluation (n = 5). The autologous bone grafts, rich in vessels and cells, were integrated in the parent bone, and only little non‐vital bone was found. The BIC% was 56.7 ± 15.6% and 54.2 ± 13.2% at the buccal and lingual aspects, respectively. At the test sites, the DBBM appeared to be embedded into connective tissue, and very little newly formed bone was encountered within the grafts. The BIC% was 5.8 ± 12.3% and 51.3 ± 14.2% at the buccal and lingual aspects, respectively.
Conclusions
Autologous bone blocks used to augment the alveolar bony crest horizontally allowed the complete osseointegration of implants installed after 3 months of healing. However, similar blocks of DBBM did not promote osseointegration, although the installed implants were stable owing to the osseointegration in the sites of the parent bone.
Aim
The first aim of the present experiment was to compare bone healing at implants installed in recipient sites prepared with conventional drills or a piezoelectric device. The second aim was to ...compare implant osseointegration onto surfaces with and without dendrimers coatings.
Material and Methods
Six Beagles dogs were used in this study. Five implants with two different surfaces, three with a ZirTi® surface (zirconia sand blasted, acid etched), and two with a ZirTi®‐modified surface with dendrimers of phosphoserine and polylysine were installed in the right side of the mandible. In the most anterior region (P2, P3), two recipient sites were prepared with drills, and one implant ZirTi® surface and one coated with dendrimers implants were installed at random. In the posterior region (P4 and M1), three recipient sites were randomly prepared: two sites with a Piezosurgery® instrument and one site with drill and two ZirTi® surface and one coated with dendrimers implants installed. Three months after the surgery, the animals were sacrificed for histological analysis.
Results
No complications occurred during the healing period. Three implants were found not integrated and were excluded from analysis. However, n = 6 was obtained. The distance IS‐B at the buccal aspect was 2.2 ± 0.8 and 1.8 ± 0.5 mm, while IS‐C was 1.5 ± 0.9 and 1.4 ± 0.6 mm at the Piezosurgery® and drill groups, respectively. Similar values were obtained between the dendrimers‐coated and ZirTi® surface implants. The BIC% values were higher at the drill (72%) compared to the Piezosurgery® (67%) sites. The BIC% were also found to be higher at the ZirTi® (74%) compared to the dendrimers‐coated (65%) implants, the difference being statistically significant.
Conclusion
This study has revealed that oral implants may osseointegrate equally well irrespective of whether their bed was prepared utilizing conventional drills with abundant cooling or Piezosurgery®. Moreover, the surface coating of implants with dendrimers phosphoserine and polylysine did not improve osseointegration.
The present article describes the case study of a "real world" HIV practice within the debate concerning the strategic role of Clinical Governance (CG) tools in the management of a National ...Healthcare System's sustainability. The study aimed at assessing the impact of a Clinical Pathway (CP) implementation, required by the Regional Healthcare Service, in terms of effectiveness (virological and immunological conditions) and efficiency (economic resources absorption), from the budget holder perspective. Data derived from a multi-centre cohort of patients treated in 6 Hospitals that provided care to approximately 42% of the total HIV+ patients, in Lombardy Region, Italy. Two phases were compared: Pre-CP (2009-2010) vs. Post-CP implementation (2011-2012). All HIV infected adults, observed in the participating hospitals during the study periods, were enrolled and stratified into the 3 categories defined by the Regional CP: first-line, switch for toxicity/other, and switch for failure. The study population was composed of 1,284 patients (Pre-CP phase) and 1,135 patients (Post-CP phase). The results showed that the same level of virological and immunological effectiveness was guaranteed to HIV+ patients: 81.2% of Pre-CP phase population and 83.2% of Post-CP phase population had undetectable HIV-RNA (defined as <50 copies/mL) at 12-month follow up. CD4+ cell counts increased by 28 ± 4 cells/mm3 in Pre-CP Phase and 39 ± 5 cells/mm3 in Post-CP Phase. From an economic point of view, the CP implementation led to a substantial advantage: the mean total costs related to the management of the HIV disease (ART, hospital admission and laboratory tests) decreased (-8.60%) in the Post-CP phase (p-value < 0.0001). Results confirmed that the CP provided appropriateness and quality of care, with a cost reduction for the budget holder.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objective
To compare peri‐implant tissue healing at implants installed in sites prepared with conventional drills or a sonic device.
Material and methods
In six Beagle dogs, the mandibular premolars ...and first molars were extracted bilaterally. After 3 months, full‐thickness muco‐periosteal flaps were elevated and recipient sites were prepared in both sides of the mandible. In the right side (control), the osteotomies were prepared using conventional drills, while, at the left side (test), a sonic device (Sonosurgery®) was used. Two implants were installed in each side of the mandible. After 8 weeks of non‐submerged healing, biopsies were harvested and ground sections prepared for histological evaluation.
Results
The time consumed for the osteotomies at the test was more than double compared to the conventional control sites. No statistically significant differences were found for any of the histological variables evaluated for hard and soft tissue dimensions. Although not statistically significant, slightly higher mineralized bone‐to‐implant contact was found at the test (65.4%) compared to the control (58.1) sites.
Conclusions
Similar healing characteristics in osseointegration and marginal hard tissue remodeling resulted at implants installed into osteotomies prepared with conventional drills or with the sonic instrument (Sonosurgery®).
Summary
To evaluate presumptive differences in osseointegration at implants installed in healed sites or extraction sockets, supporting either crowns or bridges that were functionally loaded or left ...unloaded. In six dogs, the mesial roots of the first mandibular molars were treated endodontically. Bilaterally, the teeth were hemisected, and the distal roots extracted. First and second mandibular premolars were extracted as well. After 3 months, the mandibular third and fourth distal roots were extracted after endodontic treatment of the mesial roots. Four implants were installed bilaterally, two in the healed sites corresponding to the second premolar and first molar regions, and two into the extraction sockets. Cobalt‐chrome single crowns were prepared and installed in the two most anterior implants, and bridges at the two most posterior implants, bilaterally. A 3‐unit bridge was applied to the premolars in the upper jaw only at the loaded sites. All prostheses had a flat occlusal surface and contacts in centric occlusion only at the loaded sites. Three months later, biopsies were retrieved for histological analysis. Higher levels of osseointegration and bone density were observed at the unloaded sites, both at implants installed in healed and post‐extraction sites. However, only at implants installed in the post‐extraction sites and supporting single crowns, the difference in bone‐to‐Implant contact was statistically significant. In implant installation immediately following extraction or delayed after three months, osseointegration and bone density were not affected by occlusal contact schemes.
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