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1.
Materials (Basel) ; 17(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38730744

RESUMEN

Cellulose/silica nanocomposites, synthesised through the sol-gel technique, have garnered significant attention for their unique properties and diverse applications. The distinctive characteristics of these nanocomposites are influenced by a range of factors, including the cellulose-to-silica ratio, precursor concentration, pH, catalysts, solvent selection, temperature, processing techniques, and agitation. These variables play a pivotal role in determining the nanocomposites' structure, morphology, and mechanical properties, facilitating tailoring for specific applications. Studies by Raabe et al. and Barud et al. demonstrated well-deposited silica nanoparticles within the interstitial spaces of cellulosic fibres, achieved through TEOS precursor hydrolysis and the subsequent condensation of hydroxyl groups on the cellulose fibre surface. The introduction of TEOS established a robust affinity between the inorganic filler and the polymer matrix, emphasising the substantial impact of TEOS concentration on the size and morphology of silica nanoparticles in the final composites. The successful functionalisation of cellulose fibres with the TEOS precursor via the sol-gel method was reported, resulting in reduced water uptake and enhanced mechanical strength due to the strong chemical interaction between silica and cellulose. In research conducted by Feng et al., the silica/cellulose composite exhibited reduced weight loss compared to the pristine cellulose matrix, with the integration of silica leading to an elevated temperature of composite degradation. Additionally, Ahmad et al. investigated the effects of silica addition to cellulose acetate (CA) and polyethylene glycol membranes, noting an increase in Young's modulus, tensile strength, and elongation at break with silica incorporation. However, concentrations exceeding 4% (w/v) resulted in significant phase separations, leading to a decline in mechanical properties.

2.
Vaccines (Basel) ; 12(2)2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38400186

RESUMEN

Malaria transmission intensity affects the development of naturally acquired immunity to malaria. An absolute correlate measure of protection against malaria is lacking. However, antibody-mediated functions against Plasmodium falciparum correlate with protection against malaria. In children, antibody-mediated functions against P. falciparum decline with reduced exposure. It is unclear whether adults maintain antibody-mediated functions as malaria transmission declines. This study assessed antibody-dependent respiratory burst (ADRB) in individuals from an area with declining malaria transmission. In an age-matched analysis, we compare ADRB activity during high versus low malaria transmission periods. Age significantly predicted higher ADRB activity in the high (p < 0.001) and low (p < 0.001) malaria transmission periods. ADRB activity was higher during the high compared to the low malaria transmission period in older children and adults. Only older adults during the high malaria transmission period had their median ADRB activity above the ADRB cut-off. Ongoing P. falciparum infection influenced ADRB activity during the low (p = 0.01) but not the high (p = 0.29) malaria transmission period. These findings propose that naturally acquired immunity to P. falciparum is affected in children and adults as malaria transmission declines, implying that vaccines will be necessary to induce and maintain protection against malaria.

3.
JCO Oncol Pract ; : OP2300533, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38354335

RESUMEN

PURPOSE: Health care expenditure related to oncologic treatments is skyrocketing although many treatments offer marginal, if any, clinical benefit. Financial conflicts of interest (fCOI) resulting from pharmaceutical industry (pharma) payments to physicians is increasingly recognized as a predictive factor for regulatory board approval and guideline incorporation of low-value treatments. We sought to study the extent to which pharma payments to medical oncologists occur in the Netherlands, the amount of money involved, and whether these occur more frequently and are higher for key opinion leaders (KOLs). METHODS: In our cross-sectional retrospective database study, we used several Dutch open-access databases and extracted data registered between 2019 and 2021. RESULTS: A cumulative amount of €899,863 was paid to 48.8% of the 408 registered medical oncologists. Over time, there was a marked decline in both the proportion of medical oncologists receiving payments (from 40.4% in 2019 to 19.1% in 2021) and the mean annual value of payments (from €2,962 in 2019 to €2,188 in 2021) with the latter mainly resulting from a decline in hospitality-related transactions. KOLs were more likely to receive industry payments and received a higher median payment value. DISCUSSION: Our findings should contribute to the increasing awareness in the Netherlands of the potential effects of fCOI.

4.
Nat Chem Biol ; 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38238495

RESUMEN

The bacterial ribosome is an essential drug target as many clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent resistance mechanisms to PTC-acting drugs in Gram-positive bacteria is C8-methylation of the universally conserved A2503 nucleobase by Cfr methylase in 23S ribosomal RNA. Despite its clinical importance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. Here, we report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-transfer RNAs. These structures reveal an allosteric rearrangement of nucleotide A2062 upon Cfr-mediated methylation of A2503 that likely contributes to the reduced potency of some PTC inhibitors. Additionally, we provide the structural bases behind two distinct mechanisms of engaging the Cfr-methylated ribosome by the antibiotics iboxamycin and tylosin.

5.
Org Biomol Chem ; 22(3): 590-605, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38131271

RESUMEN

Biphenyl-fused-dioxacyclodecynes are a promising class of strained alkyne for use in Cu-free 'click' reactions. In this paper, a series of functionalised derivatives of this class of reagent, containing fluorescent groups, are described. Studies aimed at understanding and increasing the reactivity of the alkynes are also presented, together with an investigation of the bioconjugation of the reagents with an azide-labelled protein.

6.
bioRxiv ; 2023 Sep 28.
Artículo en Inglés | MEDLINE | ID: mdl-37808676

RESUMEN

The ribosome is an essential drug target as many classes of clinically important antibiotics bind and inhibit its functional centers. The catalytic peptidyl transferase center (PTC) is targeted by the broadest array of inhibitors belonging to several chemical classes. One of the most abundant and clinically prevalent mechanisms of resistance to PTC-acting drugs is C8-methylation of the universally conserved adenine residue 2503 (A2503) of the 23S rRNA by the methyltransferase Cfr. Despite its clinical significance, a sufficient understanding of the molecular mechanisms underlying Cfr-mediated resistance is currently lacking. In this work, we developed a method to express a functionally-active Cfr-methyltransferase in the thermophilic bacterium Thermus thermophilus and report a set of high-resolution structures of the Cfr-modified 70S ribosome containing aminoacyl- and peptidyl-tRNAs. Our structures reveal that an allosteric rearrangement of nucleotide A2062 upon Cfr-methylation of A2503 is likely responsible for the inability of some PTC inhibitors to bind to the ribosome, providing additional insights into the Cfr resistance mechanism. Lastly, by determining the structures of the Cfr-methylated ribosome in complex with the antibiotics iboxamycin and tylosin, we provide the structural bases behind two distinct mechanisms of evading Cfr-mediated resistance.

7.
Front Immunol ; 14: 1260193, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37809108

RESUMEN

Histiocytoses encompass a wide spectrum of diseases, all characterized by tissue infiltration by CD68+ histiocytes. Most adult histiocytoses are considered clonal diseases because they highlight recurrent somatic mutations in the MAP-kinase pathway gene, primarily BRAF. The presence of BRAF mutation is associated with widespread disease in children with Langerhans cell histiocytosis (LCH) or cardiovascular/neurological involvement in Erdheim-Chester disease (ECD). Nevertheless, few data are available on adult clonal histiocytosis. This is why we have conducted a retrospective study of all patients with clonal histiocytosis in our institution and present the data according to the presence of BRAF mutation. Among 27 adult patients (10 ECD, 10 LCH, 5 Rosai-Dorfman disease (RDD), and 3 mixed ECD/LCH), 11 (39%) have BRAF mutation with gain of function (n = 9) and deletion (n = 2). Those patients had frequent multicentric disease with risk organ involvement, especially the brain and cardiovascular system. They had frequent associated myeloid neoplasms (mostly chronic myelomonocytic leukemia) and received more frequently targeted therapy as the front-line therapy. Nevertheless, its presence did not affect the overall survival or relapse-free survival probably due to the emergence of efficient therapies. To conclude, rapid and accurate molecular establishment in adult clonal histiocytoses is crucial because BRAFV600E mutation correlates with multicentric disease with organ involvement and incomplete metabolic response.


Asunto(s)
Histiocitosis , Proteínas Proto-Oncogénicas B-raf , Adulto , Niño , Humanos , Enfermedad de Erdheim-Chester/genética , Histiocitosis de Células de Langerhans/genética , Mutación , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Histiocitosis/metabolismo
9.
Sci Adv ; 9(14): eadf0259, 2023 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-37027466

RESUMEN

Several pathways for how climate change may influence the U.S. coastal hurricane risk have been proposed, but the physical mechanisms and possible connections between various pathways remain unclear. Here, future projections of hurricane activity (1980-2100), downscaled from multiple climate models using a synthetic hurricane model, show an enhanced hurricane frequency for the Gulf and lower East coast regions. The increase in coastal hurricane frequency is driven primarily by changes in steering flow, which can be attributed to the development of an upper-level cyclonic circulation over the western Atlantic. The latter is part of the baroclinic stationary Rossby waves forced mainly by increased diabatic heating in the eastern tropical Pacific, a robust signal across the multimodel ensemble. Last, these heating changes also play a key role in decreasing wind shear near the U.S. coast, further aggravating coastal hurricane risk enhanced by the physically connected steering flow changes.

10.
Lancet Infect Dis ; 23(5): 598-608, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36565714

RESUMEN

BACKGROUND: Fungal infections are common causes of death and morbidity in those with advanced HIV infection. Data on access to diagnostic tests in Africa are scarce. We aimed to evaluate the diagnostic capacity for invasive fungal infections in advanced HIV disease in Africa. METHODS: We did a continent-wide survey by collecting data from 48 of 49 target countries across Africa with a population of more than 1 million; for Lesotho, only information on the provision of cryptococcal antigen testing was obtained. This survey covered 99·65% of the African population. We did the survey in six stages: first, questionnaire development, adaptation, and improvement; second, questionnaire completion by in-country respondents; third, questionnaire review and data analysis followed by video conference calls with respondents; fourth, external validation from public or private sources; fifth, country validation by video conference with senior figures in the Ministry of Health; and sixth, through five regional webinars led by the Africa Centres for Disease Control and Prevention with individual country profiles exchanged by email. Data was compiled and visualised using the Quantum Geographic Information System software and Natural Earth vectors to design maps showing access. FINDINGS: Data were collected between Oct 1, 2020, and Oct 31, 2022 in the 48 target countries. We found that cryptococcal antigen testing is frequently accessible to 358·39 million (25·5%) people in 14 African countries. Over 1031·49 million (73·3%) of 1·4 billion African people have access to a lumbar puncture. India ink microscopy is frequently accessible to 471·03 million (33·5%) people in 23 African countries. About 1041·62 million (74·0%) and 1105·11 million (78·5%) people in Africa do not have access to histoplasmosis and Pneumocystis pneumonia diagnostics in either private or public facilities, respectively. Fungal culture is available in 41 countries covering a population of 1·289 billion (94%) people in Africa. MRI is routinely accessible to 453·59 million (32·2%) people in Africa and occasionally to 390·58 million (27·8%) people. There was a moderate correlation between antiretroviral therapy usage and external expenditure on HIV care (R2=0·42) but almost none between external expenditure and AIDS death rate (R2=0·18), when analysed for 40 African countries. INTERPRETATION: This survey highlights the enormous challenges in the diagnosis of HIV-associated Pneumocystis pneumonia, cryptococcal disease, histoplasmosis, and other fungal infections in Africa. Urgent political and global health leadership could improve the diagnosis of fungal infections in Africa, reducing avoidable deaths. FUNDING: Global Action For Fungal Infections.


Asunto(s)
Cryptococcus , Infecciones por VIH , Histoplasmosis , Infecciones Fúngicas Invasoras , Neumonía por Pneumocystis , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico , África/epidemiología , Antígenos Fúngicos
11.
ACS Omega ; 7(39): 35092-35101, 2022 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-36211070

RESUMEN

In spite of the enormous potential of cyanobacteria as a renewable energy source, elevated UV exposure is a major impediment to their commercial viability and productivity. Fremyella diplosiphon is a widely explored cyanobacterium with great biofuel capacity due to its high lipid content. To enhance UV stress tolerance in this species, we overexpressed the photoreactivation gene (phr A) that encodes for photolyase DNA repair enzyme in the wild type F. diplosiphon (B481-WT) by genetic transformation. Our efforts resulted in a transformant (B481-ViAnSa) with a 3808-fold increase in the phr A mRNA transcript level and enhanced growth under UV-B stress. Additionally, DNA strand breaks in the transformant were significantly lower after 12 and 16 h of UV radiation, with significantly higher dsDNA recovery in B481-ViAnSa (98.1%) compared to that in B481-WT (81.5%) at 48 h post irradiation. Photosystem II recovery time in the transformant was significantly reduced (48 h) compared to that in the wild type (72 h). Evaluation of high-value fatty acid methyl esters (FAMEs) revealed methyl palmitate, the methyl ester of hexadecenoic acid (C16:0), to be the most dominant component, accounting for 53.43% of the identified FAMEs in the transformant. Results of the study offer a promising approach to enhance UV tolerance in cyanobacteria, thus paving the way to large-scale open or closed pond cultivation for commercial biofuel production.

12.
J Educ Health Promot ; 11: 155, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35847151

RESUMEN

BACKGROUND: The exponential increase of cases and the emergence of the new COVID-19 variants continue to be a challenge. It remains crucial to assess whether or not minimum health standards against COVID-19 are consistently followed. This study determined the higher education students' practice of protective measures against COVID-19 of more than a year into the pandemic. MATERIALS AND METHODS: A questionnaire web survey, cross-sectional study was conducted among higher education students (n = 2309) of a public university in the Philippines. Data were analyzed using the SPSS software. RESULTS: Results indicated that students generally had a high practice of COVID-19 preventive measures. However, only 45.9% always practice physical distancing measures, and only 35.9% always seek information related to COVID-19 after more than a year into the pandemic. Female, married, graduate level, with a monthly family income of PHP 10,000 and above, and personal knowledge of someone who tested for COVID-19 had a significantly higher practice of COVID-19 protective measures. Older age, higher general self-reported health status, and higher intention to comply with recommended protective health behaviors were significantly correlated with higher practice of preventive measures against COVID-19. CONCLUSION: After more than a year of being into the pandemic, students still practice preventive health behaviors, however, this is not done consistently. As the pandemic is still not over in the country and many parts of the world, continuous monitoring and a reminder to practice minimum protective health protocols are needed to mitigate and prevent the spread of COVID-19.

13.
ChemistryOpen ; 11(7): e202200037, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35856692

RESUMEN

A novel alternative route to access rhenium(V)-phthalocyanine complexes through direct metalation of metal-free phthalocyanines (H2 Pcs) with a rhenium(VII) salt in the presence of various two-electron reducing agents is presented. Direct ion metalation of tetraamino- or tetranitrophthalocyanine with perrhenate (ReO4- ) in the presence of triphenylphosphine led to oxidative decomposition of the H2 Pcs, giving their respective phthalonitriles. Conversely, treatment of H2 Pcs with ReO4- employing sodium metabisulfite yielded the desired ReV O-Pc complex. Finally, reaction of H2 Pcs with ReO4- and NaBH4 as reducing agent led to the formation of rhenium oxide (Rex Oy ) nanoparticles (NPs). The NP synthesis was optimised, and the Rex Oy NPs were capped with folic acid (FA) conjugated with tetraaminophthalocyanine (TAPc) to enhance their cancer cell targeting ability. The cytotoxicity profile of the resultant Rex Oy -TAPc-FA NPs was assessed and found to be greater than 80 % viability in four cell lines, namely, MDA-MB-231, HCC7, HCC1806 and HEK293T. Non-cytotoxic concentrations were determined and employed in cancer cell localization studies. The particle size effect on localization of NPs was also investigated using confocal fluorescence and transmission electron microscopy. The smaller NPs (≈10 nm) were found to exhibit stronger fluorescence properties than the ≈50 nm NPs and exhibited better cell localization ability than the ≈50 nm NPs.


Asunto(s)
Nanopartículas del Metal , Renio , Células HEK293 , Humanos , Isoindoles , Sustancias Reductoras
14.
Front Immunol ; 13: 894770, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35711446

RESUMEN

Background: Plasmodium falciparum variant surface antigens (VSAs) contribute to malaria pathogenesis by mediating cytoadhesion of infected red blood cells to the microvasculature endothelium. In this study, we investigated the association between anti-VSA antibodies and clinical outcome in a controlled human malaria infection (CHMI) study. Method: We used flow cytometry and ELISA to measure levels of IgG antibodies to VSAs of five heterologous and one homologous P. falciparum parasite isolates, and to two PfEMP1 DBLß domains in blood samples collected a day before the challenge and 14 days after infection. We also measured the ability of an individual's plasma to inhibit the interaction between PfEMP1 and ICAM1 using competition ELISA. We then assessed the association between the antibody levels, function, and CHMI defined clinical outcome during a 21-day follow-up period post infection using Cox proportional hazards regression. Results: Antibody levels to the individual isolate VSAs, or to two ICAM1-binding DBLß domains of PfEMP1, were not associated with a significantly reduced risk of developing parasitemia or of meeting treatment criteria after the challenge after adjusting for exposure. However, anti-VSA antibody breadth (i.e., cumulative response to all the isolates) was a significant predictor of reduced risk of requiring treatment [HR 0.23 (0.10-0.50) p= 0.0002]. Conclusion: The breadth of IgG antibodies to VSAs, but not to individual isolate VSAs, is associated with protection in CHMI.


Asunto(s)
Malaria Falciparum , Malaria , Anticuerpos Antiprotozoarios , Antígenos de Protozoos , Antígenos de Superficie , Humanos , Inmunoglobulina G , Plasmodium falciparum
15.
PLOS Glob Public Health ; 2(2): e0000151, 2022 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-35469292

RESUMEN

Neurological impairment (NI) and disability are common in sub-Saharan Africa (SSA), but the overall burden in terms of morbidity and mortality in older children remains unknown. We estimated the burden of NI in disability-adjusted life years (DALYs), years of life lost to premature mortality (YLLs), and years lived with disability (YLDs) for older children in a defined rural setting in Kenya. We used empirical and literature estimates to model the overall burden for children aged 5-14 years in five domains: epilepsy (lifetime and active) and moderate/severe cognitive, hearing, motor, and visual impairments. We obtained internally consistent estimates of prevalence, mortality, and transitional hazards using DisMod II software. Disability weights and life expectancy estimates were based on the global burden of disease (GBD) studies. We used the most plausible parameters to calculate YLLs, YLDs, and DALYs and their bootstrapped 95% uncertainty intervals (95%UI) for the defined area. NI in the five domains resulted in a total of 4587 (95%UI 4459-4715) absolute DALYs or 53 (95%UI 39-67) DALYs per 1000 children aged 5-14 years, of which 83% were YLLs and 17% YLDs. Girls had significantly more YLLs and DALYs than boys (p-values <0.001, respectively). Besides being the leading cause of fatal and non-fatal outcomes, epilepsy accounted for the greatest proportion of the total burden for a single domain (20 DALYs per 1000, 95%UI 11-26, or 38.5% of the total DALYs). Visual impairment accounted for the least proportion of the total burden (6 per 1000, 95%UI 1-17, or 12.1%). Children with NI and disability bear a significantly high burden of fatal and non-fatal outcomes. The burden is highest among girls and those with childhood-onset epilepsy. We recommend active identification, treatment, and rehabilitative support for the affected children to prevent premature mortality and improve their quality of life.

16.
Mol Cell ; 82(7): 1329-1342.e8, 2022 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-35298909

RESUMEN

Argonautes are nucleic acid-guided proteins that perform numerous cellular functions across all domains of life. Little is known about how distinct evolutionary pressures have shaped each Argonaute's biophysical properties. We applied high-throughput biochemistry to characterize how Thermus thermophilus Argonaute (TtAgo), a DNA-guided DNA endonuclease, finds, binds, and cleaves its targets. We found that TtAgo uses biophysical adaptations similar to those of eukaryotic Argonautes for rapid association but requires more extensive complementarity to achieve high-affinity target binding. Using these data, we constructed models for TtAgo association rates and equilibrium binding affinities that estimate the nucleic acid- and protein-mediated components of the target interaction energies. Finally, we showed that TtAgo cleavage rates vary widely based on the DNA guide, suggesting that only a subset of guides cleaves targets on physiologically relevant timescales.


Asunto(s)
Proteínas Argonautas , Thermus thermophilus , Proteínas Argonautas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , ADN/genética , Endonucleasas/metabolismo , Thermus thermophilus/genética
18.
Br J Dermatol ; 186(3): 564-574, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34632574

RESUMEN

BACKGROUND: A new autoinflammatory syndrome related to somatic mutations of UBA1 was recently described and called VEXAS syndrome ('Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic syndrome'). OBJECTIVES: To describe clinical characteristics, laboratory findings and outcomes of VEXAS syndrome. METHODS: One hundred and sixteen patients with VEXAS syndrome were referred to a French multicentre registry between November 2020 and May 2021. The frequency and median of parameters and vital status, from diagnosis to the end of the follow-up, were recorded. RESULTS: The main clinical features of VEXAS syndrome were found to be skin lesions (83%), noninfectious fever (64%), weight loss (62%), lung involvement (50%), ocular symptoms (39%), relapsing chondritis (36%), venous thrombosis (35%), lymph nodes (34%) and arthralgia (27%). Haematological disease was present in 58 cases (50%): myelodysplastic syndrome (MDS; n = 58) and monoclonal gammopathy of unknown significance (n = 12; all patients with MGUS also have a MDS). UBA1 mutations included p.M41T (45%), p.M41V (30%), p.M41L (18%) and splice mutations (7%). After a median follow-up of 3 years, 18 patients died (15·5%; nine of infection and three due to MDS progression). Unsupervised analysis identified three clusters: cluster 1 (47%; mild-to-moderate disease); cluster 2 (16%; underlying MDS and higher mortality rates); and cluster 3 (37%; constitutional manifestations, higher C-reactive protein levels and less frequent chondritis). The 5-year probability of survival was 84·2% in cluster 1, 50·5% in cluster 2 and 89·6% in cluster 3. The UBA1 p.Met41Leu mutation was associated with a better prognosis. CONCLUSIONS: VEXAS syndrome has a large spectrum of organ manifestations and shows different clinical and prognostic profiles. It also raises a potential impact of the identified UBA1 mutation.


Asunto(s)
Gammopatía Monoclonal de Relevancia Indeterminada , Síndromes Mielodisplásicos , Humanos , Inflamación/genética , Mutación/genética , Síndromes Mielodisplásicos/diagnóstico , Enzimas Activadoras de Ubiquitina
19.
Dev Med Child Neurol ; 64(3): 347-356, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34536290

RESUMEN

AIM: To investigate geographical change over time in the burden of neurological impairments in school-aged children in a demographic surveillance area. METHOD: We investigated changes in neurological impairment prevalence in five domains (epilepsy and cognitive, hearing, vision, and motor impairments) using similar two-phase surveys conducted in 2001 (n=10 218) and 2015 (n=11 223) and determined changes in location-level prevalence, geographical clustering, and significant risk factors for children aged 6 to 9 years (mean 7y 6mo, SD 1y) of whom 50.4% were males. Admission trends for preterm birth, low birthweight (LBW), and encephalopathy were determined using admission data to a local hospital. RESULTS: Overall prevalence for any neurological impairment decreased from 61 per 1000 (95% confidence interval [CI] 48.0-74.0) in 2001 to 44.7 per 1000 (95% CI 40.9-48.6) in 2015 (p<0.001). There was little evidence of geographical variation in the prevalence of neurological impairments in either survey. The association between neurological impairments and some risk factors changed significantly with year of survey; for example, the increased association of adverse perinatal events with hearing impairments (exponentiated coefficient for the interaction=5.94, p=0.03). Annual admission rates with preterm birth (rate ratio 1.08, range 1.07-1.09), LBW (rate ratio 1.08, range 1.06-1.10), and encephalopathy (rate ratio 1.08, range 1.06-1.09) significantly increased between 2005 and 2016 (p<0.001). INTERPRETATION: There was a significant decline in the prevalence of neurological impairments and differential changes in the associations of some risk factors with neurological impairments over the study period. Limited geographical variation suggests that similar interventions are appropriate across the defined area.


Asunto(s)
Disfunción Cognitiva/epidemiología , Niños con Discapacidad/estadística & datos numéricos , Enfermedades del Sistema Nervioso/epidemiología , Población Rural/estadística & datos numéricos , Niño , Epilepsia/epidemiología , Femenino , Encuestas Epidemiológicas , Pérdida Auditiva/epidemiología , Humanos , Kenia/epidemiología , Masculino , Admisión del Paciente/estadística & datos numéricos , Embarazo , Complicaciones del Embarazo/epidemiología , Factores de Riesgo , Trastornos de la Visión/epidemiología
20.
ACS Omega ; 6(48): 32730-32738, 2021 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-34901621

RESUMEN

Nanoscale zero-valent iron nanoparticles (nZVIs) are known to boost biomass production and lipid yield in Fremyella diplosiphon, a model biodiesel-producing cyanobacterium. However, the impact of nZVI-induced reactive oxygen species (ROS) in F. diplosiphon has not been evaluated. In the present study, ROS in F. diplosiphon strains (B481-WT and B481-SD) generated in response to nZVI-induced oxidative stress were quantified and the enzymatic response determined. Lipid peroxidation as a measure of oxidative stress revealed significantly higher malondialdehyde content (p < 0.01) in both strains treated with 3.2, 12.8, and 51.2 mg L-1 nZVIs compared to untreated control. In addition, ROS in all nZVI-treated cultures treated with 1.6-25.6 mg L-1 nZVIs was significantly higher than the untreated control as determined by the 2',7'-dichlorodihydrofluorescein diacetate fluorometric probe. Immunodetection using densitometric analysis of iron superoxide dismutase (SOD) revealed significantly higher SOD levels in both strains treated with nZVIs at 51.2 mg L-1. In addition, we observed significantly higher (p < 0.001) SOD levels in the B481-SD strain treated with 6.4 mg L-1 nZVIs compared to 3.2 mg L-1 nZVIs. Validation using transmission electron microscopy equipped with energy-dispersive X-ray spectroscopy (EDS) revealed adsorption of nZVIs with a strong iron peak in both B481-WT and B481-SD strains. While the EDS spectra showed strong signals for iron at 4 and 12 days after treatment, a significant decrease in peak intensity was observed at 20 days. Future efforts will be aimed at studying transduction mechanisms that cause metabolic and epigenetic alterations in response to nZVIs in F. diplosiphon.

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