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1.
G3 (Bethesda) ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38564250

RESUMO

Galleria mellonella is a pest of honeybees in many countries because its larvae feed on beeswax. However, G. mellonella larvae can also eat various plastics, including polyethylene, polystyrene and polypropylene, so the species is garnering increasing interest as a tool for plastic biodegradation research. This paper presents an improved genome (99.3% completed lepidoptera_odb10 BUSCO; genome mode) for G. mellonella. This 472 Mb genome is in 221 contigs with an N50 of 6.4 MB and contains 13,604 protein-coding genes. Genes that code for known and putative polyethylene-degrading enzymes and their similarity to proteins found in other Lepidoptera are highlighted. An analysis of secretory proteins more likely to be involved in the plastic catabolic process has also been carried out.

2.
Water Res ; 254: 121426, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38471203

RESUMO

Naegleria fowleri has been detected in drinking water distribution systems (DWDS) in Australia, Pakistan and the United States and is the causative agent of the highly fatal disease primary amoebic meningoencephalitis. Previous small scale field studies have shown that Meiothermus may be a potential biomarker for N. fowleri. However, correlations between predictive biomarkers in small sample sizes often breakdown when applied to larger more representative datasets. This study represents one of the largest and most rigorous temporal investigations of Naegleria fowleri colonisation in an operational DWDS in the world and measured the association of Meiothermus and N. fowleri over a significantly larger space and time in the DWDS. A total of 232 samples were collected from five sites over three-years (2016-2018), which contained 29 positive N. fowleri samples. Two specific operational taxonomic units assigned to M. chliarophilus and M. hypogaeus, were significantly associated with N. fowleri presence. Furthermore, inoculation experiments demonstrated that Meiothermus was required to support N. fowleri growth in field-collected biofilms. This validates Meiothermus as prospective biological tool to aid in the identification and surveillance of N. fowleri colonisable sites.


Assuntos
Água Potável , Naegleria fowleri , Estudos Prospectivos , Bactérias , Biofilmes
3.
Plant J ; 117(4): 1206-1222, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38038953

RESUMO

MicroRNA (miRNA) target mimicry technologies, utilizing naturally occurring miRNA decoy molecules, represent a potent tool for analyzing miRNA function. In this study, we present a highly efficient small RNA (sRNA) target mimicry design based on G-U base-paired hairpin RNA (hpG:U), which allows for the simultaneous targeting of multiple sRNAs. The hpG:U constructs consistently generate high amounts of intact, polyadenylated stem-loop (SL) RNA outside the nuclei, in contrast to traditional hairpin RNA designs with canonical base pairing (hpWT), which were predominantly processed resulting in a loop. By incorporating a 460-bp G-U base-paired double-stranded stem and a 312-576 nt loop carrying multiple miRNA target mimicry sites (GUMIC), the hpG:U construct displayed effective repression of three Arabidopsis miRNAs, namely miR165/166, miR157, and miR160, both individually and in combination. Additionally, a GUMIC construct targeting a prominent cluster of siRNAs derived from cucumber mosaic virus (CMV) Y-satellite RNA (Y-Sat) effectively inhibited Y-Sat siRNA-directed silencing of the chlorophyll biosynthetic gene CHLI, thereby reducing the yellowing symptoms in infected Nicotiana plants. Therefore, the G-U base-paired hpRNA, characterized by differential processing compared to traditional hpRNA, acts as an efficient decoy for both miRNAs and siRNAs. This technology holds great potential for sRNA functional analysis and the management of sRNA-mediated diseases.


Assuntos
Arabidopsis , MicroRNAs , Pareamento de Bases/genética , Plantas Geneticamente Modificadas/genética , RNA Interferente Pequeno/genética , MicroRNAs/genética , Interferência de RNA , RNA Mensageiro/genética , RNA de Cadeia Dupla , Arabidopsis/genética
4.
Ann Surg Oncol ; 31(1): 460-472, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37875740

RESUMO

PURPOSE: The purpose of this paper is to report on changes in overall survival, progression-free survival, and complete cytoreduction rates in the 5-year period after the implementation of a multidisciplinary surgical team (MDT). METHODS: Two cohorts were used. Cohort A was a retrospectively collated cohort from 2006 to 2015. Cohort B was a prospectively collated cohort of patients from January 2017 to September 2021. RESULTS: This study included 146 patients in cohort A (2006-2015) and 174 patients in cohort B (2017-2021) with FIGO stage III/IV ovarian cancer. Median follow-up in cohort A was 60 months and 48 months in cohort B. The rate of primary cytoreductive surgery increased from 38% (55/146) in cohort A to 46.5% (81/174) in cohort B. Complete macroscopic resection increased from 58.9% (86/146) in cohort A to 78.7% (137/174) in cohort B (p < 0.001). At 3 years, 75% (109/144) patients had disease progression in cohort A compared with 48.8% (85/174) in cohort B (log-rank, p < 0.001). Also at 3 years, 64.5% (93/144) of patients had died in cohort A compared with 24% (42/174) of cohort B (log-rank, p < 0.001). Cox multivariate analysis demonstrated that MDT input, residual disease, and age were independent predictors of overall (hazard ratio [HR] 0.29, 95% confidence interval [CI] 0.203-0.437, p < 0.001) and progression-free survival (HR 0.31, 95% CI 0.21-0.43, p < 0.001). Major morbidity remained stable throughout both study periods (2006-2021). CONCLUSIONS: Our data demonstrate that the implementation of multidisciplinary-team, intraoperative approach allowed for a change in surgical philosophy and has resulted in a significant improvement in overall survival, progression-free survival, and complete resection rates.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/patologia , Estudos Retrospectivos , Carcinoma Epitelial do Ovário/cirurgia , Modelos de Riscos Proporcionais , Análise Multivariada , Procedimentos Cirúrgicos de Citorredução/métodos , Estadiamento de Neoplasias
5.
J Orthop ; 45: 54-60, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37854276

RESUMO

BACKGROUND: Femoral neck fractures are a common cause of morbidity and mortality in the community. Minimally displaced subcapital necks of femoral fractures are usually managed with internal fixation, although there is debate as to which method is superior. This systematic review aimed to compare the outcomes of different fixation methods in the management of this common fracture. METHODS: This systematic review was conducted in accordance with PRISMA statement guidelines. The databases searched were MEDLINE (Ovid), Cochrane Central Register of Controlled Trials, and EMBASE (Ovid). The study quality and risk of bias were assessed using the Newcastle-Ottawa Quality Assessment Scale, and relevant data were extracted and synthesised. RESULTS: Nine articles met the inclusion criteria. A total of 819 patients were included in this study. Eight of the nine studies were case series, and one was a randomised control trial. The mean risk of bias was 7.4/9 for non-randomised articles. The fixation methods used in the included studies were dynamic hip screw (DHS), cannulated screws, Smith-Peterson nail, hooknail, Moore's pins, and Knowle's pins. DHS was found to be a superior method of fixation and was supported by a clinical trial. It has high rates of union (99 %), low rates of avascular necrosis (<1 %), and low rates of fixation failure (<1 %). CONCLUSIONS: Based on the available data, DHS appears to be the superior method of fixation for the minimally displaced subcapital neck of femoral fractures. Given the general low level of evidence currently available, additional clinical trials are needed in this area.

6.
Sci Rep ; 13(1): 11762, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474628

RESUMO

The pink bollworm (Pectinophora gossypiella) is one of the world's most destructive pests of cotton. This invasive lepidopteran occurs in nearly all cotton-growing countries. Its presence in the Ord Valley of North West Australia poses a potential threat to the expanding cotton industry there. To assess this threat and better understand population structure of pink bollworm, we analysed genomic data from individuals collected in the field from North West Australia, India, and Pakistan, as well as from four laboratory colonies that originated in the United States. We identified single nucleotide polymorphisms (SNPs) using a reduced-representation, genotyping-by-sequencing technique (DArTseq). The final filtered dataset included 6355 SNPs and 88 individual genomes that clustered into five groups: Australia, India-Pakistan, and three groups from the United States. We also analysed sequences from Genbank for mitochondrial DNA (mtDNA) locus cytochrome c oxidase I (COI) for pink bollworm from six countries. We found low genetic diversity within populations and high differentiation between populations from different continents. The high genetic differentiation between Australia and the other populations and colonies sampled in this study reduces concerns about gene flow to North West Australia, particularly from populations in India and Pakistan that have evolved resistance to transgenic insecticidal cotton. We attribute the observed population structure to pink bollworm's narrow host plant range and limited dispersal between continents.


Assuntos
Resistência a Inseticidas , Mariposas , Humanos , Animais , Resistência a Inseticidas/genética , Plantas Geneticamente Modificadas/genética , Endotoxinas/genética , Proteínas Hemolisinas/genética , Proteínas de Bactérias/genética , Mariposas/genética , DNA Mitocondrial , Gossypium/genética
7.
J Med Microbiol ; 72(6)2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37326607

RESUMO

Introduction. Uninfected diabetes-related foot ulcer (DFU) progression to diabetes-related foot infection (DFI) is a prevalent complication for patients with diabetes. DFI often progresses to osteomyelitis (DFI-OM). Active (growing) Staphylococcus aureus is the most common pathogen in these infections. There is relapse in 40-60 % of cases even when the initial treatment at the DFI stage apparently clears infection.Hypothesis. S. aureus adopts the quasi-dormant Small Colony Variant (SCV) state during DFU and consequently infection, and when present in DFI cases also permits survival in non-diseased tissues as a reservoir to cause relapse.Aim. The aim of this study was to investigate the bacterial factors that facilitate persistent infections.Methodology. People with diabetes were recruited from two tertiary hospitals. Clinical and bacterial data was taken from 153 patients with diabetes (51 from a control group with no ulcer or infection) and samples taken from 102 patients with foot complications to identify bacterial species and their variant colony types, and then compare the bacterial composition in those with uninfected DFU, DFI and those with DFI-OM, of whom samples were taken both from wounds (DFI-OM/W) and bone (DFI-OM/B). Intracellular, extracellular and proximal 'healthy' bone were examined.Results. S. aureus was identified as the most prevalent pathogen in diabetes-related foot pathologies (25 % of all samples). For patients where disease progressed from DFU to DFI-OM, S. aureus was isolated as a diversity of colony types, with increasing numbers of SCVs present. Intracellular (bone) SCVs were found, and even within uninfected bone SCVs were present. Wounds of 24 % of patients with uninfected DFU contained active S. aureus. All patients with a DFI with a wound but not bone infection had previously had S. aureus isolated from an infection (including amputation), representing a relapse.Conclusion. The presence of S. aureus SCVs in recalcitrant pathologies highlights their importance in persistent infections through the colonization of reservoirs, such as bone. The survival of these cells in intracellular bone is an important clinical finding supporting in vitro data. Also, there seems to be a link between the genetics of S. aureus found in deeper infections compared to those only found in DFU.


Assuntos
Bacteriologia , Diabetes Mellitus , Pé Diabético , Osteomielite , Infecções Estafilocócicas , Humanos , Staphylococcus aureus/genética , Pé Diabético/complicações , Pé Diabético/terapia , Incidência , Infecção Persistente , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologia , Osteomielite/epidemiologia , Osteomielite/microbiologia
8.
Innovation (Camb) ; 4(4): 100454, 2023 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-37388193

RESUMO

The cotton bollworm, Helicoverpa armigera, is set to become the most economically devastating crop pest in the world, threatening food security and biosafety as its range expands across the globe. Key to understanding the eco-evolutionary dynamics of H. armigera, and thus its management, is an understanding of population connectivity and the adaptations that allow the pest to establish in unique environments. We assembled a chromosome-scale reference genome and re-sequenced 503 individuals spanning the species range to delineate global patterns of connectivity, uncovering a previously cryptic population structure. Using a genome-wide association study (GWAS) and cell line expression of major effect loci, we show that adaptive changes in a temperature- and light-sensitive developmental pathway enable facultative diapause and that adaptation of trehalose synthesis and transport underlies cold tolerance in extreme environments. Incorporating extensive pesticide resistance monitoring, we also characterize a suite of novel pesticide and Bt resistance alleles under selection in East China. These findings offer avenues for more effective management strategies and provide insight into how insects adapt to variable climatic conditions and newly colonized environments.

10.
BMJ Glob Health ; 8(2)2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36750273

RESUMO

INTRODUCTION: Reducing unmet need for modern contraception and expanding access to quality maternal health (MH) services are priorities for improving women's health and economic empowerment. To support investment decisions, we estimated the additional cost and expected health and economic benefits of achieving the United Nations targets of zero unmet need for modern contraceptive choices and 95% coverage of MH services by 2030 in select Small Island Developing States. METHODS: Five Pacific (Kiribati, Samoa, Solomon Islands, Tonga and Vanuatu) and four Caribbean (Barbados, Guyana, Jamaica and Saint Lucia) countries were considered based on population survey data availability. For each country, the Lives Saved Tool was used to model costs, health outcomes and economic benefits for two scenarios: business-as-usual (BAU) (coverage maintained) and coverage-targets-achieved, which scaled linearly from 2022 (following COVID-19 disruptions) coverage of evidence-based family planning and MH interventions to reach United Nations targets, including modern contraceptive methods and access to complete antenatal, delivery and emergency care. Unintended pregnancies, maternal deaths, stillbirths and newborn deaths averted by the coverage-targets-achieved scenario were converted to workforce, education and social economic benefits; and benefit-cost ratios were calculated. RESULTS: The coverage-targets-achieved scenario required an additional US$12.6M (US$10.8M-US$15.9M) over 2020-2030 for the five Pacific countries (15% more than US$82.4M to maintain BAU). This additional investment was estimated to avert 126 000 (40%) unintended pregnancies, 2200 (28%) stillbirths and 121 (29%) maternal deaths and lead to a 15-fold economic benefit of US$190.6M (US$67.0M-US$304.5M) by 2050. For the four Caribbean countries, an additional US$17.8M (US$15.3M-US$22.4M) was needed to reach the targets (4% more than US$405.4M to maintain BAU). This was estimated to avert 127 000 (23%) unintended pregnancies, 3600 (23%) stillbirths and 221 (25%) maternal deaths and lead to a 24-fold economic benefit of US$426.2M (US$138.6M-US$745.7M) by 2050. CONCLUSION: Achieving full coverage of contraceptive and MH services in the Pacific and Caribbean is likely to have a high return on investment.


Assuntos
COVID-19 , Morte Materna , Recém-Nascido , Feminino , Gravidez , Humanos , Anticoncepcionais , Natimorto/epidemiologia , Saúde Materna , Região do Caribe
11.
Pest Manag Sci ; 79(5): 1829-1839, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36655826

RESUMO

BACKGROUND: Bemisia tabaci is a globally significant agricultural pest including in Australia, where it exhibits resistance to numerous insecticides. With a recent label change, buprofezin (group 16), is now used for whitefly management in Australia. This study investigated resistance to pyriproxyfen (group 7C), spirotetramat (group 23) and buprofezin using bioassays and available molecular markers. RESULTS: Bioassay and selection testing of B. tabaci populations detected resistance to pyriproxyfen with resistance ratios ranging from 4.1 to 56. Resistance to spirotetramat was detected using bioassay, selection testing and sequencing techniques. In populations collected from cotton, the A2083V mutation was detected in three populations of 85 tested, at frequencies ≤4.1%, whereas in limited surveillance of populations from an intensive horticultural region the frequency was ≥75.8%. The baseline susceptibility of B. tabaci to buprofezin was determined from populations tested from 2019 to 2020, in which LC50 values ranged from 0.61 to 10.75 mg L-1 . From the bioassay data, a discriminating dose of 200 mg L-1 was developed. Recent surveillance of 16 populations detected no evidence of resistance with 100% mortality recorded at doses ≤32 mg L-1 . A cross-resistance study found no conclusive evidence of resistance to buprofezin in populations with high resistance to pyriproxyfen or spirotetramat. CONCLUSIONS: In Australian cotton, B. tabaci pest management is challenged by ongoing resistance to pyriproxyfen, while resistance to spirotetramat is an emerging issue. The addition of buprofezin provides a new mode-of-action for whitefly pest management, which will strengthen the existing insecticide resistance management strategy. © 2023 Commonwealth of Australia. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Assuntos
Hemípteros , Inseticidas , Animais , Resistência a Inseticidas/genética , Hemípteros/genética , Austrália , Inseticidas/farmacologia , Gossypium/genética
12.
JAMA Otolaryngol Head Neck Surg ; 149(3): 212-222, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36633841

RESUMO

Importance: In the US, most childhood-onset bilateral sensorineural hearing loss is genetic, with more than 120 genes and thousands of different alleles known. Primary treatments are hearing aids and cochlear implants. Genetic diagnosis can inform progression of hearing loss, indicate potential syndromic features, and suggest best timing for individualized treatment. Objective: To identify the genetic causes of childhood-onset hearing loss and characterize severity, progression, and cochlear implant success associated with genotype in a single large clinical cohort. Design, Setting, and Participants: This cross-sectional analysis (genomics) and retrospective cohort analysis (audiological measures) were conducted from 2019 to 2022 at the otolaryngology and audiology clinics of Seattle Children's Hospital and the University of Washington and included 449 children from 406 families with bilateral sensorineural hearing loss with an onset younger than 18 years. Data were analyzed between January and June 2022. Main Outcomes and Measures: Genetic diagnoses based on genomic sequencing and structural variant analysis of the DNA of participants; severity and progression of hearing loss as measured by audiologic testing; and cochlear implant success as measured by pediatric and adult speech perception tests. Hearing thresholds and speech perception scores were evaluated with respect to age at implant, months since implant, and genotype using a multivariate analysis of variance and covariance. Results: Of 406 participants, 208 (51%) were female, 17 (4%) were African/African American, 32 (8%) were East Asian, 219 (54%) were European, 53 (13%) were Latino/Admixed American, and 16 (4%) were South Asian. Genomic analysis yielded genetic diagnoses for 210 of 406 families (52%), including 55 of 82 multiplex families (67%) and 155 of 324 singleton families (48%). Rates of genetic diagnosis were similar for children of all ancestries. Causal variants occurred in 43 different genes, with each child (with 1 exception) having causative variant(s) in only 1 gene. Hearing loss severity, affected frequencies, and progression varied by gene and, for some genes, by genotype within gene. For children with causative mutations in MYO6, OTOA, SLC26A4, TMPRSS3, or severe loss-of-function variants in GJB2, hearing loss was progressive, with losses of more than 10 dB per decade. For all children with cochlear implants, outcomes of adult speech perception tests were greater than preimplanted levels. Yet the degree of success varied substantially by genotype. Adjusting for age at implant and interval since implant, speech perception was highest for children with hearing loss due to MITF or TMPRSS3. Conclusions and Relevance: The results of this cross-sectional study suggest that genetic diagnosis is now sufficiently advanced to enable its integration into precision medical care for childhood-onset hearing loss.


Assuntos
Implante Coclear , Implantes Cocleares , Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Percepção da Fala , Adulto , Feminino , Criança , Humanos , Masculino , Estudos Transversais , Estudos Retrospectivos , Surdez/cirurgia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/cirurgia , Perda Auditiva Bilateral/diagnóstico , Perda Auditiva Bilateral/genética , Proteínas de Membrana , Proteínas de Neoplasias , Serina Endopeptidases
13.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675151

RESUMO

Apicomplexan infections, such as giardiasis and cryptosporidiosis, negatively impact a considerable proportion of human and commercial livestock populations. Despite this, the molecular mechanisms of disease, particularly the effect on the body beyond the gastrointestinal tract, are still poorly understood. To highlight host-parasite-microbiome biochemical interactions, we utilised integrated metabolomics-16S rRNA genomics and metabolomics-proteomics approaches in a C57BL/6J mouse model of giardiasis and compared these to Cryptosporidium and uropathogenic Escherichia coli (UPEC) infections. Comprehensive samples (faeces, blood, liver, and luminal contents from duodenum, jejunum, ileum, caecum and colon) were collected 10 days post infection and subjected to proteome and metabolome analysis by liquid and gas chromatography-mass spectrometry, respectively. Microbial populations in faeces and luminal washes were examined using 16S rRNA metagenomics. Proteome-metabolome analyses indicated that 12 and 16 key pathways were significantly altered in the gut and liver, respectively, during giardiasis with respect to other infections. Energy pathways including glycolysis and supporting pathways of glyoxylate and dicarboxylate metabolism, and the redox pathway of glutathione metabolism, were upregulated in small intestinal luminal contents and the liver during giardiasis. Metabolomics-16S rRNA genetics integration indicated that populations of three bacterial families-Autopobiaceae (Up), Desulfovibrionaceae (Up), and Akkermanasiaceae (Down)-were most significantly affected across the gut during giardiasis, causing upregulated glycolysis and short-chained fatty acid (SCFA) metabolism. In particular, the perturbed Akkermanasiaceae population seemed to cause oxidative stress responses along the gut-liver axis. Overall, the systems biology approach applied in this study highlighted that the effects of host-parasite-microbiome biochemical interactions extended beyond the gut ecosystem to the gut-liver axis. These findings form the first steps in a comprehensive comparison to ascertain the major molecular and biochemical contributors of host-parasite interactions and contribute towards the development of biomarker discovery and precision health solutions for apicomplexan infections.


Assuntos
Criptosporidiose , Cryptosporidium , Microbioma Gastrointestinal , Giardíase , Microbiota , Camundongos , Animais , Humanos , RNA Ribossômico 16S/genética , RNA Ribossômico 16S/metabolismo , Regulação para Cima , Proteoma/metabolismo , Criptosporidiose/metabolismo , Camundongos Endogâmicos C57BL , Cryptosporidium/metabolismo , Metabolômica , Metaboloma , Fígado/metabolismo , Oxirredução
14.
Sci Rep ; 13(1): 1398, 2023 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-36697434

RESUMO

Between June and August 2020, an agent-based model was used to project rates of COVID-19 infection incidence and cases diagnosed as positive from 15 September to 31 October 2020 for 72 geographic settings. Five scenarios were modelled: a baseline scenario where no future changes were made to existing restrictions, and four scenarios representing small or moderate changes in restrictions at two intervals. Post hoc, upper and lower bounds for number of diagnosed Covid-19 cases were compared with actual data collected during the prediction window. A regression analysis with 17 covariates was performed to determine correlates of accurate projections. It was found that the actual data fell within the lower and upper bounds in 27 settings and out of bounds in 45 settings. The only statistically significant predictor of actual data within the predicted bounds was correct assumptions about future policy changes (OR 15.04; 95% CI 2.20-208.70; p = 0.016). Frequent changes in restrictions implemented by governments, which the modelling team was not always able to predict, in part explains why the majority of model projections were inaccurate compared with actual outcomes and supports revision of projections when policies are changed as well as the importance of modelling teams collaborating with policy experts.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Políticas , Previsões , Análise de Regressão
15.
J Evol Biol ; 36(2): 381-398, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36573922

RESUMO

Genomic data provide valuable insights into pest management issues such as resistance evolution, historical patterns of pest invasions and ongoing population dynamics. We assembled the first reference genome for the redlegged earth mite, Halotydeus destructor (Tucker, 1925), to investigate adaptation to pesticide pressures and demography in its invasive Australian range using whole-genome pool-seq data from regionally distributed populations. Our reference genome comprises 132 autosomal contigs, with a total length of 48.90 Mb. We observed a large complex of ace genes, which has presumably evolved from a long history of organophosphate selection in H. destructor and may contribute towards organophosphate resistance through copy number variation, target-site mutations and structural variants. In the putative ancestral H. destructor ace gene, we identified three target-site mutations (G119S, A201S and F331Y) segregating in organophosphate-resistant populations. Additionally, we identified two new para sodium channel gene mutations (L925I and F1020Y) that may contribute to pyrethroid resistance. Regional structuring observed in population genomic analyses indicates that gene flow in H. destructor does not homogenize populations across large geographic distances. However, our demographic analyses were equivocal on the magnitude of gene flow; the short invasion history of H. destructor makes it difficult to distinguish scenarios of complete isolation vs. ongoing migration. Nonetheless, we identified clear signatures of reduced genetic diversity and smaller inferred effective population sizes in eastern vs. western populations, which is consistent with the stepping-stone invasion pathway of this pest in Australia. These new insights will inform development of diagnostic genetic markers of resistance, further investigation into the multifaceted organophosphate resistance mechanism and predictive modelling of resistance evolution and spread.


Assuntos
Ácaros , Praguicidas , Animais , Austrália , Variações do Número de Cópias de DNA , Ácaros/genética , Organofosfatos , Dinâmica Populacional , Genoma
17.
J Clin Immunol ; 43(1): 151-164, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36063261

RESUMO

Pathogenic variants in LRBA, encoding the LPS Responsive Beige-Like Anchor (LRBA) protein, are responsible for recessive, early-onset hypogammaglobulinemia, severe multi-organ autoimmunity, and lymphoproliferation, with increased risk for malignancy. LRBA deficiency has a wide clinical spectrum with variable age of onset and disease severity. Three apparently unrelated patients with LRBA deficiency, of Georgian Jewish descent, were homozygous for LRBA c.6640C > T, p.R2214*, leading to a stop upstream of the LRBA BEACH domain. Despite carrying the same LRBA genotype, the three patients differed in clinical course: the first patient was asymptomatic until age 25 years; the second presented with failure to thrive at age 3 months; and the third presented at age 7 years with immune cytopenias and severe infections. Two of the patients developed malignancies: the first patient was diagnosed with recurrent Hodgkin's disease at age 36 years, and the second patient developed aggressive gastric cancer at age 15 years. Among Georgian Jews, the carrier frequency of the LRBA p.R2214* allele was 1.6% (4 of 236 Georgian Jewish controls). The allele was absent from other populations. Haplotype analysis showed a shared origin of the mutation. These three patients revealed a pathogenic LRBA founder allele in the Georgian Jewish population, support the diverse and complex clinical spectrum of LRBA deficiency, and support the possibility that LRBA deficiency predisposes to malignancy.


Assuntos
Dermatite , Judeus , Humanos , Lactente , Criança , Adulto , Adolescente , Judeus/genética , Alelos , Recidiva Local de Neoplasia/genética , Genótipo , Mutação/genética , Dermatite/genética , Proteínas Adaptadoras de Transdução de Sinal/genética
18.
Int J Gynaecol Obstet ; 160(3): 955-961, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35964250

RESUMO

OBJECTIVE: to evaluate fetal growth in pregnancies complicated by placenta accreta spectrum (PAS) and to compare fetal growth between cases stratified by ultrasound stage of PAS. METHODS: This was a prospective multicenter cohort study of women diagnosed with PAS between January 2018 and December 2021. We grouped participants into cases by ultrasound stage (PAS stage 1-3) and controls (PAS0). Fetal growth centiles at three timepoints with median gestational ages of 21 ± 1 weeks (interquartile range [IQR], 20 ± 1-22 ± 0 weeks), 28 ± 0 weeks (IQR, 27 ± 0-28 ± 5 weeks), and 33 ± 0 weeks (IQR, 32 ± 1-34 ± 0 weeks) and birth weight centiles were compared between cases and controls and between those with PAS stratified by ultrasound stage. RESULTS: A total of 53 women met inclusion criteria, with a mean age of 37 years (standard deviation, ±4.0 years) and body mass index of 27 kg/m2 (standard deviation, ±5.8 kg/m2 ). Median (IQR) fetal weight centiles were around the 50th centile at each timepoint, with no difference between groups. The incidence of small for gestational age (birth weight ≤ 10th percentile) and large for gestational age (birth weight ≥ 90th percentile) was 11.3% (n = 6) and 15.1% (n = 8), respectively, with no differences by ultrasound stage. The median birth weight centile was 64 (IQR, 26-85), with no differences between cases and controls or by ultrasound stage. CONCLUSIONS: In our cohort, a diagnosis of PAS was not associated with fetal growth restriction.


Assuntos
Placenta Acreta , Gravidez , Humanos , Feminino , Adulto , Lactente , Peso ao Nascer , Placenta Acreta/diagnóstico por imagem , Placenta Acreta/epidemiologia , Estudos de Coortes , Estudos Prospectivos , Desenvolvimento Fetal , Idade Gestacional , Retardo do Crescimento Fetal/diagnóstico por imagem , Ultrassonografia Pré-Natal , Estudos Retrospectivos
19.
J Foot Ankle Res ; 15(1): 85, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36494742

RESUMO

BACKGROUND: Adverse outcomes arising from foot and ankle surgery, including lack of pain relief, increased disability and perioperative complications are infrequent but inevitable. This mixed-methods study aims to explore the impact of adverse outcomes on patients following nonemergent foot and ankle surgery. METHODS: Patients who underwent foot and ankle surgery over a two-year period were invited to participate in this study if they reported an adverse outcome. Qualitative assessment consisted of individual semi-structured interviews, designed to explore the decision they made to have surgery and the impact of the outcome after surgery. Quantitative assessment was performed using questionnaires on demographics, current analgesia, foot pain, health-related quality of life, psychological health, and regret. RESULTS: Twelve participants (eight women) consented for inclusion in this study. Current foot pain was high in 10 participants, five met the criteria for central sensitisation syndrome and two had clinically significant pain catastrophising. Most participants regretted their decision to have surgery. The three major themes identified were expectations, communication, and alternatives. CONCLUSIONS: Self-reported adverse outcomes following foot and ankle surgery were prevalent and participants in this study consistently complained of persistent pain. Regret was common and reasons cited for their adverse outcomes centred around the feelings of inadequate communication and failure to meet expectations.


Assuntos
Tornozelo , Qualidade de Vida , Humanos , Feminino , Tornozelo/cirurgia , Inquéritos e Questionários , Manejo da Dor/métodos , Dor
20.
J Surg Res ; 280: 226-233, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36007481

RESUMO

INTRODUCTION: Routine outpatient follow-up visits for surgical patients are a source of strain on health-care resources and patients. With the COVID-19 pandemic adding a new urgency to finding the safest follow-up arrangement, text message follow-up might prove an acceptable alternative to a phone call or an in-person clinic visit. METHODS: An open-label, three-arm, parallel randomized trial was conducted. The interventions were traditional in-person appointment, a telephone call, or a text message. The primary outcome was the number of postdischarge complications identified. The secondary outcomes were patient satisfaction with follow-up, future preference, default to follow-up, and preference to receiving medical information by text message. RESULTS: Two hundred eight patients underwent randomization: 50 in the in-person group, 80 in the telephone group, and 78 in the text message group. There was no difference in the number of reported complications: 5 (10%) patients in the in-person group, 7 (9%) patients in the text group, and 11 (14%) patients in the telephone group (P = 0.613). The preferred method of follow-up was by telephone (106, 61.6%). The least preferred was the in-person follow-up (15, 8.7%, P = 0.002), which also had the highest default rate (44%). CONCLUSIONS: There was no evidence that text messages and telephone calls are unsafe and ineffective methods of follow-up. Although most patients are happy to receive results by text message, the majority of patients would prefer a telephone follow-up and are less likely to default by this method. Health-care systems should develop telehealth initiatives when planning health-care services in the wake of the COVID-19 pandemic.


Assuntos
COVID-19 , Envio de Mensagens de Texto , Humanos , COVID-19/epidemiologia , Pacientes Ambulatoriais , Assistência ao Convalescente , Pandemias , Alta do Paciente , Telefone
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