In Vitro Osteogenesis Study of Shell Nacre Cement with Older and Young Donor Bone Marrow Mesenchymal Stem/Stromal Cells.

Bone void-filling cements are one of the preferred materials for managing irregular bone voids, particularly in the geriatric population who undergo many orthopedic surgeries. However, bone marrow mesenchymal stem/stromal cells (BM-MSCs) of older-age donors often exhibit reduced osteogenic capacity. Hence, it is crucial to evaluate candidate bone substitute materials with BM-MSCs from the geriatric population to determine the true osteogenic potential, thus simulating the clinical situation. With this concept, we investigated the osteogenic potential of shell nacre cement (SNC), a bone void-filling cement based on shell nacre powder and ladder-structured siloxane methacrylate, using older donor BM-MSCs (age > 55 years) and young donor BM-MSCs (age < 30 years). Direct and indirect cytotoxicity studies conducted with human BM-MSCs confirmed the non-cytotoxic nature of SNC. The standard colony-forming unit-fibroblast (CFU-F) assay and population doubling (PD) time assays revealed a significant reduction in the proliferation potential (p < 0.0001, p < 0.05) in older donor BM-MSCs compared to young donor BM-MSCs. Correspondingly, older donor BM-MSCs contained higher proportions of senescent, ß-galactosidase (SA-ß gal)-positive cells (nearly 2-fold, p < 0.001). In contrast, the proliferation capacity of older donor BM-MSCs, measured as the area density of CellTrackerTM green positive cells, was similar to that of young donor BM-MSCs following a 7-day culture on SNC. Furthermore, after 14 days of osteoinduction on SNC, scanning electron microscopy with energy-dispersive spectroscopy (SEM-EDS) showed that the amount of calcium and phosphorus deposited by young and older donor BM-MSCs on SNC was comparable. A similar trend was observed in the expression of the osteogenesis-related genes BMP2, RUNX2, ALP, COL1A1, OMD and SPARC. Overall, the results of this study indicated that SNC would be a promising candidate for managing bone voids in all age groups.

Anti-Aging Potential of Platelet Rich Plasma (PRP): Evidence from Osteoarthritis (OA) and Applications in Senescence and Inflammaging.

Aging and age-related changes impact the quality of life (QOL) in elderly with a decline in movement, cognitive abilities and increased vulnerability towards age-related diseases (ARDs). One of the key contributing factors is cellular senescence, which is triggered majorly by DNA damage response (DDR). Accumulated senescent cells (SCs) release senescence-associated secretory phenotype (SASP), which includes pro-inflammatory cytokines, matrix metalloproteinases (MMPs), lipids and chemokines that are detrimental to the surrounding tissues. Chronic low-grade inflammation in the elderly or inflammaging is also associated with cellular senescence and contributes to ARDs. The literature from the last decade has recorded the use of platelet rich plasma (PRP) to combat senescence and inflammation, alleviate pain as an analgesic, promote tissue regeneration and repair via angiogenesis-all of which are essential in anti-aging and tissue regeneration strategies. In the last few decades, platelet-rich plasma (PRP) has been used as an anti-aging treatment option for dermatological applications and with great interest in tissue regeneration for orthopaedic applications, especially in osteoarthritis (OA). In this exploration, we connect the intricate relationship between aging, ARDs, senescence and inflammation and delve into PRP's properties and potential benefits. We conduct a comparative review of the current literature on PRP treatment strategies, paying particular attention to the instances strongly linked to ARDs. Finally, upon careful consideration of this interconnected information in the context of aging, we suggest a prospective role for PRP in developing anti-aging therapeutic strategies.

Fabrication and Characterisation of the Cytotoxic and Antibacterial Properties of Chitosan-Cerium Oxide Porous Scaffolds.

Bone damage arising from fractures or trauma frequently results in infection, impeding the healing process and leading to complications. To overcome this challenge, we engineered highly porous chitosan scaffolds (S1, S2, and S3) by incorporating 30 (wt)% iron-doped dicalcium phosphate dihydrate (Fe-DCPD) minerals and different concentrations of cerium oxide nanoparticles (CeO2) (10 (wt)%, 20 (wt)%, and 30 (wt)%) using the lyophilisation technique. The scaffolds were specifically designed for the controlled release of antibacterial agents and were systematically characterised by utilising Raman spectroscopy, X-ray diffraction, scanning electron microscopy, and energy-dispersive X-ray spectroscopy methodologies. Alterations in the physicochemical properties, encompassing pore size, swelling behaviour, degradation kinetics, and antibacterial characteristics, were observed with the escalating CeO2 concentrations. Scaffold cytotoxicity and its impact on human bone marrow mesenchymal stem cell (BM-MSCs) proliferation were assessed employing the 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay. The synthesised scaffolds represent a promising approach for addressing complications associated with bone damage by fostering tissue regeneration and mitigating infection risks. All scaffold variants exhibited inhibitory effects on bacterial growth against Staphylococcus aureus and Escherichia coli strains. The scaffolds manifested negligible cytotoxic effects while enhancing antibacterial properties, indicating their potential for reducing infection risks in the context of bone injuries.

A strategic analysis of health behaviour change initiatives in Africa.

BACKGROUND: Changed health behaviours can contribute significantly to improved health. Consequently, significant investments have been channelled towards health behaviour change initiatives in Africa. Health behaviour change initiatives that address social, economic and environmental levers for behaviour change can create more sustained impact. OBJECTIVES: Through a scoping study of the literature, we explored the literature on behaviour change initiatives in Africa, to assess their typologies. We explored whether the availability of initiatives reflected country demographic characteristics, namely life expectancy, gross domestic product (GDP), and population sizes. Finally, we assessed topical themes of interventions relative to frequent causes of mortality. METHODS: We used the Behaviour Change Wheel intervention categories to categorise each paper into a typology of initiatives. Using Pearson's correlation coefficient, we explored whether there was a correlation between the number of initiatives implemented in a country in the specified period, and socio-demographic indicators, namely, GDP per capita, total GDP, population size, and life expectancy. RESULTS: Almost 64% of African countries were represented in the identified initiatives. One in five initiatives was implemented in South Africa, while there was a dearth of literature from Central Africa and western parts of North Africa. There was a positive correlation between the number of initiatives and GDP per capita. Most initiatives focused on addressing sexually transmitted infections and were short-term trials and/or pilots. Most initiatives were downstream focused e.g. with education and training components, while upstream intervention types such as the use of incentives were under-explored. CONCLUSION: We call for more emphasis on initiatives that address contextual facilitators and barriers, integrate considerations for sustainable development, and consider intra-regional deprivation.

'As safe as houses; the risk of childhood lead exposure from housing in England and implications for public health'.

BACKGROUND AND AIM: Exposure to lead can harm a child's health, including damage to the nervous system, delayed growth, hearing loss, and many other adverse health effects, as well as implications for social, economic, educational and social well-being. Lead exposure in children is still a concern and cases require public health management to find the exposure source and interrupt the exposure pathway. Housing characteristics can indicate the presence of lead-contaminated paint and leaded water supply pipes. We aimed to explore the relationship between housing characteristics and elevated blood lead concentration (BLC) in children in England. METHODS: We used a retrospective cohort design and included all cases of lead exposure in children reported to the UK Health Security Agency between 2014 and 2020 via surveillance. A case was a child aged under 16 years, resident in England, BLC of ≥ 0.48 µmol/L (10 µg/dL) and referred for public health management. We collected case demographic details and housing characteristics (age and type). We explored associations between elevated BLC and risk factors, using generalised linear mixed effects models and compared cases' housing type to that expected nationally. RESULTS: Two hundred and sixty-six out of 290 cases met the case definition. There was no difference in BLCs between genders, age groups, deprivation, and housing type. After adjusting for reporting source, housing age and type, cases residing in housing built pre-1976 had a BLC of 0.32 (95%CI 0.02, 0.63) µmols/L (6.63 (95%CI 0.42, 13.0) µg/dL) higher than cases living in housing built after this time. Cases were 1.68 times more likely to be living in terraced housing (housing adjoined to one another) than other children and less likely to live in apartments and detached properties. CONCLUSION: This study suggests an association between housing characteristics and BLC in children. Housing age and type may act as a proxy for lead exposure risk through exposure to leaded paint, lead water pipes, and lead contaminated dust from indoor and outdoor sources. Public health action should consider targeting families more at risk in older housing by raising awareness of the potential presence of lead pipes and paint. Interventions should include working with wider stakeholders including other housing and environmental professionals, the private sector, as well as parents and carers.

Comparing The Efficacy And Safety Of Pregabalin Vs Gabapentin In Uremic Pruritus In Patients Of Chronic Kidney Injury Undergoing Haemodialysis.

BACKGROUND: World has been facing an epidemic of non-communicable diseases including heart, metabolic and renal diseases. Renal diseases have been commonly diagnosed and managed in low- and middle-income countries. Objective was to compare efficacy and safety of Pregabalin and Gabapentin in uremic pruritus among patients of chronic kidney injury undergoing haemodialysis. It was a comparative cross-sectional study, conducted at the Department of nephrology Abbottabad International Medical Institute. February 2021 to January 2022. METHODS: Total of 90 cases were included in the study, which were diagnosed as chronic kidney disease stage 5 undergoing haemodialysis and presented with pruritus. Pruritus was gauged on numeric rating scale and patients score of more than 6 were included. Patients were randomly divided into two groups via lottery method. Group A received Pregabalin while group B received Gabapentin. Efficacy and safety were assessed in both groups at the end of six months. RESULTS: Out of 90 dialysis dependent chronic kidney disease patients with significant pruritus included in the study, 61 (52.7%) patients were males and 29 (46.3%) were females. At the end of 6 weeks, we found out that 35 (38.9%) had no pruritus, 25 (27.8%) had mild, 19 (21.1%) had moderate while 11 (12.2%) had severe pruritus. After applying the chi-square test we found that Pregablin was statistically significantly more efficacious then Gabapentin (p-value-0.026). Sedation, nausea and blurred vision were found more in patients who took Pregabalin (p-value<0.001). CONCLUSIONS: Pregablin emerged out to be more efficacious with regards to reducing pruritus of the two medications compared in our study population while patients who took Gabapentin experience significantly a smaller number of side effects as compared to patients who were given Pregabalin.

Dicalcium Phosphate Dihydrate Mineral Loaded Freeze-Dried Scaffolds for Potential Synthetic Bone Applications.

Dicalcium Phosphate Dihydrate (DCPD) mineral scaffolds alone do not possess the mechanical flexibility, ease of physicochemical properties' tuneability or suitable porosity required for regenerative bone scaffolds. Herein, we fabricated highly porous freeze-dried chitosan scaffolds embedded with different concentrations of Dicalcium Phosphate Dihydrate (DCPD) minerals, i.e., 0, 20, 30, 40 and 50 (wt)%. Increasing DCPD mineral concentration led to increased scaffold crystallinity, where the % crystallinity for CH, 20, 30, 40, and 50-DCPD scaffolds was determined to be 0.1, 20.6, 29.4, 38.8 and 69.9%, respectively. Reduction in scaffold pore size distributions was observed with increasing DCPD concentrations of 0 to 40 (wt)%; coalescence and close-ended pore formation were observed for 50-DCPD scaffolds. 50-DCPD scaffolds presented five times greater mechanical strength than the DCPD mineral-free scaffolds (CH). DCPD mineral enhanced cell proliferation for the 20, 30 and 40-DCPD scaffolds. 50-DCPD scaffolds presented reduced pore interconnectivity due to the coalescence of many pores in addition to the creation of closed-ended pores, which were found to hinder osteoblast cell proliferation.

Fatal Unintentional Non-Fire Related Carbon Monoxide Poisoning: Data from Narrative Verdicts in England and Wales, 1998-2019.

Unintentional non-fire related (UNFR) carbon monoxide (CO) poisoning continues to cause fatalities. The narrative verdicts from coroners concerning fatal UNFR CO poisoning in England and Wales, 1998-2019, were collated by the Office for National Statistics. Search terms related to CO exposure were used to obtain information regarding the circumstances of death. Findings were grouped by the location of death, the source of CO, and the reason or behaviour underlying the exposure. There were 750 deaths (77% male). The annual number of deaths decreased over the period studied. Two thirds (68%) of the deaths occurred in the autumn or winter. From the records with information, 59% of deaths occurred within a dwelling (67% male). Males also predominated deaths within vehicles (91%) and garages or outbuildings (95%). From the deaths with information, domestic piped gas was the most common source of CO (36%) and the most frequent underlying factor was inadequate ventilation of exhaust gases (39%, 91% male). Despite the decrease in the annual number of deaths over the study period, there remains a clear need for measures that raise awareness of the dangers of CO poisoning, especially amongst men working alone in garages or outbuildings. Education campaigns and fitting and maintaining CO alarms in high-risk areas should be encouraged.

Interrelationships between the structural, spectroscopic, and antibacterial properties of nanoscale (< 50 nm) cerium oxides.

Bone healing is a complex process, and if not managed successfully, it can lead to non-union, metal-work failure, bacterial infections, physical and psychological patient impairment. Due to the growing urgency to minimise antibiotic dependency, alternative treatment strategies, including the use of nanoparticles, have attracted significant attention. In the present study, cerium oxide nanoparticles (Ce4+, Ce3+) have been selected due to their unique antibacterial redox capability. We found the processing routes affected the agglomeration tendency, particle size distribution, antibacterial potential, and ratio of Ce3+:Ce4+ valence states of the cerium oxide nanoparticles. The antibacterial efficacy of the nanoparticles in the concentration range of 50-200 µg/ml is demonstrated against Escherichia coli, Staphylococcus epidermis, and Pseudomonas aeruginosa by determining the half-maximal inhibitory concentration (IC50). Cerium oxide nanoparticles containing a more significant amount of Ce3+ ions, i.e., FRNP, exhibited 8.5 ± 1.2%, 10.5 ± 4.4%, and 13.8 ± 5.8% increased antibacterial efficacy compared with nanoparticles consisting mainly of Ce4+ ions, i.e., nanoparticles calcined at 815 °C.

Girls' hidden penalty: analysis of gender inequality in child mortality with data from 195 countries.

INTRODUCTION: Gender inequality has been associated with child mortality; however, sex-specific mortalities have yet to be explored. The aim of this study is to assess the associations between gender inequality and the child mortality sex ratio at country level, worldwide and to infer on possible mechanisms. METHODS: Data on sex-specific under-five mortality rates (U5MR) and the corresponding sex ratio (U5MSR) for the year 2015, by country, were retrieved from the Unicef database. Excess under-five female mortality was derived from previous published work. Gender inequality was measured using the Gender Inequality Index (GII). Additional biological and social variables have been included to explore potential mechanistic pathways. RESULTS: A total of 195 countries were included in the analysis. In adjusted models, GII was significantly negatively associated with the U5MSR (ß=-0.29 (95% CI -0.42 to -0.16), p<0.001) and borderline significantly positively associated with excess under-five female mortality (ß = 3.25 (95% CI -0.28 to 6.67, p=0.071). The association between GII and U5MSR was strong and statistically significant only in low-income and middle-income countries and in the Western Pacific area. CONCLUSION: The more gender unequal a society is, the more girls are penalised in terms of their survival chances, in particular in low-income and middle-income countries. In order to decrease child mortality and excess girl mortality, global policy should focus on reducing gender inequality surrounding measures of reproductive health, women's political empowerment, educational attainment and participation in the workforce.