Cash & Compassion: The Somali Diaspora's Role in Relief, Development & Peacebuilding

This research report, commissioned by UNDP Somalia, is based on work done in six diaspora hubs (Dubai, London, Minneapolis, Nairobi, Oslo, and Toronto) as well as in Somaliland, Puntland and South/Central Somalia. It examines the involvement of Somalis in the diaspora in dynamics in their country of origin, including collective and social remittances. Volume 1 contains the full report. Volume 2 contains the research guides, terms of reference and other annexes

Colonic drug delivery: Formulating the next generation of colon-targeted therapeutics

Colonic drug delivery can facilitate access to unique therapeutic targets and has the potential to enhance drug bioavailability whilst reducing off-target effects. Delivering drugs to the colon requires considered formulation development, as both oral and rectal dosage forms can encounter challenges if the colon's distinct physiological environment is not appreciated. As the therapeutic opportunities surrounding colonic drug delivery multiply, the success of novel pharmaceuticals lies in their design. This review provides a modern insight into the key parameters determining the effective design and development of colon-targeted medicines. Influential physiological features governing the release, dissolution, stability, and absorption of drugs in the colon are first discussed, followed by an overview of the most reliable colon-targeted formulation strategies. Finally, the most appropriate in vitro, in vivo, and in silico preclinical investigations are presented, with the goal of inspiring strategic development of new colon-targeted therapeutics

Acceptability and Satiety Evaluation of a Developed Nutritionally Balanced School Meal

Five nutritionally designed school meals were developed in a form of pastes based on leguminous seeds (lentil, chick pea, and soya) mixed with dairy ingredients. All formulas contain groundnut, and few contained crushed nuts providing inclusions inside the prototypes to test acceptance. The products were fortified with essential minerals and vitamins following the DRI guideline for children. Developed meals were served as a breakfast meal to ~200 students (6-9 years juniors; 10-14 years seniors) of one of the Sudanese basic schools (Omdurman City) for 21 days to substitute a traditional breakfast meal boiled Pigeon pea colloquially called “Balila” served routinely to the students. This paper covers acceptability of favorable products behavioral responses of senior and junior students to four meal/subject interactions coverings temptation to finishing the whole meal, reason(s) for not finishing the whole meal, time needed to finish the meal, and degree of satiety the students feel during teaching hours.Almost 95% of the senior students interacted positively with pastes based on lentil or chick pea finish the product as evidenced by the short time (90% of them confirmed satisfactory degree of satiety compared to all products offered

Restoration of Normal NF1 Function with Antisense Morpholino Treatment of Recurrent Pathogenic Patient-Specific Variant c.1466A>G; p.Y489C

Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder with almost 3000 different disease-causing variants within the NF1 gene identified. Up to 44% of these variants cause splicing errors to occur within pre-mRNA. A recurrent variant in exon 13, c.1466A>G; p.Y489C (Y489C) results in the creation of an intragenic cryptic splice site, aberrant splicing, a 62 base pair deletion from the mRNA, and subsequent frameshift. We investigated the ability of phosphorodiamidate morpholino oligomers (PMOs) to mask this variant on the RNA level, thus restoring normal splicing. To model this variant, we have developed a human iPS cell line homozygous for the variant using CRISPR/Cas9. PMOs were designed to be 25 base pairs long, and to cover the mutation site so it could not be read by splicing machinery. Results from our in vitro testing showed restoration of normal splicing in the RNA and restoration of full length neurofibromin protein. In addition, we observe the restoration of neurofibromin functionality through GTP-Ras and pERK/ERK testing. The results from this study demonstrate the ability of a PMO to correct splicing errors in NF1 variants at the RNA level, which could open the door for splicing corrections for other variants in this and a variety of diseases

Single-Cell Analysis of ADSC Interactions with Fibroblasts and Endothelial Cells in Scleroderma Skin

Adipose-derived stem cells (ADSCs) as part of autologous fat grafting have anti-fibrotic and anti-inflammatory effects, but the exact mechanisms of action remain unknown. By simulating the interaction of ADSCs with fibroblasts and endothelial cells (EC) from scleroderma (SSc) skin in silico, we aim to unravel these mechanisms. Publicly available single-cell RNA sequencing data from the stromal vascular fraction of 3 lean patients and biopsies from the skin of 10 control and 12 patients with SSc were obtained from the GEO and analysed using R and Seurat. Differentially expressed genes were used to compare the fibroblast and EC transcriptome between controls and SSc. GO and KEGG functional enrichment was performed. Ligand–receptor interactions of ADSCs with fibroblasts and ECs were explored with LIANA. Pro-inflammatory and extracellular matrix (ECM) interacting fibroblasts were identified in SSc. Arterial, capillary, venous and lymphatic ECs showed a pro-fibrotic and pro-inflammatory transcriptome. Most interactions with both cell types were based on ECM proteins. Differential interactions identified included NTN1, VEGFD, MMP2, FGF2, and FNDC5. The ADSC secretome may disrupt vascular and perivascular inflammation hubs in scleroderma by promoting angiogenesis and especially lymphangiogenesis. Key phenomena observed after fat grafting remain unexplained, including modulation of fibroblast behaviour

Legacy and emerging organohalogenated compounds in feathers of Eurasian eagle-owls (Bubo bubo) in Norway: Spatiotemporal variations and associations with dietary proxies (δ13C and δ15N)

The occurrence of organohalogenated compounds (OHCs) in wildlife has received considerable attention over the last decades. Among the matrices used for OHCs biomonitoring, feathers are particularly useful as they can be collected in a minimally or non-invasive manner. In this study, concentrations of various legacy OHCs –polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) and polybrominated diphenyl ethers (PBDEs)–, as well as emerging OHCs –per- and polyfluoroalkyl substances (PFAS) and organophosphate ester flame retardants (OPEs)– were determined in feathers of 72 Eurasian eagle-owls (Bubo bubo) from Norway, with the goal of studying spatiotemporal variation using a non-invasive approach. Molted feathers were collected at nest sites from northern, central and southern Norway across four summers (2013–2016). Additionally, two museum-archived feathers from 1979 to 1989 were included. Stable carbon (δ13C) and nitrogen isotopes (δ15N) were used as dietary proxies. In total, 11 PFAS (sum range 8.25–215.90 ng g− 1), 15 PCBs (4.19–430.01 ng g− 1), 6 OCPs (1.48–220.94 ng g− 1), 5 PBDEs (0.21–5.32 ng g− 1) and 3 OPEs (4.49–222.21 ng g− 1) were quantified. While we observed large variation in the values of both stable isotopes, suggesting a diverse diet of the eagle owls, only δ13C seemed to explain variation in PFAS concentrations. Geographic area and year were influential factors for δ15N and δ13C. Considerable spatial variation was observed in PFAS levels, with the southern area showing higher levels compared to northern and central Norway. For the rest of OHCs, we observed between-year variations; sum concentrations of PCBs, OCPs, PBDEs and OPEs reached a maximum in 2015 and 2016. Concentrations from 1979 to 1989 were within the ranges observed between 2013 and 2016. Overall, our data indicate high levels of legacy and emerging OHCs in a top predator in Norway, further highlighting the risk posed by OHCs to wildlife. Keywords: Bird of prey Feathers Isotopes OPE POP PFASpublishedVersio

Poly(D,l-lactide-co-glycolide) particles are metabolised by the gut microbiome and elevate short chain fatty acids

© 2024 The Authors. Published by Elsevier B.V. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/The production of short chain fatty acids (SCFAs) by the colonic microbiome has numerous benefits for human health, including maintenance of epithelial barrier function, suppression of colitis, and protection against carcinogenesis. Despite the therapeutic potential, there is currently no optimal approach for elevating the colonic microbiome's synthesis of SCFAs. In this study, poly(D,l-lactide-co-glycolide) (PLGA) was investigated for this application, as it was hypothesised that the colonic microbiota would metabolise PLGA to its lactate monomers, which would promote the resident microbiota's synthesis of SCFAs. Two grades of spray dried PLGA, alongside a lactate bolus control, were screened in an advanced model of the human colon, known as the M-SHIME® system. Whilst the high molecular weight (Mw) grade of PLGA was stable in the presence of the microbiota sourced from three healthy humans, the low Mw PLGA (PLGA 2) was found to be metabolised. This microbial degradation led to sustained release of lactate over 48 h and increased concentrations of the SCFAs propionate and butyrate. Further, microbial synthesis of harmful ammonium was significantly reduced compared to untreated controls. Interestingly, both types of PLGA were found to influence the composition of the luminal and mucosal microbiota in a donor-specific manner. An in vitro model of an inflamed colonic epithelium also showed the polymer to affect the expression of pro- and anti-inflammatory markers, such as interleukins 8 and 10. The findings of this study reveal PLGA's sensitivity to enzymatic metabolism in the gut, which could be harnessed for therapeutic elevation of colonic SCFAs.Peer reviewe

The effect of surface demineralization of cortical bone allograft on the properties of recombinant adeno-associated virus coatings

Freeze-dried recombinant adeno-associated virus (rAAV) coated structural allografts have emerged as an approach to engender necrotic cortical bone with host factors that will persist for weeks following surgery to facilitate revascularization, osteointegration, and remodeling. However, one major limitation is the nonporous cortical surface that prohibits uniform distribution of the rAAV coating prior to freeze-drying. To overcome this we have developed a demineralization method to increase surface absorbance while retaining the structural integrity of the allograft. Demineralized bone wafers (DBW) made from human femoral allograft rings demonstrated a significant 21.1 % (73.6 ± 3.9 % vs. 52.5 ± 2.6 %; p0.05), although the peaks occurred at 60hrs and 12hrs, respectively. To assess the transduction efficiency of rAAV-Luc coated DBW in vivo, we first performed a dose response with allografts containing 107, 109 or 1010 particles that were surgically implanted into the quadriceps of mice, and assayed by in vivo bioluminescence imaging (BLI) on days 1, 3, 5, 7, 10, 14, and 21. The results demonstrated a dose response in which the DBW coated with 1010 rAAV-Luc particles achieved peak gene expression levels on day 3, which persisted until day 21, and was significantly greater than the 107 dose throughout this time period (p<0.01). A direct comparison of mineralized versus DBW coated with 1010 rAAV-Luc particles failed to demonstrate any significant differences in transduction kinetics or efficiency in vivo. Thus, surface demineralization of human cortical bone allograft increase its absorbance for uniform rAAV coating, without affecting vector transduction efficiency