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

Development and field testing of an online instrument for measuring the real-time oxidative potential of ambient particulate matter based on dithiothreitol assay

We developed an online instrument for measuring the oxidative potential (OP) of ambient particulate matter (PM) using the dithiothreitol (DTT) assay. The instrument uses a mist chamber (MC) to continuously collect the ambient PM2.5 in water, and then determines its DTT activity using an automated syringe pump system. The instrument was deployed at an urban site in the University of Illinois campus, and its field performance was evaluated by comparing the results with the offline DTT activity measurements of simultaneously collected PM-laden filters. The online DTT activity measurements correlated well with the offline measurements but were higher than both methanol (slope&thinsp; = 1.08, R2 = 0.93) and Milli-Q water (slope&thinsp; = 1.86, R2 = 0.86) extracts of the PM filters, indicating a better efficiency of the MC for collecting the water-insoluble fraction of PM. The hourly measurements of ambient PM2.5 OP were obtained by running the online instrument intermittently for 50 days with minimal manual assistance. The daytime DTT activity levels were generally higher than at night. However, a 4-fold increase in the hourly averaged activity was observed on the night of 4 July (Independence Day fireworks display). The diurnal profile of the hourly averaged OP during weekdays showed a bimodal trend, with a sharp peak in the morning (around 07:00&thinsp;LT), followed by a broader afternoon peak which plateaus around 14:00&thinsp;LT and starts subsiding at night (around 19:00&thinsp;LT).To investigate the association of the diurnal profile of DTT activity with the emission sources at the site, we collected time-segregated composite PM filter samples in four different time periods of the day (morning, 07:00–10:00&thinsp;LT; afternoon, 10:00–15:00&thinsp;LT; evening, 15:00–19:00&thinsp;LT; and night, 19:00–07:00&thinsp;LT) and determined the diurnal variations in the redox active components (i.e., water-soluble Cu, Fe, Mn, organic carbon, elemental carbon, and water-soluble organic carbon). Based on this comparison, we attributed the daytime OP of ambient PM2.5 to the vehicular (both exhaust and non-exhaust) emissions and resuspended dust, whereas secondary photochemical transformation of primary emissions appear to enhance the OP of PM during the afternoon and evening period.</p

Effectiveness of early intervention programs for parents of preterm infants: a meta-review of systematic reviews

Background: Various intervention programs exist for parents of preterm babies and some systematic reviews (SRs) have synthesised the evidence of their effectiveness. These reviews are, however, limited to specific interventions, components, or outcomes, and a comprehensive evidence base is lacking. The aim of this meta-review was to appraise and meta-synthesise the evidence from existing SRs to provide a comprehensive evidence base on the effectiveness of interventions for parents of preterm infants on parental and infant outcomes. Methods: We conducted a comprehensive search of the following databases to identify relevant SRs: Cochrane library, Web of science, EMBASE, CINAHL, British Nursing Index, PsycINFO, Medline, ScienceDirect, Scopus, IBSS, DOAJ, ERIC, EPPI-Centre, PROSPERO, WHO Library. Additional searches were conducted using authors’ institutional libraries, Google Scholar, and the reference lists of identified reviews. Identified articles were screened in two stages against an inclusion criteria with titles and abstracts screened first followed by full-text screening. Selected SRs were appraised using the AMSTAR tool. Extracted data using a predesigned tool were synthesised narratively examining the direction of impact on outcomes. Results: We found 11 SRs eligible for inclusion that synthesised a total of 343 quantitative primary studies. The average quality of the SRs was ‘medium’. Thirty four interventions were reported across the SRs with considerable heterogeneity in the structural framework and the targeted outcomes that included maternal-infant dyadic, maternal/parental, and infant outcomes. Among all interventions, Kangaroo Care (KC) showed the most frequent positive impact across outcomes (n = 19) followed by Mother Infant Transaction Program (MITP) (n = 14). Other interventions with most consistent positive impact on infant outcomes were Modified-Mother Infant Transaction Program (M-MITP) (n = 6), Infant Health and Development Program (IHDP) (n = 5) and Creating Opportunities for Parent Empowerment (COPE) (n = 5). Overall, interventions with both home and facility based components showed the most frequent positive impact across outcomes. Conclusions: Neonatal care policy and planning for preterm babies should consider the implementation of interventions with most positive impact on outcomes. The heterogeneity in interventions and outcomes calls for the development and implementation of an integrated program for parents of preterm infants with a clearly defined global set of parental and infant outcomes

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

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

A systematic review of randomised controlled trials on the effectiveness of exercise programs on lumbo pelvic pain among postnatal women

Background: A substantial number of women tend to be affected by Lumbo Pelvic Pain (LPP) following child birth. Physical exercise is indicated as a beneficial method to relieve LPP, but individual studies appear to suggest mixed findings about its effectiveness. This systematic review aimed to synthesise evidence from randomised controlled trials on the effectiveness of exercise on LPP among postnatal women to inform policy, practice and future research. Methods: A systematic review was conducted of all randomised controlled trials published between January 1990 and July 2014, identified through a comprehensive search of following databases: PubMed, PEDro, Embase, Cinahl, Medline, SPORTDiscus, Cochrane Pregnancy and Childbirth Group’s Trials Register, and electronic libraries of authors’institutions. Randomised controlled trials were eligible for inclusion if the intervention comprised of postnatal exercise for women with LPP onset during pregnancy or within 3 months after delivery and the outcome measures included changes in LPP. Selected articles were assessed using the PEDro Scale for methodological quality and findings were synthesised narratively as meta-analysis was found to be inappropriate due to heterogeneity among included studies. Results: Four randomised controlled trials were included, involving 251 postnatal women. Three trials were rated as of ‘good’ methodological quality. All trials, except one, were at low risk of bias. The trials included physical exercise programs with varying components, differing modes of delivery, follow up times and outcome measures. Intervention in one trial, involving physical therapy with specific stabilising exercises, proved to be effective in reducing LPP intensity. An improvement in gluteal pain on the right side was reported in another trial and a significant difference in pain frequency in another. Conclusion: Our review indicates that only few randomised controlled trials have evaluated the effectiveness of exercise on LPP among postnatal women. There is also a great amount of variability across existing trials in the components of exercise programs, modes of delivery, follow up times and outcome measures. While there is some evidence to indicate the effectiveness of exercise for relieving LPP, further good quality trials are needed to ascertain the most effective elements of postnatal exercise programs suited for LPP treatment

First-time mothers’ experiences of pregnancy and birth following assisted reproductive technology treatment in Taiwan

Background Assisted Reproductive Technology (ART) treatment tends to involve significant physical and emotional commitments that can impact maternal, infant and family health and well-being. An in-depth understanding of experiences is necessary to provide adequate support for women and their families during pregnancy and transition to parenthood following ART treatment. The aim of this study was to explore first-time mothers’ experiences of pregnancy and transition to parenthood following successful ART treatment in Taiwan. Method Twelve first-time mothers who conceived and gave live birth using ART treatment were purposively selected from a fertility centre in Taipei, Taiwan. Women’s experiences in pregnancy and in their transition to motherhood were explored using semi-structured in-depth interviews. All interviews were recorded, transcribed, and analysed using the Colaizzi strategy. Results The mothers’ accounts reflected three main themes: ‘being different from mothers who became pregnant naturally’; ‘ensuring health and safety of the foetus’; and ‘welcoming new lives with excitement’. The difference mothers felt about themselves was evident in four subthemes: becoming pregnant after a long wait, feeling vulnerable during pregnancy, relying on family’s assistance and support, and worrying about the impact of ART on health. The theme on ‘ensuring health and safety of the foetus’ encompassed three subthemes: activities to protect the unborn baby, monitoring foetal movement constantly to maintain peace of mind, and receiving foetal reduction for the sake of the pregnancy. Narratives around ‘welcoming new lives with excitement’ reflected four subthemes: overcoming hardship for worthwhile results, realising one’s life and dreams, proving to be fertile enough to give birth, and return to normal life track. Conclusion Findings indicate the need for educational and psychosocial interventions to support women and their families physically and psychologically during ART treatment. The stigma related to infertility and the psychosocial support from family are aspects to consider while planning intervention programmes