The LRRK2 p.G2019S Parkinson's disease (PD) variant is associated with elevated glucocerebrosidase (GCase) activity in peripheral blood. We aimed to evaluate the association of other LRRK2 variants with PD and its association with GCase activity. LRRK2 and GBA were fully sequenced in 1123 PD patients and 576 controls from the Columbia and PPMI cohorts, in which GCase activity was measured in dried blood spots by liquid chromatography-tandem mass spectrometry. LRRK2 p.M1646T was associated with increased GCase activity in the Columbia University cohort (β = 1.58, p = 0.0003), and increased but not significantly in the PPMI cohort (β = 0.29, p = 0.58). p.M1646T was associated with PD (odds ratio = 1.18, 95% confidence interval = 1.09-1.28, p = 7.33E-05) in 56,306 PD patients and proxy-cases, and 1.4 million controls. Our results suggest that the p.M1646T variant is associated with risk of PD with a small effect and with increased GCase activity in peripheral blood.The solute carrier (SLC) transporters have been suggested to play important roles in neurodegenerative disorders. Recently, seven SLC transporters were identified to be associated with Parkinson's disease (PD) by genome-wide association studies. However, few replications were conducted, and whether rare variants in these genes were associated with PD was not explored yet. To elucidate the genetic associations of these SLCs with PD, we investigated the rare variants in 743 Chinese early-onset PD (EOPD) patients using whole-exome sequencing, and evaluated the association between rare variants and PD at allele and gene levels. Totally, 58 rare variants were identified in SLC50A1, SLC41A1, SLC45A3, SLC44A4, SLC56A2, SLC2A13 and SLC38A1. At allele level, 6 variants were nominally associated with PD, namely p.S423G in SLC45A3, p.I551V, p.T435S, p.R323C and p.V101M in SLC2A13, and p.R285Q in SLC41A1. Gene-based burden analysis showed enrichment of rare variants of SLC2A13 in EOPD. Our study systematically analyzed the genetic involvement of SLCs in EOPD, identified SLC2A13 as a risk gene for PD, and broadened the current mutation spectrum of PD. In December 2019, SARS-CoV-2, was discovered as the agent of COVID-19 disease. Cardiac arrhythmias have been reported as frequent but their incidence is unknown. The aim of this research was to assess the real incidence of cardiac arrhythmias among COVID-19 patients admitted to Portuguese hospitals and to understand the underlying prognostic implications. The Portuguese Association of Arrhythmology, Pacing and Electrophysiology (APAPE) conducted a survey in Portuguese hospitals to assess the occurrence of arrhythmias in COVID-19 patients, their clinical characteristics, the use of experimental therapies and the impact on QT interval. Twenty hospitals participated, reporting 692 hospitalized patients. An arrhythmic episode occurred in 81 (11.7%) and 64 (79%) had detailed information on these episodes. New onset arrhythmias occurred in 41 (64%) patients, 45 (70.3%) male, median age 73.5 (61-80.3) years. https://www.selleckchem.com/ There were 51 (79.7%) with associated comorbidities, mainly arterial hypertension (41, 64.1%). Of 53 paltiple organ failure. Regardless of the use of experimental drugs, the incidence of ventricular arrhythmias is low and atrial fibrillation and other supraventricular arrhythmias are the most prevalent arrythmias.Treatment with buprenorphine significantly reduces both all-cause and overdose mortality among individuals with opioid use disorder. Offering buprenorphine treatment to individuals who experience a nonfatal opioid overdose represents an opportunity to reduce opioid overdose fatalities. Although some emergency departments (EDs) initiate buprenorphine treatment, many individuals who experience an overdose either refuse transport to the ED or are transported to an ED that does not offer buprenorphine. Emergency medical services (EMS) professionals can help address this treatment gap. In this Concepts article, we describe the federal legal landscape that governs the ability of EMS professionals to administer buprenorphine treatment, and discuss state and local regulatory considerations relevant to this promising and emerging practice. Third-generation cephalosporin-resistant (3GCR) Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis (EKP) are an increasingly common cause of community-onset urinary tract infections (UTIs) in the United States. The 3GCR antimicrobial resistance pattern in these Enterobacterales species is most commonly due to production of extended-spectrum β-lactamases. We sought to provide contemporary, emergency department (ED)-focused data on 3GCR-EKP UTI regional prevalence, presentation, antibiotic susceptibility, and empiric treatment patterns, and outcomes. We performed a retrospective cohort study of all adults admitted with a febrile UTI at 21 Kaiser Permanente Northern California EDs between January 2017 and June 2019. Inclusion criteria included fever; admitting diagnosis of UTI, pyelonephritis, or sepsis; and ED urine culture with greater than 100,000 colony-forming units/mL of an EKP species. 3GCR was defined as invitro resistance to ceftriaxone, ceftazidime, or both. 3GCR-EKP cases were comparedalization were caused by 3GCR-EKP, and in these cases, initial empiric therapy was often discordant with antimicrobial susceptibility testing. 3GCR-EKP infections were associated with a longer hospital length of stay and higher 90-day mortality. Similar data from other regions and for outpatient UTIs are needed. Achieving universal immunization coverage and reaching every child with life-saving vaccines will require the implementation of pro-equity immunization strategies, especially in poorer countries. Gavi-supported countries continue to implement and report strategies that aim to address implementation challenges and improve equity. This paper summarizes the first mapping of these strategies from country reports. Thirteen Gavi-supported countries were purposively selected with emphasis on Gavi's priority countries. Following a scoping of different documents submitted to Gavi by countries, 47 Gavi Joint Appraisals (JAs) for the period 2016-2019 from the 13 selected countries were included in the mapping. We used a consolidated framework synthesized from 16 different equity and health systems frameworks, which incorporated UNICEF's coverage and equity assessment approach - an adaptation of the Tanahashi model. Using search terms, the mapping was conducted using a combination of manual search and the MAXQDA qualitative analysis tool.