Ina-Casa La Fiorita. A system for the shared regeneration of social housing

Over sixty years after their construction, many Ina-Casa neighbourhoods demonstrate the need for extensive “mending”. Specific intervention methodologies are required to redevelop them considering the many players and needs involved, the testimonial value of the patrimony, and the fragmented ownership structure. An analysis of the inadequacies and an assessment of the priorities that inhabitants attribute to them were fundamental in defining a participatory redevelopment strategy, which has been tested on “La Fiorita” in Cesena. The research developed a catalogue of solutions that can be incorporated into packages and is conceived as an intervention manual. It has been devised to foster a combination of individual and collective actions and is associated with an incentive system

Ina-Casa La Fiorita. A system for the shared regeneration of social housing

<p class="p1"><span class="s1">Over sixty years after their construction, many Ina-Casa neighbourhoods demonstrate the need for extensive “mending”. Specific intervention methodologies are required to redevelop them considering the many players and needs involved, the testimonial value of the patrimony, and the fragmented ownership structure. An analysis of the inadequacies and an assessment of the priorities that inhabitants attribute to them were fundamental in defining a participatory redevelopment strategy, which has been tested on “La Fiorita” in Cesena. The research developed a catalogue of solutions that can be incorporated into packages and is conceived as an intervention manual. It has been devised to foster a combination of individual and collective actions and is associated with an incentive system.</span></p

Visual System Impairment in a Mouse Model of Krabbe Disease: The Twitcher Mouse

Krabbe disease (KD, or globoid cell leukodystrophy; OMIM #245200) is an inherited neurodegenerative condition belonging to the class of the lysosomal storage disorders. It is caused by genetic alterations in the gene encoding for the enzyme galactosylceramidase, which is responsible for cleaving the glycosydic linkage of galatosylsphingosine (psychosine or PSY), a highly cytotoxic molecule. Here, we describe morphological and functional alterations in the visual system of the Twitcher (TWI) mouse, the most used animal model of Krabbe disease. We report in vivo electrophysiological recordings showing defective basic functional properties of the TWI primary visual cortex. In particular, we demonstrate a reduced visual acuity and contrast sensitivity, and a delayed visual response. Specific neuropathological alterations are present in the TWI visual cortex, with reduced myelination, increased astrogliosis and microglia activation, and around the whole brain. Finally, we quantify PSY content in the brain and optic nerves by high-pressure liquid chromatography-mass spectrometry methods. An increasing PSY accumulation with time, the characteristic hallmark of KD, is found in both districts. These results represent the first complete characterization of the TWI visual system. Our data set a baseline for an easy testing of potential therapies for this district, which is also dramatically affected in KD patients

A new dermoscopic algorithm for the differential diagnosis of facial lentigo maligna and pigmented actinic keratosis

The clinical and dermoscopic diagnosis of facial lentigo maligna (LM) and pigmented actinic keratosis (PAK) remains challenging, particularly at the early disease stages. To identify dermoscopic criteria that might be useful to differentiate LM from PAK, and to elaborate and validate an automated diagnostic algorithm for facial LM/PAK. We performed a retrospective multicentre study to evaluate dermoscopic images of histologically-proven LM and PAK, and assess previously described dermoscopic criteria. In the first part of the study, 61 cases of LM and 74 PAK were examined and a parsimonious algorithm was elaborated using stepwise discriminant analysis. The following eight dermoscopic criteria achieved the greatest discriminative power: (1) light brown colour; (2) a structureless zone, varying in colour from brown to brown/tan, to black; (3) in-focus, discontinuous brown lines; (4) incomplete brown or grey circles; (5) a structureless brown or black zone, obscuring the hair follicles; (6) a brown (tan), eccentric, structureless zone; (7) a blue structureless zone; and (8) scales. The newly developed algorithm was subsequently validated using an additional series of 110 LM and 75 PAK cases. Diagnostic accuracy was 86.5% (κ: 0.73, 95%&nbsp;CI: 0.63-0.83). For the diagnosis of LM vs PAK, sensitivity was 82.7% (95%&nbsp;CI: 75.7-89.8%), specificity was 92.0% (95%&nbsp;CI: 85.9-98.1%), positive predictive value was 93.8% (95%&nbsp;CI: 89.0-98.6%), and negative predictive value was 78.4% (95%&nbsp;CI: 68.4-86.5%). This algorithm may represent an additional tool for clinicians to distinguish between facial LM and PAK.Background: The clinical and dermoscopic diagnosis of facial lentigo maligna (LM) and pigmented actinic keratosis (PAK) remains challenging, particularly at the early disease stages. Objectives: To identify dermoscopic criteria that might be useful to differentiate LM from PAK, and to elaborate and validate an automated diagnostic algorithm for facial LM/PAK. Materials & Methods: We performed a retrospective multicentre study to evaluate dermoscopic images of histologically-proven LM and PAK, and assess previously described dermoscopic criteria. Results: In the first part of the study, 61 cases of LM and 74 PAK were examined and a parsimonious algorithm was elaborated using stepwise discriminant analysis. The following eight dermoscopic criteria achieved the greatest discriminative power: (1) light brown colour; (2) a structureless zone, varying in colour from brown to brown/tan, to black; (3) in-focus, discontinuous brown lines; (4) incomplete brown or grey circles; (5) a structureless brown or black zone, obscuring the hair follicles; (6) a brown (tan), eccentric, structureless zone; (7) a blue structureless zone; and (8) scales. The newly developed algorithm was subsequently validated using an additional series of 110LMand 75 PAKcases. Diagnostic accuracy was 86.5% (k: 0.73, 95% CI: 0.63-0.83). For the diagnosis of LM vs PAK, sensitivity was 82.7% (95% CI: 75.7-89.8%), specificity was 92.0% (95% CI: 85.9-98.1%), positive predictive value was 93.8% (95% CI: 89.0-98.6%), and negative predictive value was 78.4% (95% CI: 68.4-86.5%). Conclusions: This algorithm may represent an additional tool for clinicians to distinguish between facial LM and PAK

A new dermoscopic algorithm for the differential diagnosis of facial lentigo maligna and pigmented actinic keratosis

The clinical and dermoscopic diagnosis of facial lentigo maligna (LM) and pigmented actinic keratosis (PAK) remains challenging, particularly at the early disease stages. To identify dermoscopic criteria that might be useful to differentiate LM from PAK, and to elaborate and validate an automated diagnostic algorithm for facial LM/PAK. We performed a retrospective multicentre study to evaluate dermoscopic images of histologically-proven LM and PAK, and assess previously described dermoscopic criteria. In the first part of the study, 61 cases of LM and 74 PAK were examined and a parsimonious algorithm was elaborated using stepwise discriminant analysis. The following eight dermoscopic criteria achieved the greatest discriminative power: (1) light brown colour; (2) a structureless zone, varying in colour from brown to brown/tan, to black; (3) in-focus, discontinuous brown lines; (4) incomplete brown or grey circles; (5) a structureless brown or black zone, obscuring the hair follicles; (6) a brown (tan), eccentric, structureless zone; (7) a blue structureless zone; and (8) scales. The newly developed algorithm was subsequently validated using an additional series of 110 LM and 75 PAK cases. Diagnostic accuracy was 86.5% (κ: 0.73, 95%&nbsp;CI: 0.63-0.83). For the diagnosis of LM vs PAK, sensitivity was 82.7% (95%&nbsp;CI: 75.7-89.8%), specificity was 92.0% (95%&nbsp;CI: 85.9-98.1%), positive predictive value was 93.8% (95%&nbsp;CI: 89.0-98.6%), and negative predictive value was 78.4% (95%&nbsp;CI: 68.4-86.5%). This algorithm may represent an additional tool for clinicians to distinguish between facial LM and PAK.Background: The clinical and dermoscopic diagnosis of facial lentigo maligna (LM) and pigmented actinic keratosis (PAK) remains challenging, particularly at the early disease stages. Objectives: To identify dermoscopic criteria that might be useful to differentiate LM from PAK, and to elaborate and validate an automated diagnostic algorithm for facial LM/PAK. Materials & Methods: We performed a retrospective multicentre study to evaluate dermoscopic images of histologically-proven LM and PAK, and assess previously described dermoscopic criteria. Results: In the first part of the study, 61 cases of LM and 74 PAK were examined and a parsimonious algorithm was elaborated using stepwise discriminant analysis. The following eight dermoscopic criteria achieved the greatest discriminative power: (1) light brown colour; (2) a structureless zone, varying in colour from brown to brown/tan, to black; (3) in-focus, discontinuous brown lines; (4) incomplete brown or grey circles; (5) a structureless brown or black zone, obscuring the hair follicles; (6) a brown (tan), eccentric, structureless zone; (7) a blue structureless zone; and (8) scales. The newly developed algorithm was subsequently validated using an additional series of 110LMand 75 PAKcases. Diagnostic accuracy was 86.5% (k: 0.73, 95% CI: 0.63-0.83). For the diagnosis of LM vs PAK, sensitivity was 82.7% (95% CI: 75.7-89.8%), specificity was 92.0% (95% CI: 85.9-98.1%), positive predictive value was 93.8% (95% CI: 89.0-98.6%), and negative predictive value was 78.4% (95% CI: 68.4-86.5%). Conclusions: This algorithm may represent an additional tool for clinicians to distinguish between facial LM and PAK

Interferon-beta injection site reactions in patients with multiple sclerosis

Interferon-beta (IFNβ) is effective treatments for relapsing multiple sclerosis (MS). IFNβ treatment includes subcutaneous (SC) IFNβ-1b, intramuscular (IM) and SC IFNβ-1a, and SC pegylated IFNβ-1a (PEG-IFNβ-1a). PEG-IFNβ-1a offers the advantage of a prolonged duration of action with a less frequent administration (every 2 weeks) and a higher patient adherence. However, the use of SC interferons could be characterized by potential skin toxicity. Injection site reactions (ISRs), featured by erythema, edema, pain, and pruritus, are the most common adverse reactions. ISRs are mild or moderate in the vast majority of cases, but they can be severe enough to induce drug discontinuation. Therefore, it is very important to adopt strategies to minimize ISRs by proper patient education and counseling. These include rotation of injection sites, use of autoinjectors, use of medication at room temperature, cold compress, or local anesthetic cream before injection, early application of medium to high potency topical corticosteroids with gauze medication, and nonsteroidal anti-inflammatory drugs taken before and for 24 h after the injection

A new dermoscopic algorithm for the differential diagnosis of facial lentigo maligna and pigmented actinic keratosis

The clinical and dermoscopic diagnosis of facial lentigo maligna (LM) and pigmented actinic keratosis (PAK) remains challenging, particularly at the early disease stages. To identify dermoscopic criteria that might be useful to differentiate LM from PAK, and to elaborate and validate an automated diagnostic algorithm for facial LM/PAK. We performed a retrospective multicentre study to evaluate dermoscopic images of histologically-proven LM and PAK, and assess previously described dermoscopic criteria. In the first part of the study, 61 cases of LM and 74 PAK were examined and a parsimonious algorithm was elaborated using stepwise discriminant analysis. The following eight dermoscopic criteria achieved the greatest discriminative power: (1) light brown colour; (2) a structureless zone, varying in colour from brown to brown/tan, to black; (3) in-focus, discontinuous brown lines; (4) incomplete brown or grey circles; (5) a structureless brown or black zone, obscuring the hair follicles; (6) a brown (tan), eccentric, structureless zone; (7) a blue structureless zone; and (8) scales. The newly developed algorithm was subsequently validated using an additional series of 110 LM and 75 PAK cases. Diagnostic accuracy was 86.5% (κ: 0.73, 95% CI: 0.63-0.83). For the diagnosis of LM vs PAK, sensitivity was 82.7% (95% CI: 75.7-89.8%), specificity was 92.0% (95% CI: 85.9-98.1%), positive predictive value was 93.8% (95% CI: 89.0-98.6%), and negative predictive value was 78.4% (95% CI: 68.4-86.5%). This algorithm may represent an additional tool for clinicians to distinguish between facial LM and PAK

Dermoscopic similarity is an independent predictor of BRAF mutational concordance in multiple melanomas

The association of clinical and dermoscopic features with BRAF mutational status has been poorly analysed in multiple primary melanomas (MPM)

Heterogeneity of BRAF, NRAS, and TERT Promoter Mutational Status in Multiple Melanomas and Association with MC1R Genotype: Findings from Molecular and Immunohistochemical Analysis

Data on somatic heterogeneity and germline\ue2\u80\u93somatic interaction in multiple primary melanoma (MPM) patients are limited. We investigated the mutational status of BRAF, NRAS, and TERT promoter genes in 97 melanomas of 44 MPM patients and compared molecular and immunohistochemical findings. We further evaluated the association of somatic alterations with the germline MC1R genotype. Mutations in BRAF gene were identified in 41.2% (40/97) of melanomas, in NRAS in 2.1% (2/97), and in TERT promoter in 19.6% (19/97). Distribution of BRAF mutations did not differ across multiple melanomas (P = 0.85), whereas TERT promoter changes decreased from first to subsequent melanomas (P = 0.04). Intrapatient discrepancy of BRAF mutations among multiple tumors was detected in 14 of 44 MPM patients (32%) and of BRAF/NRAS/TERT promoter genes in 20 of 44 (45%). We observed a high rate of agreement between allele-specific TaqMan assay and immunohistochemistry in BRAFV600Edetection (\uce\uba = 0.83, P < 0.01) with 86 of 97 melanomas (88.7%) presenting similar BRAF status. Germline MC1R variants were identified in 81.4% (35/43) of MPM patients with no association of MC1R genotype with somatic mutations or with intrapatient concordance of somatic mutational profile. Our results support the genetic diversity of multiple melanomas and show that somatic heterogeneity is not influenced by inherited MC1R variants. Immunohistochemistry may be useful as an initial screening test

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P&lt;0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)