Synthesis and Photovoltaic Properties of Regioregular Head-to-Head Substituted Thiophene Hexadecamers

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Use of Miltefosine in a Patient With Mucosal Leishmaniasis and HIV-coinfection: A Challenge in Long-Term Management

The management of mucosal leishmaniasis in immunocompromised patients is not standardized and limited data are available on the use of miltefosine for treatment and secondary prophylaxis. We describe a case of mucosal leishmaniasis in an HIV-coinfected patient treated with miltefosine due to a severe allergic reaction to liposomal amphotericin B

Poly(3-hexylthiophene) Nanoparticles Containing Thiophene-S,S-dioxide: Tuning of Dimensions, Optical and Redox Properties, and Charge Separation under Illumination

We describe the preparation of poly(3-hexylthiophene-S,S-dioxide) nanoparticles using Rozen's reagent, HOF·CH3CN, either on poly(3-hexylthiophene) (P3HT) or on preformed P3HT nanoparticles (P3HT-NPs). In the latter case, core-shell nanoparticles (P3HT@PTDO-NPs) are formed, as confirmed by X-ray photoelectron spectroscopy measurements, indicating the presence of oxygen on the outer shell. The different preparation modalities lead to a fine-tuning of the chemical-physical properties of the nanoparticles. We show that absorption and photoluminescence features, electrochemical properties, size, and stability of colloidal solutions can be finely modulated by controlling the amount of oxygen present. Atomic force microscopy measurements on the nanoparticles obtained by a nanoprecipitation method from preoxidized P3HT (PTDO-NPs) display spherical morphology and dimensions down to 5 nm. Finally, Kelvin probe measurements show that the coexistence of p- and n-type charge carriers in all types of oxygenated nanoparticles makes them capable of generating and separating charge under illumination. Furthermore, in core-shell nanoparticles, the nanosegregation of the two materials, in different regions of the nanoparticles, allows a more efficient charge separation

Prevalence of resistance-associated substitutions to NS3, NS5A and NS5B inhibitors at DAA-failure in hepatitis C virus in Italy from 2015 to 2019

: Despite the high efficacy of direct-acting antivirals (DAAs), the selection of resistance-associated substitutions (RASs) after virological failure of hepatitis C virus (HCV) DAAs can impair the cure of chronic HCV. The aim of the study was to characterize RASs after virological failure of DAAs in Italy over the years. Within the Italian network VIRONET-C, the change in prevalence of NS3/4A-NS5A-NS5B RASs was retrospectively evaluated in patients who failed a DAA regimen over the years 2015-2019. NS3, NS5A and NS5B Sanger sequencing was performed using homemade protocols and the geno2pheno system was used to define HCV-genotype/subtype and predict drug resistance. The changes in the prevalence of RASs over time were evaluated using the chi-square test for trend. Predictors of RASs at failure were analysed by logistic regression. Among 468 HCV-infected patients, HCV genotype 1 was the most prevalent (1b in 154, 33% and 1a in 109, 23%). DAA regimens were: ledipasvir (LDV)/sofosbuvir (SOF) in 131 patients (28%), daclatasvir (DCV)/SOF in 109 (23%), ombitasvir/paritaprevir/ritonavir+dasabuvir (3D) in 89 (19%), elbasvir (EBR)/grazoprevir (GRZ) in 52 (10.5%), velpatasvir (VEL)/SOF in 53 (11%), glecaprevir (GLE)/pibrentasvir (PIB) in 27 (6%) and ombitasvir/paritaprevir/ritonavir (2D) in 7 (1.5%); ribavirin was administered in 133 (28%). The NS5A fasta sequence was available for all patients, NS5B and NS3/4A both for 93%. The prevalence of NS5A and NS3/4A RASs significantly declined from 2015 to 2019; NS5B RAS remained stable. Independent predictors of any RASs included older age and genotype 1a (vs G2 and vs G4). Notably, at least partial susceptibility to all the agents included in the GLE/PIB and VEL/SOF/Voxilaprevir (VOX) combinations was predicted in >95% of cases. As RASs remain common at the failure of DAAs, their identification could play a crucial role in optimizing re-treatment strategies. In Italy RAS prevalence has been decreasing over the years and susceptibility to the latest developed drug combinations is maintained in most cases

T-Cell Lymphoblastic Lymphoma Arising in the Setting of Myeloid/Lymphoid Neoplasms with Eosinophilia: LMO2 Immunohistochemistry as a Potentially Useful Diagnostic Marker

Simple Summary Rarely, T-lymphoblastic lymphoma (T-LBL) may develop in the setting of myeloid/lymphoid neoplasms with eosinophilia. Given important therapeutic implications, it is crucial to identify T-LBL arising in this particular context. LIM domain only 2 (LMO2) is known to be overexpressed in almost all sporadic T-LBL and not in immature TdT-positive T-cells in the thymus and in indolent T-lymphoblastic proliferations. We retrospectively evaluated the clinical, morphological, immunohistochemical and molecular features of 11 cases of T-LBL occurring in the setting of myeloid/lymphoid neoplasms with eosinophilia and investigated the immunohistochemical expression of LMO2 in this setting of T-LBL. Interestingly, 9/11 cases were LMO2 negative, with only 2 cases showing partial expression. In our study, we would suggest that LMO2 immunostaining, as part of the diagnostic panel for T-LBL, may represent a useful marker to identify T-LBL developing in the context of myeloid/lymphoid neoplasms with eosinophilia. Background: Rarely, T-lymphoblastic lymphoma (T-LBL) may develop in the setting of myeloid/lymphoid neoplasms with eosinophilia (M/LNs-Eo), a group of diseases with gene fusion resulting in overexpression of an aberrant tyrosine kinase or cytokine receptor. The correct identification of this category has relevant therapeutic implications. LIM domain only 2 (LMO2) is overexpressed in most T-LBL, but not in immature TdT-positive T-cells in the thymus and in indolent T-lymphoblastic proliferations (iT-LBP). Methods and Results: We retrospectively evaluated 11 cases of T-LBL occurring in the context of M/LNs-Eo. Clinical, histological, immunohistochemical and molecular features were collected and LMO2 immunohistochemical staining was performed. The critical re-evaluation of these cases confirmed the diagnosis of T-LBL with morphological, immunohistochemical and molecular features consistent with T-LBL occurring in M/LNs-Eo. Interestingly, LMO2 immunohistochemical analysis was negative in 9/11 cases, whereas only 2 cases revealed a partial LMO2 expression with a moderate and low degree of intensity, respectively. Conclusions: LMO2 may represent a potentially useful marker to identify T-LBL developing in the context of M/LNs-Eo. In this setting, T-LBL shows LMO2 immunohistochemical profile overlapping with cortical thymocytes and iT-LBP, possibly reflecting different molecular patterns involved in the pathogenesis of T-LBL arising in the setting of M/LNs-Eo

Prognostic value of H-index in patients surgically treated for squamous cell carcinoma of the larynx.

OBJECTIVE: Recently, a novel host-related index, the Host-index (H-index), including both inflammatory and nutritional markers, has been described and observed to stratify prognosis in patients with squamous cell carcinoma (SCC) of the oral cavity more accurately than other host-related indexes This study aimed to investigate the prognostic performance of the H-index using pretreatment blood tests in patients receiving up-front surgery for SCC of the larynx. METHODS: This retrospective observational study included a multicenter series of consecutive patients with SCC of the larynx diagnosed between 1 January 2009 and 31 July 2018, whose pretreatment blood tests were available and included the parameters necessary for the calculation of neutrophil to lymphocyte ratio (NLR) and the H-index. Their association with disease-free survival (DFS) and overall survival (OS) was measured. RESULTS: A total of 231 patients were eligible for the present analysis (median [range] age, 68 [37-96] years; 191 [82.7%] men). The median follow-up was 73 months. In multivariable Cox proportional hazards regression models, increasing age (adjusted hazard ratio [aHR], 1.07 per year; 95% CI, 1.04-1.09), advanced pT stage (aHR = 1.71 95% CI: 1.07-2.71), and having close or positive surgical margins (aHR = 2.01; 95% CI: 1.21-3.33) were significantly associated with poor OS. Among blood parameters, a higher neutrophil count was a strong predictor of both worse DFS (aHR for recurrence/death = 2.34; 95% CI: 1.24-4.40) and OS (aHR for death = 2.67; 95% CI: 1.51-4.71). Among inflammatory blood indexes, while NLR was not significantly associated with DFS or OS, patients with H-index ≥8.37 showed a higher aHR for both recurrence/death (2.82; 95% CI: 1.65-4.79) and death (2.22; 95% CI: 1.26-3.89). CONCLUSION: In conclusion, the present study confirms the prognostic value of pretreatment H-index, an easily measurable inflammatory and nutritional index, in patients with SCC of the larynx. LEVEL OF EVIDENCE: III

DECLINE OF PREVALENCE OF RESISTANCE ASSOCIATED SUBSTITUTIONS TO NS3 AND NS5A INHIBITORS AT DAA- FAILURE IN HEPATITIS C VIRUS IN ITALY OVER THE YEARS 2015 TO 2018

Background: A minority of patients fails to eliminate HCV and resistance-associated substitutions (RASs) are commonly detected at failure of interferon-free DAA regimens . Methods: Within the Italian network VIRONET-C, the prevalence of NS3/NS5A/NS5B RASs was retrospectively evaluated in patients who failed an EASL recommended DAA-regimen in 2015-2018 . The geno2pheno system and Sorbo MC et al. Drug Resistance Updates 2018 were used to infer HCV- genotype/subtype and predict drug resistance . The changes in prevalence of RASs over time were evaluated by chi-square test for trend, predictors of RASs at failure were analysed by logistic regression . Results: We included 386 HCV infected patients: 75% males, median age was 56 years (IQR 52-61), metavir fibrosis stage F4 in 76%; 106 (28%) were treatment- experienced: 91 (86%) with IFN-based treatments, 26 (25%) with DAAs. Patients with HIV and HBV coinfection were 10% (33/317) and 8% (6/72), respectively. HCV genotype was 1b in 122 pts (32%), 3 in 109 (28%), 1a in 97 (25%), 4 in 37 (10%), 2 in 21 (5%). DAA regimens were: LDV/SOF in 115 (30%), DCV/SOF in 103 (27%), 3D in 83 (21%), EBR/GRZ in 32 (8%), VEL/SOF in 29 (7%), GLE/PIB in 18 (5%) and 2D in 6 (2%); ribavirin was administered in 123 (32%) . The NS5A fasta-sequence was available for all patients, NS5B for 361 (94%), NS3 for 365 (95%) . According to the DAA failed the prevalence of any RASs was 90%, namely 80/135 (59%) in NS3, 313/359 (87%) in NS5A, 114/286 (40%) in NS5B . The prevalence of any RASs significantly declined from 2015 to 2018 (93% vs 70%, p=0.004): NS5A RASs from 90% to 72% (p=0 .29), NS3 RASs from 74% to 18% (p<0 .001), while NS5B RASs remained stable . Independent predictors of any RASs included advanced fibrosis (AOR 6.1, CI 95% 1.8-20.3, p=0 .004) and genotype (G2 vs G1a AOR 0 .03, CI 95% 0 .002- 0 .31, p=0 .004; G3 vs G1a AOR 0 .08, CI 95% 0 .01-0 .62, p=0 .02; G4 vs G1a AOR 0 .05, CI 95% 0 .006-0 .46, p=0 .008), after adjusting for age, previous HCV treatment and year of genotype . Notably, full activity was predicted for GLE/PIB in 75% of cases and for at least two components of VEL/SOF/VOX in 53% of cases, no case with full-resistance to either regimen was found . Conclusion: Despite decreasing prevalence over the years, RASs remain common at virological failure of DAA treatment, particularly in patients with the highest grade of liver fibrosis. The identification of RASs after failure could play a crucial role in optimizing retreatment strategies

Functional magnetic resonance imaging (fMRI) of attention processes in presumed obligate carriers of schizophrenia: preliminary findings

<p>Abstract</p> <p>Background</p> <p>Presumed obligate carriers (POCs) are the first-degree relatives of people with schizophrenia who, although do not exhibit the disorder, are in direct lineage of it. Thus, this subpopulation of first-degree relatives could provide very important information with regard to the investigation of endophenotypes for schizophrenia that could clarify the often contradictory findings in schizophrenia high-risk populations. To date, despite the extant literature on schizophrenia endophenotypes, we are only aware of one other study that examined the neural mechanisms that underlie cognitive abnormalities in this group. The aim of this study was to investigate whether a more homogeneous group of relatives, such as POCs, have neural abnormalities that may be related to schizophrenia.</p> <p>Methods</p> <p>We used functional magnetic resonance imaging (fMRI) to collect blood oxygenated level dependent (BOLD) response data in six POCs and eight unrelated healthy controls while performing under conditions of sustained, selective and divided attention.</p> <p>Results</p> <p>The POCs indicated alterations in a widely distributed network of regions involved in attention processes, such as the prefrontal and temporal (including the parahippocampal gyrus) cortices, in addition to the anterior cingulate gyrus. More specifically, a general reduction in BOLD response was found in these areas compared to the healthy participants during attention processes.</p> <p>Conclusion</p> <p>These preliminary findings of decreased activity in POCs indicate that this more homogeneous population of unaffected relatives share similar neural abnormalities with people with schizophrenia, suggesting that reduced BOLD activity in the attention network may be an intermediate marker for schizophrenia.</p