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The α9α10 nicotinic cholinergic receptor (nAChR) is a ligand-gated pentameric cation-permeable ion channel that mediates synaptic transmission between descending efferent neurons and mechanosensory inner ear hair cells. When expressed in heterologous systems, α9 and α10 subunits can assemble into functional homomeric α9 and heteromeric α9α10 receptors. One of the differential properties between these nAChRs is the modulation of their ACh-evoked responses by extracellular calcium (Ca2+). While α9 nAChRs responses are blocked by Ca2+, ACh-evoked currents through α9α10 nAChRs are potentiated by Ca2+ in the micromolar range and blocked at millimolar concentrations. Using chimeric and mutant subunits, together with electrophysiological recordings under two-electrode voltage-clamp, we show that the TM2-TM3 loop of the rat α10 subunit contains key structural determinants responsible for the potentiation of the α9α10 nAChR by extracellular Ca2+. Moreover, molecular dynamics simulations reveal that the TM2-TM3 loop of α10 does not contribute to the Ca2+ potentiation phenotype through the formation of novel Ca2+ binding sites not present in the α9 receptor. These results suggest that the TM2-TM3 loop of α10 might act as a control element that facilitates the intramolecular rearrangements that follow ACh-evoked α9α10 nAChRs gating in response to local and transient changes of extracellular Ca2+ concentration. This finding might pave the way for the future rational design of drugs that target α9α10 nAChRs as otoprotectants.
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Cálcio , Receptores Nicotínicos , Animais , Ratos , Acetilcolina/metabolismo , Acetilcolina/farmacologia , Sequência de Aminoácidos , Sítios de Ligação , Cálcio/metabolismo , Simulação de Dinâmica Molecular , Técnicas de Patch-Clamp , Subunidades Proteicas/metabolismo , Subunidades Proteicas/genética , Receptores Nicotínicos/metabolismo , Receptores Nicotínicos/genética , Receptores Nicotínicos/química , Xenopus laevisRESUMO
Steroid hormones are essential for the biological processes of eukaryotic organisms. The steroid endocrine system of C. elegans, which includes dafachronic acids (DA) and the nuclear receptor ceDAF-12, provides a simple model for exploring the role of steroid hormone signaling pathways in animals. In this study, we show for the first time the feasibility of designing synthetic steroids that can modulate different physiological processes, such as development, reproduction and ageing, in relation to ceDAF-12. Our results not only confirm the conclusions derived from genetic studies linking these processes but also provide new chemical tools to selectively manipulate them, as we found that different compounds produce different phenotypic results. The structures of these compounds are much more diverse than those of endogenous hormones and analogues previously described by other researchers, allowing further development of the chemical modulation of the steroid endocrine system in C. elegans and related nematodes.
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We describe a methodology of post-polymerization functionalization to enable subsequent bulk depolymerization to monomer by utilizing mechanochemical macro-radical generation. By harnessing ultrasonic chain-scission in the presence of N-hydroxyphthalimide methacrylate (PhthMA), we successfully chain-end functionalize polymers to promote subsequent depolymerization in bulk, achieving up to 81% depolymerization of poly(methyl methacrylate) (PMMA) and poly(α-methylstyrene) (PAMS) within 30 min. This method of depolymerization yields a high-purity monomer that can be repolymerized. Moreover, as compared to the most common methods of depolymerization, this work is most efficient with ultra-high molecular weight (UHMW) polymers, establishing a method with the potential to address highly persistent, non-degradable all-carbon backbone plastic materials. Lastly, we demonstrate the expansion of this depolymerization method to commercial cell cast PMMA, achieving high degrees of depolymerization from post-consumer waste. This work is the first demonstration of applying PhthMA-promoted depolymerization strategies in homopolymer PMMA and PAMS prepared by conventional polymerization methods.
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Preimplantation genetic testing (PGT) is a diagnostic procedure that has become a powerful complement to assisted reproduction techniques. PGT has numerous indications, and there is a wide range of techniques that can be used, each with advantages and limitations that should be considered before choosing the more adequate one. In this article, it is reviewed the indications for PGT, biopsy and diagnostic technologies, along with their evolution, while also broaching new emerging methods.
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Aggression is a crucial behavior that impacts access to limited resources in different environmental contexts. Androgens synthesized by the gonads promote aggression during the breeding season. However, aggression can be expressed during the non-breeding season, despite low androgen synthesis by the gonads. The brain can also synthesize steroids ("neurosteroids"), including androgens, which might promote aggression during the non-breeding season. Male song sparrows, Melospiza melodia, are territorial year-round and allow the study of seasonal changes in the steroid modulation of aggression. Here, we quantified steroids following a simulated territorial intrusion (STI) for 10â min in wild adult male song sparrows during the breeding and non-breeding seasons. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we examined 11 steroids: pregnenolone, progesterone, corticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17ß-estradiol, 17α-estradiol, estriol, and estrone. Steroids were measured in blood and 10 microdissected brain regions that regulate social behavior. In both seasons, STI increased corticosterone in the blood and brain. In the breeding season, STI had no rapid effects on androgens or estrogens. Intriguingly, in the non-breeding season, STI increased testosterone and androstenedione in several behaviorally relevant regions, but not in the blood, where androgens remained non-detectable. Also in the non-breeding season, STI increased progesterone in the blood and specific brain regions. Overall, rapid socially modulated changes in brain steroid levels are more prominent during the non-breeding season. Brain steroid levels vary with season and social context in a region-specific manner and suggest a role for neuroandrogens in aggression during the non-breeding season.
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Agressão , Androgênios , Encéfalo , Estações do Ano , Pardais , Territorialidade , Animais , Masculino , Agressão/fisiologia , Androgênios/metabolismo , Encéfalo/metabolismo , Pardais/fisiologia , Pardais/metabolismo , Aves Canoras/metabolismoRESUMO
Dyspnea can be found as a symptom of a wide range of diseases. Clinical thinking usually leads us to more common or frequent syndromes and diseases. This case report alerts us to keep investigating when faced with therapeutic failure or the arising of new symptoms. The subject in this case had dyspnea as an initial presentation of his disease and was treated initially as a case of heart dysfunction. Nevertheless, because his symptoms did not respond to the treatment and even got worse, he was sent to the emergency room where he was medicated and discharged with the same diagnostic hypothesis. In light of a new characteristic symptom - ptosis - the hospital team expanded its clinical and laboratory investigation to neuromuscular diseases, reaching out the diagnosis of myasthenia gravis.
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[This corrects the article DOI: 10.3389/fimmu.2023.1230049.].
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Aggression is a social behavior that is critical for survival and reproduction. In adults, circulating gonadal hormones, such as androgens, act on neural circuits to modulate aggressive interactions, especially in reproductive contexts. In many species, individuals also demonstrate aggression before reaching gonadal maturation. Adult male song sparrows, Melospiza melodia, breed seasonally but maintain territories year-round. Juvenile (hatch-year) males aggressively compete for territory ownership during their first winter when circulating testosterone is low. Here, we characterized the relationship between the steroid milieu and aggressive behavior in free-living juvenile male song sparrows in winter. We investigated the effect of a 10 min simulated territorial intrusion (STI) on behavior and steroid levels in blood, 10 microdissected brain regions, and four peripheral tissues (liver, pectoral muscle, adrenal glands, and testes). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS), we quantified 12 steroids: pregnenolone, progesterone, corticosterone, 11-dehydrocorticosterone, dehydroepiandrosterone, androstenedione, testosterone, 5α-dihydrotestosterone, 17ß-estradiol, 17α-estradiol, estrone, and estriol. We found that juvenile males are robustly aggressive, like adult males. An STI increases progesterone and corticosterone levels in blood and brain and increases 11-dehydrocorticosterone levels in blood only. Pregnenolone, androgens, and estrogens are generally non-detectable and are not affected by an STI. In peripheral tissues, steroid concentrations are very high in the adrenals. These data suggest that adrenal steroids, such as progesterone and corticosterone, might promote juvenile aggression and that juvenile and adult songbirds might rely on distinct neuroendocrine mechanisms to support similar aggressive behaviors.
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Aves Canoras , Humanos , Animais , Masculino , Aves Canoras/fisiologia , Corticosterona , Progesterona/farmacologia , Cromatografia Líquida , Espectrometria de Massas em Tandem , Testosterona , Androgênios , Agressão/fisiologia , Estradiol/farmacologia , Pregnenolona/farmacologiaRESUMO
Bacteria form groups comprised of cells and a secreted polymeric matrix that controls their spatial organization. These groups - termed biofilms - can act as refuges from environmental disturbances and from biotic threats, including phages. Despite the ubiquity of temperate phages and bacterial biofilms, live propagation of temperate phages within biofilms has never been characterized on cellular spatial scales. Here, we leverage several approaches to track temperate phages and distinguish between lytic and lysogenic host infections. We determine that lysogeny within E. coli biofilms initially occurs within a predictable region of cell group packing architecture on the biofilm periphery. Because lysogens are generally found on the periphery of large cell groups, where lytic viral infections also reduce local biofilm cell packing density, lysogens are predisposed to disperse into the passing liquid and are over-represented in biofilms formed from the dispersal pool of the original biofilm-phage system. Comparing our results with those for virulent phages reveals that temperate phages have previously unknown advantages in propagating over long spatial and time scales within and among bacterial biofilms.
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Iatrogenic vascular air embolism is a relatively infrequent event but is associated with significant morbidity and mortality. These emboli can arise in many clinical settings such as neurosurgery, cardiac surgery, and liver transplantation, but more recently, endoscopy, hemodialysis, thoracentesis, tissue biopsy, angiography, and central and peripheral venous access and removal have overtaken surgery and trauma as significant causes of vascular air embolism. The true incidence may be greater since many of these air emboli are asymptomatic and frequently go undiagnosed or unreported. Due to the rarity of vascular air embolism and because of the many manifestations, diagnoses can be difficult and require immediate therapeutic intervention. An iatrogenic air embolism can result in both venous and arterial emboli whose anatomic locations dictate the clinical course. Most clinically significant iatrogenic air emboli are caused by arterial obstruction of small vessels because the pulmonary gas exchange filters the more frequent, smaller volume bubbles that gain access to the venous circulation. However, there is a subset of patients with venous air emboli caused by larger volumes of air who present with more protean manifestations. There have been significant gains in the understanding of the interactions of fluid dynamics, hemostasis, and inflammation caused by air emboli due to in vitro and in vivo studies on flow dynamics of bubbles in small vessels. Intensive research regarding the thromboinflammatory changes at the level of the endothelium has been described recently. The obstruction of vessels by air emboli causes immediate pathoanatomic and immunologic and thromboinflammatory responses at the level of the endothelium. In this review, we describe those immunologic and thromboinflammatory responses at the level of the endothelium as well as evaluate traditional and novel forms of therapy for this rare and often unrecognized clinical condition.
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Embolia Aérea , Trombose , Humanos , Embolia Aérea/diagnóstico , Embolia Aérea/etiologia , Embolia Aérea/terapia , Tromboinflamação , Inflamação/terapia , Inflamação/complicações , Trombose/complicações , Doença IatrogênicaRESUMO
Concern for environmental protection has increased throughout the years from a global perspective. To date, the predominance of adsorption as treatment technique in environmental chemistry remains unchallenged. Moreover, the scientific attention for investigating nanobubbles due to their unique properties has turned the search for their application in environmental processes with special emphasis on water treatment. This study is aimed at investigating the effect of rotation on batch adsorption process using commercial activated carbon as adsorbent material, compared with the widely used method of agitation. As liquid medium, deionized water and deionized water enhanced with nanobubbles (of air) were used. The wastewater was simulated by dissolving a common dye as model pollutant, methylene blue, at concentration of 300 mg/L in the tested liquid. The results indicated that the utilization of nanobubbles resulted in an improvement on adsorption rate, compared to the corresponding values of deionized water solutions. These results may lead to promising applications in the future, since just 1 h of operation increases the water purification and thus provides a simply applied, cost-effective, and rapid alternative.
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Poluentes Químicos da Água , Purificação da Água , Adsorção , Rotação , Águas Residuárias , Poluentes Químicos da Água/química , Carvão Vegetal , Azul de Metileno/química , Purificação da Água/métodos , Cinética , Concentração de Íons de HidrogênioRESUMO
Chronic pain is common among people with human immunodeficiency virus (HIV) and detrimental to quality of life and overall health. It is often underdiagnosed, undertreated, and frankly dismissed in women with HIV, despite growing evidence that it is highly prevalent in this population. Thus, we conducted a systematic review and meta-analysis to estimate the global prevalence of chronic pain in women with HIV. The full protocol can be found on PROSPERO (identifier CRD42022301145). Of the 2984 references identified in our search, 36 were included in the systematic review and 35 in the meta-analysis. The prevalence of chronic pain was 31.2% (95% confidence interval [CI], 24.6%-38.7%; I2 = 98% [95% CI, 97%-99%]; P < .0001). In this global assessment, we found a high prevalence of chronic pain among women with HIV, underscoring the importance of understanding the etiology of chronic pain, identifying effective treatments, and conducting regular assessments in clinical practice.
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Over the last decade, activists in Latin America have expanded access to safe abortion through processes of accompaniment. Abortion accompaniment is characterised by activism and community-based strategies to facilitate access to, and safe use of, medication abortion, mainly outside clinical contexts. Drawing on findings from a survey of 515 activists who were part of Accompaniment Collectives in Latin America, this study describes the organisation of these collectives, barriers and facilitators to their activism, and how accompaniers perceive the impact and future of abortion accompaniment. Accompaniment Collectives are organised and flexible and operate in diverse social and legal contexts. The main goals of accompaniment are the normalisation and social decriminalisation of abortion culturally (84%); the social construction of autonomy (79%); and the protection of people's freedom (73%), life (71%) and health (67%). Activists in legally restrictive settings identified limited access to abortion medication (73%) and restrictive laws (71%) as the main barriers to accompaniment, while health care personnel objecting to abortion provision on grounds of conscience was most common in legally permissive settings (64%). Collectives have developed strategies to overcome such barriers to and expanding access to abortion care. Activists expect accompaniment to continue regardless of the legal status of abortion.
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This study aimed to assess whether perinatal exposure to propiconazole (PRO), glyphosate (GLY) or their mixture (PROGLY) alters key endocrine pathways and the development of the male rat mammary gland. To this end, pregnant rats were orally exposed to vehicle, PRO, GLY, or a mixture of PRO and GLY from gestation day 9 until weaning. Male offspring were euthanized on postnatal day (PND) 21 and PND60. On PND21, GLY-exposed rats showed reduced mammary epithelial cell proliferation, whereas PRO-exposed ones showed increased ductal p-Erk1/2 expression without histomorphological alterations. On PND60, GLY-exposed rats showed reduced mammary gland area and estrogen receptor alpha expression and increased aromatase expression, whereas PRO-exposed ones showed enhanced lobuloalveolar development and increased lobular hyperplasia. However, PROGLY did not modify any of the endpoints evaluated. In summary, PRO and GLY modified the expression of key molecules and the development of the male mammary gland individually but not together.
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Efeitos Tardios da Exposição Pré-Natal , Triazóis , Gravidez , Feminino , Ratos , Animais , Masculino , Humanos , Triazóis/toxicidade , Glicina/toxicidade , Glicina/metabolismo , Hiperplasia/metabolismo , Glândulas Mamárias Animais , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , GlifosatoRESUMO
INTRODUCTION: Infantile acute gastroenteritis (AGE) is a leading cause of morbidity and mortality, particularly in developing countries. The most frequent etiological agents of viral gastroenteritis in children are adenovirus, astrovirus, rotavirus, and norovirus, the last two, leading causes. Thus, the aim of this study was to identify the presence of these two viruses in children with AGE, from two cities located in the Southeast and the Northwest regions of México. METHODOLOGY: HuNoVs were detected and characterized by RT-PCR and sequencing, while RVs were detected by RNA electrophoresis. RESULTS: The presence of RV and HuNoV was evaluated in 81 stool samples; 37 were collected between April and July 2013 from patients with acute diarrhea in Merida, and 44 were collected between January and June 2017 in Chihuahua, who attended health services. Despite vaccination, RV resulted in the predominant viruses detected, with 30.8% (25/81) positivity, while HuNoV infection was present in 8.6% (7/81) of the stool samples; GII strains were identified circulating in the Southeast, while GI strains were identified in the Northwest. Moreover, co-infections with both viruses were detected at a prevalence rate of 2.4% (2/81). CONCLUSIONS: The circulation of RV and HuNoV in the country is continuous and should be constantly monitored due to their impact on public health.
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Infecções por Caliciviridae , Gastroenterite , Norovirus , Infecções por Rotavirus , Rotavirus , Vírus , Humanos , Criança , Lactente , Rotavirus/genética , Norovirus/genética , Cidades , México/epidemiologia , Gastroenterite/epidemiologia , Vírus/genética , Fezes , Infecções por Caliciviridae/epidemiologia , Infecções por Rotavirus/epidemiologiaRESUMO
Anthocyanins are the main active compounds in blueberry. However, they have poor oxidation stability. If anthocyanins are encapsulated in protein nanoparticles, their oxidation resistance could be increased as a result of the slowing down of the oxidation process. This work describes the advantages of using a γ-irradiated bovine serum albumin nanoparticle bound to anthocyanins. The interaction was characterized biophysically, mainly by rheology. By computational calculation and simulation based on model nanoparticles, we estimated the number of molecules forming the albumin nanoparticles, which allowed us to infer the ratio of anthocyanin/nanoparticles. Measurements by UV-vis spectroscopy, FTIR spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), ζ potential, electron transmission microscopy, and rheology at room (25 °C) and physiological (37 °C) temperatures were performed. The spectroscopy measurements allowed identifying additional hydrophobic sites created during the irradiation process of the nanoparticle. On the basis of the rheological studies, it was observed that the BSA-NP trend is a Newtonian flow behavior type for all the temperatures selected, and there is a direct correlation between dynamic viscosity and temperature values. Furthermore, when anthocyanins are added, the system increases its resistance to the flow as reflected in the morphological changes observed by TEM, thus confirming the relationship between viscosity values and aggregate formation.
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Antocianinas , Nanopartículas , Nanopartículas/química , Soroalbumina Bovina/química , Espectrometria de Fluorescência , OxirreduçãoRESUMO
Early menopause (<45 years) has significant impacts on bone, cardiovascular, and cognitive health. Several studies have suggested earlier menopause for women living with HIV; however, the current literature is limited by reliance on self-report data. We determined age at menopause in women living with HIV and socio-demographically similar HIV-negative women based on both self-report of menopause status (no menses for ≥12 months) and biochemical confirmation (defined as above plus follicle-stimulating hormone level ≥ 25 IU/mL). Multivariable median regression models assessed factors associated with menopause age, controlling for relevant confounders. Overall, 91 women living with HIV and 98 HIV-negative women were categorized as menopausal by self-report, compared to 83 and 92 by biochemical confirmation. Age at menopause did not differ significantly between groups, whether based on self-report (median [IQR]: 49.0 [45.3 to 53.0] vs. 50.0 [46.0 to 53.0] years; p = 0.28) or biochemical confirmation (50.0 [46.0 to 53.0] vs. 51.0 [46.0 to 53.0] years; p = 0.54). In the multivariable model, no HIV-related or psychosocial variables were associated with earlier age at menopause (all p > 0.05). Overall, HIV status per se was not statistically associated with an earlier age at menopause, emphasizing the importance of comparing socio-demographically similar women in reproductive health and HIV research.
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Menopausa , Feminino , Humanos , Autorrelato , Estudos Transversais , Menopausa/psicologiaRESUMO
Viral infections modulate bacterial metabolism and ecology. Here, we investigated the hypothesis that viruses influence the ecology of purple and green sulfur bacteria in anoxic and sulfidic lakes, analogs of euxinic oceans in the geologic past. By screening metagenomes from lake sediments and water column, in addition to publicly-available genomes of cultured purple and green sulfur bacteria, we identified almost 300 high and medium-quality viral genomes. Viruses carrying the gene psbA, encoding the small subunit of photosystem II protein D1, were ubiquitous, suggesting viral interference with the light reactions of sulfur oxidizing autotrophs. Viruses predicted to infect these autotrophs also encoded auxiliary metabolic genes for reductive sulfur assimilation as cysteine, pigment production, and carbon fixation. These observations show that viruses have the genomic potential to modulate the production of metabolic markers of phototrophic sulfur bacteria that are used to identify photic zone euxinia in the geologic past.
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In previous work, the isolated polyphenolic compound (PPC) quercetin was used as a reducing agent in the formation of silver nanoparticles (AgNPs), testing two types of quercetin. This PPC is a bioactive molecule that provides the electrons for the reduction of silver ions to zerovalent silver. The results demonstrated that quercetin in dietary supplement presentation was better than reagent grade quercetin for the synthesis of AgNPs, and the difference between them was that the dietary supplement had microcrystalline cellulose (CM) in its formulation. Therefore, this dietary anti-caking agent was added to the reagent-grade quercetin to validate this previously found improvement. AgNPs were obtained at neutral pH by a green route using quercetin as a reducing agent and microcrystalline cellulose and maltodextrin as stabilizing agents. In addition, different ratios were evaluated to find the optimum ratio. Ultraviolet-Visible spectroscopy (UV-VIS), Atomic Force Microscope (AFM), Z-potential, Dynamic Light Scattering (DLS) and X-ray Powder Diffraction (XRD) were used for characterization. The antibacterial activity of the S. aureus and E. coli agent was tested by the disk diffusion and microdilution method. According to the results, this green synthesis needs the use of food stabilizer when working at pH 7 to maintain AgNPs in the long term. The ideal ratio of reducing the agent:stabilizing agent was 1:2, since with this system stable AgNPs are obtained for 2 months and with improved antimicrobial activity, validating this method was ecologically and economically viable.
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The Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant led to a dramatic global epidemic wave following detection in South Africa in November 2021. The BA.1 Omicron lineage was dominant and responsible for most SARS-CoV-2 outbreaks in countries around the world during December 2021-January 2022, while other Omicron lineages, including BA.2, accounted for the minority of global isolates. Here, we describe the Omicron wave in the Philippines by analysing genomic data. Our results identify the presence of both BA.1 and BA.2 lineages in the Philippines in December 2021, before cases surged in January 2022. We infer that only the BA.2 lineage underwent sustained transmission in the country, with an estimated emergence around 18 November 2021 (95 per cent highest posterior density: 6-28 November), while despite multiple introductions, BA.1 transmission remained limited. These results suggest that the Philippines was one of the earliest areas affected by BA.2 and reiterate the importance of whole genome sequencing for monitoring outbreaks.