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Abstract Lipid nanoparticles (LNPs) have emerged as promising platforms for efficient in vivo mRNA delivery owing to advancements in ionizable lipids. However, maintaining the thermostability of mRNA/LNP systems remains challenging. While the importance of only a small amount of lipid impurities on mRNA inactivation is clear, a fundamental solution has not yet been proposed. In this study, we investigate an approach to limit the generation of aldehyde impurities that react with mRNA nucleosides through the chemical engineering of lipids. We demonstrated that piperidine-based lipids improve the long-term storage stability of mRNA/LNPs at refrigeration temperature as a liquid formulation. High-performance liquid chromatography analysis and additional lipid synthesis revealed that amine moieties of ionizable lipids play a vital role in limiting reactive aldehyde generation, mRNA–lipid adduct formation, and loss of mRNA function during mRNA/LNP storage. These findings highlight the importance of lipid design and help enhance the shelf-life of mRNA/LNP systems.

This study evaluates the potential deleterious impact of untreated waste water discharged into an unlined pit by the Nigerian National Petroleum Company (NNPC) on the groundwater quality of Umuakpara community in Osisioma, Abia state. Its overarching objective is to assess potential contaminant sources, distribution in groundwater using diverse techniques. Water samples collected from 14 domestic wells in two contrasting seasons (Rainy and Dry) were analyzed for Polynuclear Aromatic Hydrocarbons (PAHs) using Gas chromatography (GC). Vertical Electric Sounding (VES) technique was employed to determine the depth to water table and soil lithological layers required for good understanding of contaminants behavior along groundwater flow path. Pearson product moment correlation coefficient (r) and One-way ANOVA were used to define the interactions of detected PAHs and spatial variation in means of the PAHs components (p

Objectives: Evaluating the adherence to HIV Pre-Exposure Prophylaxis (PrEP) is essential for increasing its utilization and decreasing the risk of HIV transmission among Davao City's vulnerable groups. Methods: The research method utilized in the study is a quantitative, retrospective, descriptive research design. This method was employed to retrospectively review the de-identified data, which involved the fill and refill dates of PrEP and tablets supplied, to calculate the Proportion of Days Covered (PDC) among individuals in Davao City from January 2021 to December 2023. The study also included some demographic characteristics such as age and gender. Results: From 178 data entries collected, the age group of 25 to 34 years old was found to have the highest HIV PrEP use (52.3%), followed by those between 18 to 24 (30.9%), 35 to 44 (13.5%), and 45 years old and older (3.4%). Out of 178, only 2 clients were female. Furthermore, 73.6% of the 178 entries in the pharmacy records were identified to be taking PrEP daily. Descriptive statistics showed that the frequency of adherent clients across the years were 36.4%, 44.7% and 38.5%, respectively. Furthermore, the average PDC through the years was found to be 70.13%, 80.48%, and 72.8%. Age did not significantly affect adherence to PrEP during the years investigated (p-values > 0.05). Conclusion: Adherence to PrEP improved consistently in 2022 but declined in 2023, showing erratic adherence rates. Furthermore, adherence to HIV PrEP in Davao City was found to be suboptimal and while there are clients who are adherent, many are not. The results emphasize the need for targeted interventions and suggest that other socio-behavioral factors may play a role in this. To improve adherence and prevent HIV contractions, both short-term actions like public education campaigns about HIV PrEP and long-term plans like incorporating PrEP into the community pharmacies can be contributive.

Résumé : Œuvre de Trifonia Melibea Obono, La bastarda (2016) est essentiellement une traduction en espagnol de données sociologiques et anthropologiques fàŋ vers l'espagnol de Guinée-Équatoriale. En 2020, ce roman a été traduit de l'espagnol au français par Anne-Laure Bonvalot, ce qui contribue à accroître sa visibilité car elle permet aux multiples lecteurs de pénétrer cet univers socioculturel subsaharien. Cette étude n'est pas une critique de la traduction de l'œuvre dans son ensemble, mais celle des titres en espagnol La bastarda et français La bâtarde. L’étude consiste donc en un essai titrologique contrastif dans le domaine de l'ethnotraductologie qui convoque convoque l’horizon d’attente de la théorie de la réception. Il nous intéresse de savoir si, à travers ces deux titres, la société du roman est caractéristique de la société de référence ou si les deux auteurs naviguent à contre-courant de la pensée fàŋ. Mots-clés : Traduction – Culture – Titrologie - La bastarda - Guinée équatoriale.

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case–control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at −80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes’ degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP.

This scientific article aims to identify the most optimal healthcare financing model suitable for a country's unique healthcare context while focusing on overcoming the fragmented and costly way in which healthcare is traditionally delivered. The tasks set for this research include evaluating and benchmarking different countries and environments to identify the most efficient model, reducing transaction costs, and analysing the agents and their motivations and decision situations using agent theory and game theory. To achieve the goal and tasks, the author conducted a comprehensive study based on the transaction cost theory, which explains how inefficient contracts can lead to an inefficient healthcare system. Additionally, the author used agent theory to understand the motivations of various stakeholders involved in healthcare financing and game theory to analyse decision-making processes leading to socially and individually beneficial outcomes. The empirical segment of the research utilised data from the OECD annual healthcare database for 2016-2019. A range of analytical tools, including descriptive analysis, data visualization, correlation analysis, and hypothesis testing were employed to examine the dataset for this study. The analysis results revealed four healthcare financial models with various indicators with different levels of influence. This research provides valuable insights for senior healthcare managers and policymakers to make informed decisions and lead their organisations toward more efficient and effective healthcare financing models. In conclusion, this study fills the research gap and addresses the central research question by comprehensively analysing healthcare financing models. The results emphasize the importance of reducing transaction costs and understanding the motivations of different stakeholders for achieving more efficient and effective healthcare outcomes. Countries can move towards a more integrated and cost-effective healthcare system by implementing the most efficient model identified in this study

Chemokine G-protein coupled receptors are validated drug targets for many diseases, including cancer, neurological, and inflammatory disorders. Despite much time and effort spent on therapeutic development, very few chemokine receptor antagonists are approved for clinical use. Among potential reasons for the slow progress in developing chemokine receptor inhibitors, antagonist tolerance, a progressive reduction in drug efficacy after repeated administration, is likely to play a key role. The mechanisms leading to antagonist tolerance remain poorly understood. In many cases, antagonist tolerance is accompanied by increased receptor concentration on the cell surface after prolonged exposure to chemokine receptor antagonists. This points to a possible role of altered receptor internalization and presentation on the cell surface, as has been shown for agonist (primarily opioid) tolerance. In addition, examples of antagonist tolerance in the context of other G-protein coupled receptors suggest the involvement of noncanonical signal transduction in opposing the effects of the antagonists. In this review, we summarize the available progress and challenges in therapeutic development of chemokine receptor antagonists, describe the available knowledge about antagonist tolerance, and propose new avenues for future investigation of this important phenomenon. Furthermore, we highlight the modern methodologies that have the potential to reveal novel mechanisms leading to antagonist tolerance and to propel the field forward by advancing the development of potent “tolerance-free” antagonists of chemokine receptors.

Abstract Background Direct-access physiotherapy practice has led to a global review of the use of differential-diagnostic modalities such as musculoskeletal imaging (MI) in physiotherapy. Objective To explore the MI authority, levels of training, attitude, utilisation, and competence among clinical physiotherapists in Nigeria. Methods This national cross-sectional study analysed a voluntary response sample of 400 Nigerian physiotherapists that completed the online version of the Physiotherapist’s Musculoskeletal Imaging Profiling Questionnaire (PMIPQ), using descriptive statistics, Spearman’s correlation, Mann-Whitney U, Kruskal-Wallis, and Friedman’s ANOVA tests. Results Of the 400 participants, 93.2% believed that physiotherapists should use MI in clinical practice. However, only 79.8% reported having MI authority in their practice settings. The participants’ median (interquartile range) levels of training =10 (24) and competence =16 (24) were moderate. Nonetheless, levels of training (χ2 [15] = 1285.899, p = 0.001), and competence (χ2 [15] = 1310.769, p

Environmental conditions and photoperiod length drive the seasonal variability of gas exchange in plants. Still, little is known about trees' adaptation to climate change, expressed as a delay in decreasing photosynthetic capacity at the end of the growing season. We investigated the effect of elevated air humidity (RH) and sampling period (from July to September) on the variability of net photosynthesis ([A.sub.n]), dark respiration (R), daytime ([g.sub.l_day]) and night-time ([g.sub.l_night]) leaf conductance, an index of leaf chlorophyll content (SPAD), and [A.sub.n]:SPAD ratio in cut shoots of silver birch (Betula pendula Roth). Measurements of cut shoots were conducted in a climate chamber to eliminate the direct effect of field conditions. The [A.sub.n], [A.sub.n]:SPAD ratio, and [g.sub.l_day] were higher in the humidification treatment (H) than in the control (C) (P < 0.05) in autumn. The R was higher in the control than in the humidification treatment across the study period. The [g.sub.l_night] increased considerably in September in both treatments (P < 0.05) and was significantly correlated with R. Our findings suggest that autumnal leaf conductance and gas exchange in silver birch are considerably influenced by long-term exposure to elevated RH and are probably related to a complex of leaf senescence processes, including nitrogen retranslocation. Key words: abscisic acid, global climate change, leaf senescence, night-time, photoperiod. Les conditions environnementales et la duree de la photoperiode influencent la variabilite saisonniere de l'echange gazeux des plantes. Nous en savons toutefois tres peu sur l'adaptation des arbres aux changements climatiques exprimee comme un retard dans la diminution de la capacite photosynthetique a la fin de la saison de croissance. Nous avons examine l'effet de l'humidite elevee de l'air (RH) et la periode d'echantillonnage (de juillet a septembre) sur la variabilite de la photosynthese nette ([A.sub.n]), la respiration nocturne (R), la conductance des feuilles le jour ([g.sub.l_day]) et la nuit ([g.sub.l_night]) et l'indice du contenu de chlorophylle dans les feuilles (SPAD) ainsi que le taux de l'[A.sub.n]:SPAD dans les tiges coupees du bouleau verruqueux (Betula pendula Roth). Les mesures des tiges coupees ont ete effectuees dans une chambre climatique afin d'eliminer l'effet direct des conditions du terrain. L'[A.sub.n], le taux de l'[A.sub.n]:SPAD et le [g.sub.l_day] etaient plus eleves dans l'humidification (H) que dans le traitement (P < 0,05) de controle (C) en automne. La R etait plus elevee dans le controle que dans le traitement d'humidification tout au long de la periode de l'etude. Le [g.sub.l_night] a augmente considerablement en septembre dans les deux traitements (P < 0,05) et etait largement correle avec notre R. Nos conclusions suggerent que la conductance des feuilles automnales et l'echange gazeux dans le bouleau verruqueux sont considerablement influences par l'exposition a long terme a une RH elevee et sont probablement relies a des processus complexes de senescence des feuilles, y compris la retranslocation de l'azote. [Traduit par la Redaction] Mots-cles: acide abscissique, changements climatiques a l'echelle mondiale, senescence des feuilles, periode nocturne, photoperiode., Introduction Global climate change leads to longer growing seasons at high latitudes and is responsible for changes in the functionality and productivity of forest ecosystems. Moreover, climate change creates considerable [...]

Abstract Background S100B is an established biomarker of brain development and damage. Lutein (LT) is a naturally occurring xanthophyll carotenoid mainly concentrated in the central nervous system (CNS), but its neurotrophic role is still debated. We investigated whether LT cord blood concentrations correlate with S100B in a cohort of preterm and term healthy newborns. Methods We conducted a prospective study on the distribution of LT and S100B in arterial cord blood of healthy preterm (n = 50) and term (n = 50) newborns. Results S100B and LT showed a pattern of concentration characterized by higher levels (P

Abstract The emergence of green materials has attracted considerable attention in the field of optoelectronics. Copper-based lead-free metal halide (with a near-unity quantum yield) obtained from Cs3Cu2I5 nanocrystals (NCs) can exhibit blue emission with a wavelength of 440 nm and provide outstanding stability for various applications. However, in practical applications, colloidal dispersion purity and film quality are inadequate toward a high-performance device. In this study, antisolvent-free gel permeation chromatography is used to purify Cs3Cu2I5 NCs. The purified Cs3Cu2I5 NCs exhibit a high photoluminescent quantum yield and provide a highly oriented single-crystal film. Density functional theory calculation results indicate that the iodide-rich surface in the NCs makes them highly stable. In addition, it has been demonstrated for the first time that the mixture of polymethyl methacrylate (PMMA) and Cs3Cu2I5 NCs has waterproofing capabilities. The composite film consisting of Cs3Cu2I5 NCs and PMMA can survive in water for several days. This result opens up more possibilities for the application of these green material.

The measurement of blood pH and gas analytes (BPGA), soon after birth, constitutes the first-line standard of care procedure in high-risk newborns. However, no data is available in capillary blood on perinatal bias such as gestational age (GA), weight at birth (BW), delivery mode, and gender. The aims of the present study were to investigate whether in a cohort of healthy preterm (PT) and term (T) infants BPGA were GA, BW, delivery mode and gender dependent, thus affecting BPGA reliability as diagnostic test.We performed a prospective case-control study in 560 healthy infants (PT: n=115, T: n=445). BPGA was measured within 24-h from birth. Perinatal characteristics, outcomes, and clinical examination were also recorded.PT infants showed higher (p<0.001) carbon dioxide partial pressure (pCO2), fraction of fetal hemoglobin (HbF), base excess (BE), bicarbonate (HCO3), and lower lactate (Lac) levels. When corrected for delivery mode, higher (p<0.001) HbF, BE, HCO3, and lower Lac levels were found. Similarly, higher (p<0.05, for all) pCO2, HbF, BE, HCO3 and lower Lac levels were found between female and male PT and T infants. Repeated multiple logistic regression analysis showed that BPGA was GA, BW, delivery mode and gender dependent.The present results showing that BPGA can be affected by a series of perinatal outcomes open the way to further investigations providing longitudinal BPGA reference curves in the transitional phase, thus empowering BPGA role as a reliable diagnostic and therapeutic strategies efficacy marker. [ABSTRACT FROM AUTHOR]

Breast milk (BM) is a unique food due to its nutritional composition and anti-inflammatory characteristics. Evidence has emerged on the role of Presepsin (PSEP) as a reliable marker of early sepsis diagnosis. In the present study, we aimed to investigate the measurability of PSEP in BM according to different maturation stages (colostrum, C; transition, Tr; and mature milks, Mt) and corrected for delivery mode and gender. We conducted a multicenter prospective case–control study in women who had delivered 22 term (T) and 22 preterm (PT) infants. A total of 44 human milk samples were collected and stored at −80 °C. BM PSEP (pg/mL) levels were measured by using a rapid chemiluminescent enzyme immunoassay. PSEP was detected in all samples analyzed. Higher (p < 0.05) BM PSEP concentrations were observed in the PT compared to the T infants. According to the grade of maturation, higher (p < 0.05) levels of PSEP in C compared to Tr and Mt milks were observed in the whole study population. The BM subtypes' degrees of maturation were delivery mode and gender dependent. We found that PSEP at high concentrations supports its antimicrobial action both in PT and T infants. These results open the door to further studies investigating the role of PSEP. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of maternal morbidity and death from pregnancy loss before 28 weeks in referral‐level hospitals in Nigeria. Design: Secondary analysis of a nationwide cross‐sectional study. Setting: Fifty‐four referral‐level hospitals. Population: Women admitted for complications arising from pregnancy loss before 28 weeks between 1 September 2019 to 31 August 2020. Methods: Frequency and type of pregnancy loss were calculated using the extracted data. Multilevel logistic regression was used to determine sociodemographic and clinical factors associated with early pregnancy loss. Factors contributing to death were also analysed. Main outcome measures: Prevalence and outcome of pregnancy loss at <28 weeks; sociodemographic and clinical predictors of morbidity after early pregnancy loss; contributory factors to death. Results: Of the 4798 women who had pregnancy loss at <28 weeks of pregnancy, spontaneous abortion accounted for 49.2%, followed by missed abortion (26.9%) and ectopic pregnancy (15%). Seven hundred women (14.6%) had a complication following pregnancy loss and 99 women died (2.1%). Most complications (26%) and deaths (7%) occurred after induced abortion. Haemorrhage was the most frequent complication in all types of pregnancy loss with 11.5% in molar pregnancy and 6.9% following induced abortion. Predictors of complication or death were low maternal education, husband who was not gainfully employed, grand‐multipara, pre‐existing chronic medical condition and referral from another facility or informal setting. Conclusion: Pregnancy loss before 28 weeks is a significant contributor to high maternal morbidity and mortality in Nigeria. Socio‐economic factors and delays in referral to higher levels of care contribute significantly to poor outcomes for women. [ABSTRACT FROM AUTHOR]

See also the Commentary on this article by Chater, 243: 503–505. [ABSTRACT FROM AUTHOR]

In this study, the process from the foundation of Yugoslavia to its collapse was examined by considering Norbert Elias’s figurations. Yugoslavia serves as evidence of how accurate Elias’s figurations are in the context of states. It also signifies the delicate balances inherent in these figurations. Yugoslavia stands as proof of how the disruption of balance in figurations can lead to undesirable outcomes. In this context, Elias’ definition of four figurations was applied to the case of Yugoslavia, and a figurative answer was sought for the reason for the collapse of Yugoslav identity. The way different nations came together and the factors influencing this union were examined within the framework of Elias’s “survival unit”. Yugoslavia’s disintegration was exemplified by the figuration of the survival unit. As known, in Yugoslavia, an effort was made to establish a “we” among different nations coming together, but since every nation couldn’t abandon the “I” mentality, this endeavour proved unsuccessful. The cooperation of different nations for survival, how this cooperation process functioned, and the fact that nations continued to compete despite all cooperation were evaluated within the framework of the “cooperation and competition balance” figuration. The “involvement and detachment figuration”, exemplified by a football match in Yugoslavia, serves as a compelling example of this balance. [ABSTRACT FROM AUTHOR]

Early sepsis detection and diagnosis still constitutes an open issue since the accuracy of standard-of care parameters is biased by a series of perinatal factors including hypoxia. Therefore, we aimed at investigating the effect of fetal chronic hypoxia insult on urine levels of a promising new marker of sepsis, namely presepsin (P-SEP). We conducted a prospective case-control study in 22 cases of early-intrauterine growth restriction (E-IUGR) compared with 22 small-for-gestational-age (SGA) newborns and 66 healthy controls. P-SEP urine samples were collected over the first 72 h from birth. Blood culture and C-reactive protein (CRP) blood levels were measured in E-IUGR and SGA infants. Perinatal standard monitoring parameters and main outcomes were also recorded. No significant urinary P-SEP differences (p>0.05, for all) were observed among studied groups. Moreover, no significant correlations (p>0.05, for both) between urinary P-SEP and blood CRP levels in both E-IUGR and SGA groups (R=0.08; R=0.07, respectively) were observed. The present results showing the lack of influence of fetal chronic hypoxia on urinary P-SEP levels offer additional data to hypothesize the possible use of urinary P-SEP measurement in neonates in daily clinical practice. Further multicenter prospective data are needed, including infants with early-onset sepsis. [ABSTRACT FROM AUTHOR]

Contamination of agricultural soils by quarry activities is posing serious challenges food security in greater parts of the Sub-Saharan Africa. This study determined the heavy metals in soils and cassava (Manihot esculentum) tubers obtained from three different quarry sites in Umunneochi, Abia State Nigeria. Samples of soil and cassava tubers were collected in replicates following the direction of natural drainage, while control samples were obtained against the direction of natural drainage from the quarry pits. Soil and cassava tuber samples were collected and subjected to standard physicochemical analyses. Heavy metal concentration in the quarry soil and cassava tubers varied significantly from the control except for Cd (mg/kg) at P

Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 μg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE. [ABSTRACT FROM AUTHOR]

Thermostability is one of the pre-requisites for the reliability of analytes in clinical practice and biomedical research. Although presepsin represents a promising new biomarker for the early diagnosis of sepsis in newborns, data on its stability under different storage conditions are lacking. We aimed to investigate presepsin thermostability in blood, urine and saliva samples after thawing at 4 predetermined monitoring time-points in a cohort of preterm and term infants. We conducted an observational study, where each case served as its own control, in 24 preterm and term infants. Blood, urine and saliva samples were stored at −80 °C for 18 months, and presepsin measured in different biological fluids at thawing (T0), 24 (T1), 48 (T2) and at 72 (T3) hours after thawing. No significant differences (p>0.05, for all) in presepsin levels were observed at T0–T3 in the different biological fluids. Furthermore, no differences at T0–T3 were observed in presepsin levels between blood and saliva fluids, whilst urine levels were significantly higher (p<0.05, for all) than blood and saliva at T0–T3. Results on presepsin pre-analytical thermo-stability in different biological fluids after long-term refrigeration support the reliability of this biomarker in the diagnosis and monitoring of perinatal sepsis. [ABSTRACT FROM AUTHOR]

Aim: To investigate the effects of caffeine loading/maintenance administration on near‐infrared spectroscopy cerebral, kidney and splanchnic patterns in preterm infants. Methods: We conducted a multicentre case–control prospective study in 40 preterm infants (gestational age 29 ± 2 weeks) where each case acted as its own control. A caffeine loading dose of 20 mg/kg and a maintenance dose of 5 mg/kg after 24 h were administered intravenously. Near infrared spectroscopy monitoring parameters were monitored 30 min before, 30 min during and 180 min after caffeine therapy administration. Results: A significant increase (p < 0.05) in splanchnic regional oxygenation and tissue function and a decrease (p < 0.05) in cerebral tissue function after loading dose was shown. A preferential hemodynamic redistribution from cerebral to splanchnic bloodstream was also observed. After caffeine maintenance dose regional oxygenation did not change in the monitored districts, while tissue function increased in kidney and splanchnic bloodstream. Conclusion: Different caffeine administration modalities affect cerebral/systemic oxygenation status, tissue function and hemodynamic pattern in preterm infants. Future studies correlating near infrared spectroscopy parameters and caffeine therapy are needed to determine the short/long‐term effect of caffeine in preterm infants. [ABSTRACT FROM AUTHOR]