Sub-microscopic Plasmodium falciparum infections and multiple drug resistant single nucleotide polymorphic alleles in pregnant women from southwestern Nigeria.

OBJECTIVES: The study evaluated sub-microscopic malaria infections in pregnancy using two malaria Rapid Diagnostic Tests (mRDTs), microscopy and RT-PCR and characterized Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and Plasmodium falciparum dihydropteroate synthase (Pfdhps) drug resistant markers in positive samples. METHODS: This was a cross sectional survey of 121 pregnant women. Participants were finger pricked, blood drops were collected for rapid diagnosis with P. falciparum histidine-rich protein 11 rapid diagnostic test kit and the ultra-sensitive Alere Pf malaria RDT, Blood smears for microscopy and dried blood spots on Whatman filter paper for molecular analysis were made. Real time PCR targeting the var acidic terminal sequence (varATS) gene of P. falciparum was carried out on a CFX 96 real time system thermocycler (BioRad) in discriminating malaria infections. For each run, laboratory strain of P. falciparum 3D7 and nuclease free water were used as positive and negative controls respectively. Additionally, High resolution melt analyses was employed for genotyping of the different drug resistance markers. RESULTS: Out of one hundred and twenty-one pregnant women sampled, the SD Bioline™ Malaria Ag P.f HRP2-based malaria rapid diagnostic test (mRDT) detected eight (0.06%) cases, the ultra-sensitive Alere™ malaria Ag P.f rapid diagnostic test mRDT had similar outcome in the same samples as detected by the HRP2-based mRDT. Microscopy and RT-PCR confirmed four out of the eight infections detected by both rapid diagnostic tests as true positive and RT-PCR further detected three false negative samples by the two mRDTs providing a sub-microscopic malaria prevalence of 3.3%. Single nucleotide polymorphism in Pfdhps gene associated with sulphadoxine resistance revealed the presence of S613 mutant genotypes in three of the seven positive isolates and isolates with mixed wild/mutant genotype at codon A613S. Furthermore, four mixed genotypes at the A581G codon were also recorded while the other Pfdhps codons (A436G, A437G and K540E) showed the presence of wild type alleles. In the Pfdhfr gene, there were mutations in 28.6%, 28.6%, and 85.7% at the I51, R59 and N108 codons respectively. Mixed wild and mutant type genotypes were also observed in 28.6% each of the N51I, and C59R codons. For the Pfcrt, two haplotypes CVMNK and CVIET were observed. The SVMNT was altogether absent. Triple mutant CVIET 1(14.3%) and triple mutant + wild genotype CVIET + CVMNK 1(14.3%) were observed. The Pfmdr1 haplotypes were single mutants YYND 1(14.3%); NFND 1(14.3%) and double mutants YFND 4(57.1%); YYDD 1(14.3%).

Coconut leaf midrib skewer as a cause for small bowel obstruction and perforation: A case report.

Foreign body ingestion is an infrequent cause of small bowel obstruction and, rarely, perforation. It is a common occurrence among pediatric patients, mentally impaired and the edentulous elderly population majority of which will pass through the gastrointestinal tract uneventfully. The likelihood of complications such as perforation, bleeding or fistula formation increases markedly particularly for sharp, stiff, and elongated objects (i.e. toothpicks, meat bones, pins, and razor blades). Diagnosis can be difficult as frequently patients are incognizant of the nature and time of ingestion. Imaging is commonly non-specific as well. We present an unusual case of a 65-year-old male who had an ileal perforation secondary to a coconut leaf midrib skewer initially presenting as small bowel obstruction. Intraoperatively, adhesions were seen in the ileum with note of the foreign body perforating two bowel loops that was not identified in preoperative imaging. This case highlights the importance of considering atypical causes of small bowel obstruction even in the background of previous surgery. Finally, early recognition, accurate diagnosis, and timely intervention are essential to improve patient outcomes and decrease mortality in such cases.

A stable microtubule bundle formed through an orchestrated multistep process controls quiescence exit.

Cells fine-tune microtubule assembly in both space and time to give rise to distinct edifices with specific cellular functions. In proliferating cells, microtubules are highly dynamics, and proliferation cessation often leads to their stabilization. One of the most stable microtubule structures identified to date is the nuclear bundle assembled in quiescent yeast. In this article, we characterize the original multistep process driving the assembly of this structure. This Aurora B-dependent mechanism follows a precise temporality that relies on the sequential actions of kinesin-14, kinesin-5, and involves both microtubule-kinetochore and kinetochore-kinetochore interactions. Upon quiescence exit, the microtubule bundle is disassembled via a cooperative process involving kinesin-8 and its full disassembly is required prior to cells re-entry into proliferation. Overall, our study provides the first description, at the molecular scale, of the entire life cycle of a stable microtubule structure in vivo and sheds light on its physiological function.

Computational identification of potential modulators of heme-regulated inhibitor (HRI) for pharmacological intervention against sickle cell disease.

Sickle cell disease (SCD) poses a significant health challenge and therapeutic approaches often target fetal hemoglobin (HbF) to ameliorate symptoms. Hydroxyurea, a current therapeutic option for SCD, has shown efficacy in increasing HbF levels. However, concerns about myelosuppression and thrombocytopenia necessitate the exploration of alternative compounds. Heme-regulated inhibitor (HRI) presents a promising target for pharmacological intervention in SCD due to its association with HbF modulation. This study screened compounds for their potential inhibitory functions against HRI. Small-molecule compounds from 17 folkloric plants were subjected to in silico screening against HRI. Molecular docking was performed, and free binding energy calculations were determined using molecular mechanics with generalized born and surface area (MMGBSA). Lead compounds were subjected to molecular dynamics simulation at 100 ns. Computational quantum mechanical modeling of the lead compounds was subsequently performed. We further examined the pharmacodynamics, pharmacokinetic and physiological properties of the identified compounds. Five potential HRI inhibitors, including kaempferol-3-(2G-glucosyrutinoside), epigallocatechin gallate, tiliroside, myricetin-3-O-glucoside and cannabiscitrin, with respective docking scores of -16.0, -12.17, -11.37, -11.56 and 11.07 kcal/mol, were identified. The MMGBSA analysis of the complexes yielded free-binding energies of -69.76, -71.17, -60.44, -53.55 and -55 kcal/mol, respectively. The identified leads were stable within HRI binding pocket for the duration of the 100 ns simulation. The study identified five phytoligands with potential inhibitory effects on HRI. This finding holds promise for advancing SCD treatment strategies. However, additional preclinical analyses are warranted to validate the chemotherapeutic properties of the lead compounds.Communicated by Ramaswamy H. Sarma.

The tricot approach: an agile framework for decentralized on-farm testing supported by citizen science. A retrospective.

Matching crop varieties to their target use context and user preferences is a challenge faced by many plant breeding programs serving smallholder agriculture. Numerous participatory approaches proposed by CGIAR and other research teams over the last four decades have attempted to capture farmers' priorities/preferences and crop variety field performance in representative growing environments through experimental trials with higher external validity. Yet none have overcome the challenges of scalability, data validity and reliability, and difficulties in capturing socio-economic and environmental heterogeneity. Building on the strengths of these attempts, we developed a new data-generation approach, called triadic comparison of technology options (tricot). Tricot is a decentralized experimental approach supported by crowdsourced citizen science. In this article, we review the development, validation, and evolution of the tricot approach, through our own research results and reviewing the literature in which tricot approaches have been successfully applied. The first results indicated that tricot-aggregated farmer-led assessments contained information with adequate validity and that reliability could be achieved with a large sample. Costs were lower than current participatory approaches. Scaling the tricot approach into a large on-farm testing network successfully registered specific climatic effects of crop variety performance in representative growing environments. Tricot's recent application in plant breeding networks in relation to decision-making has (i) advanced plant breeding lines recognizing socio-economic heterogeneity, and (ii) identified consumers' preferences and market demands, generating alternative breeding design priorities. We review lessons learned from tricot applications that have enabled a large scaling effort, which should lead to stronger decision-making in crop improvement and increased use of improved varieties in smallholder agriculture.

Antimicrobial and Synergistic Effects of Syzygium cumini, Moringa oleifera, and Tinospora cordifolia Against Different Candida Infections.

Introduction The burden of multiple drug resistance in human pathogens has necessitated the search for and development of antimicrobial agents with a wide range of structural classes and potentials to selectively act on the several mechanisms of actions exhibited by the pathogens. However, most synthetic antimicrobial agents have been linked with adverse side effects and high costs, furthering the need to explore more options. Syzygium cumini, Moringa oleifera, and Tinospora cordifolia are three medicinal plants used in traditional medicine systems for various infectious diseases. They contain various phytochemicals that exhibit antimicrobial activities against various bacteria, fungi, and parasites. The mechanisms of their antimicrobial action may involve the disruption of microbial cell walls and membranes, the inhibition of microbial enzyme and biofilm formation, the modulation of microbial gene expression and quorum sensing, and the induction of microbial cell death. Therefore, the present study evaluated the potentials of aqueous and ethanol extracts of S. cumini, M. oleifera, and T. cordifolia in managing infections as measured by their inhibitory effects on species. Materials and method Syzygium cumini, M. oleifera, and T. cordifolia were obtained and authenticated, and their aqueous and ethanol extracts were prepared. The antibacterial properties of the aqueous and ethanol extracts were examined. In addition to broth microdilution and biofilm development experiments, we also employed disk diffusion and agar-well diffusion techniques. The inocula of various species, including krusei, parapsilosis, utilis, albicans, and glabrata, were prepared for these assays. The synergistic effect of plant extracts with fluconazole was also evaluated. Results Syzygium cumini, M. oleifera, and T. cordifolia emerge as promising sources for the development of effective and sustainable antimicrobial interventions. Interestingly, the aqueous and ethanol extracts were effective against the selected species. Also, the synergistic combination of plant extracts with fluconazole was observed to triple the potency of the extracts. Furthermore, the potency of the plant extract as an antifungal and synergistic agent was ranked as S. cumini > M. oleifera > T. cordifolia. Conclusively, the plant extracts are effective in the management of opportunistic fungal infections.

Exploring the genetic diversity of Eimeria acervulina: A polymerase chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) approach.

Eimeria, protozoan parasites that can cause the disease coccidiosis, pose a persistent challenge to poultry production and welfare. Control is commonly achieved using good husbandry supplemented with routine chemoprophylaxis and/or live parasite vaccination, although widespread drug resistance and challenges to vaccine supply or cost can prove limiting. Extensive effort has been applied to develop subunit anticoccidial vaccines as scalable, cost-effective alternatives, but translation to the field will require a robust understanding of parasite diversity. Using a new Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) panel we begin to describe the genetic diversity of Eimeria acervulina populations in Africa and Europe. PCR-RFLP genotyping E. acervulina populations sampled from commercial broiler and layer chickens reared in Nigeria or the United Kingdom (UK) and Republic of Ireland (RoI) revealed comparable levels of haplotype diversity, in direct contrast to previous descriptions from the close relative E. tenella. Here, 25 distinct PCR-RFLP haplotypes were detected from a panel of 42 E. acervulina samples, including 0.7 and 0.5 haplotypes per sample in Nigeria (n = 20) and the UK/RoI (n = 14), respectively. All but six haplotypes were found to be country-specific. The PCR-RFLP markers immune mapped protein 1 (IMP1) and heat shock protein 90 (HSP90) were most informative for Nigerian E. acervulina, while microneme protein 3 (MIC3) and HSP90 were most informative in UK/RoI populations. High haplotype diversity within E. acervulina populations may indicate frequent genetic exchange and potential for rapid dissemination of genetic material associated with escape from selective barriers such as anticoccidial drugs and future subunit vaccines.

Groundwater pollution and risk assessment using indexed-based models: a case study of Igbo-Etiti area, eastern Nigeria.

Water is one of the most abundant resources on earth not evenly distributed. Due to the high shortage of water sources in Igbo-Etiti and intensive agricultural practices in the area, assessment of groundwater pollution and its potential risk to contamination is imperative, as its remediation when contaminated is extremely challenging. Vertical electrical sounding (VES) and physicochemical analysis were carried out in twenty (20) locations and five groundwater samples, respectively, with the aim to evaluate the groundwater pollution indices and the ecological and human health risk associated with its pollution. The VES results delineated five geologic layers and ten characteristic curve types. The fourth layer with the aid of the VES results constrained by the borehole lithologic information on the water bearing geologic unit was delineated as the major exploitable aquifer layer. Results of groundwater vulnerability to pollution classified the area into low (15%), moderate (60%), and high (20%) vulnerability. Physicochemical analysis results on the studied groundwater revealed acidic (pH 4.6) to alkaline (pH 7.2) groundwater conditions. Pollution index of groundwater results delineated a moderate to very high pollution index, with cadmium and arsenic consistently identified as the heavy metals contaminating the groundwater. Ecological risk assessment revealed a moderate to very high integrated potential ecological risk, while human health risk results delineated a target hazard index greater than one in all the studied groundwater samples. This study will serve as a guide to the residents and society in sustainable development decision-making that will preserve the quality of the study area groundwater.

Discovery and structural assignment of (S)-sydosine from amphipod-derived Aspergillus sydowii MBC15-11F through HRMS, advanced Mosher, and molecular modelling analyses.

AIMS: This study aims to prioritize fungal strains recovered from under-explored habitats that produce new metabolites. HRMS dereplication is used to avoid structure redundancy, and molecular modelling is used to assign absolute configuration. METHODS AND RESULTS: MBC15-11F was isolated from an amphipod and identified using ITS, 28S, and ß-tubulin phylogeny as Aspergillus sydowii. Chemical profiling using taxonomic-based dereplication identified structurally diverse metabolites, including unreported ones. Large-scale fermentation led to the discovery of a new N-acyl adenosine derivative: (S)-sydosine (1) which was elucidated by NMR and HRESIMS analyses. Two known compounds were also identified as predicted by the initial dereplication process. Due to scarcity of 1, molecular modelling was used to assign its absolute configuration without hydrolysis, and is supported by advanced Mosher derivatization. When the isolated compounds were assessed against a panel of bacterial pathogens, only phenamide (3) showed anti-Staphylococcus aureus activity. CONCLUSION: Fermentation of A. sydowii yielded a new (S)-sydosine and known metabolites as predicted by HRESIMS-aided dereplication. Molecular modelling prediction of the absolute configuration of 1 agreed with advanced Mosher analysis.

Cyclopropane-Containing Specialized Metabolites from the Marine Cyanobacterium cf. Lyngbya sp.

Marine cyanobacteria are known to produce structurally diverse bioactive specialized metabolites during bloom occurrence. These ecologically active allelochemicals confer chemical defense for the microalgae from competing microbes and herbivores. From a collection of a marine cyanobacterium, cf. Lyngbya sp., a small quantity of a new cyclopropane-containing molecule, benderadiene (2), and lyngbyoic acid (1) were purified and characterized using spectroscopic methods. Using live reporter quorum-sensing (QS) inhibitory assays, based on P. aeruginosa PAO1 lasB-gfp and rhlA-gfp strains, both compounds were found to inhibit QS-regulated gene expression in a dose-dependent manner. In addition to lyngbyoic acid being more active in the PAO1 lasB-gfp biosensor strain (IC50 of 20.4 µM), it displayed anti-biofilm activity when incubated with wild-type P. aeruginosa. The discovery of lyngbyoic acid in relatively high amounts provided insights into its ecological significance as a defensive allelochemical in targeting competing microbes through interference with their QS systems and starting material to produce other related analogs. Similar strategies could be adopted by other marine cyanobacterial strains where the high production of other lipid acids has been reported. Preliminary evidence is provided from the virtual molecular docking of these cyanobacterial free acids at the ligand-binding site of the P. aeruginosa LasR transcriptional protein.

Dataset on biochemical inhibiting activities of selected phytochemicals in Azadirachta indica L as potential NS2B-NS3 proteases inhibitors.

The anti-NS2B-NS3 proteases activities of Azadirachta indica L. were investigated via the data obtained from selected bioactive compounds from Azadirachta indica L. The work was investigated using insilico approach and the series of computational software were used to execute the task. The software used were Spartan 14, material studio, Padel, Pymol, Autodock tool, Autodock vina and discovery studio. The obtained descriptors from 2D and 3D of the optimized compounds were screened and they were used to develop QSAR model using material studio software. Also, biological interaction between the selected bioactive compounds from Azadirachta indica L. and NS2B-NS3 proteases (PDB ID: 2fom) were accomplished using docking method and the calculated binding affinity as well as the residues involved in the interaction were reported. More so, the ADMET features for [(5S,6R,7S,8R,9S,10R,11S,12R,13S,17R)-17-(2,5-dihydroxy-2,5-dihydrofuran-3-yl)-11,12-dihydroxy-6­methoxy-4,4,8,10,13-pentamethyl-1,16-dioxo-6,7,9,11,12,17-hexahydro-5H-cyclopenta[a]phenanthren-7-yl] 3-methylbut-2-enoate (Compound 6) and (10R,13S,14S,17S)-17-[1-(3,4-dihydroxy-5,5-dimethyloxolan-2-yl)ethyl]-4,4,10,13,14-pentamethyl-1,2,5,6,9,11,12,15,16,17-decahydrocyclopenta[a]phenanthren-3-one (compound 12) with lowest binding affinity were investigated and reported.

Enhancement of anti-tumor efficacy of immune checkpoint blockade by alpha-TEA.

Cancer immunotherapy such as anti-PD-1/anti-PD-L1 immune checkpoint blockade (ICB) can provide significant clinical benefit in patients with advanced malignancies. However, most patients eventually develop progressive disease, thus necessitating additional therapeutic options. We have developed a novel agent, a-TEA-LS, that selectively induces tumor cell death while sparing healthy tissues, leading to increased activation of tumor-reactive T cells and tumor regression. In the current study, we explored the impact of combined a-TEA-LS + ICB in orthotopic and spontaneously arising murine models of mammary carcinoma. We found that a-TEA-LS + ICB led to increased production of pro-inflammatory cytokines that were associated with a reduction in tumor growth and prolonged survival. Together, these data demonstrate the potential utility of a-TEA-LS + ICB for the treatment of breast cancer and provide the rationale for clinical translation of this novel approach.

Investigation of the Mechanical and Microstructural Properties of Masonry Mortar Made with Seashell Particles.

In order to study the mechanical and microstructural properties of masonry mortar, combined particles of cockle and scallop seashell wastes were incorporated and analysed through destructive and non-destructive tests. River sand was replaced with the combined seashell particles (SPs) at seven mixes, viz., 0, 5, 10, 15, 20, 25, and 30% with a 0.5 constant water-to-cement ratio (W/C). A mortar mix design of M4-type of BS EN 1996-1-1 was adopted with a target compressive strength of 5.17 MPa at 28 days. The physical, chemical and mineralogy properties of the SPs were analysed through BS standard sieving, X-ray fluorescence (XRF), scanning electron microscopy (SEM), and X-ray diffraction (XRD) methods. The hardened SP-based mortars were subjected to direct compressive strength, rebound hammer, ultrasonic pulse velocity tests, and nonevaporable degree of hydration analysis. The XRF, SEM, and XRD analysis results of the SPs showed over 86% calcium oxide content, irregular and needle-like particles, and hydroxyapatite/calcium silicates, respectively. The direct compressive strength and the non-destructive test results revealed that up to 30% sand replacement with SP in masonry mortar, an improvement of 45% compressive strength could be attained over the control sample. The nonevaporable water method of the degree of hydration analysis showed that after 28 days, hydration increased considerably for the SP-blended mortars over the control, especially the SPM-30 with 30% sand replacement. Therefore, the study concludes that the investigated SPs in blended masonry mortar could benefit an eco-friendly environment and conservation of natural resources.

Challenges of hepatitis B treatment in rural Sub-Saharan Africa: Treatment initiation and outcomes from a public hospital-based clinic in Kono, Sierra Leone.

Despite a high prevalence, there are few successful models for de-centralizing diagnosis and treatment of chronic hepatitis B virus (HBV) infection among rural communities in Sub-Saharan Africa. We report baseline characteristics and 1 year retention outcomes for patients enrolled in a HBV clinic integrated within chronic disease services in a rural district hospital in Sierra Leone. We conducted a retrospective cohort study of patients with HBV infection enrolled between 30 April 2019 and 30 April 2021. Patients were eligible for 1 year follow-up if enrolled before 28 February 2020. Treatment eligibility at baseline was defined as cirrhosis (diagnosed by clinical criteria of decompensated cirrhosis, ultrasonographic findings or aspartate-aminotransferase-to-platelet ratio >2) or co-infection with HIV or HCV. Retention in care was defined as a documented follow-up visit at least 1 year after enrolment. We enrolled 623 individuals in care, median age of 30 years (IQR 23-40). Of 617 patients with available data, 97 (15.7%) had cirrhosis. Treatment was indicated among 113 (18.3%) patients and initiated among 74 (65.5%). Of 39 patients eligible for 1 year follow-up on treatment at baseline, 20 (51.3%) were retained at 1 year, among whom 12 (60.0%) had documented viral suppression. Among the 232 patients not initiated on treatment eligible for 1 year follow-up, 75 (32.3%) were retained at 1 year. Although further interventions are required to improve outcomes, our findings demonstrated feasibility of retention and treatment of patients with HBV infection in a rural district in Sub-Saharan Africa, when integrated with other chronic disease services.

Antiparasitic Activities of Compounds Isolated from Aspergillus fumigatus Strain Discovered in Northcentral Nigeria.

In this study, we explored a fungal strain UIAU-3F identified as Aspergillus fumigatus isolated from soil samples collected from the River Oyun in Kwara State, Nigeria. In order to explore its chemical diversity, the fungal strain UIAU-3F was cultured in three different fermentation media, which resulted in different chemical profiles, evidenced by LC-ESI-MS-based metabolomics and multivariate analysis. The methanolic extract afforded two known compounds, fumitremorgin C (1) and pseurotin D (2). The in vitro antiparasitic assays of 1 against Trypanosoma cruzi and Plasmodium falciparum showed moderate activity with IC50 values of 9.6 µM and 2.3 µM, respectively, while 2 displayed IC50 values > 50 µM. Molecular docking analysis was performed on major protein targets to better understand the potential mechanism of the antitrypanosomal and antiplasmodial activities of the two known compounds.

Surgical Management of Patients With GI Tuberculosis.

BACKGROUND: The Philippines ranks 10th in tuberculosis prevalence worldwide. Aside from pulmonary tuberculosis, GI tuberculosis remains an important cause of morbidity and mortality, particularly in endemic areas. OBJECTIVE: This study aimed to describe the clinicopathologic profile and surgical outcomes of patients with GI tuberculosis. DESIGN: Retrospective descriptive study. SETTING: Department of Surgery at the Philippine General Hospital, Manila, Philippines. PATIENTS: This study included all newly diagnosed cases of GI tuberculosis from January 1, 2009, to December 31, 2019. MAIN OUTCOME MEASURES: Clinical response to surgery. RESULTS: A total of 241 confirmed new cases were managed during an 11-year period. Of these, 208 patients (86.30%) underwent outright surgery, whereas the remaining patients (13.69%) received antituberculous therapy. Fifteen medically managed patients eventually required surgery, bringing the total surgically managed patients to 223. The patients' age ranged from 19 to 72 years, with a 1.9:1 male to female ratio. The most common complaint was abdominal pain. Intestinal obstruction was the most common indication for surgery. A right hemicolectomy was the most often performed procedure, with the ileocecal area as the most frequently involved segment. The most common histopathologic findings were epithelioid granuloma and caseation necrosis. Postoperative length of stay ranged from 0 to 59 days (mean, 7 days). Morbidity rate was 5.38% and mortality rate was 3.14%. Four deaths were operative and resulted from septic shock because of hollow viscus perforation. LIMITATIONS: This study was limited to histopathologic basis for diagnosis. CONCLUSION: The recommended initial therapy for all forms of extrapulmonary tuberculosis is a 6-month regimen of antituberculous therapy unless the organisms are known or suspected to be resistant to first-line drugs. Surgery is reserved for complications of intra-abdominal tuberculosis: obstruction, perforation, or severe bleeding. Timely surgical intervention, coupled with medical management led to the best outcomes for these patients. See Video Abstract at http://links.lww.com/DCR/C56. MANEJO QUIRRGICO DE PACIENTES CON TUBERCULOSIS GASTROINTESTINAL: ANTECEDENTES:Las Filipinas ocupa el décimo lugar en prevalencia de tuberculosis en todo el mundo. Aparte de la tuberculosis pulmonar, la tuberculosis gastrointestinal sigue siendo una causa importante de morbilidad y mortalidad, especialmente en las zonas endémicas.OBJETIVO:Este estudio tuvo como objetivo describir el perfil clinicopatológico y los resultados quirúrgicos de pacientes con tuberculosis gastrointestinal.DISEÑO:Estudio descriptivo retrospectivo.AJUSTE:Departamento de Cirugía del Hospital General de Filipinas, Manila, Filipinas.PACIENTES:Todos los casos de tuberculosis gastrointestinal recién diagnosticados desde el 1 de Enero del 2009 hasta el 31 de Diciembre del 2019.MEDIDAS DE RESULTADO PRINCIPAL:Respuesta clínica a la cirugía.RESULTADOS:Se manejaron un total de 241 casos nuevos confirmados durante un período de 11 años. De estos, 208 (86,30%) pacientes fueron intervenidos directamente quirúrgicamente mientras que el resto recibió tratamiento antituberculoso (13,69%). Quince pacientes manejados médicamente finalmente requirieron cirugía, lo que elevó el total de pacientes manejados quirúrgicamente a 223. Las edades de los pacientes oscilaron entre 19 y 72 años, con una proporción de 1,9: 1 entre hombres y mujeres. La queja más común fue el dolor abdominal. La obstrucción intestinal fue la indicación más frecuente para cirugía. La hemicolectomía derecha fue el procedimiento más realizado, siendo la zona ileocecal el segmento más afectado. Los hallazgos histopatológicos más comunes fueron granuloma epitelioide y necrosis caseosa. La estancia postoperatoria varió de 0 a 59 días (media, 7 días). Las tasas de morbilidad y mortalidad fueron 5,38% y 3,14%, respectivamente. Cuatro fueron muertes operatorias por choque séptico debido a perforación de víscera.LIMITACIONES:Este estudio se limitó a la base histopatológica para el diagnóstico.CONCLUSIÓN:La terapia inicial recomendada para todas las formas de tuberculosis extrapulmonar es un régimen de 6 meses de terapia antituberculosa a menos que se sepa o se sospeche que los organismos son resistentes a los medicamentos de primera línea. La cirugía se reserva para las complicaciones de la tuberculosis intraabdominal, es decir, obstrucción, perforación o hemorragia grave. La intervención quirúrgica oportuna, junto con el manejo médico, condujo a mejores resultados para estos pacientes. Consulte el Resumen del Video en http://links.lww.com/DCR/C56. (Traducción- Dr. Yesenia Rojas-Khalil).

Teaching bioengineering using a blended online teaching and learning strategy: a new pedagogy for adapting classrooms in developing countries.

Research and academia have been recently affected by the Coronavirus (COVID-19), and physical classrooms and laboratory experiments have been affected significantly due to the recent laboratory closures. This has led to innovative approaches to curb this problem. To address these difficulties in teaching bioengineering related courses that is of significant interest to students of the Faculty of Engineering in Ahmadu Bello University, Zaria, Nigeria, and of course, useful for engineering-based higher education institutions (HEI), a transitional pedagogy: Communicate, Active, Collaborate, Problem-based Solving, Learning and Assessment (CACPLA), which encompasses blended learning, was developed as a new teaching and learning strategy. In this study, we show that this new strategy can initiate a steady transition from physical classrooms to full online instruction for some subjects in engineering. This method has been trialled as an exercise for a module as part of an envisioned biomedical engineering degree programme which can be integrated with local industries and research institutions in sub-Saharan Africa. The teaching materials and environment were carefully designed and 253 students of third and final year classes participated as the experimental group. Also, the effect of critical thinking, pre-lecture, and post lecture on the overall performance of the students was assessed. Two questionnaires were designed for data collection, (a) for technical questions, (b) for receptiveness. The result of a student survey suggests favourable reception of the teaching methodology, which aided their understanding of the general bioengineering concept as applied to the materials chemistry and mechanical measurements context. It was noticed that 80% of the students indicated that the blended learning method was sufficient in achieving the learning outcomes of the study. The method is envisioned as a useful and sustainable complement to traditional teaching pedagogies and workshops due to the convenience and relatively high accessibility to Zoom and Google Meet Apps which can be readily employed without incurring significant costs.

Evidence of reduced academic performance among schoolchildren with helminth infection.

BACKGROUND: Soil-transmitted helminths (STHs) pose a formidable health risk to school-age children in resource-limited settings. Unfortunately, mass deworming campaigns have been derailed since the onset of the coronavirus disease 2019 pandemic. The present study assessed the cross-sectional associations between STHs, nutritional status and academic performance of schoolchildren in the Banda District of Ghana. METHODS: Schoolchildren (5-16 y of age; n=275) were recruited through both school and household visits by community health workers using a multistage cluster sampling technique. In addition to school microscopy, anthropometric records were also taken. RESULTS: The prevalence of geohelminthiasis was 40.4% (95% confidence interval 34.6 to 46.2). STHs targeted for elimination by the World Health Organization and national programmes were detected among schoolchildren. Children with intestinal parasite infection (53.7 [standard deviation {SD} 11.5]) had lower mean academic scores compared with uninfected children (59.6 [SD 16.9]) (p=0.034). In multiple regression analysis, intestinal parasite infection status and z-scores for weight-for-age showed a collective significant effect on the academic score (F1117=8.169, p<0.001, R2=0.125). CONCLUSIONS: Schoolchildren with STHs had poorer academic performance compared with uninfected children, despite their nutritional status. In addition to school feeding programmes, school-based mass drug administration campaigns may be critical for improving learning outcomes in young schoolchildren.

Computational identification of potential modulators of heme-regulated inhibitor (HRI) for pharmacological intervention against sickle cell disease.

Background: Sickle cell disease (SCD) poses a significant health challenge and therapeutic approaches often target fetal hemoglobin (HbF) to ameliorate symptoms. Hydroxyurea, a current therapeutic option for SCD, has shown efficacy in increasing HbF levels. However, concerns about myelosuppression and thrombocytopenia necessitate the exploration of alternative compounds. Heme-regulated inhibitor (HRI) presents a promising target for pharmacological intervention in SCD due to its association with HbF modulation. This study systematically screened compounds for their potential inhibitory functions against HRI. Methods: Small-molecule compounds from 17 plants commonly utilized in traditional SCD management were subjected to in silico screening against HRI. Molecular docking was performed, and free binding energy calculations were determined using molecular mechanics with generalized born and surface area (MMGBSA). The lead compounds were subjected to molecular dynamics simulation at 100 ns. Computational quantum mechanical modelling of the lead compounds was subsequently performed. We further examined the pharmacodynamics, pharmacokinetic and physiological properties of the identified compounds. Results: Five potential HRI inhibitors, including kaempferol-3-(2G-glucosyrutinoside), epigallocatechin gallate, tiliroside, myricetin-3-O-glucoside, and cannabiscitrin, with respective docking scores of -16.0, -12.17, -11.37, -11.56 and 11.07 kcal/mol, were identified. The MMGBSA analysis of the complexes yielded free-binding energies of -69.76, -71.17, -60.44, 53.55, and - 55 kcal/mol, respectively. The identified leads were stable within HRI binding pocket for the duration of 100 ns simulation. Conclusions: The study successfully identified five phytoligands with potential inhibitory effects on HRI, opening avenues for their use as modulators of HbF in SCD patients. This finding holds promise for advancing treatment strategies in SCD. However, additional preclinical analyses are warranted to validate the chemotherapeutic properties of the lead compounds.