Controlled Delivery of Pan-PAD-Inhibitor Cl-Amidine Using Poly(3-Hydroxybutyrate) Microspheres.

This study deals with the process of optimization and synthesis of Poly(3-hydroxybutyrate) microspheres with encapsulated Cl-amidine. Cl-amidine is an inhibitor of peptidylarginine deiminases (PADs), a group of calcium-dependent enzymes, which play critical roles in a number of pathologies, including autoimmune and neurodegenerative diseases, as well as cancer. While Cl-amidine application has been assessed in a number of in vitro and in vivo models; methods of controlled release delivery remain to be investigated. P(3HB) microspheres have proven to be an effective delivery system for several compounds applied in antimicrobial, wound healing, cancer, and cardiovascular and regenerative disease models. In the current study, P(3HB) microspheres with encapsulated Cl-amidine were produced in a size ranging from ~4-5 µm and characterized for surface morphology, porosity, hydrophobicity and protein adsorption, in comparison with empty P(3HB) microspheres. Cl-amidine encapsulation in P(3HB) microspheres was optimized, and these were found to be less hydrophobic, compared with the empty microspheres, and subsequently adsorbed a lower amount of protein on their surface. The release kinetics of Cl-amidine from the microspheres were assessed in vitro and expressed as a function of encapsulation efficiency. There was a burst release of ~50% Cl-amidine in the first 24 h and a zero order release from that point up to 16 days, at which time point ~93% of the drug had been released. As Cl-amidine has been associated with anti-cancer effects, the Cl-amidine encapsulated microspheres were assessed for the inhibition of vascular endothelial growth factor (VEGF) expression in the mammalian breast cancer cell line SK-BR-3, including in the presence of the anti-proliferative drug rapamycin. The cytotoxicity of the combinatorial effect of rapamycin with Cl-amidine encapsulated P(3HB) microspheres was found to be 3.5% more effective within a 24 h period. The cells treated with Cl-amidine encapsulated microspheres alone, were found to have 36.5% reduction in VEGF expression when compared with untreated SK-BR-3 cells. This indicates that controlled release of Cl-amidine from P(3HB) microspheres may be effective in anti-cancer treatment, including in synergy with chemotherapeutic agents. Using controlled drug-delivery of Cl-amidine encapsulated in Poly(3-hydroxybutyrate) microspheres may be a promising novel strategy for application in PAD-associated pathologies

‘They’re more like ordinary stroppy British women’: Attitudes and expectations of maternity care professionals to UK-born ethnic minority women

Objective To explore the attitudes and expectations of maternity care professionals to UK-born ethnic minority mothers. Methods Qualitative in-depth interviews with 30 professionals from eight NHS maternity units in England that provide services for large proportions of women of black Caribbean, black African, Indian, Pakistani and Irish descent. Results All the professionals reported providing care to both UK-born and migrant mothers from ethnic minorities. Most of them felt that they could differentiate between UK-born and migrant mothers based mainly on language fluency and accent. ‘Westernized dress’ and ‘freedom’ were also cited as indicators. Overall, professionals found it easier to provide services to UK-born mothers and felt that their needs were more like those of white English mothers than those of migrant mothers. UK-born mothers were generally thought to be assertive and expressive, and in control of care-related decision-making whereas some South Asian Muslim women were thought to be constrained by family influences. Preconceived ideas about ethnic minority mothers' tolerance of pain in labour, use of pharmacological pain relief measures and mode of delivery were recurring themes. Women's education and social class were felt to be major influences on the uptake of maternity care, regardless of ethnicity. Conclusions Professionals appeared to equate the needs of UK-born ethnic minority women with those of white English women. Overall, this has positive implications for care provision. Despite this, specific behavioural expectations and unconscious stereotypical views were evident and have the potential to affect clinical practice

Late antenatal care initiation and neonatal outcomes in an ethnically diverse maternal cohort

Background Ethnic minority status and maternal socio-economic deprivation are linked to delayed access to health care during pregnancy. The link between late antenatal care initiation and neonatal outcomes in settings with high ethnic diversity and social disadvantage is seldom explored. This study examined associations between late antenatal care initiation (first antenatal appointment >12 weeks gestation) and neonatal outcomes of preterm birth (<37 weeks gestation) and low birth weight (<2500 g) in an ethnically diverse socially disadvantaged maternal cohort. Methods A retrospective cross sectional study using routinely collected anonymous data of singleton births between April 2007 - March 2016 from a large UK National Health Service maternity unit in an ethnically diverse, socially disadvantaged area. Univariate and multivariate logistic regression models were used to examine the associations between late antenatal care initiation and prevalence of preterm birth and low birth weight. Results Of the 46,307 singleton births recorded, more than one third (34.8%) were to mothers from Black African, Black Caribbean, Indian, Pakistani, and Bangladeshi mothers. Gestational week at first antenatal appointment was available for 99.31% births among which 79.2% had their first appointment at ≤ 12 weeks, 12% at 13-20 weeks, and 8.8% at > 20 weeks. Mothers who booked at 13+ weeks were significantly more likely to have a preterm and/or low birth weight baby. Compared to mothers who booked at ≤ 12 weeks, those booking at > 20 weeks were 4.08 times (95% CI: 3.29,5.07) as likely to have an extremely preterm baby (<28 weeks of gestation) and 3.12 (CI 2.66, 3.67) times as likely to have a baby born with extremely low birthweight (<1500g). Conclusions Mothers in ethnically diverse socially deprived areas who started antenatal care late were at increased risk of adverse neonatal outcomes. Targeted intervention programmes and services are needed to support these mothers. Key messages Mothers who start antenatal care late are more likely to have a preterm and/or low birth weight baby in ethnically diverse socially disadvantaged areas. There is a need for targeted programmes and services to support mothers in ethnically diverse socially disadvantaged areas to start antenatal care on time

A qualitative study of healthcare professionals' experiences of providing maternity care for Muslim women in the UK.

BACKGROUND: A growing Muslim population in the UK suggests the need for healthcare professionals (HCPs) to gain a better understanding of how the Islamic faith influences health related perceptions and healthcare seeking behaviour. Although some researchers have explored the experiences of Muslim women as recipients of healthcare, little attention has been paid to the challenges HCPs face as service providers on a day-to-day basis whilst caring for Muslim women. The aim of this study was to investigate HPCs lived experiences of providing maternity care for Muslim women. METHOD: Data was collected through twelve semi-structured one-to-one qualitative interviews with HCPs in a large National Health Service (NHS) maternity unit located in the North West of England. Interview participants included Community and specialist clinic (e.g. clinic for non-English speakers), Midwives in a variety of specialist roles (7), Gynaecology Nurses (2), Breastfeeding Support Workers (2) and a Sonographer (1). The audio-recorded interviews were transcribed and analysed thematically. RESULTS: The majority of participants expressed an understanding of some religious values and practices related to Muslim women, such as fasting the month of Ramadhan and that pregnant and breastfeeding women are exempt from this. However, HCPs articulated the challenges they faced when dealing with certain religious values and practices, and how they tried to respond to Muslim women's specific needs. Emerging themes included: 1) HCPs perceptions about Muslim women; 2) HCPs understanding and awareness of religious practices; 3) HCPs approaches in addressing and supporting Muslim women's religious needs; 4) Importance of training in providing culturally and religiously appropriate woman-centred care. CONCLUSION: Through this study we gained insight into the day-to-day experiences of HCPs providing care provision for Muslim women. HCPs showed an understanding of the importance of religious and cultural practices in addressing the needs of Muslim women as part of their role as maternity care providers. However, they also identified a need to develop training programmes that focus on cultural and religious practices and their impact on women's health care needs. This will help support HCPs in overcoming the challenges faced when dealing with needs of women from different backgrounds

Couple relationships in families with dependent children after a diagnosis of maternal breast cancer in the United Kingdom: Perspectives from mothers and fathers

This article examines the facilitators and the barriers to couple relationships in families in the UK with dependent children after a diagnosis of maternal breast cancer. Qualitative data were collected through in-depth semi-structured interviews with 23 participants, including 10 couples and three women whose partners did not take part. Recorded interviews were analysed using a thematic approach identifying themes and patterns in the interview transcripts and categorizing them using a framework. Key individual and contextual factors perceived as barriers or facilitators to couple relationships included: being a “young” family with young children, frustration and resentment from male partners, women’s reactions to the illness, individual communication styles, differing needs for “personal space,” body image concerns, and social support. Findings indicated the need for strengthening “family focus” in services with adequate support for male partners. Health and family services should consider variability in the experiences of couples with dependent children and be sensitive to the needs of partners alongside the women

Rod and Cone Pathway Signalling Is Altered in the P2X7 Receptor Knock Out Mouse

The P2X7 receptor (P2X7-R) is expressed in the retina and brain and has been implicated in neurodegenerative diseases. However, whether it is expressed by neurons and plays a role as a neurotransmitter receptor has been the subject of controversy. In this study, we first show that the novel vesicular transporter for ATP, VNUT, is expressed in the retina, verifying the presence of the molecular machinery for ATP to act as neurotransmitter at P2X7-Rs. Secondly we show the presence of P2X7-R mRNA and protein in the retina and cortex and absence of the full length variant 1 of the receptor in the P2X7-R knock out (P2X7-KO) mouse. The role of the P2X7-R in neuronal function of the retina was assessed by comparing the electroretinogram response of P2X7-KO with WT mice. The rod photoreceptor response was found to be similar, while both rod and cone pathway post-photoreceptor responses were significantly larger in P2X7-KO mice. This suggests that activation of P2X7-Rs modulates output of second order retinal neurons. In line with this finding, P2X7-Rs were found in the outer plexiform layer and on inner retinal cell classes, including horizontal, amacrine and ganglion cells. The receptor co-localized with conventional synapses in the IPL and was expressed on amacrine cells post-synaptic to rod bipolar ribbon synapses. In view of the changes in visual function in the P2X7-KO mouse and the immunocytochemical location of the receptor in the normal retina, it is likely the P2X7-R provides excitatory input to photoreceptor terminals or to inhibitory cells that shape both the rod and cone pathway response

Presynaptic partner selection during retinal circuit reassembly varies with timing of neuronal regeneration in vivo

Whether neurons can restore their original connectivity patterns during circuit repair is unclear. Taking advantage of the regenerative capacity of zebrafish retina, we show here the remarkable specificity by which surviving neurons reassemble their connectivity upon regeneration of their major input. H3 horizontal cells (HCs) normally avoid red and green cones, and prefer ultraviolet over blue cones. Upon ablation of the major (ultraviolet) input, H3 HCs do not immediately increase connectivity with other cone types. Instead, H3 dendrites retract and re-extend to contact new ultraviolet cones. But, if regeneration is delayed or absent, blue-cone synaptogenesis increases and ectopic synapses are made with red and green cones. Thus, cues directing synapse specificity can be maintained following input loss, but only within a limited time period. Further, we postulate that signals from the major input that shape the H3 HC's wiring pattern during development persist to restrict miswiring after damage