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Background: According to the American Academy of Aesthetic Plastic Surgeons, more than 11 million cosmetic surgical and nonsurgical procedures were performed by board-certified plastic surgeons, dermatologists and otolaryngologists in the United States, totaling more than 12 billion dollars. Of that total, more than 7 billion was spent on surgical procedures and more than 5 billion was spent on nonsurgical procedures. More than 1,872,172 people received Hyaluronic Acid (HA) injections in 2013. Moreover, filler treatments are the most popular procedures performed by dermatologists. Objective: Evaluate, with a new imaging system, durability, efficacy and safety of a nasolabial fold treatment with a cross-linked HA of non-animal origin with different molecular weights. Material and methods: A cross-linked HA (25 mg/ml, 1000-2000 kDa, 23 ± 3 Newton [N] extrusion force, 1,4-Butanediol Diglycidyl Ether (BDDE) content < 0.1 ppm) was used in order to perform the treatment. The product is commercially available with the trademark Aliaxin®GP (Global Performance) and distributed by IBSA Farmaceutici Italia Srl. 25 female subjects aged 40 and 60 years with a photoageing level III according Rubin or type III according Glogau were recruited for the treatment and 0.5 ml of the product were injected for single nasolabial fold. The aesthetic result and the duration of the aesthetic correction were evaluated by the analysis of the skin microreliefs through confocal microscopy and by Glogau's Scale. Additionally, pictures of each patient were collected by Canon PowerShot G10 Digital Camera (14.7 megapixels) before and after treatment. Below the description of the experimental schedule: T0: Baseline, evaluation and treatment; T1: second visit, 4 months after the treatment; T2: third visit, 6 months after the treatment. Results: From 25 patients, 150 silicone casts were obtained: 75 casts of the right nasolabial fold and 75 casts of the left nasolabial fold. Roughness arithmetical average (Ra) was assessed by profilometry. This parameter represents the arithmetic mean deviation of the profile points compared to the average value. The Ra of the right fold at T2 decreased by 50% versus T0 and by 40% compared to T1; Ra of the left fold at T2 decreased by the 45% versus T0 and by 35% compared to T1. No side effects were reported during the observation period beyond mild symptoms (pain, sensation of heat, reddening in the injection site) also described by the product technical sheet. Conclusion: The results proved the efficacy and safety of the nasolabial folds treatment with the tested product and the durability of the aesthetic correction.

We present here a novel approach to fabricate nanoporous membranes based on the use of sacrificial template structures to individually define pore parameters such as geometry, shape, and placement. Based on this rationale two different nano-fabrication methods were developed; one resulting in conical multilayered nanopores arrays with openings with critical dimensions down to 60 nm; and a second one resulting in high aspect ratio nanopores with diameters down to 17 nm and 1 μm length. The presented methods are relevant for the fields of nanofabrication and nanofluidics since they extend the shapes, geometries and materials into which nanoporous membranes can be obtained.

SummaryBackground Mycosis fungoides (MF) is the major subtype of cutaneous T-cell lymphomas (CTCL). It usually has a prolonged indolent clinical course with a minority of cases acquiring a more aggressive biological profile and resistance to conventional therapies, partially attributed to the persistent activation of Nuclear Factor-kappa B (NF-κB) pathway. In the last decade, several papers suggested an important role for the FK506-binding protein 51 (FKBP51), an immunophilin initially cloned in lymphocytes, in the control of NF-κB pathway in different types of human malignancies. Objectives We aimed to investigate the possible value of FKBP51 expression as a new reliable marker of outcome in MF patients. Methods We assessed by immunohistochemistry (IHC) FKBP51 expression in 44 patients with MF, representative of different stages of the disease. Immunohistochemical results were subsequently confirmed at mRNA level with quantitative PCR (qPCR) in a subset of enrolled patients. In addition, IHC and qPCR served to study the expression of some NF-κB target genes, including the tumour necrosis factor receptor-associated factor 2 (TRAF2). Results Our results show that FKBP51 was expressed in all evaluated cases, with the highest level of expression characterizing MFs with the worst prognosis. Moreover, a significant correlation subsisted between FKBP51 and TRAF2 IHC expression scores. Conclusions we hypothesize a role for FKBP51 as a prognostic marker for MF and suggest an involvement of this immunophilin in deregulated NF-κB pathway of this CTCL. This article is protected by copyright. All rights reserved.

Non-metastatic primary prostate cancers frequently contain multiple independent histologic foci of cancer, and appear as truly multifocal tumors, since these different foci are often genetically distinct (Aihara et al., Urology 43:60-66, 1994; Bostwick et al., Cancer 83:1995-2002,1998; Macintosh et al., Cancer Res 58:23-28, 1998; Mehra et al., Cancer Res 67:7991-7995, 2007; Clark et al., Oncogene 27:1993-2003, 2008). By converse, multiple metastases in the same patient are clonally related, indicating that advanced prostate cancer is monoclonal both at molecular and cytogenetic level (Mehra et al., Cancer Res 68:3584-3590, 2008; Liu et al. 2009). Genomics will hopefully allow the sub-typing of prostate cancer for diagnostic purposes, overcoming the limits of morphology to prognostically evaluate this tumor (Taylor et al., Cancer Cell 18(1):11-22, 2010). The major part of studies searching for genetic variants correlated with prostate cancer, have yielded preferentially results indicating that several genetic loci impact early stages of prostate cancer development. Few data exist, to date, on the existence of loci unequivocally correlated with prostate cancer progression (Liu et al., Front Endocrinol (Lausanne) 3:72, 2012). Recently, however, integrative genomic analysis techniques identified copy number variation as a biomarker predictive of prostate cancer outcome (Ding et al., Nature 470(7333):269-273, 2011), and comparative oncogenomics have derived a four-gene signature and an additional pathway-representative fourteen-gene panel that resulted better prognostic biomarkers with respect to PSA (Ding et al., Nature 470(7333):269-273, 2011). Moreover, the use of a five-SNP panel was found useful to predict the aggressive behavior of prostate cancer (Lin et al., Cancer Epidemiol Biomarkers Prev 20:954-961, 2011). Thus, the advancement of genetic techniques has opened up the promising scenario of a next coming mapping of prostate cancer aggressiveness loc

Objectives Several studies suggested that CD30 expression is a favorable prognostic marker in transformed mycosis fungoides (tMF). However, evidence in this field is still unclear. This systematic review and meta-analysis aimed to evaluate the prognostic significance of CD30 in tMF. Methods Electronic databases were searched from their inception to June 2020 for all studies assessing the prognostic value of CD30 in tMF. Pooled hazard ratio (HR) for death was calculated; a P value less than .05 was considered significant. Inconsistency index (I2) was used to assess statistical heterogeneity among studies. Results Seven studies with 323 patients were included. CD30 expression in tMF was significantly associated with a decreased hazard of death both on univariate (HR, 0.459; 95% confidence interval [CI], 0.319-0.660; P < .001) and multivariate analysis (HR, 0.503; 95% CI, 0.345-0.734; P < .001), and the statistical heterogeneity among studies was null in all analyses (I2 = 0%). Conclusions tMF cases with CD30 expression in large cells have a hazard of death two times lower than CD30-negative cases.

Background: Cases of severe autoimmune blistering diseases (AIBDs) have recently been reported in association with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Aims: To describe a report of oropharyngeal Pemphigus Vulgaris (OPV) triggered by the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/ BioNTech) and to analyze the clinical and immunological characteristics of the AIBDs cases reported following the SARS-CoV-2 vaccination. Methods: The clinical and immunological features of our case of OPV were documented. A review of the literature was conducted and only cases of AIBDs arising after the SARS-CoV-2 vaccination were included. Case report: A 60-year old female patients developed oropharyngeal and nasal bullous lesions seven days after the administration of a second dose of the mRNABNT162b2 vaccine (Comirnaty®/ Pfizer/BioNtech). According to the histology and direct immunofluorescence findings showing the presence of supra-basal blister and intercellular staining of IgG antibodies and the presence of a high level of anti-Dsg-3 antibodies (80 U/ml; normal < 7 U/ml) in the serum of the patients, a diagnosis of oropharyngeal Pemphigus Vulgaris was made. Review: A total of 35 AIBDs cases triggered by the SARS-CoV-2 vaccination were found (including our report). 26 (74.3%) were diagnosed as Bullous Pemphigoid, 2 (5.7%) as Linear IgA Bullous Dermatosis, 6 (17.1%) as Pemphigus Vulgaris and 1 (2.9%) as Pemphigus Foliaceus. The mean age of the sample was 72.8 years and there was a predominance of males over females (F:M=1:1.7). In 22 (62.9%) cases, the disease developed after Pfizer vaccine administration, 6 (17.1%) after Moderna, 3 (8.6%) after AstraZeneca, 3 (8.6%) after CoronaVac (one was not specified). All patients were treated with topical and/or systemic corticosteroids, with or without the addition of immunosuppressive drugs, with a good clinical response in every case. Conclusion: Clinicians should be aware of the potential, though rare, occurrence of AIBDs as a possible adverse event after the SARS-CoV-2 vaccination. However, notwithstanding, they should encourage their patients to obtain the vaccination in order to assist the public health systems to overcome the COVID-19 pandemic.

Mycosis fungoides (MF) represents the most common type of cutaneous lymphoma. In the majority of patients, the disease has a slow evolution and a protracted course; however, a subset of patients shows poor oncologic outcomes. Unfortunately, there are no reliable prognostic markers for MF, and the currently available treatments are only effective in a minority of patients. This study aimed to evaluate the expression and clinical significance of PARP-1 and CAF-1/p60 in MF. Sixty-four MF representatives of the different stages of disease were assessed by immunohistochemistry for PARP-1 and CAF-1/p60. The association of PARP-1 and CAF-1/p60 with the MF stage and outcome was assessed by using Fisher’s exact test and Kaplan-Meier survival analysis with the Log-rank test; a p value II (p = 0.034) but not with the risk of death (p = 0.237). CAF-1/p60 was overexpressed in 26.8% of MF and was significantly associated with decreased overall survival (p p = 1). A significant association was found between PARP-1 overexpression and CAF-1/p60 overexpression (p = 0.0025). Simultaneous overexpression of PARP-1 and CAF-1/p60 was significantly associated with decreased overall survival (p χ2 = 14.916 vs 21.729, respectively). In MF, PARP-1 is overexpressed in advanced stages, while CAF-1/p60 is overexpressed in the cases with shorter overall survival, appearing as a significant prognostic marker. A role for PARP-1 inhibitors and anti-CAF-1/p60 targeted therapy may be reasonably hypothesized in MF.

Ameloblastic carcinoma is a rare malignant odontogenic neoplasm with a poor prognosis. It can arise de novo or from a pre-existing ameloblastoma. Research into stemness marker expression in ameloblastic tumours is lacking. This study aimed to explore the immunohistochemical expression of stemness markers nestin, CD138, and alpha-smooth muscle actin (alpha-SMA) for the characterisation of ameloblastic tumours. Six cases of ameloblastoma and four cases of ameloblastic carcinoma were assessed, including one case of ameloblastic carcinoma arising from desmoplastic ameloblastoma. In all tumour samples, CD138 was positive, whilst alpha-SMA was negative. Nestin was negative in all but one tumour sample. Conversely, the presence or absence of these markers varied in stroma samples. Nestin was observed in one ameloblastic carcinoma stroma sample, whilst CD138 was positive in one ameloblastoma case, one desmoplastic ameloblastoma case, and in two ameloblastic carcinoma stroma samples. Finally, alpha-SMA was found positive only in the desmoplastic ameloblastoma stroma sample. Our results suggest nestin expression to be an indicator for ameloblastic carcinoma, and CD138 and alpha-SMA to be promising biomarkers for the malignant transformation of ameloblastoma. Our data showed that nestin, CD138, and alpha-SMA are novel biomarkers for a better understanding of the origins and behaviour of ameloblastic tumours.

Aims: Several studies suggested that high expression of Bcl2 and/or p53 in Hodgkin/Reed-Sternberg cells is an unfavorable prognostic factor in Hodgkin lymphoma (HL). However, results in this field appear contrasting. We aimed to assess the prognostic value of p53 and Bcl2 in HL through a systematic review and meta-analysis. Methods: Electronic databases were searched from January 2000 to December 2020 for all studies assessing the prognostic value of p53 and Bcl2 in HL. The association of high p53 or Bcl2 expression with overall survival (OS), progression-free survival (PFS) and response to treatment was assessed by using hazard ratio (HR) and odds ratio (OR). Results: Eighteen studies were included. Bcl2 overexpression was significantly associated with decreased PFS (HR = 2.202; p < 0.0001), while the associations with decreased OS (HR = 1.565; p = 0.257) and refractoriness to treatment (OR = 0.482; p = 0.068) were non-significant. p53 overexpression was not significantly associated with refractoriness to treatment (OR = 0.904; p = 0.155); the analysis of OS and PFS was not feasible, but published data suggested the absence of a significant association. Conclusions: In HL, Bcl2 overexpression is associated with decreased PFS, while a significant prognostic value could not be demonstrated for p53. Defining optimal criteria for interpreting Bcl2 and p53 immunostaining is necessary to draw definitive conclusions.

Simple Summary NRP-1, a co-receptor of the EGFR, represented an interesting candidate to investigate in HNSCC, as Cetuximab, in combination with radio and chemotherapy, provided the first targeted therapy scheme approved by the FDA as a standard of care for patients with recurrent or metastatic HNSCC. High levels of NRP-1 expression significantly correlated with a shorter overall survival in both Oral Squamous Cell Carcinoma and Oropharyngeal Squamous Cell Carcinoma diagnosed patients, suggesting a prognostic role for this protein. In HNSCC cell lines in vitro experiments, NRP-1 sustained EGFR activation upon CDDP exposure, together with activation of downstream MAPK/AKT pathways. Furthermore, NRP-1 modulated the responsiveness to CDDP treatment. Abstract Head and neck squamous cell carcinoma (HNSCC) includes a group of aggressive malignancies characterized by the overexpression of the epidermal growth factor receptor (EGFR) in 90% of cases. Neuropilin-1 (NRP-1) acts as an EGFR co-receptor, enhancing, upon ligand stimulation, EGFR signaling in several cellular models. However, NRP-1 remains poorly characterized in HNSCC. By utilizing in vitro cellular models of HNSCC, we report that NRP-1 is involved in the regulation of EGFR signaling. In fact, NRP-1 can lead to cisplatin-induced EGFR phosphorylation, an escape mechanism activated by cancer cells upon cytotoxic stress. Furthermore, we evaluated Neuropilin-1 staining in tissue samples of an HNSCC case series (n = 218), unraveling a prognostic value for the Neuropilin-1 tissue expression. These data suggest a potential role for NRP-1 in HNSCC cancer progression, expanding the repertoire of signaling in which NRP-1 is involved and eliciting the need for further investigations on NRP-1 as a suitable target for HNSCC novel therapeutic approaches.