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Gambian infants frequently acquire Streptococcus pneumoniae soon after birth. We investigated the indirect effect of 7-valent pneumococcal conjugate vaccine (PCV-7) on pneumococcal acquisition in newborn Gambian babies. Twenty-one villages were randomised to receive PCV-7 to all subjects (11 vaccinated villages) or to infants aged 2-30 months (10 control villages). Other control villagers received Meningococcal C conjugate vaccine. From 328 babies born during the trial, nasopharyngeal swabs were collected after birth, then weekly until 8 weeks of age when they received their first dose of PCV-7. Pneumococcal carriage and acquisition rates were compared between the study arms and with a baseline study. 57.4% of 2245 swabs were positive for S. pneumoniae. Overall carriage was similar in both arms. In vaccinated villages fewer infants carried pneumococci of vaccine serotypes (VT) (16.9% [31/184] vs. 37.5% [54/144], p<0.001) and more carried pneumococci of non-vaccine serotypes (NVT) (80.9% [149/184] vs. 75.7% [109/144], p = 0.246). Infants from vaccinated villages had a significantly lower acquisition rate of VT (HR 0.39 [0.26-0.58], p<0.001) and increased acquisition of NVT (HR 1.16 [0.87-1.56], p = 0.312). VT carriage (51.6% vs. 37.5%, p = 031 in control and 46.1% vs. 16.8%, p<0.001 in vaccinated villages) and acquisition rates (HR 0.68 [0.50-0.92], p = 0.013 in control villages and HR 0.31 [0.19-0.50], p<.001 in vaccinated villages) were significantly lower in both study arms than in the baseline study. NVT carriage (63.2% vs. 75.7%, p = 0.037 in control and 67.2% vs. 75.3%, p = 0.005 in vaccinated villages) and acquisition rates (HR 1.48 [1.06-2.06], p = 0.022) and (HR 1.52 [1.11-2.10], p = 0.010 respectively) were significantly higher. PCV-7 significantly reduced carriage of VT pneumococci in unvaccinated infants. This indirect effect likely originated from both the child and adult vaccinated populations. Increased carriage of NVT pneumococci needs ongoing monitoring. ISRCTN Register 51695599.

Interleukin-3 (IL-3) stimulates the survival and proliferation of the FDCP-Mix 1 multipotent stem cell line. The possible involvement of guanyl nucleotide regulatory protein(s) in the IL-3 stimulated proliferative response has been evaluated. Pertussis toxin (PT) can partially inhibit IL-3 stimulated DNA synthesis and this inhibition is bypassed by TPA. The ADP-ribosylation of the PT substrate G protein in vivo is complete in 2 hours without concomitant inhibition of IL-3 stimulated hexose transport and Na+/H+ exchange. When loaded into FDCP-Mix 1 cells fluoroaluminate and CTP-∂-S, which can directly activate G proteins, are not capable of mimicking the effects of IL-3. Evidence is also presented that IL-3 does not stimulate a membrane-bound high affinity GTPase activity in the FDCP-Mix 1 cell line. These data suggest that a PT substrate G protein(s) can influence the IL-3 signalling cascade in an indirect or permissive manner, but that the IL-3 receptor does not directly couple to this G protein.IL-3 stimulates a transient fall in intracellular cyclic AMP levels in the absence of a cyclic AMP phosphodiesterase inhibitor which is not observed in the presence of the inhibitor. However, IL-3 has no long-term effects on the cyclic AMP levels of the FDCP-Mix 1 cells. The cells are shown to be competent for receptor-mediated increases in adenylate cyclase activity in response to PGE2 and NECA respectively. Both of these agents markedly elevate cyclic AMP levels and are shown to inhibit IL-3 stimulated DNA synthesis. Furthermore, long-term incubations with either cholera toxin or pertussis toxin also causes an increase in intracellular cyclic AMP levels. Thus, whilst there is no evidence of a second messenger role for cyclic AMP in IL-3 action, elevated levels of the cyclic nucleotide appeared to have an inhibitory effect on IL-3 stimulated proliferation.Also, a highly enriched population (>90%) of Granulocyte-Macrophage Colony-Forming Cells (GM-CFC) was prepared from bone marrow. These cells respond to Stem Cell Factor (SCF) and M-CSF by proliferation and development, forming granulocytic and monocytic cells respectively. Characterization of the molecular signals elicited by SCF in GM-CFC shows that an amiloride-sensitive Na+/H+ antiport is activated without inositol lipid hydrolysis. Furthermore, SCF-induced DNA synthesis is not sensitive to pertussis toxin. The potential of deciphering the molecular basis of lineage-restricted development by comparing the signalling events elicited by SCF and M-CSF in this cell population is highlighted.

Background Lagos state is the industrial nerve centre of Nigeria and was the epicentre of the 2014 Ebola outbreak in Nigeria as it is now for the current Coronavirus Disease (COVID-19) outbreak. This paper describes how the lessons learned from the Ebola outbreak in 2014 informed the emergency preparedness of the State ahead of the COVID-19 outbreak and guided response. Discussion Following the Ebola outbreak in 2014, the Lagos State government provided governance by developing a policy on emergency preparedness and biosecurity and provided oversight and coordination of emergency preparedness strategies. Capacities for emergency response were strengthened by training key staff, developing a robust surveillance system, and setting up a Biosafety Level 3 laboratory and biobank. Resource provision, in terms of finances and trained personnel for emergencies was prioritized by the government. With the onset of COVID-19, Lagos state was able to respond promptly to the outbreak using the centralized Incident Command Structure and the key activities of the Emergency Operations Centre. Contributory to effective response were partnerships with the private sectors, community engagement and political commitment. Conclusion Using the lessons learned from the 2014 Ebola outbreak, Lagos State had gradually prepared its healthcare system for a pandemic such as COVID-19. The State needs to continue to expand its preparedness to be more resilient and future proof to respond to disease outbreaks. Looking beyond intra-state gains, lessons and identified best practices from the past and present should be shared with other states and countries.

Heart disease is a significant global health issue, causing millions of deaths annually. Despite advancements in medical technology, early and accurate diagnosis remains challenging. This study aims to detect heart diseases using binary classification machine learning models. The methodology employed a Heart Failure Prediction Dataset from Kaggle, with no issues of duplicates, missing data, outliers, or multicollinearity. Five machine learning models, including K-Neighbor Classifier, decision tree, support vector machine, random forest, and logistic regression, were trained and tested. The random forest model with hyper-parameters 'n_estimators': list (range (5,40,3)), 'max_features': ['log2', 'sqrt'] yielded the highest accuracy rate of 87.5%, precision rate of 90.4%, recall rate of 87.9%, f1_score of 89.1%, and auc_score of 93.6%. These results indicate that the random forest model has a notable capacity for accurate heart disease prediction, offering potential benefits such as reduced mortality rates and improved patient outcomes. Further research is recommended to establish standard data collection and analysis methods and to develop prediction models that consider the unique characteristics of diverse populations.

Background Recent studies have shown parasites as accumulation indicators that give critical information about the bioavailability of pollutants. To further buttress parasites in the assessment of metal sink potentials, the parasite Cosmocerca sp. was analyzed in a total of 168 host toads, Sclerophrys regularis , from three (3) study stations sampled around dumpsites and natural habitats in selected parts of Lagos Metropolis. Method Concentrations of Zn, Ni, Co, Cu, and Pb in the soil, parasite, intestine, and liver of toads at each location were analyzed using flame atomic absorption spectrometry. Results Comparison based on the concentrations of metals in S. regularis liver regardless of the collection site (dumpsite and natural habitat) showed that the most accumulated metal was zinc. Zinc significantly accumulated in the liver of the uninfected toad at the dumpsite, followed by the infected counterparts. There was also significant bioaccumulation of lead in the liver of the uninfected toads followed by the infected toads at the dumpsites. The accumulation of lead in the toads in their natural habitats was insignificant. The significant biota-sediment accumulation of copper in the liver was in the order of infected toad at dumpsite > infected toad at natural habitat > uninfected toad at habitat. Copper accumulation in the uninfected toad at the dumpsites was insignificant. As for cobalt, the significant biota-sediment accumulation in the liver was in the order of uninfected toad at dumpsite > infected toad at dumpsite > infected toad at habitat. Insignificant bioaccumulation occurred only in the uninfected toad at the natural habitat. A strong positive correlation (0.9546) between the concentrations of metals in the liver and the intestine indicated a common source of contamination and relatively proportional accumulation rates. Although there was a significant positive correlation between the concentrations of metals in the intestine and the parasites, a significantly negative correlation relationship, however, occurred between the concentrations of metals in the liver and the parasites. Conclusions This current study has demonstrated the possibility of employing Cosmocerca sp. as a bio-sink and bioindicator for zinc contamination. The parasites may therefore be promising in protecting S. regularis and safeguarding the health of the associated populace.

AbstractBackground: Amphibians are subjected to a variety of natural and artificial stresses that can compromise physiological balance. This study explored the variations in oxidative stress markers in Cosmocercan parasitized and non-parasitized Amietophrynus regularis in diverse conditions. The toad specimens were collected from natural habitats and dumpsites of three (3) major areas of Lagos. 15 g wet weight of the liver, intestine, and parasites were separately prepared and analyzed for oxidative stress parameters including; SOD, CAT, GSH, and MDA activities according to well-established protocols. Result: Based on stations, there were significant differences in the SOD levels in the liver and intestine of infected and uninfected toads obtained at the dumpsite and the natural habitat at p < 0.001. Also, the concentration of SOD in the parasites (238.86 ± 7.72 min/mg prot.) recovered from the toads at the dumpsite was very much significantly higher than the concentration in those recovered from the toads in the natural habitat (p < 0.001). The study has shown that the level of SOD released by the antioxidant defense system in response to the oxidative stress in the organism makes it a reliable tool for ecotoxicological assessment. All the oxidative stress markers except for MDA showed significant differences at p < 0.05 between the host tissues and the parasites irrespective of sampling locations indicating both organisms were stressed either due to the host-parasite relationship or from other environmental contaminants. Conclusions: The toad’s antioxidant defense system was typically sensitive and adaptable to environmental conditions, suggesting that it could be used in future research on effective ecotoxicological evaluation tools.

Telomeres are major determinants of chromosome integrity, and when poorly regulated, they have been shown to contribute critically to malignant transformation. However, in gynaecological malignancies, telomeres are interpreted inconsistently and have yet to be smoothly incorporated into diverse disease types. The review incorporates the existing evidence of the relationship between telomere dysfunction and the evolution of cervical, ovarian, endometrial, vulvar, and vaginal cancer. The review discusses the joint causes of telomere erosion, defective capping, defective integrity, and dysregulated telomerase activity in gynaecological cancer development, and the ensuing genomic instability, disruption in tissue homeostasis, inflammation, immune evasion, clonal evolution, and changes in individual organ physiology. According to this integrative framework, there are common and cancer-specific processes, new biomarkers for telomere maintenance, and therapeutic prospects focused on telomere maintenance pathways. The development of standardized, longitudinal methodologies will be key to translating telomere biology into clinically actionable approaches in gynaecological oncology.

Background: The induction of the mitochondrial membrane permeability transition (MMPT) pore has been implicated in the cascade of events involved in apoptosis (programmed cell death). Olax subscorpioidea is traditionally used for the treatment of several diseases and infection. However, its role on MMPT is not yet established. This study was aimed at evaluating the effects of varying concentrations of the methanol leaf extract of O. subscorpioidea (MEOS) on MMPT pore opening, mitochondrial adenosine triphosphatase (ATPase), and mitochondrial lipid peroxidation. Materials and Methods: Opening of the pore was spectrophotometrically assayed under succinate-energized conditions. Results: In the absence of triggering agent (calcium), MEOS induced MMPT pore opening by 350, 612, 827, 845% at 36, 60, 86 and 112 μg/ml, respectively. MEOS further induced MMPT pore opening in the presence of a triggering agent by 866, 905, 831, 840, 949% at 12, 36, 60, 86 and 112 μg/ml, respectively. The extract significantly induced mitochondrial membrane lipid peroxidation in all the concentration used. MEOS also significantly increased mitochondrial ATP hydrolysis by mitochondrial ATPase in all concentration of the extract used. Conclusion: It may be deduced from this results, that MEOS contains certain bioactive components that may find use in pathological conditions that require an enhanced rate of apoptosis.