Discovery and Rational Mutagenesis of Methionine Sulfoxide Reductase Biocatalysts To Expand the Substrate Scope of the Kinetic Resolution of Chiral Sulfoxides

Methionine sulfoxide reductase A (MsrA) enzymes have recently found applications as nonoxidative biocatalysts in the enantioselective kinetic resolution of racemic sulfoxides. This work describes the identification of selective and robust MsrA biocatalysts able to catalyze the enantioselective reduction of a variety of aromatic and aliphatic chiral sulfoxides at 8–64 mM concentration with high yields and excellent ees (up to 99%). Moreover, with the aim to expand the substrate scope of MsrA biocatalysts, a library of mutant enzymes has been designed via rational mutagenesis utilizing in silico docking, molecular dynamics, and structural nuclear magnetic resonance (NMR) studies. The mutant enzyme MsrA33 was found to catalyze the kinetic resolution of bulky sulfoxide substrates bearing non-methyl substituents on the sulfur atom with ees up to 99%, overcoming a significant limitation of the currently available MsrA biocatalysts

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Il capitale relazionale nei rapporti con le amministrazioni pubbliche

Il contributo analizza le metodologie di analisi delle attività svolte dalle università declinate sulla valorizzazione del capitale relazionale, uno degli elementi fondanti del capitale intellettuale, in considerazione dell’importanza che esso riveste nella terza missione universitaria

Unusual Osteoblastic Secondary Lesion as Predominant Metastatic Disease Spread in Two Cases of Uterine Leiomyosarcoma

Uterine smooth muscle tumors range from benign leiomyomata to low- and high-grade leiomyosarcomas. A leiomyosarcoma is a rare malignant smooth muscle tumor that infrequently metastasizes to the bone. In fact, initial presentation or recurrence as osseous metastases is extremely uncommon in patients with a history of leiomyosarcoma. On imaging, these bone lesions generally appear as lytic foci. The authors report here two cases of osteoblastic bone lesions in leiomyosarcoma of the uterus with predominant metastatic lesions localized in the bone

The treatment of irreparable massive rotator cuff tears with inspace balloon: rational and medium-term results

The treatment of irreparable massive rotator cuff tears (MIRCTs) represents a challenge for the orthopedic surgeon both for the affected population and for the intrinsic characteristics of the injury. There are different types of treatment ranging from bursectomy to reverse shoulder prosthesis and subacromial spacers. The aim of the work is to establish the clinical and functional improvement of patients treated with subacromial spacer

Short-term clinical and radiological comparisons between two Medial Pivot Total Knee Arthroplasty implants with different geometries

Background and aim: Different total knee arthroplasty (TKA) implants were created for the treatment of severe symptomatic gonarthrosis and Medial Pivot TKA (MP TKA) seem to reproduce the normal kinematics of the knee. We compare two different prosthetic designs of MP TKA in order to identify whether there is a difference between the two in terms of degree of patient satisfaction. &nbsp;Methods: A total of 89 patients were analyzed. A group of 46 patients who benefited from a TKA with the Evolution® prosthesis and one of 43 patients who received a TKA with the Persona® prosthesis. KSS, OKS, FJS and the ROM were analyzed at follow up. Results: The values of KSS and OKS were similar between the two groups (p&gt;0,05). Our statistical analysis revealed a statistically significant increase (p &lt;0.05) in ROM in the Persona® group and in FJS in the Evolution® group. No radiolucent lines were observed in both groups at the radiological final follow-up. &nbsp;Conclusions: MP TKA models analysed are a valuable tool to achieve satisfactory clinical outcomes. This study demonstrates that the FJS is an important score for the evaluation of patient's satisfaction: a ROM's limitation can be accepted by the patient in exchange for a more natural perceived knee