Relation of salivary cotinine to blood pressure in middle-aged cigarette smokers

BACKGROUND: In laboratory research, nicotine administration is associated with increases in blood pressure. In epidemiologic research, however, the amount of reported cigarette smoking has no consistent relation with blood pressure. The objective of this study was to examine the relation of a nicotine metabolite (salivary cotinine) to systolic and diastolic blood pressure in current smokers being screened for entry to a clinical trial. METHODS AND RESULTS: Data were obtained from 5164 middle-aged cigarette smokers during screening for the Lung Health Study. Multiple linear regression was used to examine the association of salivary cotinine and number of cigarettes smoked per day to systolic and diastolic blood pressure with age, body mass, years of education, alcohol intake, and recent caffeinated beverage use controlled in all analyses. Although smoking frequency was unrelated to blood pressure, salivary cotinine was related to greater systolic blood pressure in both men and women and greater diastolic blood pressure in men. CONCLUSIONS: The association between salivary cotinine and blood pressure in these analyses suggests that long-term nicotine exposure may be related to modest elevations in blood pressure in cigarette smokers.     

International league of associations for rheumatology recommendations for the management of psoriatic arthritis in resource-poor settings

Clinical Rheumatology - Psoriatic arthritis (PsA) is a challenging heterogeneous disease. The European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and...     

Silica vesicles as nanocarriers and adjuvants for generating both antibody and T-cell mediated immune resposes to Bovine Viral Diarrhoea Virus E2 protein

Bovine Viral Diarrhoea Virus (BVDV) is widely distributed in cattle industries and causes significant economic losses worldwide annually. A limiting factor in the development of subunit vaccines for BVDV is the need to elicit both antibody and T-cell-mediated immunity as well as addressing the toxicity of adjuvants. In this study, we have prepared novel silica vesicles (SV) as the new generation antigen carriers and adjuvants. With small particle size of 50 nm, thin wall (∼6 nm), large cavity (∼40 nm) and large entrance size (5.9 nm for SV-100 and 16 nm for SV-140), the SV showed high loading capacity (∼ 250 μg/mg) and controlled release of codon-optimised E2 (oE2) protein, a major immunogenic determinant of BVDV. The in vivo functionality of the system was validated in mice immunisation trials comparing oE2 plus Quil A (50 μg of oE2 plus 10 μg of Quil A, a conventional adjuvant) to the oE2/SV-140 (50 μg of oE2 adsorbed to 250 μg of SV-140) or oE2/SV-140 together with 10 μg of Quil A. Compared to the oE2 plus Quil A, which generated BVDV specific antibody responses at a titre of 10⁴, the oE2/SV-140 group induced a 10 times higher antibody response. In addition, the cell-mediated response, which is essential to recognise and eliminate the invading pathogens, was also found to be higher [1954-2628 spot forming units (SFU)/million cells] in mice immunised with oE2/SV-140 in comparison to oE2 plus Quil A (512–1369 SFU/million cells). Our study has demonstrated that SV can be used as the next-generation nanocarriers and adjuvants for enhanced veterinary vaccine delivery.     

Equations to describe brain size across the continuum of human lifespan

Equations fitting the normative values for gender-specific brain size changes are available. However, these equations do not fit for all age ranges across the human lifespan and particularly have failed to examine the fit across the continuum of prenatal and postnatal human life. We sought to develop a parametric equation that best describes the changes in gender-specific brain size as a function of age across the continuum of prenatal and postnatal human life. Brain weight and brain volume data retrieved from the literature were combined to perform a meta-analysis. Additions to previously published findings included collecting a dataset that spanned the continuum of human lifespan, logarithmic transformation of the data and utilization of the Birch equation. We used Akaike’s Information Criterion (AIC) for quantitative evaluation of the new equations. A total of 2,011 brain weight data points spanning from 10 weeks of fetal gestation to over 90 years of age were retrieved. Using our approach, we developed equations with improved fits and lower or similar AIC values compared to the published equations. The new equations are modifications of the basic Birch model. These equations are the first to describe the gender-specific brain weight changes through the continuum of both prenatal and postnatal human life while achieving a level of accuracy similar to or better than the previous, more age-restricted models. The new equations are improved compared to previously used equations and may be useful to those who study brain development, particularly researchers interested in prenatal and postnatal brain size.     

Platelet activation and hypercoagulability following treatment with porcine factor VIII (HYATE:C)

Activation of platelets and coagulation in vivo was studied in nine patients with hemophilia A and inhibitors to human Factor VIII, prior to and following treatment with porcine Factor VIII (PFVIII; HYATE:C). In addition, six hemophiliac patients were similarly studied after treatment with recombinant Factor VIII (rFVIII). Platelet activation was also examined in vitro using porcine von Willebrand factor (PvWF)-enriched and PvWF-depleted fractions obtained by fractionation of PFVIII. Coagulation was assessed by measuring the concentrations of plasma prothrombin fragment 1+2 concentrations (prothrombinase generation) and Factor Xa-ATIII. Patients treated with PFVIII had significantly increased numbers of circulating platelets expressing CD62 and CD63 (markers of platelet activation) and annexin V (marker of platelet procoagulant activity) compared to patients treated with rFVIII; the former patients also demonstrated an increase in plasma coagulability after therapy. In in vitro experiments it was observed that the platelet-activating and procoagulant capacity of PFVIII resided in the PvWF-enriched fraction, and the same was true for the plasma hypercoagulability following exposure of platelets to PFVIII. These results support the hypothesis that PFVIII-induced platelet activation provides a mechanism for enhancing hemostasis, separate from, and additional to, that due to increased circulating Factor VIII, and it is due to residual PvWF in the PFVIII preparation.     

Effects of EGIS-7625, a Selective and Competitive 5-HT2B Receptor Antagonist

Our aim was to specify the 5-HT(2) subtype selectivity of EGIS-7625 (1-benzyl-4-[(2-nitro-4-methyl-5-amino)-phenyl]-piperazine), a new 5-HT(2B) ligand, in receptor binding studies and characterize its pharmacology at 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors in in vivo experiments and in isolated organs, in vitro. EGIS-7625 had high affinity for recombinant human 5-HT(2B) receptors (pK(i) = 9.0) but much weaker affinity for 5-HT(2A) and 5-HT(2C) receptors (pK(i) = 6.2 and 7.7, respectively). In the classic 5-HT(2B) test, EGIS-7625 produced a concentration-related parallel rightward shift in the concentration-response relationship for the 5-HT-induced smooth muscle constriction in rat stomach fundus strips with a pA(2) of 9.4. On the other hand, EGIS-7625 was a weak competitive antagonist at 5-HT(2A) receptors as it shifted 5-HT-induced concentration-response curves to the right at high concentrations (pA(2) = 6.7) in rabbit pulmonary artery strips. The m-chlorophenylpiperazine-induced hypomotility and hypophagia was only partially attenuated by EGIS-7625 even at a dose of 30 mg/kg i.p. while mianserin, a non-selective 5-HT antagonist was almost fully effective in these tests at 3 mg/kg i.p., suggesting weak antagonistic effect of EGIS-7625 at neuronal 5-HT(2C) receptors, in vivo. In conclusion, EGIS-7625 is a potent, selective and competitive 5-HT(2B) antagonist that seems to be a good research tool for the separation of the functional roles of vascular 5-HT(2A) and 5-HT(2B) receptors.     

The impact of COVID-19 on home,social, and productivity integration of people with chronic traumatic brain injury or stroke living in the community

Compare community integration of people with stroke or traumatic brain injury (TBI) living in the community before and during the coronavirus severe acute respiratory syndrome coronavirus 2 disease (COVID-19) when stratifying by injury: participants with stroke (G1) and with TBI (G2); by functional independence in activities of daily living: independent (G3) and dependent (G4); by age: participants younger than 54 (G5) and older than 54 (G6); and by gender: female (G7) and male (G8) participants.Prospective observational cohort studyIn-person follow-up visits (before COVID-19 outbreak) to a rehabilitation hospital in Spain and on-line during COVID-19.Community dwelling adults (≥18 years) with chronic stroke or TBI.Community integration questionnaire (CIQ) the total-CIQ as well as the subscale domains (ie, home-CIQ, social-CIQ, productivity CIQ) were compared before and during COVID-19 using the Wilcoxon ranked test or paired t test when appropriate reporting Cohen effect sizes (d). The functional independence measure was used to assess functional independence in activities of daily living.Two hundred four participants, 51.4% with stroke and 48.6% with TBI assessed on-line between June 2020 and April 2021 were compared to their own in-person assessments performed before COVID-19.When analyzing total-CIQ, G1 (d = −0.231), G2 (d = −0.240), G3 (d = −0.285), G5 (d = −0.276), G6 (d = −0.199), G7 (d = −0.245), and G8 (d = −0.210) significantly decreased their scores during COVID-19, meanwhile G4 was the only group with no significant differences before and during COVID-19.In productivity-CIQ, G1 (d = −0.197), G4 (d = −0.215), G6 (d = −0.300), and G8 (d = −0.210) significantly increased their scores, meanwhile no significant differences were observed in G2, G3, G5, and G7.In social-CIQ, all groups significantly decreased their scores: G1 (d = −0.348), G2 (d = −0.372), G3 (d = −0.437), G4 (d = −0.253), G5 (d = −0.394), G6 (d = −0.319), G7 (d = −0.355), and G8 (d = −0.365).In home-CIQ only G6 (d = −0.229) significantly decreased, no significant differences were observed in any of the other groups.The largest effect sizes were observed in total-CIQ for G3, in productivity-CIQ for G6, in social-CIQ for G3 and in home-CIQ for G6 (medium effect sizes).Stratifying participants by injury, functionality, age or gender allowed identifying specific CIQ subtotals where remote support may be provided addressing them.     

Drug eluting biliary stents to decrease stent failure rates: A review of the literature

Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.