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lentus' JLT2010T. Nuciferine ic50 Activities of the lipase, trypsin, α-chymotrypsin and gelatinase and utilization pattern of carbon sources differentiate strain ALE3EIT from M. ophiurae KMM 3046T. The genome of strain ALE3EIT is 3.0 Mbp long and its ANI and AAI values against 'A. lentus' JLT2010T were 76.58 and 72.76, respectively, however, AAI values against members in other genera were lower than 72%. The phylogenomic tree inferred by PhyloPhlAn clearly differentiated the strain ALE3EIT together with strain JLT2010T from other genera in the Falvobacteriaceae. This polyphasic taxonomic data indicates that strain ALE3EIT should be identified as a novel species in the genus 'Altibacter', however, the name has not been validated. Therefore, the strain is classified as a novel genus and is proposed as Constantimarinum furrinae gen. nov., sp. nov. The type strain is ALE3EIT (= KCCM 43303T = JCM 33022T).
Crizotinib was the first oral targeted therapy approved by the US Food and Drug Administration (FDA), on 11 March 2016, for c-ros oncogene 1 (ROS1)-positive advanced non-small-cell lung cancer (NSCLC). Data to support long-term clinical benefit in a real-world setting are limited.
This study aimed to assess real-world clinical outcomes among patients with ROS1-positive advanced NSCLC treated with crizotinib in the US community oncology setting.
We conducted a retrospective cohort study using iKnowMed electronic health record data to identify adult patients with ROS1-positive advanced NSCLC who initiated crizotinib between 17 January 2013 (time of the addition of crizotinib for ROS1-positive NSCLC to National Comprehensive Cancer Network (NCCN) treatment guidelines) and 1 June 2019 with a potential follow-up period through 1 December 2019. Patient characteristics were assessed descriptively. Kaplan-Meier analyses were used to evaluate time to treatment discontinuation (TTD), time to next treatment (TTNT)oorer ECOG performance status than those investigated in clinical trials. Nevertheless, our findings support the clinical benefit of crizotinib in this patient population with ROS1-positive advanced NSCLC.
This ROS1-positive NSCLC real-world population was older and had a higher proportion of smokers and of patients with poorer ECOG performance status than those investigated in clinical trials. Nevertheless, our findings support the clinical benefit of crizotinib in this patient population with ROS1-positive advanced NSCLC.
Data have suggested that SARS-CoV-2 infection causes an antibody response at least as strong as one BNT162b2 vaccine dose. Nevertheless, some aspects require further investigation to better understand the immunogenicity of one vaccine dose among infected individuals. Thus, we evaluated how previous SARS-CoV-2 infection may influence the humoral immunity after a single Pfizer BNT162b mRNA vaccine dose in a sample of healthcare workers (HCWs).
As part of the routine surveillance activity conducted among HCWs of the Policlinico Riuniti Foggia Hospital (Apulia region, Italy), we conducted a retrospective serosurvey in the period January-March 2021. We compared specific antibody titres (anti-spike IgGs measured by enzyme-linked immunoassay, ELISA) after SARS-CoV-2 infection and after the first dose of the BNT162b2 vaccine, analysing the impact of sex, age, time since infection, and presence of symptoms on the humoral response.
We included in the study 58 HCWs (mean age 44.1years, 48.2% male) with anti-spike ion of protection in this group can be drawn from our study.Positron emission tomography (PET) provides a unique tool to study the biochemistry of the human brain in vivo. By using PET probes that are binding selectively to certain receptor subtypes, brain PET allows the quantification of receptor levels in various brain areas of human subjects. This approach has the potential to reveal abnormal receptor expressions that may contribute to the physiopathology of some psychiatric and neurological disorders. This approach also has the potential to assist in the drug development process by determining receptor occupancy in vivo allowing selection of proper drug dosage to produce therapeutic effects. Several PET tracers have been developed for histamine H3 receptors (H3R). However, despite the potential of PET to elucidate the role of H3R in vivo, only limited work has been conducted so far. This article reviews the work that has been done in this area. Notably, we will cover the limitations of the first-generation PET radioligand for H3R and present the advantages of novel radioligands that promise an explosion of clinical PET research on the role of H3R in vivo.The evaluation and treatment of patients with epilepsy is not limited to the type of epilepsy, but it must incorporate the common comorbid neurologic, psychiatric, and medical disorders, as the latter can bare an impact on the course and response to treatment of the seizure disorder and vice versa. In this article we review the bidirectional relations among epilepsy and two of its most common comorbidities, mood disorders and migraine and examine the implications of these relations on the selection of therapies of these three disorders and their response to treatment. We also review the most salient common pathogenic mechanisms that may explain such relations.The urge to seek and consume excessive alcohol is intensified by prior experiences with social stress, and this cascade can be modeled under systematically controlled laboratory conditions in rodents and non-human primates. Adaptive coping with intermittent episodes of social defeat stress often transitions to maladaptive responses to traumatic continuous stress, and alcohol consumption may become part of coping responses. At the circuit level, the neural pathways subserving stress coping intersect with those for alcohol consumption. Increasingly discrete regions and connections within the prefrontal cortex, the ventral and dorsal striatum, thalamic and hypothalamic nuclei, tegmental areas as well as brain stem structures begin to be identified as critical for reacting to and coping with social stress while seeking and consuming alcohol. Several candidate molecules that modulate signals within these neural connections have been targeted in order to reduce excessive drinking and relapse. In spite of some early clinical failures, neuropeptides such as CRF, opioids, or oxytocin continue to be examined for their role in attenuating stress-escalated drinking. Recent work has focused on neural sites of action for peptides and steroids, most likely in neuroinflammatory processes as a result of interactive effects of episodic social stress and excessive alcohol seeking and drinking.Anhedonia is frequently observed among individuals with eating disorders (ED), though its relevance to ED pathology and clinical outcomes remain poorly understood. This chapter will present the latest findings regarding anhedonia in ED, with the majority of data available for anorexia nervosa (AN) and bulimia nervosa (BN). We consider anhedonia from the mechanistic lens of altered reward processing, with attention given to subjective experience, neurotransmitter function, neural correlates, and cognitive performance corresponding to distinct components of reward (i.e., liking, wanting, and learning). Findings from animal models are also highlighted. The chapter concludes with a discussion of implications for treatment and future directions aimed at better understanding anhedonia in ED.
Quality assurance review is an integral part of point-of-care ultrasound (POCUS) programs but may not be routine practice in community hospitals. Lack of image acquisition and documentation can result in suboptimal patient care. In cases with an adverse outcome and no record of images, there is no mechanism for quality improvement.
Our goal was to implement a system of POCUS image archiving in a community hospital. Our SMART (Specific, Measurable, Actionable, Realistic, Timely) aim was to have > 50% of emergency department (ED) POCUS users archiving scans, and > 80% of all billed POCUS scans archived, measuring improvements bi-weekly over a period of 9months.
The study was conducted at a single-community ED between August 2020 and April 2021. The POCUS archiving workflow was developed and refined through multiple plan-do-study-act (PDSA) cycles. Surveys, stakeholder meetings, audits, and feedback were used to generate and re-evaluate the interventions. These included introduction of QPathE© softwain a Canadian Community ED.
Tumour hypoxia promotes an aggressive tumour phenotype and enhances resistance to anticancer treatments. Following the recent observation that the mitochondrial inhibitor atovaquone increases tumour oxygenation in NSCLC, we sought to assess whether atovaquone affects tumour subregions differently depending on their level of hypoxia.
Patients with resectable NSCLC participated in the ATOM trial (NCT02628080). Cohort 1 (n = 15) received atovaquone treatment, whilst cohort 2 (n = 15) did not. Hypoxia-related metrics, including change in mean tumour-to-blood ratio, tumour hypoxic volume, and fraction of hypoxic voxels, were assessed using hypoxia PET imaging. Tumours were divided into four subregions or distance categories edge, outer, inner, and centre, using MATLAB.
Atovaquone-induced reduction in tumour hypoxia mostly occurred in the inner and outer tumour subregions, and to a lesser extent in the centre subregion. Atovaquone did not seem to act in the edge subregion, which was the only tumour subregion that was non-hypoxic at baseline. Notably, the most intensely hypoxic tumour voxels, and therefore the most radiobiologically resistant areas, were subject to the most pronounced decrease in hypoxia in the different subregions.
This study provides insights into the action of atovaquone in tumour subregions that help to better understand its role as a novel tumour radiosensitiser.
ClinicalTrials.gov, NCT0262808. Registered 11th December 2015, https//clinicaltrials.gov/ct2/show/NCT02628080.
ClinicalTrials.gov, NCT0262808. Registered 11th December 2015, https//clinicaltrials.gov/ct2/show/NCT02628080.
Systematic and structural inequities in power and privilege create differential attainment whereby differences in average levels of performance are observed between students from different socio-demographic groups. This paper reviews the international evidence on differential attainment related to ethnicity/race in medical school, drawing together the key messages from research to date to provide guidance for educators to operationalize and enact change and identify areas for further research.
Authors first identified areas of conceptual importance within differential attainment (learning, assessment, and systems/institutional factors) which were then the focus of atargeted review of the literature on differential attainment related to ethnicity/race in medical education and, where available and relevant, literature from higher education more generally. Each author then conducted areview of the literature and proposed guidelines based on their experience and research literature. The guidelines were iterat within our medical schools, particularly related to inequity in teaching and learning.
Differential attainment related to ethnicity/race is a complex, systemic problem reflective of unequal norms and practices within broader society and evident throughout assessment practices, the learning environment and student experiences at medical school. Currently, the strongest empirical evidence is around assessment processes themselves. There is emerging evidence of minoritized students facing discrimination and having different learning experiences in medical school, but more studies are needed. There is a pressing need for research on how to effectively redress systemic issues within our medical schools, particularly related to inequity in teaching and learning.