Why Our Next President May Keep His or her Senate Seat: A Conjecture on the Constitution’s Incompatibility Clause

Heart diseases are common and significant contributors to worldwide mortality and morbidity. During recent years complement mediated inflammation has been shown to be an important player in a variety of heart diseases. Despite some negative results from clinical trials using complement inhibitors, emerging evidence points to an association between the complement system and heart diseases. Thus, complement seems to be important in coronary heart disease as well as in heart failure, where several studies underscore the prognostic importance of complement activation. Furthermore, patients with atrial fibrillation often share risk factors both with coronary heart disease and heart failure, and there is some evidence implicating complement activation in atrial fibrillation. Moreover, Chagas heart disease, a protozoal infection, is an important cause of heart failure in Latin America, and the complement system is crucial for the protozoa-host interaction. Thus, complement activation appears to be involved in the pathophysiology of a diverse range of cardiac conditions. Determination of the exact role of complement in the various heart diseases will hopefully help to identify patients that might benefit from therapeutic complement intervention

RAMSTRONG: AN EMPLOYEE WELLNESS INITIATIVE

The RAMSTRONG project’s mission is to create a mobile website accessible online and through the VCU Mobile app that provides VCU employees with user-friendly, accessible resources to support their holistic well-being. The RAMSTRONG project seeks to meet three basic needs. First, while VCU and the Greater Richmond area offer a plethora of resources to promote health, information about these resources is not readily accessible, and especially not accessible from one website or mobile app. RAMSTRONG aims to provide an accessible means for employees to learn about and take advantage of these resources. Second, while a growing body of scientific literature indicates employer sponsored health promotion programs increase job satisfaction, productivity, and retention, these programs are only effective if they are utilized. RAMSTRONG aims to increase their utilization by promoting awareness of their availability. Third, our society invests a substantial sum of resources to the care of those suffering from injury and illness and less to promoting our health and well-being. The RAMSTRONG project is motivated by a vision of a society that invests significantly in the promotion of wellness so as to reduce the incidence of injury and illness and to increase the prevalence of personal and social satisfaction at work and in life. Our model for the RAMSTRONG app draws from the public health concept of the Wheel of Wellness, which specifies eight interrelated and interdependent dimensions of health: emotional, environmental, financial, social, spiritual, occupational, physical, and intellectual. When a person can demonstrate strength and well-being in each of these areas, they are more productive and receive greater satisfaction in life. Universities, including Princeton University, that have implemented similar website resources and the National Wellness Institute define wellness as “an active process through which people become aware of, and make choices toward, a more successful existence”. Our RAMSTRONG website and mobile app will provide employees with an efficient, friendly means for becoming aware of campus and community resources and making choices that actively contribute to individual and community well-being in each of the eight dimensions. It is our hope that with the implementation of this project, VCU employees will have the resources to take charge of their wellness in each dimension and become RAMSTRONG

Hvordan kan pårørendes omsorgsbelastning identifiseres og begrenses i forbindelse med hjemmeboende personer med demens?

Bakgrunn: Pårørende spiller en essensiell rolle for hjemmeboende pasienter med en demensdiagnose. I dag lever rundt 101 000 personer i Norge med demens, og innen år 2050 er det forventet mer enn det dobbelte. Dette er hovedsakelig på grunn av økende antall eldre mennesker i samfunnet. To tredeler av dem som lever med demens i Norge i dag, bor hjemme og det kan derfor antas at de hjemmeboende demente personene er en økende gruppe i samfunnet i fremtiden (Folkehelseinstituttet, 2021). Dette vil kunne medføre et enda større omsorgs trykk på pasientens pårørende. Ettersom vi mennesker er forskjellige, håndterer vi også omsorgsbelastning forskjellig. Det er viktig at pårørende til hjemmeboende pasienter med demens håndterer omsorgsbelastningen på best mulig måte. Dersom omsorgsbelastningen blir for stor, kan det gå utover omsorgen og pleien til pasienten samt den pårørendes psykososiale behov. Hensikt: Hensikten med denne oppgaven var å undersøke om det finnes faktorer som kan bidra i å forklare omsorgsbyrden som pårørende til hjemmeboende pasienter med demens opplever. Eventuelt hvilke tiltak som kan settes inn for å lette byrden til de pårørende. Metode: Metoden som er brukt i denne oppgaven er en integrativ litteraturstudie. Den baserer seg på fem forskningsartikler, som belyser ulike sider av pårørendeperspektivet til hjemmeboende personer med demens. Artiklene er basert på både kvantitative og kvalitative metoder, og er fagfellevurdert. Resultater: Resultatene viser at det finnes flere faktorer som bidrar til å øke omsorgsbelastningen for pårørende med et omsorgsansvar. Disse deles inn i underkategoriene: sosiodemografiske faktorer, familiedynamikk og dens påvirkning i tillegg til indre faktorer hos den pårørende. Samtidig finnes det ulike tiltak som kan bidra å redusere belastningen. Disse fokuserer hovedsakelig på individualiserte tiltak som skal redusere sosial isolasjon og dårlig psykisk helse hos den pårørende. Nøkkelord: Demens, pårørende, hjemmeboende pasienter og omsorgsbelastning

Influenza Adverse Events in Patients with Rheumatoid Arthritis, Ulcerative Colitis, or Psoriatic Arthritis in the Tofacitinib Clinical Development Programs

Gripe; Artritis psoriásica; Colitis ulcerosaInfluenza; Psoriatic arthritis; Ulcerative colitisGrip; Artritis psoriàsica; Colitis ulcerosaIntroduction This post hoc analysis evaluated influenza adverse events (AEs) across rheumatoid arthritis (RA), ulcerative colitis (UC), and psoriatic arthritis (PsA) tofacitinib clinical programs. Methods Available data from phase 1, randomized phase 2/3/3b/4 clinical trials (completed by 2018), and long-term extension (LTE) studies (up to May 2019) in patients with RA, UC, and PsA were included [randomized or Overall (phase 1–3b/4 and LTE studies) tofacitinib cohorts]. Incidence rates (IRs; events per 100 patient-years) of combined influenza AEs (seasons 2004/2005 to 2018/2019) were analyzed, including by tofacitinib dose [5 or 10 mg twice daily (BID)] and age (< 65 versus ≥ 65 years). Logistic regression models evaluated risk factors for influenza AEs in the RA Overall tofacitinib cohort. Results In randomized cohorts, combined influenza AE IRs were generally similar across tofacitinib, adalimumab, methotrexate, and placebo groups, across indications. Among Overall tofacitinib cohorts, combined influenza AE IRs with tofacitinib 5/10 mg BID, respectively, were higher in the UC (3.66/5.09) versus RA (2.38/2.19) and PsA (1.74/1.29) cohorts. IRs were generally similar across tofacitinib dose and age groups. Most influenza AEs were nonserious and did not require changes to tofacitinib treatment. Significant risk factors for influenza AEs in patients with RA were geographic region, baseline oral corticosteroid and methotrexate use, and tofacitinib dose. Conclusions In the RA, UC, and PsA clinical programs, combined influenza AE IRs were highest in UC, while in each indication they were generally similar across tofacitinib, placebo, and comparator groups. Influenza AEs were predominantly nonserious and not associated with changes to tofacitinib treatment.This study was sponsored by Pfizer. Medical writing support was funded by Pfizer. The journal’s Rapid Service Fee for this article was also funded by Pfizer

The early transcriptomic response to interleukin 1β and interleukin 33 in rat neonatal cardiomyocytes

In the heart, inflammatory cytokines including interleukin (IL) 1β are implicated in regulating adaptive and maladaptive changes, whereas IL33 negatively regulates cardiomyocyte hypertrophy and promotes cardioprotection. These agonists signal through a common co-receptor but, in cardiomyocytes, IL1β more potently activates mitogen-activated protein kinases and NFκB, pathways that regulate gene expression. We compared the effects of external application of IL1β and IL33 on the cardiomyocyte transcriptome. Neonatal rat cardiomyocytes were exposed to IL1β or IL33 (0.5, 1 or 2h). Transcriptomic profiles were determined using Affymetrix rat genome 230 2.0 microarrays and data were validated by quantitative PCR. IL1β induced significant changes in more RNAs than IL33 and, generally, to a greater degree. It also had a significantly greater effect in downregulating mRNAs and in regulating mRNAs associated with selected pathways. IL33 had a greater effect on a small, select group of specific transcripts. Thus, differences in intensity of intracellular signals can deliver qualitatively different responses. Quantitatively different responses in production of receptor agonists and transcription factors may contribute to qualitative differences at later times resulting in different phenotypic cellular responses

Comparative Analysis of Hematology Results From the IDEXX ProCyte Dx™ Hematology Analyzer and the ADVIA® 2120i Hematology System

Mange klinikker benytter resultater fra egne hematologi-maskiner for å diagnostisere og behandle pasienter, og vi ønsket å undersøke om resultatene man får samsvarer med resultater fra et referanselaboratorium. Tidligere studier har indikert at inspeksjon av cytogram og stjernemarkeringer er viktig for å avvise blodprøver som kan gi ukorrekte resultater. I denne studien ble 99 blodprøver fra hunder analysert med IDEXX- ProCyte Dx™ Hematology Analyzer og ADVIA 2120i Hematologi System ved Veterinærhøgskolen NMBU. ProCyte WBC-cytogram og stjernemarkeringer ble vurdert for alle prøver, og en manuell differensialtelling av leukocytter ble utført på 17 prøver. Statistisk analyse ble utført før og etter inspeksjon av cytogrammer. Resultatene viste at differensialtelling av leukocytter samsvarte bedre dersom prøver med uakseptable leukocyttpopulasjoner og/eller stjernemarkeringer fra ProCyte ble eliminert. Blodutstryk kan brukes for å bekrefte automatiserte resultater og vurdere cellemorfologi. Det ble sett en trend der ProCyte feilklassifiserte nøytrofile som lymfocytter og/eller monocytter hos pasienter med systemisk inflammasjon. Både ProCyte og ADVIA anga en falsk trombocytopeni i flere blodprøver på grunn av plateaggregater. Et lavt platetall må verifiseres ved å vurdere et blodutstryk. Bias var minimal til moderat ved analyse av RBC, HGB og HCT, som indikerer at klinikeren kan stole på disse verdiene

Avoiding shellfish toxicity by lowering mussel plant below the pycnocline

In recent years, diarrhetic shellfish poison due to toxic dinoflagellates has been a threat against the developing mussel industry in southern Norway. A raft of catamaran type equipped with hydraulic winch and frames for suspension of mussels was constructed. The frames could be lowered and raised separately and also raised 3 m above the sea surface for destroying predators and fouling organisms. Total capacity of the raft is 15 tons of mussels. Toxic mussels, which in June were lowered below the pycnocline to 30 m depth where Dinophysis spp. occurred in low numbers only, stayed toxic until December. The meat content decreased gradually during this period, but increased when the mussels were raised to the surface water. It is concluded that due to low temperature and poor nutrient conditions in subsurface water, the activity of the mussels was low and they kept the toxins as a result of low metabolic rate. NORSK SAMMENDRAG. I senere år har diarefremkallende skjellgift forårsaket av giftige dinoflagellater vært en trussel mot utvikling av blåskjellindustri i Sør-Norge. For i perioder å kunne senke blåskjell til dyp med bare små mengder giftige alger ble det bygget en flåte av katamarankonstruksjon forsynt med hydraulisk vinsj og rammer for oppheng av blåskjell. Rammene kunne senkes og heves enkeltvis i sjøen og også løftes over vannflaten for å kunne inspisere skjellene og for å kvitte seg med begroingsorganismer og beitere som f.eks. sjøstjerner. Flåten har kapasitet til å bare ca 15 tonn blåskjell. I juni ble en ramme med giftige blåskjell senket til 30 m dyp, d.v.s. under overflatelaget hvor potensielt toksiske dinoflagellater av slekten Dinophysis vanligvis finnes. De skjellene forble giftige i 6 måneder. Kondisjonen avtok delvis og skjellene fikk i løpet av sommeren dårlig kvalitet og var ikke brukelige til konsum. Etter at skjellene ble hevet til overflaten i oktober, økte matinnholdet raskt. På grunn av lav temperatur og lavt innhold av næringspartikler i dypvannet ble skjellenes stoffskifte lavt. Dette gjorde at skjellene forble giftige lenge

Homologous Recombination Deficiency Across Subtypes of Primary Breast Cancer

Homologous recombination; Primary breast cancerRecombinació homòloga; Càncer de mama primariRecombinación homóloga; Cáncer de mama primarioPURPOSE Homologous recombination deficiency (HRD) is highly prevalent in triple-negative breast cancer (TNBC) and associated with response to PARP inhibition (PARPi). Here, we studied the prevalence of HRD in non-TNBC to assess the potential for PARPi in a wider group of patients with breast cancer. METHODS HRD status was established using targeted gene panel sequencing (360 genes) and BRCA1 methylation analysis of pretreatment biopsies from 201 patients with primary breast cancer in the phase II PETREMAC trial (ClinicalTrials.gov identifier: NCT02624973). HRD was defined as mutations in BRCA1, BRCA2, BRIP1, BARD1, or PALB2 and/or promoter methylation of BRCA1 (strict definition; HRD-S). In secondary analyses, a wider definition (HRD-W) was used, examining mutations in 20 additional genes. Furthermore, tumor BRCAness (multiplex ligation-dependent probe amplification), PAM50 subtyping, RAD51 nuclear foci to test functional HRD, tumor-infiltrating lymphocyte (TIL), and PD-L1 analyses were performed. RESULTS HRD-S was present in 5% of non-TNBC cases (n = 9 of 169), contrasting 47% of the TNBC tumors (n = 15 of 32). HRD-W was observed in 23% of non-TNBC (n = 39 of 169) and 59% of TNBC cases (n = 19 of 32). Of 58 non-TNBC and 30 TNBC biopsies examined for RAD51 foci, 4 of 4 (100%) non-TNBC and 13 of 14 (93%) TNBC cases classified as HRD-S had RAD51 low scores. In contrast, 4 of 17 (24%) non-TNBC and 15 of 19 (79%) TNBC biopsies classified as HRD-W exhibited RAD51 low scores. Of nine non-TNBC tumors with HRD-S status, only one had a basal-like PAM50 signature. There was a high concordance between HRD-S and either BRCAness, high TIL density, or high PD-L1 expression (each P < .001). CONCLUSION The prevalence of HRD in non-TNBC suggests that therapy targeting HRD should be evaluated in a wider breast cancer patient population. Strict HRD criteria should be implemented to increase diagnostic precision with respect to functional HRD.Supported by unrestricted grants from The K.G. Jebsen Foundation [SKGJ-MED-020 to H.P.E., S.K., P.E.L.], Helse Vest [912008 to P.E.L.], The Norwegian Research Council [273354 to P.E.L.] and The Norwegian Cancer Society [190281-2017 to S.K., 190275-2017 to P.E.L.]. Research funding was provided by Grieg Foundation (to H.P.E. and T.A.), Helse Vest [912252; Clinical researcher fellowship to H.P.E.], Generalitat de Catalunya [PERIS, SLT017/20/000081 to A.H.R.], “la Caixa” Foundation and European Institute of Innovation and Technology/Horizon 2020 [LCF/TR/CC19/52470003 to A.L.G.], Asociación Española Contra el Cáncer [AECC, INVES20095LLOP to A.L.G.], Generalitat de Catalunya (PERIS Fellowship SLT002/16/00477 to A.L.G.) ERA PerMed [2019-215 to V.S.] and Miguel Servet fellowship (CPII19/00033 to V.S.). Additional funding and study medication was provided by Illumina [grant number 9529854], Pfizer [WI206347] and AstraZeneca [ESR-14-10077] to H.P.E., S.K., P.E.L

IL-18 and IL-18 binding protein are related to disease severity and parasitemia during falciparum malaria

Background - Several inflammatory molecules participate in the immune response to malaria. Interleukin (IL)-18 is an inflammatory cytokine activated by NLRP3 inflammasomes. In clinical falciparum malaria, with and without HIV co-infection, data on IL-18 and in particular on its binding protein, IL-18bp, is scarce. Methods - Clinical data and blood samples were collected from adults in Mozambique with P. falciparum infection, with (n = 70) and without (n = 61) HIV co-infection, from HIV-infected patients with similar symptoms without malaria (n = 58) and from healthy controls (n = 52). In vitro studies were performed in endothelial cells using hemozoin crystals. Results - (i) IL-18 and IL-18bp were markedly up-regulated during falciparum malaria with particular high levels in malaria patients co-infected with HIV and severe malaria disease. (ii) In the malaria group as a whole, both IL-18 and IL-18bp were positively correlated with disease severity, parasitemia, and endothelial cell activation as assessed by vWF in plasma. (iii) Whereas there was no change in IL-18 levels in malaria patients co-infected with HIV during follow-up, the patients with malaria only had slightly increased IL-18 levels. Further, the IL-18pb levels declined and thereby contributed to an increase in IL-18/IL-18bp ratio in all subgroups of malaria patients. (iv) IL-27, previously shown to be up-regulated in this malaria cohort, markedly induced a release of IL-18bp from endothelial cells in vitro, and notably, this presumably anti-inflammatory effect was counteracted by hemozoin. Conclusions - Our findings suggest that the IL-18 system could be an important mediator in the immune pathogenesis during falciparum malaria, potentially also representing a target for therapy

Plasma tumour necrosis factor correlates with mRNA expression of tumour necrosis factor and mitochondrial transcription factors in skeletal muscle in patients with chronic heart failure treated with cardiac resynchronization therapy: potential role in myopathy

Chronic heart failure (CHF) is characterized by inflammation and skeletal muscle myopathy, including impaired fibre type distribution and reduced capillary density, reduced cytochrome oxidase activity and reduced mitochondrial density. The myopathy is associated with activation of the interleukin-6–C-reactive protein pathway and the prototypical inflammatory cytokine tumour necrosis factor (TNF) with alterations in the mRNA expression of enzymes essential in mitochondrial biogenesis. Central in this process are peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nicotinamide phosphoribosyltransferase (NAMPT), nicotinamide adenine dinucleotide and mitochondrial transcription factor (TFAM). The covariance over time between plasma levels of TNF and skeletal muscle mRNA expression of this pro-inflammatory cytokine, and the correlation between TNF and mRNA expression of enzymes essential in mitochondrial biogenesis and skeletal muscle pathology has not previously been evaluated in patients with CHF on stable medical treatment. The methods have been described previously and are briefly presented here.acceptedVersio