The cell cycle regulatory DREAM complex is disrupted by high expression of oncogenic B-Myb.

Overexpression of the oncogene MYBL2 (B-Myb) is associated with increased cell proliferation and serves as a marker of poor prognosis in cancer. However, the mechanism by which B-Myb alters the cell cycle is not fully understood. In proliferating cells, B-Myb interacts with the MuvB core complex including LIN9, LIN37, LIN52, RBBP4, and LIN54, forming the MMB (Myb-MuvB) complex, and promotes transcription of genes required for mitosis. Alternatively, the MuvB core interacts with Rb-like protein p130 and E2F4-DP1 to form the DREAM complex that mediates global repression of cell cycle genes in G0/G1, including a subset of MMB target genes. Here, we show that overexpression of B-Myb disrupts the DREAM complex in human cells, and this activity depends on the intact MuvB-binding domain in B-Myb. Furthermore, we found that B-Myb regulates the protein expression levels of the MuvB core subunit LIN52, a key adapter for assembly of both the DREAM and MMB complexes, by a mechanism that requires S28 phosphorylation site in LIN52. Given that high expression of B-Myb correlates with global loss of repression of DREAM target genes in breast and ovarian cancer, our findings offer mechanistic insights for aggressiveness of cancers with MYBL2 amplification, and establish the rationale for targeting B-Myb to restore cell cycle control

Establishing an antimicrobial stewardship program in Sierra Leone: a report of the experience of a low-income country in West Africa

Antimicrobial Resistance (AMR) is a growing global health challenge that threatens to undo gains in human and animal health. Prevention and control of AMR requires functional antimicrobial stewardship (AMS) program, which is complex and often difficult to implement in low- and middle-income countries. We aimed to describe the processes of establishing and implementing an AMS program at Connaught Hospital in Sierra Leone. The project involved the setting up of an AMS program, capacity building and performing a global point prevalence survey (GPPS) at Sierra Leone's national referral hospital. Connaught Hospital established a multidisciplinary AMS subcommittee in 2021 to provide AMS services such as awareness campaigns, education and training and review of guidelines. We performed a GPPS on 175 patients, of whom more than half (98, 56.0%) were prescribed an antibiotic: 63 (69.2%) in the surgical wards and 53 (51.2%) in the medical wards. Ceftriaxone (60, 34.3%) and metronidazole (53, 30.3%) were the most common antibiotics prescribed to patients. In conclusion, it is feasible to establish and implement an AMS program in low-income countries, where most hospitalized patients were prescribed an antibiotic

ENHANCEMENT OF REAL-TIME SCAN MATCHING FOR UAV INDOOR NAVIGATION USING VEHICLE MODEL

Autonomous Unmanned Aerial Vehicles (UAVs) have drawn great attention from different organizations, because of the various applications that save time, cost, effort, and human lives. The navigation of autonomous UAV mainly depends on the fusion between Global Navigation Satellite System (GNSS) and Inertial Measurement System (IMU). Navigation in indoor environments is a challenging task, because of the GNSS signal unavailability, especially when the utilized IMU is low-cost. Light Detection and Ranging Radar (LIDAR) is one of the mainly utilized sensors in the indoor environment for localization through scan matching of successive scans. The process of calculating the rotation and translation from successive scans can employ different approaches, such as Iterative Closest Point (ICP) with its variants, and Hector SLAM. ICP and Hector SLAM iterative fashion can greatly increase the matching time, and the convergence is not guaranteed in case of harsh maneuvers, moving objects, and short-range LIDAR as it may get stuck in local minima. This paper proposes enhanced real-time ICP and Hector SLAM algorithms based on vehicle model (VM) during sharp maneuvers. The vehicle model serves as initialization step (coarse alignment) then the ICP/Hector serve as fine alignment step. Test cases of quadcopter flight with harsh maneuvers were carried out with LIDAR to evaluate the proposed approach to enhance the ICP/Hector convergence time and accuracy. The proposed algorithm is convenient for UAVs where there are limitations regarding the size, weight, and power limitations, as it is a stand-alone algorithm that does not require any additional sensors

A large pseudoautosomal region on the sex chromosomes of the frog Silurana tropicalis

Sex chromosome divergence has been documented across phylogenetically diverse species, with amphibians typically having cytologically nondiverged (“homomorphic”) sex chromosomes. With an aim of further characterizing sex chromosome divergence of an amphibian, we used “RAD-tags” and Sanger sequencing to examine sex specificity and heterozygosity in theWestern clawed frog Silurana tropicalis (also known as Xenopus tropicalis). Our findings based on approximately 20 million genotype calls and approximately 200 polymerase chain reaction-amplified regions across multiple male and female genomes failed to identify a substantially sized genomic region with genotypic hallmarks of sex chromosome divergence, including in regions known to be tightly linked to the sex-determining region.Wealso foundthat expression andmolecular evolutionof genes linked to the sex-determining region did not differ substantially from genes in other parts of the genome. This suggests that the pseudoautosomal region, where recombination occurs, comprises a large portion of the sex chromosomes of S. tropicalis. These resultsmay in part explainwhy African clawed frogs have such a high incidence of polyploidization, shed light onwhy amphibians have a high rate of sex chromosome turnover, and raise questions about why homomorphic sex chromosomes are so prevalent in amphibians

EVALUATION OF THE QUALITY OF DIFFERENT BRANDS OF ASCORBIC ACID IN FREETOWN, SIERRA LEONE

Objective: This study evaluates the registration status and the quality of nine brands of Vitamin C sold in Freetown, Sierra Leone, using official and non-official methods of analysis. Methods: The parameters taken into consideration during the study include non-official methods (friability and disintegration) and the official methods (identification test, uniformity of dosage unit, and assay by titrimetric and colorimetric tests). The different brands of vitamin C were selected and classified as registered and unregistered based on the data derived from the National Medicines Regulatory Authority. Results: One vitamin C product collected was unregistered at the National medicines regulatory authority (Pharmacy Board of Sierra Leone). All nine vitamin C products met the requirements for uniformity of dosage unit. The vitamin C products also conformed to the BP specification for friability and identification test (retention factor). The identification test showed that each brand contained vitamin C (ascorbic acid). The disintegration test was not applicable for chewable tablets. Three of the four non-chewable vitamin C products complied with the BP specification for disintegration, while one failed and did not meet the requirement. The assay results for ascorbic acid using titration and colourimetric method were comparable and appropriate for determining vitamin C. Out of a total of nine samples; seven met the requirement for BP specification (Passed) for assay. In contrast, one product did not meet the BP requirement (failed), and one sample had more vitamin C than the Pharmacopoeia limit. Conclusion: Periodic quality evaluation and routine checks for pharmaceutical products can ascertain the quality of products, their storage conditions and identify potential counterfeit medications

Climate-smart fisheries: CO2 emissions reduction and food security are complementary

In the global north, climate-smart fisheries (CSF) policies prioritise steps to combat CO2 emissions from SSF, in a response to the fact that globally, CO2 emissions from small-scale fisheries (SSFs) increased by over 5.8 times between 1950 and 2016. However, in the global south, CSF policies on SSF prioritise food and income security over CO2 emission reduction. In this paper, we examine this apparently contrasting interpretation of CSF as a conceptual framework to interpret the case study of Sierra Leone, one of Africa's poorest countries where we found that small-scale coastal fishers are preoccupied with mitigating the impact of climate change on their food and income security rather than with lowering their CO2 emissions. The self-image of SSF in Sierra Leone is that of being victims of climate change rather than perpetrators of it, and they justify this stance by claiming their livelihoods are being threatened by climate change. However, it could be argued that the best way to keep Sierra Leonean SSF CO2 emissions low is to prioritise their food and income security: in other words, that food security and CO2 reductions are complementary not contradictory. This, at any rate, is the argument of the current paper. The fieldwork for this study entailed co-created research in Sierra Leone and it involved 103 stakeholders who met face-to-face and online between January and March 2022 and through village meetings. The results of this fieldwork showed that food and income security and not CO2 emissions are the priorities in the stakeholders’ interpretation of CSF. However, if food and income security are not prioritised, communities are likely to adopt maladaptive strategies which undermine marine protected areas (MPAs) and exacerbate overfishing, thereby increasing CO2 emissions. Moreover, investment in aquaculture as a supplementary or alternative livelihood can directly increase food security and incomes and at the same time indirectly serve as a CO2 mitigation measure. In addition, weather information communication is an important CSF measure which both protects fishers from the impact of climate change and reduces their CO2 emissions. Accordingly, we argue that the contrast between reducing CO2 emissions and protecting food security from climate change may be more apparent than real in Sierra Leone coastal fisheries, since both policies may work in tandem together. This study therefore contributes a new interpretation of CSF in the global south: instead of seeing it as posing a conflict between CO2 emissions reductions and food security, we have shown the two objectives can be complementary. The wider implication of this paper is that CSF strategies for SSFs do not have to be polarised between the global north's focus on the reduction of CO2 emissions from fishing vessels and the global south's focus on the mitigation of the impact of global warming on SSFs. There are circumstances when the two objectives may be in harmony

Functional status of masticatory system, excutive function and episodic memory in older persons.

Findings from human experimental studies suggest that mastication positively influences cognitive function. The participants in those studies were relatively young. The goal of this study was to examine the relationship between the functional status of the masticatory system, episodic memory, and executive functions in elderly people. The participants, elderly people living independently at home, were divided into two groups. One group had a full complement of natural teeth (n = 19) and the other group had full dentures (n = 19). The functional status of the masticatory system was assessed by measuring mandibular excursions (i.e. the distances over which the mandible can move in the open, lateral, and forward directions), bite force, number of occluding pairs and complaints of the masticatory system (facial pain, headaches/migraine). Executive functions and episodic memory were assessed by neuropsychological tests. Backward regression analysis showed that only in the group of elderly people with full dentures, 22% of executive functions were predicted by complaints of the masticatory system and 19.4% of episodic memory was predicted by masticatory performance (composed of mandibular excursions and bite force). The conclusion of this study is that only in older persons with full dentures the relationship between mastication, episodic memory, and executive function becomes evident when the functional status of the masticatory system decreases

Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC).

<p>Resource Planning for Neglected Tropical Disease (NTD) Control Programs: Feasibility Study of the Tool for Integrated Planning and Costing (TIPAC)</p

An Assessment of Medication Errors Among Pediatric Patients in Three Hospitals in Freetown Sierra Leone: Findings and Implications for a Low-Income Country

Onome T Abiri,1,2 Alex Ninka,3 Joshua Coker,4 Fawzi Thomas,2,5 Isaac O Smalle,6 Sulaiman Lakoh,4 Foday Umaro Turay,7 James Komeh,2,3 Mohamed Sesay,2,7 Joseph Sam Kanu,8 Ayeshatu M Mustapha,9 Nellie VT Bell,9 Thomas Ansumus Conteh,2,5 Sarah Kadijatu Conteh,10 Alhaji Alusine Jalloh,10 James BW Russell,4 Noah Sesay,3 Mohamed Bawoh,1 Mohamed Samai,1 Michael Lahai7 1Department of Pharmacology and Therapeutics, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 2Department of Pharmacovigilance and Clinical Trials, Pharmacy Board of Sierra Leone, Freetown, Sierra Leone; 3Department of Clinical Pharmacy and Therapeutics, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 4Department of Internal Medicine, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 5Department of Pharmaceutics, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 6Department of Surgery, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 7Department of Pharmaceutical Chemistry, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 8Department of Community Medicine, College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone; 9Department of Pediatrics, Ola During Children Hospital, Freetown, Sierra Leone; 10Department of Pediatrics, King Harman Road Maternity and Children Hospital, Freetown, Sierra LeoneCorrespondence: Onome T Abiri, Department of Pharmacology and Therapeutics, College of Medicine and Allied Health Sciences, University of Sierra Leone Freetown, Sierra Leone/Department of Pharmacovigilance and Clinical Trials, Pharmacy Board of Sierra Leone, Freetown, Sierra Leone, Tel +23276370315, Email [email protected]: Pediatric patients are prone to medicine-related problems like medication errors (MEs), which can potentially cause harm. Yet, this has not been studied in this population in Sierra Leone. Therefore, this study investigated the prevalence and nature of MEs, including potential drug-drug interactions (pDDIs), in pediatric patients.Methods: The study was conducted in three hospitals among pediatric patients in Freetown and consisted of two phases. Phase one was a cross-sectional retrospective review of prescriptions for completeness and accuracy based on the global accuracy score against standard prescription writing guidelines. Phase two was a point prevalence inpatient chart review of MEs categorized into prescription, administration, and dispensing errors and pDDIs. Data was analyzed using frequency, percentages, median, and interquartile range. Kruskal–Wallis H and Mann–Whitney U-tests were used to compare the prescription accuracy between the hospitals, with p< 0.05 considered statistically significant.Results: Three hundred and sixty-six (366) pediatric prescriptions and 132 inpatient charts were reviewed in phases one and two of the study, respectively. In phase one, while no prescription attained the global accuracy score (GAS) gold standard of 100%, 106 (29.0%) achieved the 80– 100% mark. The patient 63 (17.2%), treatment 228 (62.3%), and prescriber 33 (9.0%) identifiers achieved an overall GAS range of 80– 100%. Although the total GAS was not statistically significant (p=0.065), the date (p=0.041), patient (p=< 0.001), treatment (p=0.022), and prescriber (p=< 0.001) identifiers were statistically significant across the different hospitals. For phase two, the prevalence of MEs was 74 (56.1%), while that of pDDIs was 54 (40.9%). There was a statistically positive correlation between the occurrence of pDDI and number of medicines prescribed (r=0.211, P=0.015).Conclusion: A Low GAS indicates poor compliance with prescription writing guidelines and high prescription errors. Medication errors were observed at each phase of the medication use cycle, while clinically significant pDDIs were also reported. Thus, there is a need for training on prescription writing guidelines and medication errors.Keywords: pediatrics, prescription, medication errors, drug-drug interactions, Sierra Leon