Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by a complex association between tremendous genotypic multiplicity and great phenotypic heterogeneity. The severity ...of the clinical manifestation depends on penetrance and expressivity of the disease-gene. Also, various interactions between gene expression and environmental factors have been hypothesized. More than 250 genes with ~4500 causative mutations have been reported to be involved in different RP-related mechanisms. Nowadays, not more than the 50% of RPs are attributable to identified genes, whereas the rest of molecular defects are still undetectable, especially in populations where few genetic screenings have been performed. Therefore, new genetic strategies can be a remarkably useful tool to aid clinical diagnosis, potentially modifying treatment options, and family counseling. Genome-wide analytical techniques (array comparative genomic hybridization and single-nucleotide polymorphism genotyping) and DNA sequencing strategies (arrayed primer extension, Sanger sequencing, and ultra high-throughput sequencing) are successfully used to early make molecular diagnosis detecting single or multiple mutations in the huge heterogeneity of RPs. To date, further research needs to be carried out to better investigate the genotype/phenotype correlation, putting together genetic and clinical findings to provide detailed information concerning the risk of RP development and novel effective treatments.
PurposeTo investigate the efficacy of early therapeutic deep anterior lamellar keratoplasty (DALK) in eradicating fungal keratitis that is poorly responsive to medical treatment.Patients and ...methodsTwenty-three eyes (23 patients) underwent early therapeutic DALK within 15 to 50 days from the onset of symptoms. The adopted eligibility criteria for early DALK included the following: active fungal keratitis affecting the optical zone with ulcer confined in the 6.00 mm central cornea; deeper than 150 μm but not exceeding 300 μm; and poorly responsive to medical treatment.ResultsThe big bubble technique was accomplished in 74% (17) of eyes, whereas manual dissection was performed in the remaining 26% (6) of eyes. Histopathological examination did not show any sign of fungal colonization in the peripheral and deep stromal lamellae in any case. All grafts were transparent postoperatively, and no recurrence of infection occurred. Median best spectacle corrected visual acuity significantly improved from 2.0 (1.0 interquartile range) logMAR to 0.1 (0.1 interquartile range) logMAR (P<0.01). The mean follow-up was 32±10 months. Neither episode of rejection nor graft failure was noted during the follow-up period.ConclusionEarly DALK could represent a safe therapeutic approach to eradicate fungal keratitis that affects the optical zone and is poorly responsive to medical treatment.Eye advance online publication, 1 December 2017; doi:10.1038/eye.2017.228.
The depletion of tumor-associated macrophages (TAMs), involved in different stages of cancer development and progression, is an appealing strategy in cancer therapy.
We developed novel ...Clodronate-containing liposomes (Clo-Lipo-DOTAP) presenting physicochemical properties (size distribution, polydispersity index and Z-potential) suited for safe storage and injections.
In vitro, Clo-Lipo-DOTAP inhibited proliferation, reduced viability and induced apoptosis of a macrophage-like cell line in a dose- and time-dependent manner.
In proof of functionality experiments, Clo-Lipo-DOTAP depleted macrophages in a genetic mouse model of chronic hepatitis and hepatocellular carcinoma leading to a significant reduction of F4/80-positive cells in the liver and spleen of treated mice compared to PBS-treated controls. The number of granulocytes, B and T lymphocytes was not affected.
In B16/F10 subcutaneous melanoma-bearing mice, Clo-Lipo-DOTAP significantly reduced the volume of primary tumors (P<0.001). Within the tumors, the expression F4/80 and α-SMA was significantly lowered. Plasma levels of IL-10, Mo KC, TNF-α, VEGF and PDGF-bb were statistically decreased. In B16/F10 lung metastatic melanoma model, treatment with Clo-Lipo-DOTAP significantly reduced the number of pulmonary nodules (P<0.05). F4/80-positive cells and microvessel density were statistically decreased.
In conclusion, the depletion of TAMs in primary and metastatic melanoma presents anti-tumor efficacy via inhibition of angiogenesis and modulation of inflammation related cytokines.
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Randomized response estimation in multiple frame surveys Rueda, M.; Cobo, B.; Perri, P. F.
International Journal of Computer Mathematics/International journal of computer mathematics,
02/2020, Letnik:
97, Številka:
1-2
Journal Article
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Large-scale surveys are increasingly delving into sensitive topics such as gambling, alcoholism, drug use, sexual behaviour and domestic violence. Sensitive, stigmatizing or even incriminating themes ...are difficult to investigate by using standard data-collection techniques since respondents are generally reluctant to release information concerning their personal sphere. Furthermore, such topics usually pertain elusive population (e.g. irregular immigrants and homeless, alcoholics, drug users, rape and sexual assault victims) which are difficult to sample since not adequately covered in a single sampling frame. On the other hand, researchers often utilize more than one data-collection mode (i.e. mixed-mode surveys) in order to increase response rates and/or improve coverage of the population of interest. Surveying sensitive and elusive populations and mixed-mode researches are strictly connected with multiple frame surveys which are becoming widely used to decrease bias due to undercoverage of the target population. In this work, we combine sensitive research and multiple frame surveys. In particular, we consider statistical techniques for handling sensitive data coming from multiple frame surveys using complex sampling designs. Our aim is to estimate the mean of a sensitive variable connected to undesirable behaviours when data are collected by using the randomized response theory. Some estimators are constructed and their properties theoretically investigated. Variance estimation is also discussed by means of the jackknife technique. Finally, a Monte Carlo simulation study is conducted to evaluate the performance of the proposed estimators and the accuracy of variance estimation.
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BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Abstract Aim The present study was specifically designed to assess the major clinical and pathological variables of patients with colorectal peritoneal carcinomatosis in order to investigate whether ...currently used criteria appropriately select candidates for peritonectomy procedures (cytoreductive surgery) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Patients and methods Preoperative, operative and follow-up data on 146 consecutive patients presenting with peritoneal carcinomatosis of colorectal origin and treated by surgical cytoreduction combined with HIPEC in 5 Italian Hospital and University Centers were prospectively entered in a common database. Univariate and multivariate analyses were used to assess the prognostic value of clinical and pathologic factors. Results Over a minimum 24-month follow-up, the overall morbidity rate was 27.4% (mortality rate: 2.7%) and was directly related to the extent of surgery. Peritoneal cancer index (PCI), unfavorable peritoneal sites, synchronous or previously resected liver metastasis and the completeness of cytoreduction, all emerged as independent prognostic factors correlated with survival. Conclusions Until research provides more effective criteria for selecting patients based upon the biomolecular features of carcinomatosis, patients should be selected according to the existing independent prognostic variables.
Neuroblastoma (NB), the most common and deadly extracranial solid tumour of childhood, represents a challenging in paediatric oncology. Soluble tumour necrosis factor (TNF)-related apoptosis-inducing ...ligand (sTRAIL) is a cancer cell-specific molecule exerting remarkable anti-tumour activities against paediatric malignancies both in vitro and in preclinical settings. However, due to its too fast elimination and to the undesired related side effects, the improvement of sTRAIL in vivo bioavailability and the specific delivery to the tumour is mandatory for increasing its therapeutic efficacy. In this manuscript, we developed an innovative pegylated liposomal formulation carrying the sTRAIL at the outer surface (sTRAIL-SL) with the intent to improve its serum half-life and increase its efficacy in vivo, while reducing side effects. Furthermore, the possibility to combine sTRAIL-SL with the proteasome inhibitor Bortezomib (BTZ) was investigated, being BTZ able to sensitize tumour cells toward TRAIL-induced apoptosis. We demonstrated that sTRAIL preserved and improved its anti-tumour activity when coupled to nanocarriers. Moreover, sTRAIL-SL ameliorated its PK profile in blood allowing sTRAIL to exert a more potent anti-tumour activity, which led, upon BTZ priming, to a statistically significant enhanced life spans in two models of sTRAIL-resistant NB-bearing mice. Finally, mechanistic studies indicated that the combination of sTRAIL with BTZ sensitized sTRAIL-resistant NB tumour cells to sTRAIL-induced cell death, both in vitro and in vivo, through the Akt/GSK3/β-catenin axis-dependent mechanism. In conclusion, our results suggest that sTRAIL-SL might be an efficient vehicle for sTRAIL delivery and that its use in clinic, in combination with BTZ, might represent an adjuvant strategy for the treatment of stage IV, sTRAIL-resistant, NB patients.
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Estrogen Receptors and Chronic Venous Disease Serra, R; Gallelli, L; Perri, P ...
European journal of vascular and endovascular surgery,
07/2016, Letnik:
52, Številka:
1
Journal Article
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Objective/Background Chronic venous disease (CVD) is a common and relevant problem affecting Western people. The role of estrogens and their receptors in the venous wall seems to support the major ...prevalence of CVD in women. The effects of the estrogens are mediated by three estrogen receptors (ERs): ERα, ERβ, and G protein-coupled ER (GPER). The expression of ERs in the vessel walls of varicose veins is evaluated. Methods In this prospective study, patients of both sexes, with CVD and varicose veins undergoing open venous surgery procedures, were enrolled in order to obtain vein samples. To obtain control samples of healthy veins, patients of both sexes without CVD undergoing coronary artery bypass grafting with autologous saphenous vein were recruited (control group). Samples were processed in order to evaluate gene expression. Results Forty patients with CVD (10 men 25%, 30 women 75%, mean age 54.3 years median 52 years, range 33–74 years) were enrolled. Five patients without CVD (three men, two women aged 61–73 years) were enrolled as the control group. A significant increase of tissue expression of ERα, ERβ and GPER in patients with CVD was recorded ( p < .01), which was also related to the severity of venous disease. Conclusion ERs seem to play a role in CVD; in this study, the expression of ERs correlated with the severity of the disease, and their expression was correlated with the clinical stage.
Abstract Endocrine orbitopathy (EO) can have important consequences, such as exophthalmos and restrictive strabismus. A retrospective study was performed of 35 patients with EO who underwent orbital ...decompression surgery and restrictive strabismus correction. Two surgical techniques for orbital decompression were analyzed: fat decompression by Olivari technique and three-wall bony expansion with fat decompression. Strabismus surgery was performed using adjustable or non-adjustable sutures under topical anaesthesia. Patients were divided into two groups according to the type of intra-orbital decompression performed, and the postoperative values resulting from the different fat decompression techniques were recorded. The preoperative and postoperative mean degrees of exophthalmos were 22.3 and 19.9 mm, respectively, for the fat decompression group, and 24.3 and 19.8 mm, respectively, for the bony expansion with transpalpebral fat decompression (combined form) group. The difference in residual prism dioptres between adjustable and non-adjustable suture techniques in patients who had previously undergone combined decompression was statistically significant. The management of patients with EO requires a multidisciplinary approach based on the collaboration of maxillofacial surgeons, ophthalmologists, and orthoptists. These results will allow the development of a more adequate strategy for the surgical treatment of restrictive strabismus in EO patients.
Inclusion health is a service, research, and policy agenda that aims to prevent and redress health and social inequities among the most vulnerable and excluded populations. We did an evidence ...synthesis of health and social interventions for inclusion health target populations, including people with experiences of homelessness, drug use, imprisonment, and sex work. These populations often have multiple overlapping risk factors and extreme levels of morbidity and mortality. We identified numerous interventions to improve physical and mental health, and substance use; however, evidence is scarce for structural interventions, including housing, employment, and legal support that can prevent exclusion and promote recovery. Dedicated resources and better collaboration with the affected populations are needed to realise the benefits of existing interventions. Research must inform the benefits of early intervention and implementation of policies to address the upstream causes of exclusion, such as adverse childhood experiences and poverty.
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