Weighted norm inequalities for polynomial expansions associated to some measures with mass points

Fourier series in orthogonal polynomials with respect to a measure $\nu$ on $[-1,1]$ are studied when $\nu$ is a linear combination of a generalized Jacobi weight and finitely many Dirac deltas in $[-1,1]$. We prove some weighted norm inequalities for the partial sum operators $S_n$, their maximal operator $S^*$ and the commutator $[M_b, S_n]$, where $M_b$ denotes the operator of pointwise multiplication by b \in \BMO. We also prove some norm inequalities for $S_n$ when $\nu$ is a sum of a Laguerre weight on $\R^+$ and a positive mass on $0$

Management of locked volar radio-ulnar joint dislocation

Isolated volar dislocation of the distal radio-ulnar joint is an extremely rare lesion. Diagnosis is commonly missed. The authors report their experience about a case of an acute locked volar distal radio-ulnar joint dislocation. A correct clinical and radiological diagnosis was done in the Emergency Department, and a closed reduction was achieved only after an axillary block, after a first failed attempt under slight sedation. A K-wire blocking the prono-supination and a short removable forearm cast protected the reduction for 25 days. Two weeks after the removal of the immobilization, the patient presented a complete functional recovery, with full range of motion. The authors highlight the importance of the clinical and radiological findings: a dorsal dimple at the ulnar side leads to a high index of suspicion, and represent the most relevant aid in diagnosis, associated to a proper imaging assessment. Prompt management allows a minimally invasive approach and a rapid functional recovery

Median nerve injury caused by screw malpositioning in percutaneous scaphoid fracture fixation

An unusual complication of percutaneous fixation of a schapoid fracture in a 36-year-old man is described. After this surgery, the patient complained of numbness and tingling within the median nerve distribution and thenar weakness. An Electromyography showing moderate CTS had led to carpal tunnel decompression, which resulted unsuccessful. When the patient presented to us, both sensory and motor median nerve impairment were present, interfering with his professional activity. A computed tomography scan performed to assess the scaphoid screw position, showed that the screw had been placed volar to the scaphoid, adjacent to the median nerve. Surgery confirmed median nerve compression by the screw, especially during complete wrist extension. The surgical removal of the screw led to immediate improvement of both the motor and sensory functions of the nerve, with complete clinical restoration of nerve function and resolution of the symptoms 2 months postoperatively

Quantitative chemical proteomics identifies novel targets of the anti-cancer multi-kinase inhibitor E-3810

Novel drugs are designed against specific molecular targets, but almost unavoidably they bind non-targets, which can cause additional biological effects that may result in increased activity or, more frequently, undesired toxicity. Chemical proteomics is an ideal approach for the systematic identification of drug targets and off-targets, allowing unbiased screening of candidate interactors in their natural context (tissue or cell extracts). E-3810 is a novel multi-kinase inhibitor currently in clinical trials for its anti-angiogenic and anti-tumor activity. In biochemical assays, E-3810 targets primarily vascular endothelial growth factor and fibroblast growth factor receptors. Interestingly, E-3810 appears to inhibit the growth of tumor cells with low to undetectable levels of these proteins in vitro, suggesting that additional relevant targets exist. We applied chemical proteomics to screen for E-3810 targets by immobilizing the drug on a resin and exploiting stable isotope labeling by amino acids in cell culture to design experiments that allowed the detection of novel interactors and the quantification of their dissociation constant (Kd imm) for the immobilized drug. In addition to the known target FGFR2 and PDGFRα, which has been described as a secondary E-3810 target based on in vitro assays, we identified six novel candidate kinase targets (DDR2, YES, LYN, CARDIAK, EPHA2, and CSBP). These kinases were validated in a biochemical assay and-in the case of the cell-surface receptor DDR2, for which activating mutations have been recently discovered in lung cancer-cellular assays. Taken together, the success of our strategy-which integrates large-scale target identification and quality-controlled target affinity measurements using quantitative mass spectrometry-in identifying novel E-3810 targets further supports the use of chemical proteomics to dissect the mechanism of action of novel drugs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc

Evidence of SARS-CoV-2 RNA in an Oropharyngeal Swab Specimen, Milan, Italy, Early December 2019

We identified severe acute respiratory syndrome coronavirus 2 RNA in an oropharyngeal swab specimen collected from a child with suspected measles in early December 2019, ≈3 months before the first identified coronavirus disease case in Italy. This finding expands our knowledge on timing and mapping of novel coronavirus transmission pathways

Efficacy and safety of vandetanib in progressive and symptomatic medullary thyroid Cancer: Post hoc analysis from the ZETA trial

PURPOSE We conducted a post hoc analysis of the vandetanib phase III trial involving patients with advanced medullary thyroid cancer (MTC) to assess the efficacy and safety of vandetanib in patients with progressive and symptomatic MTC. The primary objective of the analysis was to determine progression-free survival (PFS) of these patients. PATIENTS AND METHODS Eligible patients from the ZETA trial were divided into 4 disease severity subgroups: progression and symptoms, symptoms only, progression only, and no progression and no symptoms assessed at baseline. PFS, determined from objective tumor measurements performed by the local investigator, overall survival (OS), time to worsening of pain (TWP), and objective response rate (ORR) were evaluated. RESULTS Of the 331 patients in this trial, 184 had symptomatic and progressive disease at baseline. In this subgroup, results were similar in magnitude to those observed in the overall trial for PFS (hazard ratio [HR], 0.43; 95% CI, 0.28 to 0.64; P, .0001), OS (HR, 1.08; 95% CI, 0.72 to 1.61; P 5 .71), and TWP (HR, 0.67; 95% CI, 0.43 to 1.04; P 5 .07), and the observed adverse events were consistent with the known safety profile of vandetanib. In this subgroup, the ORR was 37% in the treatment arm versus 2% in the placebo arm. CONCLUSION Vandetanib demonstrated clinical benefit—specifically, increased PFS—in patients with symptomatic and progressive MTC

Measles surveillance activities in the Metropolitan Area of Milan during 2017-2018

Introduction In Italy, the transmission of measles is still endemic, and 7,919 cases were reported to the National Surveillance System between January 2017 and December 2018. Aim of this study is to report the results of the measles surveillance activities in the Metropolitan City of Milan from March 2017 to December 2018, and to evaluate the surveillance performance WHO indicators. Methods The Local Health Units (LHUs) carried out case investigations and collected specimens to send to the EpiSoMI Lab (Subnational Reference Laboratory, SRL) of the University of Milan for cases/outbreaks confirmation and genotyping performed according to the WHO Guidelines. Results Overall, 610 suspected measles cases were reported by the surveillance system of the Metropolitan City of Milan. A total of 439 out of 540 cases with adequate specimens were laboratory-confirmed by molecular and/or serological assays. Two-hundred and thirty-six cases were notified as sporadic and 203 as related to 94 outbreaks. The most confirmed cases were aged 15\u201339 years, almost all not vaccinated. Overall, 282 cases were genotype D8 and 118 genotype B3. The evaluation of a set of indicators to monitor the quality of surveillance activities demonstrated the proficiency of the EpiSoMI Lab. Conclusions A well-done investigation of cases and outbreaks by the surveillance local system, in a timely manner, in order to notify and investigate suspected cases and to laboratory confirm or discard cases is fundamental to reduce morbidity, to prevent further virus transmission and to achieve measles elimination

HPV genotypes detected in the oropharyngeal mucosa of HIV-infected men who have sex with men in Northern Italy

The aim of this study was to investigate the epidemiological profile of HPV oropharyngeal infections in HIV-infected men who have sex with men. A total of 135 subjects were enrolled at the L. Sacco University Hospital (Milan, Italy) to evaluate their HPV oropharyngeal infection status at baseline and at a follow-up visit at least 12 months later. HPV DNA was detected from oropharyngeal swabs using an in-house nested PCR that amplifies a segment of the L1 gene. The PCR products were then sequenced and genotyped. A greater percentage of high-risk genotypes was identified compared to low-risk genotypes (13\ub77% vs. 6\ub79%, P < 0\ub705), and two uncommon alpha-HPV genotypes were detected, i.e. HPV-102 and HPV-114. HPV infection prevalence was 24\ub74% and the cumulative incidence was 24\ub71%. During the follow-up period, one case of HPV infection (HPV-33) persisted, while the overall rate of infection clearance was 58\ub73%. HPV oropharyngeal infection was widespread in the cohort examined, and most of the infections were transient and cleared within 12 months. These results may help to clarify the role of HPV in the oropharynx and may also improve our understanding of the need to implement preventive strategies in at-risk populations

Molecular characterization and phylogenetic analysis of human influenza A viruses in three consecutive seasons with different epidemiological profiles

Introduction. Influenza activity and influenza virus circulation were observed in Lombardy (northern Italy) during three con- secutive seasons and the molecular characteristics of circulating viruses analysed to control for introduction of new variants. Methods. The molecular characterization of 38 isolates, namely 20 A/H3N2 and 18 A/H1N1 influenza strains from the 2005/06, 2006/07 and 2007/08 seasons, was performed by sequence analy- sis of the globular head region of the HA protein (HA1 subunit), specific for influenza virus A/H3 and A/H1. Results and discussion. The last three influenza seasons in the study region were characterized by medium-low activity. A typical co-circulation of several variants was shown for A/H3 viruses for approximately two years and were subsequently almost entirely substituted by new emerging variants. Vice versa, A/H1 viruses had a more homogeneous circulation with a single lineage clearly dominating each season. The HA sequences of the A/H3 and the A/H1 viruses isolated in the last three seasons fell into 4 and 3 principal phylogenetic groups, respectively. No evidence of positive or negative selection in the sequence align- ments was observed. Conclusions. Molecular characterization of the influenza viruses in three consecutive seasons highlighted considerable heteroge- neity in their HA sequences. A careful surveillance of genetic changes in the HA1 domain during seasonal influenza epidemics may reveal immune escape and provide early information on newly emerging strains with epidemiologic inference