Increased activity of MAPKAPK2 within mesenchymal cells as a target for inflammation associated fibrosis in Crohn's Disease.

BACKGROUND: Mesenchymal stromal cells are suggested to play a critical role in the Crohn's Disease (CD) associated fibrosis. MAPKAPK2 (MK2) has emerged as a potential therapeutic target to reduce inflammation in CD. However, cell-specific pattern of pMK2 activation and its role in the CD associated fibrosis are unknown. The objectives of this study were to evaluate cell-specific changes in MK2 activity between predominantly inflammatory CD versus CD with fibrotic complication and define the role of stromal cell-specific MK2 activation in CD-associated fibrosis. METHODS: CD tissue, CD tissue derived mesenchymal stromal cells known as myo-/fibroblasts (CD-MFs), fibroblast specific MK2 conditional KO mice were used. RESULTS: We observed that in the inflamed area of predominantly inflammatory CD, high MK2 activity was equally distributed between mesenchymal and hematopoietic cells. By contrast, in CD with fibrotic complications, high MK2 activity was mostly associated with mesenchymal stromal cells. Using ex vivo CD tissue explants and IL-10KO murine colitis model, we demonstrated that pro-fibrotic responses are significantly reduced by treatment with the MK2 inhibitor PF-3644022. Inhibition of MK2 activity in primary cultures of CD-MFs significantly reduced basal and TGF-ß1-induced profibrotic responses. Using fibroblast-specific MK2 knockout mice in chronic DSS colitis, we demonstrated that fibroblast intrinsic MK2 signaling is among the key processes involved in the chronic inflammation induced profibrotic responses. CONCLUSIONS: Our data suggest that activation of MK2 within fibroblasts contributes to the chronic inflammation induced fibrosis in CD and that targeting MK2 has potential for the development of novel therapeutic approaches for fibrosis in CD.

HPV vaccination and cervical screening: the knowledge and attitudes of mothers of adolescent girls.

OBJECTIVE: Mothers play a significant role in decision making about human papillomavirus (HPV) vaccination for their daughters and about cervical screening attendance for themselves. This study had three objectives, to explore: (1) mothers' knowledge and attitudes about HPV and HPV vaccination, (2) their knowledge and attitudes about cervical cancer and screening, and (3) whether their daughter's HPV vaccination invitation was an opportunity to nudge mothers to attend screening. DESIGN: 138 women from North Staffordshire completed a cross-sectional survey and 15 took part in follow-up focus groups. RESULTS: Despite high self-reported engagement with both the cervical screening and HPV vaccination programmes, relatively low levels of knowledge and some uncertainty were evident. There was mixed opinion about the potential of using the vaccination invite as an opportunity to nudge mothers to attend cervical screening. CONCLUSION: Even amongst women who do engage positively with the programmes, knowledge is not as complete and certain as it could be. Further research is needed with women who are less likely to accept the vaccination for their daughters. Women need to be better informed, which may go some way to reversing the decline in screening and maintaining high levels of vaccination.

Racism, Chronic Disease, and Mental Health: Time to Change Our Racialized System of Second-Class Care.

In this article, we describe how the "weathering hypothesis" and Adverse Childhood Experiences set the stage for higher rates of chronic disease, mental health disorders and maternal mortality seen in African American adults. We illustrate the toll that untreated and overtreated mental health disorders have on Black individuals, who have similar rates of mental health disorders as their white counterparts but have fewer outpatient mental health services and higher rates of hospitalizations. We discuss the history of Medicaid, which, while passed alongside Medicare during the Civil Rights era, was Congress's concession to Southern states unwilling to concede federal oversight and funds to the provision of equal healthcare for poor and Black people. Medicaid, which covers 33% of all Blacks in the US and suffers from chronic underfunding and state efforts to weaken it through demonstration waivers, is a second-class system of healthcare with eligibility criteria that vary by state and year. We propose the adoption of a national, single payer Medicare for All system to cover everyone equally, from conception to death. While this will not erase all structural racism, it will go a long way towards leveling the playing field and achieving greater equity in the US.

A survey of knowledge, attitudes and awareness of the human papillomavirus among healthcare professionals across the UK.

BACKGROUND: Human papillomavirus (HPV) is a common sexually transmitted infection implicated in 5% of cancers worldwide including most cervical cancer cases. In the UK, the HPV vaccine has been offered routinely to girls aged 11-13 since 2008 while cervical screening is offered to women aged 25-64. HPV testing will soon replace cytology as the primary screening method. This research evaluates what healthcare professionals (HCPs) across the UK know about HPV. METHODS: A total of 643 UK-based HCPs from primary and secondary care took part in an anonymous cross-sectional survey between March and April 2018. The survey measured general HPV knowledge; HPV triage and test of cure knowledge; HPV vaccine knowledge; attitudes to the HPV vaccine and self-perceived adequacy of knowledge. RESULTS: Participants had a generally good understanding of HPV and the vaccination but there were gaps in detailed knowledge of the National Health Service HPV testing processes. There were some gaps in knowledge about the health sequelae of HPV for males. Years since HPV training was associated with triage and test of cure and vaccine knowledge scores. Furthermore, nurses and doctors in colposcopy clinics had much greater odds of having higher knowledge across all domains than other roles. In total, 76.2% of participants felt adequately informed about HPV and 35.6% made suggestions for improvements in training, many of which requested additional frequency and topics. CONCLUSION: Our results suggest that additional training is needed to ensure HCPs are equipped to deal with the changing landscape of HPV screening and vaccination in the UK.

Copolymerization of cyclohexene oxide and carbon dioxide using (salen)Co(III) complexes: synthesis and characterization of syndiotactic poly(cyclohexene carbonate).

Synthetic routes to a series of new (salen-1)CoX (salen-1 = N,N'-bis(salicylidene)-1,2-diaminoalkane; X = halide or carboxylate) species are described and the X-ray crystal structures of two (salen-1)CoX (salen- = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminocyclohexane; X = Cl, I) complexes are presented. (R,R)-(salen-)CoX (X = Cl, Br, I, OAc, pentafluorobenzoate (OBzF(5))) catalysts are active for the copolymerization of cyclohexene oxide (CHO) and CO(2), yielding syndiotactic poly(cyclohexene carbonate) (PCHC), a previously unreported PCHC microstructure. Variation of the salen ligand and reaction conditions, as well as the inclusion of [PPN]Cl ([PPN]Cl = bis(triphenylphosphine)iminium chloride) cocatalysts, has dramatic effects on the polymerization rate and the resultant PCHC tacticity. Catalysts rac-(salen-)CoX (salen- = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminopropane; X = Br, OBzF(5)) have high activities for CHO/CO(2) copolymerization, yielding syndiotactic PCHCs with up to 81% r-centered tetrads. Using Bernoullian statistical methods, PCHC tetrad and triad sequences were assigned in the (13)C NMR spectra of these polymers in the carbonyl and methylene regions, respectively.

Cobalt catalysts for the alternating copolymerization of propylene oxide and carbon dioxide: combining high activity and selectivity.

Synthetic pathways to (salcy)CoX (salcy = N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-diaminocyclohexane; X = halide or carboxylate) complexes are described. Complexes (R,R)-(salcy)CoCl, (R,R)-(salcy)CoBr, (R,R)-(salcy)CoOAc, and (R,R)-(salcy)CoOBzF(5) (OBzF(5) = pentafluorobenzoate) are highly active catalysts for the living, alternating copolymerization of propylene oxide (PO) and CO(2), yielding poly(propylene carbonate) (PPC) with no detectable byproducts. The PPC generated using these catalyst systems is highly regioregular and has up to 99% carbonate linkages with a narrow molecular weight distribution (MWD). Inclusion of the cocatalysts [PPN]Cl or [PPN][OBzF(5)] ([PPN] = bis(triphenylphosphine)iminium) with complex (R,R)-(salcy)CoCl, (R,R)-(salcy)CoBr, or (R,R)-(salcy)CoOBzF(5) results in remarkable activity enhancement of the copolymerization as well as improved stereoselectivity and regioselectivity with maximized reactivity at low CO(2) pressures. In the case of [PPN]Cl with (R,R)-(salcy)CoOBzF(5), an unprecedented catalytic activity of 620 turnovers per hour is achieved for the copolymerization of rac-PO and CO(2), yielding iso-enriched PPC with 94% head-to-tail connectivity. The stereochemistry of the monomer and catalyst used in the copolymerization has dramatic effects on catalytic activity and the PPC microstructure. Using catalyst (R,R)-(salcy)CoBr with (S)-PO/CO(2) generates highly regioregular PPC, whereas using (R)-PO/CO(2) with the same catalyst gives an almost completely regiorandom copolymer. The rac-PO/CO(2) copolymerization with catalyst rac-(salcy)CoBr yields syndio-enriched PPC, an unreported PPC microstructure. In addition, (R,R)-(salcy)CoOBzF(5)/[PPN]Cl copolymerizes (S)-PO and CO(2) with a turnover frequency of 1100 h(-1), an activity surpassing that observed in any previously reported system.

A highly active, isospecific cobalt catalyst for propylene oxide polymerization.

A highly active cobalt complex ((salph)CoOAc; salph = N,N'-bis(3,5-di-tert-butylsalicylidine-1,2-benzenediamine)) was discovered for the isospecific polymerization of rac-propylene oxide.