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1.
Geobiology ; 22(2): e12589, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38465505

RESUMO

The Black Sea is a permanently anoxic, marine basin serving as model system for the deposition of organic-rich sediments in a highly stratified ocean. In such systems, archaeal lipids are widely used as paleoceanographic and biogeochemical proxies; however, the diverse planktonic and benthic sources as well as their potentially distinct diagenetic fate may complicate their application. To track the flux of archaeal lipids and to constrain their sources and turnover, we quantitatively examined the distributions and stable carbon isotopic compositions (δ13 C) of intact polar lipids (IPLs) and core lipids (CLs) from the upper oxic water column into the underlying sediments, reaching deposits from the last glacial. The distribution of IPLs responded more sensitively to the geochemical zonation than the CLs, with the latter being governed by the deposition from the chemocline. The isotopic composition of archaeal lipids indicates CLs and IPLs in the deep anoxic water column have negligible influence on the sedimentary pool. Archaeol substitutes tetraether lipids as the most abundant IPL in the deep anoxic water column and the lacustrine methanic zone. Its elevated IPL/CL ratios and negative δ13 C values indicate active methane metabolism. Sedimentary CL- and IPL-crenarchaeol were exclusively derived from the water column, as indicated by non-variable δ13 C values that are identical to those in the chemocline and by the low BIT (branched isoprenoid tetraether index). By contrast, in situ production accounts on average for 22% of the sedimentary IPL-GDGT-0 (glycerol dibiphytanyl glycerol tetraether) based on isotopic mass balance using the fermentation product lactate as an endmember for the dissolved substrate pool. Despite the structural similarity, glycosidic crenarchaeol appears to be more recalcitrant in comparison to its non-cycloalkylated counterpart GDGT-0, as indicated by its consistently higher IPL/CL ratio in sediments. The higher TEX86 , CCaT, and GDGT-2/-3 values in glacial sediments could plausibly result from selective turnover of archaeal lipids and/or an archaeal ecology shift during the transition from the glacial lacustrine to the Holocene marine setting. Our in-depth molecular-isotopic examination of archaeal core and intact polar lipids provided new constraints on the sources and fate of archaeal lipids and their applicability in paleoceanographic and biogeochemical studies.


Assuntos
Archaea , Éteres de Glicerila , Água , Archaea/química , Mar Negro , Sedimentos Geológicos/química , Glicerol , Lipídeos/química , Água do Mar/química
2.
ISME J ; 18(1)2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38365230

RESUMO

Hadarchaeota inhabit subsurface and hydrothermally heated environments, but previous to this study, they had not been cultured. Based on metagenome-assembled genomes, most Hadarchaeota are heterotrophs that grow on sugars and amino acids, or oxidize carbon monoxide or reduce nitrite to ammonium. A few other metagenome-assembled genomes encode alkyl-coenzyme M reductases (Acrs), ß-oxidation, and Wood-Ljungdahl pathways, pointing toward multicarbon alkane metabolism. To identify the organisms involved in thermophilic oil degradation, we established anaerobic sulfate-reducing hexadecane-degrading cultures from hydrothermally heated sediments of the Guaymas Basin. Cultures at 70°C were enriched in one Hadarchaeon that we propose as Candidatus Cerberiarchaeum oleivorans. Genomic and chemical analyses indicate that Ca. C. oleivorans uses an Acr to activate hexadecane to hexadecyl-coenzyme M. A ß-oxidation pathway and a tetrahydromethanopterin methyl branch Wood-Ljungdahl (mWL) pathway allow the complete oxidation of hexadecane to CO2. Our results suggest a syntrophic lifestyle with sulfate reducers, as Ca. C. oleivorans lacks a sulfate respiration pathway. Comparative genomics show that Acr, mWL, and ß-oxidation are restricted to one family of Hadarchaeota, which we propose as Ca. Cerberiarchaeaceae. Phylogenetic analyses further indicate that the mWL pathway is basal to all Hadarchaeota. By contrast, the carbon monoxide dehydrogenase/acetyl-coenzyme A synthase complex in Ca. Cerberiarchaeaceae was horizontally acquired from Bathyarchaeia. The Acr and ß-oxidation genes of Ca. Cerberiarchaeaceae are highly similar to those of other alkane-oxidizing archaea such as Ca. Methanoliparia and Ca. Helarchaeales. Our results support the use of Acrs in the degradation of petroleum alkanes and suggest a role of Hadarchaeota in oil-rich environments.


Assuntos
Alcanos , Mesna , Anaerobiose , Filogenia , Alcanos/metabolismo , Oxirredução , Oxirredutases/genética , Oxirredutases/metabolismo , Sulfatos/metabolismo
3.
IJID Reg ; 10: 200-206, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38371726

RESUMO

Background: Liberia reported a large outbreak of measles involving all the counties in 2022. We conducted a descriptive analysis of the measles surveillance data to understand the trend of the outbreak and guide further policy action to prevent future outbreaks. Methods: We analyzed the measles surveillance data from Epi week 1 to 51, 2022. All the laboratory-confirmed cases, clinically compatible and epidemiologically linked cases were included in the analysis, the variables of interest included the patient's age, sex, place of residence, measles classification, measles vaccination status, and outcome. We cleaned and analyzed the data using R version 4.2.0 and Arc GIS Pro. The demographic characteristics of the cases were presented, the progression of the cases was presented in Epicurve and the spatial distribution and the case fatality rate (CFR) of the case were presented at the district level using the Arc GIS Pro. Results: The median age of the cases was 4 years (interquartile range: 2-8 years). Children under five years of age constituted 60% of the cases (4836/8127), and females accounted for 52% (4204/8127) of the cases. Only 1% (84/8127) of the cases had documentary evidence of receiving at least one dose of measles-containing vaccine (MCV). Only 3 out of 92 health districts in the country did not report a case of measles during the period under review. The overall cases fatality rate was 1% however CFR of up to 10% were reported in some districts. Conclusion: The outbreak of measles involved almost all the districts of the country, exposing a possible nationwide suboptimal immunization coverage for MCV. The high CFR reported in some districts needs further investigation.

4.
Sci Total Environ ; 912: 169626, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38159761

RESUMO

Glycerol dialkyl glycerol tetraether core lipids (GDGTs) are microbial biomarkers ubiquitously distributed in terrestrial and marine environments. Dispersal and fate of GDGTs in an estuary largely depends on sediment grain size, however, their size distribution patterns remain poorly understood. Here, surface sediments collected from the Changjiang Estuary were separated into <20, 20-32, 32-63, 63-125 and >125 µm fractions, and analyzed for GDGTs as well as total organic carbon (TOC), stable isotopic composition (δ13C) of TOC and lignin phenols, to investigate the size and spatial distributions of GDGTs and the particle size effects on GDGTs proxies in this large river delta-front estuary. The concentrations of isoprenoidal GDGTs (isoGDGTs) were higher in the finest fractions and in off-estuary sites. On the contrary, branched GDGTs (brGDGTs) were high not only in the finest fractions but in coarser fractions (>32 µm fractions), and thus at both near- and off-estuary sites. The branched and isoprenoid tetraether (BIT) index increased with increasing grain size, and decreased sharply from the estuary (~0.52) to the shelf (~0.16). BrGDGTs were positively correlated with crenarcheaol in both high and low BIT regions. The brGDGTIIIa/IIa ratios in all size fractions were <0.59, further indicating that the brGDGTs were mainly derived from terrestrial input with minimum in-situ production. Fractional TOC source assignments derived from the BIT index was significantly positively correlated with the fractions of terrestrial OC from a mixing model based on δ13C-TOC and lignin contents, indicating that BIT may track a broader pool of terrestrial OC than just soil OC. This work provides novel, yet preliminary insights into the size fractionated distribution characteristics of GDGTs and the applicability of BIT as a proxy for OC sources in estuarine sediments. More work is needed to further clarify the particle size effects on other GDGTs proxies in estuarine systems.

5.
J Ren Nutr ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38000521

RESUMO

Hemodialysis (HD) and pressure injuries (PI) are both hypercatabolic states that may contribute to protein-energy wasting development. These conditions require increased energy and protein to prevent losses from HD and support wound healing. Nutrition support therapy using intradialytic parenteral nutrition (IDPN) with or without a combination of oral nutrition supplements has yielded positive outcomes among patients receiving HD with protein-energy wasting. However, IDPN is not a standard of care for patients with PI and receiving HD. No existing guidelines support its use with these combined complex medical conditions. We present a case of an older adult with PI receiving HD who required supplemental IDPN. This case demonstrated that IDPN helps wound healing, reduces the hospital length of stay, and enhances quality of life.

6.
Dement Geriatr Cogn Disord ; 52(1): 39-46, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36808103

RESUMO

BACKGROUND: Cardiovascular disease (CVD), including elevated blood pressure (BP), is known to promote Alzheimer's disease (AD) risk. Although brain amyloid load is a recognized hallmark of pre-symptomatic AD, its relationship to increased BP is less known. The objective of this study was to examine the relationship of BP to brain estimates of amyloid-ß (Aß) and standard uptake ratio (SUVr). We hypothesized that increased BP is associated with increased SUVr. METHODS: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we stratified BP according to the Seventh Joint National Committee (JNC) on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Classification (JNC VII). Florbetapir (AV-45) SUVr was derived from the averaged frontal, anterior cingulate, precuneus, and parietal cortex relative to the cerebellum. A linear mixed-effects model enabled the elucidation of amyloid SUVr relationships to BP. The model discounted the effects of demographics, biologics, and diagnosis at baseline within APOE genotype groups. The least squares means procedure was used to estimate the fixed-effect means. All analyses were performed using the Statistical Analysis System (SAS). RESULTS: In non-ɛ4 carrier MCI subjects, escalating JNC categories of BP was associated with increasing mean SUVr using JNC-4 as a reference point (low-normal (JNC1) p = 0.018; normal (JNC-1) p = 0.039; JNC-2 p = 0.018 and JNC-3 p = 0.04). A significantly higher brain SUVr was associated with increasing BP despite adjustment for demographics and biological variables in non-ɛ4 carriers but not in ɛ4-carriers. This observation supports the view that CVD risk may promote increased brain amyloid load, and potentially, amyloid-mediated cognitive decline. CONCLUSION: Increasing levels of JNC classification of BP is dynamically associated with significant changes in brain amyloid burden in non-ɛ4 carriers but not in ɛ4-carrier MCI subjects. Though not statistically significant, amyloid burden tended to decrease with increasing BP in ɛ4 homozygote, perhaps motivated by increased vascular resistance and the need for higher brain perfusion pressure.


Assuntos
Doença de Alzheimer , Doenças Cardiovasculares , Disfunção Cognitiva , Humanos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Pressão Sanguínea , Tomografia por Emissão de Pósitrons/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Disfunção Cognitiva/psicologia , Peptídeos beta-Amiloides , Neuroimagem , Amiloide/metabolismo
7.
ACS Chem Neurosci ; 14(1): 87-98, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36542544

RESUMO

Alzheimer's disease is imposing a growing social and economic burden worldwide, and effective therapies are urgently required. One possible approach to modulation of the disease outcome is to use small molecules to limit the conversion of monomeric amyloid (Aß42) to cytotoxic amyloid oligomers and fibrils. We have synthesized modulators of amyloid assembly that are unlike others studied to date: these compounds act primarily by sequestering the Aß42 monomer. We provide kinetic and nuclear magnetic resonance data showing that these perphenazine conjugates divert the Aß42 monomer into amorphous aggregates that are not cytotoxic. Rapid monomer sequestration by the compounds reduces fibril assembly, even in the presence of pre-formed fibrillar seeds. The compounds are therefore also able to disrupt monomer-dependent secondary nucleation, the autocatalytic process that generates the majority of toxic oligomers. The inhibitors have a modular design that is easily varied, aiding future exploration and use of these tools to probe the impact of distinct Aß42 species populated during amyloid assembly.


Assuntos
Doença de Alzheimer , Perfenazina , Humanos , Peptídeos beta-Amiloides , Amiloide , Proteínas Amiloidogênicas , Fragmentos de Peptídeos
8.
J Med Phys ; 47(2): 181-188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36212206

RESUMO

Background: Accuracy of dose delivery in radiation therapy is a primary requirement for effective cancer treatment. In practice, dose delivery accuracy of ±5% is desired. To achieve this accuracy level, an accurate method for calculating the dose distributions in the tumor volume is required. Monte-Carlo method is one of the methods considered to be the most accurate for calculating dose distributions. Materials and Methods: G4 linac-MT code was used to simulate a 6 MV photon beam. The initial electron beam parameters were tuned to validate the beam modeling from depth doses and beam profile. The dose distributions measured in water phantom were compared to the calculated dose distributions based on gamma index criterion. Results: The beam tuning showed the initial electron energy, sigma and full width at half maximum of 6.2 MeV, 0.8 MeV, and 1.18 mm, respectively, best match the measured dose distributions. The gamma index tests showed the calculated depth doses and beam profile were generally comparable with measurements, passing the standard acceptance criterion of 2%/2 mm. The simulated photon beam was justified by the index of beam quality, which showed excellent agreement with measured doses with a discrepancy of 0.1%. Conclusion: The observed agreement confirm the accuracy of the simulated 6 MV photon beam. It can therefore be used as radiation source for calculating dose distributions and further investigations aimed at improving dose delivery and planning in cancer patients.

9.
J Vasc Surg Cases Innov Tech ; 8(3): 494-495, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36052206

RESUMO

The increasing use of endovascular aneurysm repair to treat abdominal aortic aneurysms has mandated solutions to the limitations of this operation, including the requirement for additional procedures. A 64-year-old man had presented with symptomatic thrombosis of the left iliac limb after endovascular aneurysm repair. We have reported the use of an innovative endovascular repair for our patient.

10.
Front Microbiol ; 13: 869479, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35865931

RESUMO

One of the most distinctive characteristics of archaea is their unique lipids. While the general nature of archaeal lipids has been linked to their tolerance to extreme conditions, little is known about the diversity of lipidic structures archaea are able to synthesize, which hinders the elucidation of the physicochemical properties of their cell membrane. In an effort to widen the known lipid repertoire of the piezophilic and hyperthermophilic model archaeon Thermococcus barophilus, we comprehensively characterized its intact polar lipid (IPL), core lipid (CL), and polar head group compositions using a combination of cutting-edge liquid chromatography and mass spectrometric ionization systems. We tentatively identified 82 different IPLs based on five distinct CLs and 10 polar head group derivatives of phosphatidylhexoses, including compounds reported here for the first time, e.g., di-N-acetylhexosamine phosphatidylhexose-bearing lipids. Despite having extended the knowledge on the lipidome, our results also indicate that the majority of T. barophilus lipids remain inaccessible to current analytical procedures and that improvements in lipid extraction and analysis are still required. This expanded yet incomplete lipidome nonetheless opens new avenues for understanding the physiology, physicochemical properties, and organization of the membrane in this archaeon as well as other archaea.

11.
Genet Epidemiol ; 46(3-4): 170-181, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35312098

RESUMO

Genome-wide association studies (GWAS) have successfully identified thousands of single nucleotide polymorphisms (SNPs) associated with complex traits; however, the identified SNPs account for a fraction of trait heritability, and identifying the functional elements through which genetic variants exert their effects remains a challenge. Recent evidence suggests that SNPs associated with complex traits are more likely to be expression quantitative trait loci (eQTL). Thus, incorporating eQTL information can potentially improve power to detect causal variants missed by traditional GWAS approaches. Using genomic, transcriptomic, and platelet phenotype data from the Genetic Study of Atherosclerosis Risk family-based study, we investigated the potential to detect novel genomic risk loci by incorporating information from eQTL in the relevant target tissues (i.e., platelets and megakaryocytes) using established statistical principles in a novel way. Permutation analyses were performed to obtain family-wise error rates for eQTL associations, substantially lowering the genome-wide significance threshold for SNP-phenotype associations. In addition to confirming the well known association between PEAR1 and platelet aggregation, our eQTL-focused approach identified a novel locus (rs1354034) and gene (ARHGEF3) not previously identified in a GWAS of platelet aggregation phenotypes. A colocalization analysis showed strong evidence for a functional role of this eQTL.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Humanos , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas/genética , Receptores de Superfície Celular , Transcriptoma
12.
Appl Environ Microbiol ; 88(4): e0215421, 2022 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-34936840

RESUMO

Butanetriol and pentanetriol dibiphytanyl glycerol tetraethers (BDGTs and PDGTs, respectively) are recently identified classes of archaeal membrane lipids that are prominent constituents in anoxic subseafloor sediments. These lipids are intriguing, as they possess unusual backbones with four or five carbon atoms instead of the canonical three-carbon glycerol backbone. In this study, we examined the biosynthesis of BDGTs and PDGTs by the methanogen Methanomassiliicoccus luminyensis, the only available isolate known to produce these compounds, via stable isotope labeling with [methyl-13C]methionine followed by mass spectrometry analysis. We show that their biosynthesis proceeds from transfer(s) of the terminal methyl group of methionine to the more common archaeal membrane lipids, i.e., glycerol dibiphytanyl glycerol tetraethers (GDGTs). As this methylation targets a methylene group, a radical mechanism involving a radical S-adenosylmethionine (SAM) enzyme is probable. Over the course of the incubation, the abundance of PDGTs relative to BDGTs, expressed as backbone methylation index, increased, implying that backbone methylation may be related to the growth shift to stationary conditions, possibly due to limited energy and/or substrate availability. The increase of the backbone methylation index with increasing sediment age in a sample set from the Mediterranean Sea adds support for such a relationship. IMPORTANCE Butanetriol and pentanetriol dibiphytanyl glycerol tetraethers are membrane lipids recently discovered in anoxic environments. These lipids differ from typical membrane-spanning tetraether lipids because they possess a non-glycerol backbone. The biosynthetic pathway and physiological role of these unique lipids are currently unknown. Here, we show that in the strain Methanomassiliicoccus luminyensis, these lipids are the result of methyl transfer(s) from an S-adenosyl methionine (SAM) intermediate. We observed a relative increase of the doubly methylated compound, pentanetriol dibiphytanyl glycerol tetraether, in the stationary phase of M. luminyensis as well as in the subseafloor of the Mediterranean Sea and thus introduced a backbone methylation index, which could be used to further explore microbial activity in natural settings.


Assuntos
Archaea , Euryarchaeota , Archaea/metabolismo , Glicerol/metabolismo , Lipídeos de Membrana/metabolismo , Metilação
13.
Head Neck Pathol ; 15(4): 1399-1403, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33616851

RESUMO

Myeloid neoplasms with PDGFRA rearrangement are rare, and most commonly present with features of chronic eosinophilic leukemia; however, they rarely manifest as acute myeloid or lymphoblastic leukemia. Patients typically present with symptoms of hypereosinophilia including cardiovascular and pulmonary symptoms. An increase in mast cells is also a common feature of this disease, and there may be elevated serum tryptase with significant clinical overlap with systemic mastocytosis. Here, we present an unusual case of a myeloid neoplasm with PDGFRA rearrangement manifesting as a retromolar pad mass in a patient with a prior diagnosis of systemic mastocytosis. This case highlights the possibility of soft tissue involvement by myeloid neoplasms with PDGFRA rearrangement in the oral cavity. The identification of this entity is of significant clinical importance because many patients can be effectively treated with tyrosine kinase inhibitors.


Assuntos
Síndrome Hipereosinofílica/diagnóstico , Síndrome Hipereosinofílica/genética , Leucemia/diagnóstico , Leucemia/genética , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/genética , Idoso , Biomarcadores Tumorais/análise , Biópsia , Diagnóstico Diferencial , Rearranjo Gênico , Humanos , Síndrome Hipereosinofílica/patologia , Leucemia/patologia , Masculino , Neoplasias Bucais/patologia , Neoplasias de Tecidos Moles/patologia
14.
BMC Med Res Methodol ; 21(1): 29, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568059

RESUMO

BACKGROUND: Statistical methods for modeling longitudinal and time-to-event data has received much attention in medical research and is becoming increasingly useful. In clinical studies, such as cancer and AIDS, longitudinal biomarkers are used to monitor disease progression and to predict survival. These longitudinal measures are often missing at failure times and may be prone to measurement errors. More importantly, time-dependent survival models that include the raw longitudinal measurements may lead to biased results. In previous studies these two types of data are frequently analyzed separately where a mixed effects model is used for the longitudinal data and a survival model is applied to the event outcome. METHODS: In this paper we compare joint maximum likelihood methods, a two-step approach and a time dependent covariate method that link longitudinal data to survival data with emphasis on using longitudinal measures to predict survival. We apply a Bayesian semi-parametric joint method and maximum likelihood joint method that maximizes the joint likelihood of the time-to-event and longitudinal measures. We also implement the Two-Step approach, which estimates random effects separately, and a classic Time Dependent Covariate Model. We use simulation studies to assess bias, accuracy, and coverage probabilities for the estimates of the link parameter that connects the longitudinal measures to survival times. RESULTS: Simulation results demonstrate that the Two-Step approach performed best at estimating the link parameter when variability in the longitudinal measure is low but is somewhat biased downwards when the variability is high. Bayesian semi-parametric and maximum likelihood joint methods yield higher link parameter estimates with low and high variability in the longitudinal measure. The Time Dependent Covariate method resulted in consistent underestimation of the link parameter. We illustrate these methods using data from the Framingham Heart Study in which lipid measurements and Myocardial Infarction data were collected over a period of 26 years. CONCLUSIONS: Traditional methods for modeling longitudinal and survival data, such as the time dependent covariate method, that use the observed longitudinal data, tend to provide downwardly biased estimates. The two-step approach and joint models provide better estimates, although a comparison of these methods may depend on the underlying residual variance.


Assuntos
Modelos Estatísticos , Teorema de Bayes , Viés , Simulação por Computador , Humanos , Estudos Longitudinais , Análise de Sobrevida
15.
Front Mol Neurosci ; 14: 752403, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35110995

RESUMO

BACKGROUND: DNA methylation at CpG sites is a vital epigenetic modification of the human genome affecting gene expression, and potentially, health outcomes. However, evidence is just budding on the effects of aerobic exercise-induced adaptation on DNA methylation in older mild cognitively impaired (MCI) elderly African American (AAs). Therefore, we examined the effects of a 6-month aerobic exercise-intervention on genome-wide DNA methylation in elderly AA MCI volunteers. DESIGN: Elderly AA volunteers confirmed MCI assigned into a 6-month program of aerobic exercise (eleven participants) underwent a 40-min supervised-training 3-times/week and controls (eight participants) performed stretch training. Participants had maximal oxygen consumption (VO2max) test and Genome-wide methylation levels at CpG sites using the Infinium HumanMethylation450 BeadChip assay at baseline and after a 6-month exercise program. We computed false discovery rates (FDR) using Sidak to account for multiplicity of tests and performed quantitative real-time polymerase chain-reaction (qRT-PCR) to confirm the effects of DNA methylations on expression levels of the top 5 genes among the aerobic participants. CpG sites identified from aerobic-exercise participants were similarly analyzed by the stretch group to quantify the effects of exercise-induced methylation changes among the group of stretch participants. RESULTS: Eleven MCI participants (aerobic: 73% females; mean age 72.3 ± 6.6 years) and eight MCI participants (stretch: 75% female; mean age 70.6 ± 6.7 years) completed the training. Aerobic exercise-training was associated with increases in VO2max and with global hypo- and hypermethylation changes. The most notable finding was CpG hypomethylation within the body of the VPS52 gene (P = 5.4 × 10-26), a Golgi-associated protein, involved in intracellular protein trafficking including amyloid precursor protein. qRT-PCR confirmed a nearly twofold increased expression of VPS52. Other top findings with FDR q-value < 10-5, include hypomethylations of SCARB1 (8.8 × 10-25), ARTN (6.1 × 10-25), NR1H2 (2.1 × 10-18) and PPP2R5D (9.8 × 10-18). CONCLUSION: We conclude that genome-wide DNA methylation patterns is associated with exercise training-induced methylation changes. Identification of methylation changes around genes previously shown to interact with amyloid biology, intracellular protein trafficking, and lipoprotein regulations provide further support to the likely protective effect of exercise in MCI. Future studies in larger samples are needed to confirm our findings.

17.
J Public Health Afr ; 11(1): 1214, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-33209234

RESUMO

The Yaoundé Gynaeco-Obstetric and Pediatric Hospital (YGOPH) faced challenges of high debts and sub-optimal care delivery. Performance-Based-Management (PBM) provides an environment of checks and balances, increased transparency, competition and autonomy, thereby improving clinical as well as financial indicators. We describe the transition from resource-based to PBM at the YGOPH over a seven-year period. There was an increase of 4.5% in OB/GYN and 8.1% in prenatal consultations, 8.4% in C-sections, 6.1% of children vaccinated, and 30.5% of women seen for family planning, 51.1% of people living with the Human Immunodeficiency Virus on treatment and 29.4% of indigent patients. These results occurred in spite of a 14% reduction in staff. Annual revenue increased by 5.75%. The share of hospital income from care on overall hospital revenue increased from 55.11% to 60.00%. With this self-financing PBM model, the hospital remains a social, humane and financially viable structure delivering improved quality care.

18.
Front Microbiol ; 11: 1034, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32582055

RESUMO

Planktonic archaea include predominantly Marine Group I Thaumarchaeota (MG I) and Marine Group II Euryarchaeota (MG II), which play important roles in the oceanic carbon cycle. MG I produce specific lipids called isoprenoid glycerol dibiphytanyl glycerol tetraethers (GDGTs), which are being used in the sea surface temperature proxy named TEX86. Although MG II may be the most abundant planktonic archaeal group in surface water, their lipid composition remains poorly characterized because of the lack of cultured representatives. Circumstantial evidence from previous studies of marine suspended particulate matter suggests that MG II may produce both GDGTs and archaeol-based lipids. In this study, integration of the 16S rRNA gene quantification and sequencing and lipid analysis demonstrated that MG II contributed significantly to the pool of archaeal tetraether lipids in samples collected from MG II-dominated surface waters of the Northwestern Pacific Ocean (NWPO). The archaeal lipid composition in MG II-dominated NWPO waters differed significantly from that of known MG I cultures, containing relatively more 2G-OH-, 2G- and 1G- GDGTs, especially in their acyclic form. Lipid composition in NWPO waters was also markedly different from MG I-dominated surface water samples collected in the East China Sea. GDGTs from MG II-dominated samples seemed to respond to temperature similarly to GDGTs from the MG I-dominated samples, which calls for further study using pure cultures to determine the exact impact of MG II on GDGT-based proxies.

19.
Clim Change ; 163: 1795-1813, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33867603

RESUMO

Built infrastructures are increasingly disrupted by climate-related extreme events. Being able to monitor what climate change implies for US infrastructures is of considerable importance to all levels of decision-makers. A capacity to develop cross-cutting, widely applicable indicators for more than a dozen different kinds of infrastructure, however, is severely limited at present. The development of such indicators must be considered an ongoing activity that will require expansion and refinement. A number of recent consensus reports suggest four priorities for indicators that portray the impacts of climate change, climate-related extreme events, and other driving forces on infrastructure. These are changes in the reliability of infrastructure services and the implications for costs; changes in the resilience of infrastructures to climate and other stresses; impacts due to the interdependencies of infrastructures; and ongoing adaptation in infrastructures.

20.
S Afr Med J ; 111(1): 57-60, 2020 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-33404007

RESUMO

BACKGROUND: Namaqualand hip dysplasia (NHD) is a mild form of spondyloepiphyseal dysplasia in which progressive arthropathy of the hip joint is a major manifestation. The disorder was documented in a multigenerational South African (SA) family with antecedents from Namaqualand, a region in the north-west of the country. Linkage analysis revealed a locus that includes the collagen type II gene, COL2A1. OBJECTIVES: To identify the pathogenic COL2A1 variant causing NHD in an SA family. METHODS: One affected male with a clear diagnosis of NHD was selected for whole-exome sequencing (WES) on the Ion Torrent Proton platform. A probe-based assay and direct cycle sequencing were used to confirm that the prioritised variant segregated with the phenotype in the NHD family and was not present in unrelated controls from the same population. RESULTS: WES identified one heterozygous variant, c.2014G>T; p.(Gly672Cys), in the coding sequence of the COL2A1 gene. The variant segregated with NHD in 23 affected family members and was previously reported in a Caucasian male with Perthes disease-like presentation. CONCLUSIONS: It is now possible to provide a molecular diagnosis of NHD before hip problems present. The large, clinically well-characterised NHD family is a valuable resource that could provide more insight into the mechanisms responsible for the variable expression observed in individuals with this variant.


Assuntos
Colágeno Tipo II/genética , Luxação Congênita de Quadril/diagnóstico , Osteocondrodisplasias/congênito , Adulto , Criança , Sequenciamento de Nucleotídeos em Larga Escala , Luxação Congênita de Quadril/genética , Luxação Congênita de Quadril/fisiopatologia , Humanos , Doença de Legg-Calve-Perthes/diagnóstico , Doença de Legg-Calve-Perthes/genética , Masculino , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/genética , Osteocondrodisplasias/fisiopatologia , África do Sul , Sequenciamento do Exoma
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