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The issues and problems of mandatory vaccination policy and roll out in First Nations communities are unique and do not concern the safety and effectiveness of vaccines. These issues are also independent of more specific arguments of mandatory vaccination of healthcare workers as a condition of employment. As important as these issues are, they do not consider the complex politics of ongoing settler colonialism and First Nations community relations. In this paper, we also set aside the very real problems of disinformation, hesitancy, scientific and health illiteracy, and other concerns that drive vaccine hesitancy and refusal. These affect all communities, including First Nations communities. We, instead describe the dominant arguments in favour of mandatory vaccination and critique them in terms of the disputed legitimacy of Settler-Colonial decision-making as it impacts First Nations communities. We contend cultural responsiveness and safety—not state compulsion—must remain the first principles of any engagement—including vaccination—with First Nations Peoples, families, and communities. [ABSTRACT FROM AUTHOR]

Recent investigations of dust-density waves in a dusty plasma under microgravity conditions [ K. O. Menzel et al. Phys. Rev. Lett. 104 235002 (2010)] showed that the wave field consists of distinct regions of different frequencies. These so-called frequency clusters are known from simulations of chains of mutually coupled van der Pol oscillators. The behavior of distinct oscillators adjacent to the cluster boundaries were studied numerically. The interaction of these oscillators leads to periodic frequency pulling, a typical feature of driven van der Pol oscillators that is also observed in our experiments. [ABSTRACT FROM AUTHOR]

Density waves in a dusty plasma emerge spontaneously at low gas pressures and high dust densities. These acousticlike wave modes were studied in a radio-frequency discharge under microgravity conditions. The complex three-dimensional wave pattern shows a spatially varying wavelength that leads to bifurcations, i.e., topological defects, where wave fronts split or merge. The calculation of instantaneous wave attributes from the spatiotemporal evolution of the dust density allows a precise analysis of those structures. Investigations of the spatial frequency distribution inside the wave field revealed that the wave frequency decreases from the bulk to the edge of the cloud in terms of frequency jumps. Between those jumps, regions of almost constant frequency appear. The formation of frequency clusters is strongly correlated with defects that occur exclusively at the cluster boundaries. It is shown that the nonlinearity of the waves has a significant influence on the topology of the wave pattern. [ABSTRACT FROM AUTHOR]

The cathepsins D (CTSD), B (CTSB) and L (CTSL) are important for the intracellular degradation of proteins. Increased cathepsin expression is associated with inflammatory diseases. We have shown previously an induction of CTSD expression in intestinal macrophages (IMAC) in inflamed mucosa of patients with inflammatory bowel disease (IBD). Here we investigated the regulation of CTSB and CTSL in IMAC during IBD and effects of CTSD and CTSB/CTSL inhibition in vivo. Human IMAC were isolated from normal and inflamed mucosa. Reverse transcription–polymerase chain reaction (RT–PCR) was performed for CTSB and CTSL mRNA. Immunostaining was used to confirm PCR results. Cathepsin inhibition was investigated in the dextran–sulphate–sodium (DSS) colitis model in mice with application of pepstatin A (CTSD inhibitor), CA-074 (CTSB inhibitor) and Z-Phe-Tyr-aldehyde (CTSL inhibitor). CTSL mRNA was significantly up-regulated in IMAC isolated from IBD mucosa. Up-regulated protein expression was found mainly in areas of mucosal damage by immunostaining. Inhibition of CTSD in mouse DSS colitis was followed by an amelioration of the disease. Inhibitor-treated mice showed a significant lower histological score (HS) and less colon reduction in comparison to controls. Similarly, simultaneous inhibition of CTSB/CTSL was followed by a significant amelioration of colitis. Expression of tissue-degrading cathepsins is increased in IMAC in IBD. Inhibition of CTSD as well as CTSB/CTSL is followed by an amelioration of experimental colitis. The prevention of mucosal damage by cathepsin inhibition could represent a new approach for the therapy of IBD. [ABSTRACT FROM AUTHOR]

B Background: b The risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. B Conclusion: b Blood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated. [Extracted from the article]

B Background: b The risk assessment of intraductal papillary mucinous neoplasms (IPMN) to either guide patients to surgical resection or watchful waiting is still under debate. B Conclusion: b Blood fibrinogen differed between low and high risk IPMNs and therefore, the use of fibrinogen as an additional discriminator in the pre-operative risk assessment of IPMNs should be further evaluated. [Extracted from the article]

Haem oxygenase-1 (HO-1) up-regulation was suggested to reduce mucosal tissue damage in inflammatory bowel disease (IBD) and an up-regulation of HO-1 expression in patients with Crohn's disease (CD) and ulcerative colitis (UC) was demonstrated. A HO-1 gene promoter microsatellite (GT)n dinucleotide repeat polymorphism was associated with regulation of HO-1 in response to inflammatory stimuli. We therefore hypothesized that IBD patients might segregate into phenotypes with high or low HO-1 inducibility. Ethylenediamine tetraacetic acid blood samples were obtained from 179 CD patients, 110 UC patients and 56 control patients without inflammation. Genomic DNA was purified and the 5′-flanking region of the HO-1 gene containing the (GT)n dinucleotide repeat was amplified. Polymerase chain reaction (PCR) products were purified and the length of the PCR fragments was analysed. The number of (GT)n repeats in the population studied ranged from 13 to 42. The distribution of the allele frequencies was comparable in patients and controls for both the short and the long alleles. The frequencies of short-, middle- and long-sized alleles were not changed among the groups studied. No correlation was found between IBD and microsatellite instability detected in five individals. Our data indicate that (GT)n dinucleotide repeats of the HO-1 promotor region have no significance for the pathophysiology and disease course of IBD. [ABSTRACT FROM AUTHOR]

Recently we demonstrated that in inflammatory bowel disease (IBD) macrophage-oxidative burst activity is increased and NADPH oxidase mRNA is induced. The herbal phenylethanoid acteoside isolated from Plantago lanceolata L. was shown to exhibit anti-oxidative potential. Using the dextran sulphate sodium (DSS)-induced colitis model, in this study we have assessed whether systemic application of acteoside affects colitis. Colitis was induced by DSS in Balb/c mice. Treatment with acteoside (120, 600 µg/mouse/day) was performed intraperitoneally. The colon lengths were determined. Colonic tissue was scored histologically (max. score 8) by a blinded investigator. T cells isolated from mesenteric lymph nodes (MLN) were stimulated with anti-CD3 antibody in the presence of interleukin (IL)-2 (final concentration 10 U/ml). After incubation for 24 h, IL-1β, IL-6, IL-12 tumour necrosis factor (TNF)-α and interferon (IFN)-γ levels in supernatants were analysed by the beadlyte® cytokine detection system. Histological scoring of colonic tissue revealed that application of acteoside was followed by a significantly improved histological score. In acute colitis the histological score was 3·2 with acteoside versus 5·2 with phosphate-buffered saline (PBS) ( P < 0·02). In chronic colitis both 120 µg (3·3 versus 5·2) or 600 µg acteoside (3·0 versus 5·2) significantly ameliorated colitis (both P < 0·02). Stimulated MLN from mice with chronic DSS-induced colitis treated with acteoside showed a significant down-regulation of IFN-γ secretion (195 pg/ml with 600 µg acteoside versus 612 pg/ml with PBS, P < 0·02). Inhibition of oxidative burst activity with acteoside reduced mucosal tissue damage in DSS colitis and could be a therapeutic alternative for IBD treatment. Further studies of this agent are warranted. [ABSTRACT FROM AUTHOR]

Left ventricular assist device (LVAD) implantation and survival is increasing. With patients living longer on device support, LVAD-related healthcare costs and hospitalizations, including those for volume overload, are on the rise as well. The Johns Hopkins Heart Failure Bridge Clinic (HFBC), a HF-trained Nurse Practitioner (NP) led clinic with ability to administer outpatient intravenous (IV) diuretics, has resulted in significant reductions in HF readmission rates. We developed a protocol for LVAD patient assessment and management via the HFBC, and describe our initial experience regarding the role and efficacy of this unique program in outpatient management of HF in LVAD patients. LVAD patients were evaluated by an LVAD provider and subsequently referred to the diuresis clinic for volume overload thought not to be related to an LVAD issue. If seen in the diuresis clinic, patients then had repeat evaluation with the LVAD/HF team within one week. Baseline characteristics and HF outcomes were assessed. Nineteen LVAD patients were seen in the diuresis clinic a total of 65 times. IV furosemide was administered 31 times to 13 patients (mean dose 80 ± 23.5 mg). Urine output during first in clinic void after IV diuretic was 125 ± 53 mL. At 30 of 65 (46%) visits, oral diuretic dose was uptitrated. Potassium was given at 18 of the 65 (27.7%) visits. There were no significant changes in blood pressure, renal function, or electrolytes post diuresis. Only 1 of 65 patient visits resulted in direct hospital admission (hyponatremia). All other visits discharged to home in improved/stable condition and avoidance of hospitalization for heart failure. During follow up, only 6 of 19 patients were hospitalized for a primary diagnosis of volume overload. We describe successful implementation of an outpatient IV diuresis protocol for treatment of HF in LVAD patients. The strategy has major implications in reducing LVAD-related HF hospitalizations and healthcare utilization [ABSTRACT FROM AUTHOR]