Explore the vast range of titles available.

Ultra-pure NaI(Tl) crystals are the key element for a model-independent verification of the long standing DAMA result and a powerful means to search for the annual modulation signature of dark matter interactions. The SABRE collaboration has been developing cutting-edge techniques for the reduction of intrinsic backgrounds over several years. In this paper we report the first characterization of a 3.4 kg crystal, named NaI-33, performed in an underground passive shielding setup at LNGS. NaI-33 has a record low 39K contamination of 4.3 ± 0.2 ppb as determined by mass spectrometry. We measured a light yield of 11.1 ± 0.2 photoelectrons/keV and an energy resolution of 13.2% (FWHM/E) at 59.5 keV. We evaluated the activities of 226Ra and 228Th inside the crystal to be 5.9±0.6μBq/kg and 1.6±0.3μBq/kg, respectively, which would indicate a contamination from 238U and 232Th at part-per-trillion level. We measured an activity of 0.51 ± 0.02 mBq/kg due to 210Pb out of equilibrium and a α quenching factor of 0.63 ± 0.01 at 5304 keV. We illustrate the analyses techniques developed to reject electronic noise in the lower part of the energy spectrum. A cut-based strategy and a multivariate approach indicated a rate, attributed to the intrinsic radioactivity of the crystal, of ∼1 count/day/kg/keV in the [5–20] keV region.

Marianecci C, Rinaldi F, Di Marzio L, et al. Int J Nanomedicine. 2014;9(1):635–651. The Editor and Publisher of International Journal of Nanomedicine wish to retract the published article. Concerns were raised regarding the alleged duplication of TEM images in Figure 1. Specifically, * Figure 1A, F1, appears to have been duplicated with the same image for Figure 1C, F3 and Figure 1D, F3AG. The authors did respond to our queries but were unable to explain how the duplication of images occurred, nor were they able to provide the original TEM images from the reported study. The decision was made to retract the article and the authors were notified of this. Our decision-making was informed by our policy on publishing ethics and integrity and the COPE guidelines on retraction. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”. This retraction relates to this paper

The use of biopolymers is increasing in drug delivery, thanks to the peculiar properties of these compounds such as their biodegradability, availability, and the possibility of modulating their physico-chemical characteristics. In particular, protein-based systems such as albumin are able to interact with many active compounds, modulating their biopharmaceutical properties. Zein is a protein of 20-40 kDa made up of many hydrophobic amino acids, generally regarded as safe (GRAS) and used as a coating material. In this investigation, zein was combined with various surfactants in order to obtain stable nanosystems by means of the nanoprecipitation technique. Specific parameters, eg, temperature, pH value, Turbiscan Stability Index, serum stability, in vitro cytotoxicity and entrapment efficiency of various model compounds were investigated, in order to identify the nanoformulation most useful for a systemic drug delivery application. The use of non-ionic and ionic surfactants such as Tween 80, poloxamer 188, and sodium deoxycholate allowed us to obtain nanoparticles characterized by a mean diameter of 100-200 nm when a protein concentration of 2 mg/mL was used. The surface charge was modulated by means of the protein concentration and the nature of the stabilizer. The most suitable nanoparticle formulation to be proposed as a colloidal drug delivery system was obtained using sodium deoxycholate (1.25% w/v) because it was characterized by a narrow size distribution, a good storage stability after freeze-drying and significant feature of retaining lipophilic and hydrophilic compounds. The sodium deoxycholate-coated zein nanoparticles are stable biocompatible colloidal carriers to be used as useful drug delivery systems.

Mosquito-borne diseases are an emerging threat in Europe. West Nile virus (WNV) is an arbovirus commonly transmitted in an enzootic cycle involving ornithophilic mosquitoes as major vectors. In recent years, global climate change has been identified as a significant driver of the increased spread of this virus. In Italy, outbreaks of WNV infection have been recorded every year in northern Italy. The Apulia region of southern Italy was not considered a high-risk region until 2023, when an unexpected increase in WNV infections occurred. The aim of this study was to evaluate the prevalence of anti-WNV antibodies in a wide sample of blood donors in the Apulia region of southern Italy enrolled between November 2023 and February 2024. In addition, the use of protective measures against mosquito bites was assessed. A retrospective cross-sectional study was conducted on a total of 1,579 blood donors. All sera were tested for anti-WNV IgG by ELISA. Reactive serum samples were also tested by CLIA and by the plaque reduction neutralization test (PRNT). All healthy donors answered a short anonymous questionnaire. Data analysis was performed using StataMP14.0® (StataCorp LLC, CollegeStation, TX77845-4512, USA). The median age was 47 years (IQR: 37-53), and 75% were male. The questionnaires administered revealed that 68.6% of the subjects had not made any trips in the few weeks prior to blood sampling, and 30.5% remembered being bitten by mosquitoes in the previous 15 days or longer. While 17 samples tested by ELISA were positive for anti-WNV IgG, only six were also positive by CLIA testing. Analysis by PRNT for WNV confirmed 5 cases. The findings revealed a WNV seroprevalence of 0.32% (95% CI: 0.07-0.59). Among the subjects who tested positive, none recalled being bitten by mosquitoes or regularly using mosquito repellents. Our study suggests the circulation of WNV in Apulia and highlights the potential human health concerns associated with this emerging virus. Strengthening the integrated surveillance system and planning adequate preventive strategies are crucial next steps to address the potential massive spread of WNV in southern Italy.

Background Mosquito-borne diseases are an emerging threat in Europe. West Nile virus (WNV) is an arbovirus commonly transmitted in an enzootic cycle involving ornithophilic mosquitoes as major vectors. In recent years, global climate change has been identified as a significant driver of the increased spread of this virus. In Italy, outbreaks of WNV infection have been recorded every year in northern Italy. The Apulia region of southern Italy was not considered a high-risk region until 2023, when an unexpected increase in WNV infections occurred. The aim of this study was to evaluate the prevalence of anti-WNV antibodies in a wide sample of blood donors in the Apulia region of southern Italy enrolled between November 2023 and February 2024. In addition, the use of protective measures against mosquito bites was assessed. Methods A retrospective cross-sectional study was conducted on a total of 1,579 blood donors. All sera were tested for anti-WNV IgG by ELISA. Reactive serum samples were also tested by CLIA and by the plaque reduction neutralization test (PRNT). All healthy donors answered a short anonymous questionnaire. Data analysis was performed using StataMP14.0® (StataCorp LLC, CollegeStation, TX77845-4512, USA). Results The median age was 47 years (IQR: 37–53), and 75% were male. The questionnaires administered revealed that 68.6% of the subjects had not made any trips in the few weeks prior to blood sampling, and 30.5% remembered being bitten by mosquitoes in the previous 15 days or longer. While 17 samples tested by ELISA were positive for anti-WNV IgG, only six were also positive by CLIA testing. Analysis by PRNT for WNV confirmed 5 cases. The findings revealed a WNV seroprevalence of 0.32% (95% CI: 0.07–0.59). Among the subjects who tested positive, none recalled being bitten by mosquitoes or regularly using mosquito repellents. Conclusions Our study suggests the circulation of WNV in Apulia and highlights the potential human health concerns associated with this emerging virus. Strengthening the integrated surveillance system and planning adequate preventive strategies are crucial next steps to address the potential massive spread of WNV in southern Italy.

Atypical ulcers show atypical clinical features, histology, localization, and resistance to standard therapies. The persistence of a chronic ulcer despite treatment with standard therapies requires a more specific diagnostic investigation. Diagnosis involves obtaining the history and performing clinical examination and additional tests. A skin biopsy is frequently used to confirm unclear diagnosis. In difficult cases, microbiological and immunohistochemical examinations, laboratory blood tests, or instrumental tests should be evaluated. The treatment of atypical wounds is characterized by local systemic therapy and pain control. Our results highlight the need for early diagnosis, and standardized and targeted management by a multidisciplinary wound healing center.

Liquorice extracts demonstrate therapeutic efficacy in treating dermatitis, eczema, and psoriasis when compared with corticosteroids. In this work, nonionic surfactant vesicles (niosomes, NSVs) containing polysorbate 20 (Tween 20), cholesterol, and cholesteryl hemisuccinate at different molar concentrations were used to prepare monoammonium glycyrrhizinate (AG)-loaded NSVs. The anti-inflammatory properties of AG-loaded NSVs were investigated in murine models. The physicochemical properties of the NSVs were characterized using dynamic light scattering. The fluidity of the lipid bilayer was evaluated by measuring the fluorescence intensity of diphenylhexatriene. The drug entrapment efficiency of AG was assessed using high-performance liquid chromatography. The physicochemical stability of the NSVs was evaluated as a function of time using dynamic light scattering combined with Turbiscan Lab Expert analysis. Serum stability was determined by incubating the NSVs with 10% v/v fetal bovine serum. The cytotoxic effects of the NSVs were investigated in human dermal fibroblasts using the Trypan blue dye exclusion assay (for cell mortality) and an MTT assay (for cell viability). Release profiles for the AG-loaded NSVs were studied in vitro using cellulose membranes. NSVs showing the most desirable physicochemical properties were selected to test for in vivo anti-inflammatory activity in murine models. The anti-inflammatory activity of the NSVs was investigated by measuring edema and nociception in mice stimulated with chemical agents. NSVs showed favorable physicochemical properties for in vitro and in vivo administration. In addition, they demonstrated long-term stability based on Turbiscan Lab Expert analysis. The membrane fluidity of the NSVs was not affected by self-assembling of the surfactants into colloidal structures. Fluorescence anisotropy was found to be independent of the molar ratios of cholesteryl hemisuccinate and/or cholesterol during preparation of the NSVs. The anti-inflammatory AG drug showed no effect on the stability of the NSVs. In vivo experiments demonstrated that AG-loaded NSVs decreased edema and nociceptive responses when compared with AG alone and empty NSVs. In vitro and in vivo results demonstrated that pH sensitive and neutral NSVs show no statistical significant difference. NSVs were nontoxic and showed features favorable for potential administration in vivo. In addition, neutral NSVs showed signs of increased anti-inflammatory and antinociceptive responses when compared with AG.

The anti-programmed-death-receptor-1 (PD-1) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma. We compared the efficacy and safety of pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in patients with ipilimumab-refractory advanced melanoma. In an open-label, international, multicentre expansion cohort of a phase 1 trial, patients (aged ≥18 years) with advanced melanoma whose disease had progressed after at least two ipilimumab doses were randomly assigned with a computer-generated allocation schedule (1:1 final ratio) to intravenous pembrolizumab at 2 mg/kg every 3 weeks or 10 mg/kg every 3 weeks until disease progression, intolerable toxicity, or consent withdrawal. Primary endpoint was overall response rate (ORR) assessed with the Response Evaluation Criteria In Solid Tumors (RECIST, version 1.1) by independent central review. Analysis was done on the full-analysis set (all treated patients with measurable disease at baseline). This study is registered with ClinicalTrials.gov, number NCT01295827. 173 patients received pembrolizumab 2 mg/kg (n=89) or 10 mg/kg (n=84). Median follow-up duration was 8 months. ORR was 26% at both doses—21 of 81 patients in the 2 mg/kg group and 20 of 76 in the 10 mg/kg group (difference 0%, 95% CI −14 to 13; p=0·96). Treatment was well tolerated, with similar safety profiles in the 2 mg/kg and 10 mg/kg groups and no drug-related deaths. The most common drug-related adverse events of any grade in the 2 mg/kg and 10 mg/kg groups were fatigue (29 [33%] vs 31 [37%]), pruritus (23 [26%] vs 16 [19%]), and rash (16 [18%] vs 15 [18%]). Grade 3 fatigue, reported in five (3%) patients in the 2 mg/kg pembrolizumab group, was the only drug-related grade 3 to 4 adverse event reported in more than one patient. The results suggest that pembrolizumab at a dose of 2 mg/kg or 10 mg/kg every 3 weeks might be an effective treatment in patients for whom there are few effective treatment options. Merck Sharp and Dohme.

Poly(ADP-ribose) polymerase (PARP) is implicated in DNA repair and transcription regulation. Niraparib (MK4827) is an oral potent, selective PARP-1 and PARP-2 inhibitor that induces synthetic lethality in preclinical tumour models with loss of BRCA and PTEN function. We investigated the safety, tolerability, maximum tolerated dose, pharmacokinetic and pharmacodynamic profiles, and preliminary antitumour activity of niraparib. In a phase 1 dose-escalation study, we enrolled patients with advanced solid tumours at one site in the UK and two sites in the USA. Eligible patients were aged at least 18 years; had a life expectancy of at least 12 weeks; had an Eastern Cooperative Oncology Group performance status of 2 or less; had assessable disease; were not suitable to receive any established treatments; had adequate organ function; and had discontinued any previous anticancer treatments at least 4 weeks previously. In part A, cohorts of three to six patients, enriched for BRCA1 and BRCA2 mutation carriers, received niraparib daily at ten escalating doses from 30 mg to 400 mg in a 21-day cycle to establish the maximum tolerated dose. Dose expansion at the maximum tolerated dose was pursued in 15 patients to confirm tolerability. In part B, we further investigated the maximum tolerated dose in patients with sporadic platinum-resistant high-grade serous ovarian cancer and sporadic prostate cancer. We obtained blood, circulating tumour cells, and optional paired tumour biopsies for pharmacokinetic and pharmacodynamic assessments. Toxic effects were assessed by common toxicity criteria and tumour responses ascribed by Response Evaluation Criteria in Solid Tumors (RECIST). Circulating tumour cells and archival tumour tissue in prostate patients were analysed for exploratory putative predictive biomarkers, such as loss of PTEN expression and ETS rearrangements. This trial is registered with ClinicalTrials.gov, NCT00749502. Between Sept 15, 2008, and Jan 14, 2011, we enrolled 100 patients: 60 in part A and 40 in part B. 300 mg/day was established as the maximum tolerated dose. Dose-limiting toxic effects reported in the first cycle were grade 3 fatigue (one patient given 30 mg/day), grade 3 pneumonitis (one given 60 mg/day), and grade 4 thrombocytopenia (two given 400 mg/day). Common treatment-related toxic effects were anaemia (48 patients [48%]), nausea (42 [42%]), fatigue (42 [42%]), thrombocytopenia (35 [35%]), anorexia (26 [26%]), neutropenia (24 [24%]), constipation (23 [23%]), and vomiting (20 [20%]), and were predominantly grade 1 or 2. Pharmacokinetics were dose proportional and the mean terminal elimination half-life was 36·4 h (range 32·8–46·0). Pharmacodynamic analyses confirmed PARP inhibition exceeded 50% at doses greater than 80 mg/day and antitumour activity was documented beyond doses of 60 mg/day. Eight (40% [95% CI 19–64]) of 20 BRCA1 or BRCA2 mutation carriers with ovarian cancer had RECIST partial responses, as did two (50% [7–93]) of four mutation carriers with breast cancer. Antitumour activity was also reported in sporadic high-grade serous ovarian cancer, non-small-cell lung cancer, and prostate cancer. We recorded no correlation between loss of PTEN expression or ETS rearrangements and measures of antitumour activity in patients with prostate cancer. A recommended phase 2 dose of 300 mg/day niraparib is well tolerated. Niraparib should be further assessed in inherited and sporadic cancers with homologous recombination DNA repair defects and to target PARP-mediated transcription in cancer. Merck Sharp and Dohme.

[...]both lidocaine and placebo arms of the trial are not justified because amiodarone was definitely superior in a head-to-head randomized comparison either I with lidocaine2 or placebo3 for achieving higher survival rates to hospital admission.