Knowledge of female genital cutting among health and social care professionals in Francophone Belgium: A cross-sectional survey.

The provision of optimal, equitable and gender-sensitive health-care to women and girls with FGM/C is challenging. Research indicates that health-professionals in receiving countries lack knowledge, confidence and competence in managing FGM/C. In order to develop policies that are suitable to the wide heterogeneity of women from FGM/C practising groups, it is paramount to identify what appropriate care might consist of and what are the knowledge gaps of health and social-care providers. The study-objective was to gain an understanding of the knowledge and practices of professionals working in the area of health in Francophone Belgium where no previous KAP has been done. An anonymous questionnaire with 24 questions was developed targeting healthcare and social-care professionals. The questionnaire was distributed between 6 May and 30 August 2021 via professional organisations for midwifery, social work, GPs, infectious disease specialists, paediatricians and gynaecologists. The results are presented as frequencies, differences in proportions between groups were tested with Pearson's Chi-square, when applicable. Correlations were tested by the Pearson correlation coefficient. The threshold of statistical significance is 5%. Four-hundred-and-sixty individuals filled in the questionnaire of which 42% were medical-doctors, 6% nurses, 27% midwives and 25% non-medical professionals (social-workers and psychologists). 55% of non-medical professionals had provided support for women with FGM/C. Almost 40% of health-professionals knew that there were 4 types of FGM and were able to correctly describe them, 15% were unable to correctly describe any of the 4 types. Those who had already provided care for women with FGM/C were more numerous to know that there were 4 types (52%). Two health-professionals had received requests to perform FGM/C. Twenty-seven midwives and medical-doctors had received requests for re-infibulation. Growing numbers of health and social-care professionals are providing care for women with FGM/C. However, knowledge of FGM/C is suboptimal. Continuous professional training is crucial.

Enabling non-viral DNA delivery using lipid nanoparticles co-loaded with endogenous anti-inflammatory lipids.

Lipid nanoparticles (LNPs) have transformed genetic medicine, recently shown by their use in COVID-19 mRNA vaccines. While loading LNPs with mRNA has many uses, loading DNA would provide additional advantages such as long-term expression and availability of promoter sequences. However, here we show that plasmid DNA (pDNA) delivery via LNPs (pDNA-LNPs) induces acute inflammation in naïve mice which we find is primarily driven by the cGAS-STING pathway. Inspired by DNA viruses that inhibit this pathway for replication, we co-loaded endogenous lipids that inhibit STING into pDNA-LNPs. Specifically, loading nitro-oleic acid (NOA) into pDNA-LNPs (NOA-pDNA-LNPs) ameliorates serious inflammatory responses in vivo enabling prolonged transgene expression (at least 1 month). Additionally, we demonstrate the ability to iteratively optimize NOA-pDNA-LNPs' expression by performing a small LNP formulation screen, driving up expression 50-fold in vitro. Thus, NOA-pDNA-LNPs, and pDNA-LNPs co-loaded with other bioactive molecules, will provide a major new tool in the genetic medicine toolbox, leveraging the power of DNA's long-term and promoter-controlled expression.

A Yeast Modular Cloning (MoClo) Toolkit Expansion for Optimization of Heterologous Protein Secretion and Surface Display in Saccharomyces cerevisiae.

Saccharomyces cerevisiae is an attractive host for the expression of secreted proteins in a biotechnology context. Unfortunately, many heterologous proteins fail to enter, or efficiently progress through, the secretory pathway, resulting in poor yields. Similarly, yeast surface display has become a widely used technique in protein engineering but achieving sufficient levels of surface expression of recombinant proteins is often challenging. Signal peptides (SPs) and translational fusion partners (TFPs) can be used to direct heterologous proteins through the yeast secretory pathway, however, selection of the optimal secretion promoting sequence is largely a process of trial and error. The yeast modular cloning (MoClo) toolkit utilizes type IIS restriction enzymes to facilitate an efficient assembly of expression vectors from standardized parts. We have expanded this toolkit to enable the efficient incorporation of a panel of 16 well-characterized SPs and TFPs and five surface display anchor proteins into S. cerevisiae expression cassettes. The secretion promoting signals are validated by using five different proteins of interest. Comparison of intracellular and secreted protein levels reveals the optimal secretion promoting sequence for each individual protein. Large, protein of interest-specific variations in secretion efficiency are observed. SP sequences are also used with the five surface display anchors, and the combination of SP and anchor protein proves critical for efficient surface display. These observations highlight the value of the described panel of MoClo compatible parts to allow facile screening of SPs and TFPs and anchor proteins for optimal secretion and/or surface display of a given protein of interest in S. cerevisiae.

Prenatal Stress Exposure Amplifies Effect of Maternal Suicidal Ideation on Early Childhood Behavioral Trajectories.

The in utero environment influences fetal development and may predispose to disease later in life. This study examines whether maternal suicidal ideation during pregnancy is associated with children's behavioral trajectories across early childhood, and whether prenatal maternal traumatic stress accelerates the trajectories. The study included mother-child dyads (N = 331, 51.1% boys) from the longitudinal Stress In Pregnancy study; 31.1% (n = 103) mothers were Exposed to Superstorm Sandy. During their second trimester, 12.4% (n = 41) women reported suicidal ideation during pregnancy. Mothers completed the Behavior Assessment Scale for Children-2 annually from ages 2- to 6-years-old to assess multiple behavioral domains. Hierarchical linear modeling estimated within-person longitudinal trajectories of clinical behaviors, and between-person effects of maternal suicidal ideation and disaster-related stress in utero on changes in child behavior. For children exposed to both risks, Atypical behaviors (i.e., unusual behaviors, social disconnection) increased linearly across early childhood. Exposure to Superstorm Sandy and maternal suicidal ideation were independently associated with non-linear increases in Anxiety severity and maternal suicidal ideation during pregnancy was associated with a linear increase in Attention problems across early childhood. Maternal suicidal ideation during pregnancy is associated with increased risk for a range of behavioral and emotional difficulties in early childhood and the trajectory of atypical behaviors was amplified by disaster-related traumatic stress. Findings highlight the need for health professionals to screen for suicidal ideation among their pregnant patients. Pregnant women who experience severe stress may require additional monitoring and support to reduce risk for poorer early childhood outcomes.

Redefining Fatherhood in a Migratory Context: A Narrative Inquiry into the Experiences of African First-time Fathers in Belgium.

Many African fathers face practices in their host countries that conflict with the conceptions of fatherhood in their countries of origin. They deal with negative stereotypes, including notions of paternal irresponsibility when it comes to embracing child care. This article looks at how exposure to the Belgian norms of fatherhood may redefine the fatherhood practices of African first-time fathers residing in Belgium. Drawing on a qualitative narrative approach, this article explores the perceptions and experiences of African migrant fathers in Belgium and examines how they adapt to a different fathering culture. The findings show that while African first-time fathers acknowledged their primary role as providers, they also embraced new practices that transgress defined gender lines in African culture. In the absence of a larger family support network, respondents face the responsibility of providing prenatal and postnatal support and sharing in child care responsibilities. Findings also shed light on how African fathers with European partners engage in shared decision-making and negotiate on core African values such as male circumcision.

Involving the health sector in the prevention and care of female genital mutilation: results from formative research in Guinea.

BACKGROUND: Despite efforts to reduce the burden of female genital mutilation (FGM) in Guinea, the practice remains prevalent, and health care providers are increasingly being implicated in its medicalization. This formative study was conducted to understand the factors that facilitate or impede the health sector in providing FGM prevention and care services to inform the development of health sector-based interventions. METHODS: Between April and May 2018, a mixed methods formative study was carried out using a rapid assessment methodology in three regions of Guinea-Faranah, Labe and Conakry. A structured questionnaire was completed by one hundred and fifty health care providers of different cadres and 37 semi-structured interviews were conducted with health care providers, women seeking services at public health clinics and key stakeholders, including health systems managers, heads of professional associations and schools of nursing, midwifery, and medicine as well as representatives of the Ministry of Health. Eleven focus group discussions were conducted with female and male community members. RESULTS: This study revealed health systems factors, attitudinal factors held by health care providers, and other factors, that may not only promote FGM medicalization but also impede a comprehensive health sector response. Our findings confirm that there is currently no standardized pre-service training on how to assess, document and manage complications of FGM nor are there interventions to promote the prevention of the practice within the health sector. This research also demonstrates the deeply held beliefs of health care providers and community members that perpetuate this practice, and which need to be addressed as part of a health sector approach to FGM prevention. CONCLUSION: As integral members of FGM practicing communities, health care providers understand community beliefs and norms, making them potential change agents. The health sector can support them by incorporating FGM content into their clinical training, ensuring accountability to legal and policy standards, and promoting FGM abandonment as part of a multi-sectoral approach. The findings from this formative research have informed the development of a health sector intervention that is being field tested as part of a multi-country implementation research study in Guinea, Kenya, and Somalia.

Despite the implementation of various interventions to prevent female genital mutilation (FGM), it is still widely practiced in Guinea, and health care providers are increasingly being implicated in the practice. We conducted research in three regions of Guinea, namely, Faranah, Labe and Conakry, to understand factors that might be addressed to strengthen the role of the health sector in prevention and care of women and girls who have undergone FGM. Our findings highlight the need to strengthen the capacity of health care providers to be able to identify cases of FGM and manage complications. The study also highlights the importance of engaging health care providers in efforts to prevent FGM, which will require that any trainings include an opportunity to discuss their own values and beliefs around FGM so that they are better equipped to communicate with their clients and patients in a sensitive and non-judgmental manner, whether during consultation visits or community health outreach activities. The results of this research have informed the development of a health system strengthening intervention package for the prevention and care of FGM, which is being tested in Kenya, Somalia, and Guinea.

Intraoperative indocyanine green fluorescence navigation in a robot-assisted partial nephrectomy for a large renal cell carcinoma in a horseshoe kidney.

A man in his 60s was referred to the urology department with an incidental finding of large 75 mm mass within a horseshoe kidney. CT imaging highlighted the well-known aberrant arterial anatomy seen in horseshoe kidney which often causes significant surgical challenges.After careful preoperative planning, the mass was resected successfully during a robot-assisted partial nephrectomy. Intraoperatively, indocyanine green fluorescence navigation helped to confirm arteries supplying area of resection were appropriately clamped, allowing for safe resection of the mass. Histology revealed a chromophobe renal cell carcinoma with clear margins. The patient was discharged on day 4 postoperatively and continues to be cancer free on routine surveillance imaging.

Prenatal Exposure to a Climate-Related Disaster Results in Changes of the Placental Transcriptome and Infant Temperament.

Maternal stress during pregnancy exerts long-term effects on the mental well-being of the offspring. However, the long-term effect of prenatal exposure on the offspring's mental status is only partially understood. The placenta plays a vital role in connecting the maternal side to the fetus, thereby serving as an important interface between maternal exposure and fetal development. Here, we profiled the placental transcriptome of women who were pregnant during a hurricane (Superstorm Sandy), which struck New York City in 2012. The offspring were followed longitudinally and their temperament was assessed during the first 6-12 months of age. The data identified a significant correlation between a Superstorm Sandy stress factor score and infant temperament. Further, analysis of the placental transcriptomes identified an enrichment of functional pathways related to inflammation, extracellular matrix integrity and sensory perception in the specimen from those infants with "Slow-to-Warm-up" temperament during the first year of life. Together, these findings provide initial evidence that maternal exposure to climate-related disasters results in altered placental transcriptome, which may be related to long-term emotional and behavioral consequences in children.

'There Were Moments We Wished She Could Just Die': The Highly Gendered Burden of Nodding Syndrome in Northern Uganda.

Nodding Syndrome (NS) occurs within a wide spectrum of epilepsies seen in onchocerciasis endemic areas of sub-Saharan Africa. It has debilitating consequences on affected individuals and increases the socio-economic, physical and psychological burden on care-givers and their households, diminishing their standing within the community. Social science research on the disproportionate burden of the disease on females is limited. Based on ethnographic research over 3 years in northern Uganda, we explored the burden of being ill and care-giving for persons with NS from a gendered perspective. We found that NS-affected females were at greater risk of physical and psychological abuse, sexual violence, unwanted pregnancies, sexually transmitted infections and stigma, in a context of deteriorating socio-economic conditions. Primary care-givers of the NS-affected, mostly women, struggled to make ends meet and were subjected to stigma and abandonment. Targeted interventions, including legal protection for affected females, stigma reduction, and psycho-social and financial support are needed.

Pleasure, womanhood and the desire for reconstructive surgery after female genital cutting in Belgium.

Growing numbers of women are showing interest in clitoral reconstructive surgery after 'Female Genital Mutilation'. The safety and success of reconstructive surgery, however, has not clearly been established and due to lack of evidence the World Health Organization does not recommend it. Based on anthropological research among patients who requested surgery at the Brussels specialist clinic between 2017 and 2020, this paper looks at two cases of women who actually enjoy sex and experience pleasure but request the procedure to become 'whole again' after stigmatising experiences with health-care professionals, sexual partners or gossip among African migrant communities. An ethnographic approach was used including indepth interviews and participant observation during reception appointments, gynecological consultations, sexology and psychotherapy sessions. Despite limited evidence on the safety of the surgical intervention, surgery is often perceived as the ultimate remedy for the 'missing' clitoris. Such beliefs are nourished by predominant discourses of cut women as 'sexually mutilated'. Following Butler, this article elicits how discursive practices on the physiological sex of a woman can shape her gender identity as a complete or incomplete person. We also examine what it was that changed the patients' mind about the surgery in the process of re-building their confidence through sexology therapy and psychotherapy.

Nodal metastases in small rectal neuroendocrine tumours.

AIM: Rectal neuroendocrine tumours (NETs) are the most common type of gastrointestinal NET. European Neuroendocrine Tumour Society guidelines suggest that rectal NETs measuring ≤10 mm are indolent with low risk of spread. In practice, many patients with lesions ≤1 cm do not undergo complete tumour staging. However, the size of the lesion may not be the only risk factor for nodal involvement/metastases. The aim of this study was to determine if MRI ± nuclear medicine imaging alters tumour stage in patients with rectal NETs ≤10 mm. METHODS: Patients referred to a tertiary NET centre between 2005 and 2020 who met the inclusion criteria of a rectal NET ≤10 mm, full cross-sectional imaging, primarily an MRI scan and, if abnormal findings were identified, a subsequent 68 Ga-DOTATATE positron emission tomography scan were included. All patients were followed up at our institution. RESULTS: In all, 32 patients with rectal NETs 10 mm or less were included in the study: 16 women; median age 58 years (range 33-71); 47% (n = 15) were referred from bowel cancer screening procedures. The median size of the lesions was 5 mm (range 2-10 mm). 81% (n = 26) were World Health Organization Grade 1 tumours with Ki67 <3%. Radiological staging confirmed nodal involvement in 25% (8/32); two cases had distant metastatic disease. Lymphovascular invasion was present in 3% (1/32) of patients but none demonstrated peri-neural invasion. CONCLUSION: This study demonstrates that small rectal NETs can develop nodal metastases; therefore it is important to stage these tumours accurately with MRI at baseline and, if there are concerns regarding potential lymph node metastases, to consider 68 Ga-DOTATATE positron emission tomography imaging.

Onchocerca volvulus transmission in the Mbam valley of Cameroon following 16 years of annual community-directed treatment with ivermectin, and the description of a new cytotype of Simulium squamosum.

BACKGROUND: The onchocerciasis focus surrounding the lower Mbam and Sanaga rivers, where Onchocerca volvulus is transmitted by Simulium damnosum s.l. (Diptera: Simuliidae), was historically the largest in the southern regions of Cameroon. Annual community-directed treatment with ivermectin (CDTI) has been taking place since 2000, but recent studies have shown that new infections are occurring in children. We aimed to investigate blackfly biting and O. volvulus transmission rates along the lower Mbam river 16 years after the formal onset of annual CDTI. METHODS: Black flies were collected for three consecutive days each month between July 2016 and June 2017 at two riverside villages and two inland sites situated 4.9 km and 7.9 km from the riverside. Specimens collected at each site were dissected on one of the three collection days each month to estimate parity rates and O. volvulus infection rates, while the remaining samples were preserved for pool screening. RESULTS: In total, 93,573 S. damnosum s.l. black flies were recorded biting humans and 9281 were dissected. Annual biting rates of up to 606,370 were estimated at the riverside, decreasing to 20,540 at 7.9 km, while, based on dissections, annual transmission potentials of up to 4488 were estimated at the riverside, decreasing to 102 and 0 at 4.9 km and 7.9 km, respectively. However, pool screening showed evidence of infection in black flies at the furthest distance from the river. Results of both methods demonstrated the percentage of infective flies to be relatively low (0.10-0.36%), but above the WHO threshold for interruption of transmission. In addition, a small number of larvae collected during the dry season revealed the presence of Simulium squamosum E. This is the first time S. squamosum E has been found east of Lake Volta in Ghana, but our material was chromosomally distinctive, and we call it S. squamosum E2. CONCLUSIONS: Relatively low O. volvulus infection rates appear to be offset by extremely high densities of biting black flies which are sustaining transmission along the banks of the lower Mbam river.

Executive Functioning and the Pursuit of Happiness.

Executive functioning and happiness are each associated with successful learning and other desirable individual and societal outcomes; however, it is unclear whether a relation exists between them. Executive regulation of happiness pursuits in daily life, operationalized as hedonic (e.g., pursuing pleasure) and eudaimonic (e.g., pursuing personal growth) motives for action, may be a way the constructs relate to each other. In this initial investigation, we aimed to explore whether objectively measured executive functioning skills relate to happiness motives. A sample of 119 college students completed six objective neuropsychological measures of executive functioning and self-reported levels of hedonic and eudaimonic motives for action in daily life. Correlation and regression analyses examined the relations among temporal discounting and two latent executive functioning factors (inhibitory control and working memory) with hedonic and eudaimonic motives, as well as their interaction. Results suggested a possible association between higher levels of eudaimonic motives and preference for higher delayed rewards, as well as poorer working memory. Further analyses suggested that endorsing high levels of eudaimonic and hedonic motives simultaneously (i.e., the "full life") was associated with poorer inhibitory control and working memory performance, whereas endorsing low levels of both simultaneously (i.e., the "empty life") was associated with a preference for more immediate monetary rewards. Findings are discussed in the context of goal conflict and risk assessment among individuals who endorse the "full life". Overall, these findings suggest that complex relations may exist between executive functioning and trait-level happiness pursuits, and have implications for possible interventions aimed at enhancing happiness-related motives and cognitive processes to facilitate learning. Given the exploratory nature of the present study, further investigations are necessary.

Diarrhoea and preadmission antibiotic exposure in COVID-19: a retrospective cohort study of 1153 hospitalised patients.

OBJECTIVE: The aims of this study were to describe community antibiotic prescribing patterns in individuals hospitalised with COVID-19, and to determine the association between experiencing diarrhoea, stratified by preadmission exposure to antibiotics, and mortality risk in this cohort. DESIGN/METHODS: Retrospective study of the index presentations of 1153 adult patients with COVID-19, admitted between 1 March 2020 and 29 June 2020 in a South London NHS Trust. Data on patients' medical history (presence of diarrhoea, antibiotic use in the previous 14 days, comorbidities); demographics (age, ethnicity, and body mass index); and blood test results were extracted. Time to event modelling was used to determine the risk of mortality for patients with diarrhoea and/or exposure to antibiotics. RESULTS: 19.2% of the cohort reported diarrhoea on presentation; these patients tended to be younger, and were less likely to have recent exposure to antibiotics (unadjusted OR 0.64, 95% CI 0.42 to 0.97). 19.1% of the cohort had a course of antibiotics in the 2 weeks preceding admission; this was associated with dementia (unadjusted OR 2.92, 95% CI 1.14 to 7.49). After adjusting for confounders, neither diarrhoea nor recent antibiotic exposure was associated with increased mortality risk. However, the absence of diarrhoea in the presence of recent antibiotic exposure was associated with a 30% increased risk of mortality. CONCLUSION: Community antibiotic use in patients with COVID-19, prior to hospitalisation, is relatively common, and absence of diarrhoea in antibiotic-exposed patients may be associated with increased risk of mortality. However, it is unclear whether this represents a causal physiological relationship or residual confounding.

The Consequences of Female Genital Mutilation on Psycho-Social Well-Being: A Systematic Review of Qualitative Research.

The health consequences of female genital mutilation (FGM) have been described previously; however, evidence of the social consequences is more intangible. To date, few systematic reviews have addressed the impact of the practice on psycho-social well-being, and there is limited understanding of what these consequences might consist. To complement knowledge on the known health consequences, this article systematically reviewed qualitative evidence of the psycho-social impact of FGM in countries where it is originally practiced (Africa, the Middle East, and Asia) and in countries of the diaspora. Twenty-three qualitative studies describing the psycho-social impact of FGM on women's lives were selected after screening. This review provides a framework for understanding the less visible ways in which women and girls with FGM experience adverse effects that may affect their sense of identity, their self-esteem, and well-being as well as their participation in society.

Novel findings and expansion of phenotype in a mosaic RASopathy caused by somatic KRAS variants.

Mosaic KRAS variants and other RASopathy genes cause oculoectodermal, encephalo-cranio-cutaneous lipomatosis, and Schimmelpenning-Feuerstein-Mims syndromes, and a spectrum of vascular malformations, overgrowth and other associated anomalies, the latter of which are only recently being characterized. We describe eight individuals in total (six unreported cases and two previously reported cases) with somatic KRAS variants and variably associated features. Given the findings of somatic overgrowth (in seven individuals) and vascular or lymphatic malformations (in eight individuals), we suggest mosaic RASopathies (mosaic KRAS variants) be considered in the differential diagnosis for individuals presenting with asymmetric overgrowth and lymphatic or vascular anomalies. We expand the association with embryonal tumors, including the third report of embryonal rhabdomyosarcoma, as well as novel findings of Wilms tumor and nephroblastomatosis in two individuals. Rare or novel findings in our series include the presence of epilepsy, polycystic kidneys, and T-cell deficiency in one individual, and multifocal lytic bone lesions in two individuals. Finally, we describe the first use of targeted therapy with a MEK inhibitor for an individual with a mosaic KRAS variant. The purposes of this report are to expand the phenotypic spectrum of mosaic KRAS-related disorders, and to propose possible mechanisms of pathogenesis, and surveillance of its associated findings.

Attitudes of health care providers regarding female genital mutilation and its medicalization in Guinea.

BACKGROUND: Guinea has a high prevalence of female genital mutilation (FGM) (95%) and it is a major concern affecting the health and the welfare of women and girls. Population-based surveys suggest that health care providers are implicated in carrying out the practice (medicalization). To understand the attitudes of health care providers related to FGM and its medicalization as well as the potential role of the health sector in addressing this practice, a study was conducted in Guinea to inform the development of an intervention for the health sector to prevent and respond to this harmful practice. METHODOLOGY: Formative research was conducted using a mixed-methods approach, including qualitative in-depth interviews with health care providers and other key informants as well as questionnaires with 150 health care providers. Data collection was carried out in the provinces of Faranah and Labé and in the capital, Conakry. RESULTS: The majority of health care providers participating in this study were opposed to FGM and its medicalization. Survey data showed that 94% believed that it was a serious problem; 89% felt that it violated the rights of girls and women and 81% supported criminalization. However, within the health sector, there is no enforcement or accountability to the national law banning the practice. Despite opposition to the practice, many (38%) felt that FGM limited promiscuity and 7% believed that it was a good practice. CONCLUSION: Health care providers could have an important role in communicating with patients and passing on prevention messages that can contribute to the abandonment of the practice. Understanding their beliefs is a key step in developing these approaches.

In pursuit of a cure: The plural therapeutic landscape of onchocerciasis-associated epilepsy in Cameroon - A mixed methods study.

BACKGROUND: A high prevalence of epilepsy has been observed in several onchocerciasis-endemic villages in the Sanaga River basin, Cameroon. Recent studies suggest that ivermectin, a drug that is distributed annually with the aim of eliminating onchocerciasis, may have a protective effect against acquiring onchocerciasis-associated epilepsy (OAE). This study, therefore, provides an in-depth understanding of both the complex therapeutic landscape for epilepsy as well as the experiences related to the 'community-directed treatment with ivermectin' (CDTI) campaign in order to identify a more trenchant path forward in the fight against epilepsy. METHODOLOGY/PRINCIPAL FINDINGS: Based on a mixed methods study combining a qualitative strand with a quantitative survey, we found that epilepsy was perceived to have had an epidemic emergence in the past and was still considered an important health issue in the study area. Socio-economic status, availability and accessibility of drugs and practitioners, as well as perceived aetiology shaped therapeutic itineraries for epilepsy, which included frequenting (in)formal biomedical health care providers, indigenous and/or faith healing practitioners. Ivermectin uptake for onchocerciasis was generally well known and well regarded. The CDTI faced structural and logistical bottlenecks undermining equal access and optimal adherence to the drug. CONCLUSIONS/SIGNIFICANCE: Locally accessible, uninterrupted, sustainable and comprehensive health-service delivery is essential to help alleviate the epilepsy burden on afflicted households. Addressing structural challenges of CDTI and communicating the potential link with epilepsy to local populations at risk could optimize the uptake of this potentially significant tool in OAE prevention.

Impact of C-Terminal Chemistry on Self-Assembled Morphology of Guanosine Containing Nucleopeptides.

Herein, we report the design and characterization of guanosine-containing self-assembling nucleopeptides that form nanosheets and nanofibers. Through spectroscopy and microscopy analysis, we propose that the peptide component of the nucleopeptide drives the assembly into ß-sheet structures with hydrogen-bonded guanosine forming additional secondary structures cooperatively within the peptide framework. Interestingly, the distinct supramolecular morphologies are driven not by metal cation responsiveness common to guanine-based materials, but by the C-terminal peptide chemistry. This work highlights the structural diversity of self-assembling nucleopeptides and will help advance the development of applications for these supramolecular guanosine-containing nucleopeptides.

PLGA-PEG Nanoparticles Show Minimal Risks of Interference with Platelet Function of Human Platelet-Rich Plasma.

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0-2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.