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The development of sustainable routes to organic building blocks is a critical endeavor for reducing the environmental impact of chemical synthesis. Biocatalysts are poised to play an important role in sustainable synthesis, as they perform highly selective reactions under mild conditions. The application of enzymes to organic synthesis requires an approach which is operationally simple, inexpensive to prepare, and reasonably scalable. In this work, we demonstrated the utility of a Type I ring-cleaving dioxygenase CatA (P. putida KT2440) for preparative-scale synthesis of muconic acid derivatives. Muconic acids are important precursors in the synthesis of polymers and commodity chemicals. In this work, we optimized the performance of CatA under millimolar substrate concentrations and characterized the activity of the enzyme with an array of catechol substrates. Furthermore, we developed a scalable platform using cellular lysates to produce diverse muconic acids, generating up to a gram of the desired product. A simple trituration procedure was utilized for the purification of these muconic acids that obviated the need for chromatographic purification and reduced overall solvent waste.
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Biocatálise , Ácido Sórbico , Ácido Sórbico/análogos & derivados , Ácido Sórbico/metabolismo , Ácido Sórbico/química , Ácido Sórbico/síntese química , Pseudomonas putida/enzimologia , Pseudomonas putida/metabolismo , Dioxigenases/metabolismo , Estrutura MolecularRESUMO
There is paucity of data assessing levels of food/beverage waste in long-term care (LTC) facilities, especially in Ontario. Observations in the Veteran's Centre (VC) at Sunnybrook Health Sciences Centre (Sunnybrook) indicated food/beverage waste may be high, potentially impacting sustainability efforts within our institution. Before proceeding with waste reduction efforts, we conducted a comprehensive 3-day waste-audit of food/beverage items provided to VC residents with the goal of understanding the extent of food/beverage waste at VC, items wasted, and any other factors that may inform future changes. Our results indicate that 28% of items served to residents were wasted. Lunch was the meal with greatest waste at 31% and waste of solid items was 12% higher than that of liquids. We observed a large variability in waste between residents and within each resident, with 15% of residents wasting >50% of items provided. This study provides a deeper insight into the magnitude of food/beverage waste in a LTC population and highlights the importance of considering individualized strategies to address waste to avoid negative impact on residents.
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Assistência de Longa Duração , Ontário , Humanos , Gerenciamento de Resíduos , Refeições , Serviços de Alimentação/estatística & dados numéricos , Veteranos/estatística & dados numéricos , Resíduos SólidosRESUMO
Cosmological and exoplanetary science using transformative telescopes like the ELT will demand precise calibration of astrophysical spectrographs in the blue-green, where stellar absorption lines are most abundant. Astrocombs-lasers providing a broadband sequence of regularly-spaced optical frequencies on a multi-GHz grid-promise an atomically-traceable calibration scale, but their realization in the blue-green is challenging for current infrared-laser-based technology. Here, we introduce a concept achieving a broad, continuous spectrum by combining second-harmonic generation and sum-frequency-mixing in an MgO:PPLN waveguide to generate 390-520 nm light from a 1 GHz Ti:sapphire frequency comb. Using a Fabry-Pérot filter, we extract a 30 GHz sub-comb spanning 392-472 nm, visualizing its thousands of modes on a high-resolution spectrograph. Experimental data and simulations demonstrate how the approach can bridge the spectral gap present in second-harmonic-only conversion. Requiring only [Formula: see text]100 pJ pulses, our concept establishes a new route to broadband UV-visible generation at GHz repetition rates.
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The clouds of Venus are believed to be composed of sulfuric acid (H2SO4) and minor constituents including iron-bearing compounds, and their respective concentrations vary with height in the thick Venusian atmosphere. This study experimentally investigates possible iron-bearing mineral phases that are stable under the unique conditions within Venusian clouds. Our results demonstrate that ferric iron can react with sulfuric acid to form two mineral phases: rhomboclase [(H5O2)Fe(SO4)2·3H2O] and acid ferric sulfate [(H3O)Fe(SO4)2]. A combination of these two mineral phases and dissolved Fe3+ in varying concentrations of sulfuric acid are shown to be good candidates for explaining the 200- to 300-nm and 300- to 500-nm features of the reported unknown UV absorber. We, therefore, hypothesize a rich and largely unexplored heterogeneous chemistry in the cloud droplets of Venus that has a large effect on the optical properties of the clouds and the behavior of trace gas species throughout Venus's atmosphere.
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Alzheimer's disease (AD) is the leading cause of dementia and lacks highly effective treatments. Tau-based therapies hold promise. Tau reduction prevents amyloid-ß-induced dysfunction in preclinical models of AD and also prevents amyloid-ß-independent dysfunction in diverse disease models, especially those with network hyperexcitability, suggesting that strategies exploiting the mechanisms underlying Tau reduction may extend beyond AD. Tau binds several SH3 domain-containing proteins implicated in AD via its central proline-rich domain. We previously used a peptide inhibitor to demonstrate that blocking Tau interactions with SH3 domain-containing proteins ameliorates amyloid-ß-induced dysfunction. Here, we identify a top hit from high-throughput screening for small molecules that inhibit Tau-FynSH3 interactions and describe its optimization with medicinal chemistry. The resulting lead compound is a potent cell-permeable Tau-SH3 interaction inhibitor that binds Tau and prevents amyloid-ß-induced dysfunction, including network hyperexcitability. These data support the potential of using small molecule Tau-SH3 interaction inhibitors as a novel therapeutic approach to AD.
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Doença de Alzheimer , Proteínas tau , Humanos , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/toxicidade , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Ensaios de Triagem em Larga EscalaRESUMO
Anthracnose fruit rot (AFR), caused by the fungal pathogen Colletotrichum fioriniae, is among the most destructive and widespread fruit disease of blueberry, impacting both yield and overall fruit quality. Blueberry cultivars have highly variable resistance against AFR. To date, this pathogen is largely controlled by applying various fungicides; thus, a more cost-effective and environmentally conscious solution for AFR is needed. Here we report three quantitative trait loci associated with AFR resistance in northern highbush blueberry (Vaccinium corymbosum). Candidate genes within these genomic regions are associated with the biosynthesis of flavonoids (e.g. anthocyanins) and resistance against pathogens. Furthermore, we examined gene expression changes in fruits following inoculation with Colletotrichum in a resistant cultivar, which revealed an enrichment of significantly differentially expressed genes associated with certain specialized metabolic pathways (e.g. flavonol biosynthesis) and pathogen resistance. Using non-targeted metabolite profiling, we identified a flavonol glycoside with properties consistent with a quercetin rhamnoside as a compound exhibiting significant abundance differences among the most resistant and susceptible individuals from the genetic mapping population. Further analysis revealed that this compound exhibits significant abundance differences among the most resistant and susceptible individuals when analyzed as two groups. However, individuals within each group displayed considerable overlapping variation in this compound, suggesting that its abundance may only be partially associated with resistance against C. fioriniae. These findings should serve as a powerful resource that will enable breeding programs to more easily develop new cultivars with superior resistance to AFR and as the basis of future research studies.
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Precise determination of transgene zygosity is essential for use of transgenic mice in research. Because integration loci of transgenes are usually unknown due to their random insertion, assessment of transgene zygosity remains a challenge. Current zygosity genotyping methods (progeny testing, qPCR, and NGS-computational biology analysis) are time consuming, prone to error or technically challenging. Here, we developed a novel method to determine transgene zygosity requiring no knowledge of transgene insertion loci. This method applies allele-specific restriction enzyme digestion of PCR products (RE/PCR) to rapidly and reliably quantify transgene zygosity. We demonstrate the applicability of this method to three transgenic strains of mice (Atm TgC3001L, Nes-Cre, and Syn1-Cre) harboring a unique restriction enzyme site on either the transgene or its homologous sequence in the mouse genome. This method is as accurate as the gold standard of progeny testing but requires 2 d instead of a month or more. It is also exceedingly more accurate than the most commonly used approach of qPCR quantification. Our novel method represents a significant technical advance in determining transgene zygosities in mice.
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Genótipo , Camundongos , Animais , Alelos , Transgenes/genética , Camundongos Transgênicos , Sequência de BasesRESUMO
Background: Patients with cancer often pursue nutrition as an avenue to positively impact their care management and disease outcomes. Nutritional interventions are increasing in popularity, especially intermittent fasting as an adjunct to chemotherapy. However, limited research is available on the impact of intermittent fasting on patients with cancer. Methods: A comprehensive literature search was conducted using Ovid MEDLINE, Ovid EMBASE, and CINAHL databases. Results: 514 articles were identified from the three databases. Seven studies remained after applying inclusion and exclusion criteria. The seven studies included in this review examined fasting compliance, malnutrition, therapy side effects, endocrine parameters, quality of life measures, and cancer outcomes. Data suggest overall good compliance, no malnutrition, minimal side effects, a trend toward improved endocrine parameters, unchanged quality of life (QOL), and mixed results for cancer outcomes. Conclusion: Intermittent fasting as an adjunct to chemotherapy in normal-weight patients with cancer has potential as a safe, tolerable, and feasible nutritional intervention that could positively impact treatment outcomes and QOL. Large-scale randomized controlled trials are needed to validate these findings and determine what future role intermittent fasting may play in cancer management.
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Mutations in Kv1.1 (Kcna1) voltage-gated potassium channels in humans and mice generate network hyperexcitability, enhancing aberrant postnatal neurogenesis in the dentate subgranular zone, resulting in epilepsy and hippocampal hypertrophy. While Kcna1 loss stimulates proliferation of progenitor cell subpopulations, the identity of extrinsic molecular triggers linking network hyperexcitability to aberrant postnatal neurogenesis remains incomplete. System x-c (Sxc) is an inducible glutamate/cysteine antiporter that regulates extracellular glutamate. Here, we find that the functional unit of Sxc, xCT (Slc7a11), is upregulated in regions of Kcna1 knockout (KO) hippocampus, suggesting a contribution to both hyperplasia and epilepsy. However, Slc7a11 KO suppressed and rescued hippocampal enlargement without altering seizure severity in Kcna1-Slc7a11-KO mice. Microglial activation, but not astrocytosis, was also reduced. Our study identifies Sxc-mediated glutamate homeostasis as an essential non-synaptic trigger coupling aberrant postnatal neurogenesis and neuroimmune crosstalk, revealing that neurogenesis and epileptogenesis in the dentate gyrus are not mutually contingent events.
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Epilepsia , Neurogênese , Animais , Camundongos , Epilepsia/genética , Glutamatos , Hipocampo , Canal de Potássio Kv1.1/genética , Camundongos KnockoutRESUMO
Dark chamber experiments were conducted to study the SOA formed from the oxidation of α-pinene and Δ-carene under different peroxy radical (RO2) fate regimes: RO2 + NO3, RO2 + RO2, and RO2 + HO2. SOA mass yields from α-pinene oxidation were <1 to â¼25% and strongly dependent on available OA mass up to â¼100 µg m-3. The strong yield dependence of α-pinene oxidation is driven by absorptive partitioning to OA and not by available surface area for condensation. Yields from Δ-carene + NO3 were consistently higher, ranging from â¼10-50% with some dependence on OA for <25 µg m-3. Explicit kinetic modeling including vapor wall losses was conducted to enable comparisons across VOC precursors and RO2 fate regimes and to determine atmospherically relevant yields. Furthermore, SOA yields were similar for each monoterpene across the nominal RO2 + NO3, RO2 + RO2, or RO2 + HO2 regimes; thus, the volatility basis sets (VBS) constructed were independent of the chemical regime. Elemental O/C ratios of â¼0.4-0.6 and nitrate/organic mass ratios of â¼0.15 were observed in the particle phase for both monoterpenes in all regimes, using aerosol mass spectrometer (AMS) measurements. An empirical relationship for estimating particle density using AMS-derived elemental ratios, previously reported in the literature for non-nitrate containing OA, was successfully adapted to organic nitrate-rich SOA. Observations from an NO3- chemical ionization mass spectrometer (NO3-CIMS) suggest that Δ-carene more readily forms low-volatility gas-phase highly oxygenated molecules (HOMs) than α-pinene, which primarily forms volatile and semivolatile species, when reacted with NO3, regardless of RO2 regime. The similar Δ-carene SOA yields across regimes, high O/C ratios, and presence of HOMs, suggest that unimolecular and multistep processes such as alkoxy radical isomerization and decomposition may play a role in the formation of SOA from Δ-carene + NO3. The scarcity of peroxide functional groups (on average, 14% of C10 groups carried a peroxide functional group in one test experiment in the RO2 + RO2 regime) appears to rule out a major role for autoxidation and organic peroxide (ROOH, ROOR) formation. The consistently substantially lower SOA yields observed for α-pinene + NO3 suggest such pathways are less available for this precursor. The marked and robust regime-independent difference in SOA yield from two different precursor monoterpenes suggests that in order to accurately model SOA production in forested regions the chemical mechanism must feature some distinction among different monoterpenes.
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Salmonella is one of the leading causes of foodborne illnesses worldwide. The rapid emergence of multidrug-resistant Salmonella strains has increased global concern for salmonellosis. Recent studies have shown that bacteriophages (phages) are novel and the most promising antibacterial agents for biocontrol in foods because phages specifically kill target bacteria without affecting other bacteria, do not alter organoleptic properties or nutritional quality of foods, and are safe and environmentally friendly. Due to the vast variation in Salmonella serotypes, large numbers of different and highly virulent Salmonella phages with broad host ranges are needed. This study isolated 14 Salmonella phages from turkey fecal and cecal samples. Six phages (Φ205, Φ206, Φ207, ΦEnt, ΦMont, and Φ13314) were selected for characterization. These phages were from all three families in the Caudovirales order. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) revealed that each phage had a unique structural protein profile. Each phage had a distinct host range. Φ207 and ΦEnt are both siphophages. They shared eight hosts, including seven different Salmonella serovars and one Shigella sonnei strain. These two phages showed different restriction banding patterns generated through EcoRI or HindIII digestion, but shared three bands from EcoRI digestion. ΦEnt displayed the broadest and very unusual host range infecting 11 Salmonella strains from nine serovars and three Shigella strains from two species, and thus was further characterized. The one-step growth curve revealed that ΦEnt had a short latent period (10 min) and relatively large burst size (100 PFU/infected cell). ΦEnt and its host showed better thermal stabilities in tryptic soy broth than in saline at 63 or 72°C. In the model food system (cucumber juice or beef broth), ΦEnt infection [regardless of the multiplicity of infections (MOIs) of 1, 10, and 100] resulted in more than 5-log10 reduction in Salmonella concentration within 4 or 5 h. Such high lytic activity combined with its remarkably broad and unusual host range and good thermal stability suggested that ΦEnt is a novel Salmonella phage with great potential to be used as an effective biocontrol agent against diverse Salmonella serovars in foods.
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A progressive neurological disorder was identified in purebred Dalmatian dogs. The disease is characterized by anxiety, pacing and circling, hypersensitivity, cognitive decline, sleep disturbance, loss of coordination, loss of control over urination and defecation, and visual impairment. Neurological signs first became apparent when the dogs were approximately 18 months of age and progressed slowly. Two affected littermates were euthanized at approximately 7 years, 5 months and 8 years, 2 months of age due to the severity of neurological impairment. The mother of the affected dogs and four other relatives exhibited milder, later-onset neurological signs. Pronounced accumulations of autofluorescent intracellular inclusions were found in cerebral cortex, cerebellum, optic nerve, and cardiac muscle of the affected dogs. These inclusions co-localized with immunolabeling of the lysosomal marker protein LAMP2 and bound antibodies to mitochondrial ATPase subunit c, indicating that the dogs suffered from a lysosomal storage disease with similarities to the neuronal ceroid lipofuscinoses. Ultrastructural analysis indicated that the storage bodies were surrounded by a single-layer membrane, but the storage granules were distinct from those reported for other lysosomal storage diseases. Whole genome sequences, generated with DNA from the two euthanized Dalmatians, both contained a rare, homozygous single-base deletion and reading-frame shift in CNP which encodes the enzyme CNPase (EC 3.1.4.37). The late-onset disease was exhibited by five of seven related Dalmatians that were heterozygous for the deletion allele and over 8 years of age, whereas none of 16 age-matched reference-allele homozygotes developed neurologic signs. No CNPase antigen could be detected with immunohistochemical labeling in tissues from the dogs with the earlier-onset disorder. Similar to the later-onset Dalmatians, autofluorescent storage granules were apparent in brain and cardiac tissue from transgenic mice that were nullizygous for Cnp. Based on the clinical signs, the histopathological, immunohistochemical, ultrastructural, and molecular-genetic findings, and the finding that nullizygous Cnp mice accumulate autofluorescent storage granules, we propose that the earlier-onset Dalmatian disorder is a novel lysosomal storage disease that results from a loss-of-function mutation in CNP and that shares features characteristic of the neuronal ceroid lipofuscinoses. That the later-onset disorder occurred only in dogs heterozygous for the CNP deletion variant suggests that this disorder is a result of the variant allele's presence.
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Doenças por Armazenamento dos Lisossomos , Lipofuscinoses Ceroides Neuronais , Alelos , Animais , Cerebelo/patologia , Cães , Homozigoto , Doenças por Armazenamento dos Lisossomos/genética , Doenças por Armazenamento dos Lisossomos/patologia , Doenças por Armazenamento dos Lisossomos/veterinária , Camundongos , Lipofuscinoses Ceroides Neuronais/genéticaRESUMO
This study analyzes the COVID-19 homelessness response in King County, Washington, in which people were moved out of high-density emergency shelters into hotel rooms. This intervention was part of a regional effort to de-intensify the shelter system and limit the transmission of the virus to protect vulnerable individuals experiencing homelessness. This study used quantitative and qualitative methods to describe the experiences of and outcomes on individuals who were moved from shelters to noncongregate hotel settings. The study highlights a new approach to shelter delivery that not only responded to the public health imperatives of COVID-19, but also indicated positive health and social outcomes compared to traditional congregate settings. The findings establish an evidence base to help inform future strategic responses to homelessness as well as to contribute to the broader policy conversations on our nation's response to homelessness.
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BACKGROUND: Twenty percent of women referred to colposcopy have a type 3 transformation zone-where colposcopic assessment for high-grade dysplasia (CIN2+) is not possible. This study examines the effectiveness of HPV biomarkers and genotyping in combination with techniques that sample an endocervical TZ. METHODS: A prospective diagnostic accuracy study. Women booked for large-loop excision (LLETZ) with squamous dyskaryosis, high-risk HPV and a TZ3 were recruited. Immediately prior to LLETZ samples were collected for p16/Ki-67 dual-stained cytology, HPV genotyping and H&E, p16- and Ki-67-stained endocervical curettings. RESULTS: In women with low-grade screening (n = 64), 35.9% had CIN2+; dual-stained cytology had the greatest effect on the PPV of routine screening (76.1% vs 35.9%) and perfectly predicted the absence of CIN2+. In women with a high-grade screening result (n = 37); 75.6% had CIN2+ and dual-stained curettings improved the PPV (96.5 vs 75.6%). CONCLUSIONS: With high-grade screening and a TZ3, LLETZ appears safest as three quarters have CIN2+ . Women with low-grade screening and a TZ3 have a twofold increased risk of CIN2+ when compared to women where the TZ is visible. The use of dual-stained cytology may help identify those women who can be safely offered surveillance and those who require treatment.
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Biomarcadores Tumorais/genética , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Genótipo , Antígeno Ki-67/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/complicações , Displasia do Colo do Útero/diagnóstico , Adulto , Colposcopia/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Papillomaviridae/isolamento & purificação , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/metabolismo , Infecções por Papillomavirus/virologia , Estudos Prospectivos , Esfregaço Vaginal/métodos , Displasia do Colo do Útero/genética , Displasia do Colo do Útero/virologiaRESUMO
This paper assesses the asset building of households that take part in shared-equity homeownership (SEH) models. The contribution of this paper is a comparison of outcomes for households participating in shared-equity programs to other low- and moderate-income households who rent or own properties without restrictions on appreciation. We matched participants in SEH programs to households with similar characteristics from the Panel Study of Income Dynamic (PSID) over the 1997-2017 period. The findings indicate that in real terms, median SEH homeowners accumulated about $1,700 in housing wealth annually or around $10,000 during their holding period. This amount is lower than the $2,100 median annual gain in home equity experienced by similar PSID owners but statistically and economically significantly larger than the $16 in annual gain experienced by similar PSID renters. The findings provide evidence that households participating in SEH programs experienced positive, but modest, wealth gains that were slightly lower than homeowners in unrestricted units but substantially higher than renters.
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Sexual issues and treatment side effects are not routinely discussed with men receiving treatment for prostate cancer, and support to address these concerns is not consistent across settings. This study evaluates a brief e-learning resource designed to improve sexual wellbeing support and examine its effects on healthcare professionals' sexual attitudes and beliefs. Healthcare professionals (n = 44) completed an online questionnaire at baseline which included a modified 12-item sexual attitudes and beliefs survey (SABS). Follow-up questionnaires were completed immediately after the e-learning and at 4 weeks. Data were analysed using one-way, repeat measures ANOVAs to assess change in attitudes and beliefs over time. Significant improvements were observed at follow-up for a number of survey statements including 'knowledge and understanding', 'confidence in discussing sexual wellbeing' and the extent to which participants felt 'equipped with the language to initiate conversations'. The resource was seen as concise, relevant to practice and as providing useful information on potential side effects of treatment. In brief, e-learning has potential to address barriers to sexual wellbeing communication and promote delivery of support for prostate cancer survivors. Practical methods and resources should be included with these interventions to support implementation of learning and long-term changes in clinical behaviour.
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Instrução por Computador , Neoplasias da Próstata , Atitude do Pessoal de Saúde , Humanos , Masculino , Projetos Piloto , Neoplasias da Próstata/terapiaRESUMO
Sudden Unexpected Death in Epilepsy is a leading cause of epilepsy-related mortality, and the analysis of mouse Sudden Unexpected Death in Epilepsy models is steadily revealing a spectrum of inherited risk phenotypes based on distinct genetic mechanisms. Serotonin (5-HT) signalling enhances post-ictal cardiorespiratory drive and, when elevated in the brain, reduces death following evoked audiogenic brainstem seizures in inbred mouse models. However, no gene in this pathway has yet been linked to a spontaneous epilepsy phenotype, the defining criterion of Sudden Unexpected Death in Epilepsy. Most monogenic models of Sudden Unexpected Death in Epilepsy invoke a failure of inhibitory synaptic drive as a critical pathogenic step. Accordingly, the G protein-coupled, membrane serotonin receptor 5-HT2C inhibits forebrain and brainstem networks by exciting GABAergic interneurons, and deletion of this gene lowers the threshold for lethal evoked audiogenic seizures. Here, we characterize epileptogenesis throughout the lifespan of mice lacking X-linked, 5-HT2C receptors (loxTB Htr2c). We find that loss of Htr2c generates a complex, adult-onset spontaneous epileptic phenotype with a novel progressive hyperexcitability pattern of absences, non-convulsive, and convulsive behavioural seizures culminating in late onset sudden mortality predominantly in male mice. RNAscope localized Htr2c mRNA in subsets of Gad2+ GABAergic neurons in forebrain and brainstem regions. To evaluate the contribution of 5-HT2C receptor-mediated inhibitory drive, we selectively spared their deletion in GAD2+ GABAergic neurons of pan-deleted loxTB Htr2c mice, yet unexpectedly found no amelioration of survival or epileptic phenotype, indicating that expression of 5-HT2C receptors in GAD2+ inhibitory neurons was not sufficient to prevent hyperexcitability and lethal seizures. Analysis of human Sudden Unexpected Death in Epilepsy and epilepsy genetic databases identified an enrichment of HTR2C non-synonymous variants in Sudden Unexpected Death in Epilepsy cases. Interestingly, while early lethality is not reflected in the mouse model, we also identified variants mainly among male Sudden Infant Death Syndrome patients. Our findings validate HTR2C as a novel, sex-linked candidate gene modifying Sudden Unexpected Death in Epilepsy risk, and demonstrate that the complex epilepsy phenotype does not arise solely from 5-HT2C-mediated synaptic disinhibition. These results strengthen the evidence for the serotonin hypothesis of Sudden Unexpected Death in Epilepsy risk in humans, and advance current efforts to develop gene-guided interventions to mitigate premature mortality in epilepsy.
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BACKGROUND: Sexual dysfunction is a frequent side effect associated with different prostate cancer treatment approaches. It can have a substantial impact on men and their partners and is associated with increased psychological morbidity. Despite this, sexual concerns are often not adequately addressed in routine practice. Evidence-based web-based interventions have the potential to provide ongoing information and sexual well-being support throughout all stages of care. OBJECTIVE: The aim of this study is to examine the efficacy of a web-based self-management intervention designed to maximize sexual well-being in men living with prostate cancer and explore user perspectives on usability and acceptability. METHODS: We used a single-arm study design, and participants were provided with access to the 5-step intervention for a period of 3 months. The intervention content was tailored based on responses to brief screening questions on treatment type, relationship status, and sexual orientation. Efficacy was assessed by using two-tailed, paired sample t tests for comparing the mean differences between pre- and postintervention measurements for exploring the participants' self-reported knowledge and understanding, sexual satisfaction, and comfort in discussing sexual issues. Usability and acceptability were determined based on the program use data and a postintervention survey for exploring perceived usefulness. RESULTS: A total of 109 participants were recruited for this study. Significant postintervention improvements at follow-up were observed in the total scores (out of 20) from the survey (mean 12.23/20 points, SD 2.46 vs mean 13.62/20, SD 2.31; t88=9.570; P=.001) as well as in individual item scores on the extent to which the participants agreed that they had sufficient information to manage the impact that prostate cancer had on their sex life (mean 2.31/4 points, SD 0.86 vs mean 2.57/4, SD 0.85; t88=3.660; P=.001) and had the potential to have a satisfying sex life following treatment (mean 2.38/4 points, SD 0.79 vs mean 3.17/4, SD 0.78; t88=7.643; P=.001). The median number of intervention sessions was 3 (range 1-11), and intervention sessions had a median duration of 22 minutes (range 8-77). Acceptable usability scores were reported, with the highest result observed for the question on the extent to which the intervention provided relevant information. CONCLUSIONS: This study provides evidence on the efficacy of a tailored web-based intervention for maximizing sexual well-being in men living with prostate cancer. The results indicate that the intervention may improve one's self-perceived knowledge and understanding of how to manage sexual issues and increase self-efficacy or the belief that a satisfactory sex life could be achieved following treatment. The findings will be used to refine the intervention content before testing as part of a larger longitudinal study for examining its effectiveness.
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Intervenção Baseada em Internet , Neoplasias da Próstata , Autogestão , Humanos , Estudos Longitudinais , Masculino , Neoplasias da Próstata/terapia , Comportamento SexualRESUMO
Ultraviolet (UV) light has long been invoked as a source of energy for prebiotic chemical synthesis, but experimental support does not involve sources of UV light that look like the young Sun. Here we experimentally investigate whether the UV flux available on the surface of early Earth, given a favorable atmosphere, can facilitate a variety of prebiotic chemical syntheses. We construct a solar simulator for the UV light of the faint young Sun on the surface of early Earth, called StarLab. We then attempt a series of reactions testing different aspects of a prebiotic chemical scenario involving hydrogen cyanide (HCN), sulfites, and sulfides under the UV light of StarLab, including hypophosphite oxidation by UV light and hydrogen sulfide, photoreduction of HCN with bisulfite, the photoanomerization of α-thiocytidine, the production of a chemical precursor of a potentially prebiotic activating agent (nitroprusside), the photoreduction of thioanhydrouridine and thioanhydroadenosine, and the oxidation of ethanol (EtOH) by photochemically generated hydroxyl radicals. We compare the output of StarLab to the light of the faint young Sun to constrain the timescales over which these reactions would occur on the surface of early Earth. We predict that hypophosphite oxidation, HCN reduction, and photoproduction of nitroprusside would all operate on the surface of early Earth in a matter of days to weeks. The photoanomerization of α-thiocytidine would take months to complete, and the production of oxidation products from hydroxyl radicals would take years. The photoreduction of thioanhydrouridine with hydrogen sulfide did not succeed even after a long period of irradiation, providing a lower limit on the timescale of several years. The photoreduction of thioanhydroadenosine with bisulfite produced 2'-deoxyriboadenosine (dA) on the timescale of days. This suggests the plausibility of the photoproduction of purine deoxyribonucleotides, such as the photoproduction of simple sugars, proceeds more efficiently in the presence of bisulfite.
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Planeta Terra , Atmosfera , Fotoquímica , Raios UltravioletaRESUMO
BACKGROUND: Long-term side-effects associated with different prostate cancer treatment approaches are common. Sexual challenges are the most frequently occurring issues and can result in increased psychological morbidity. It is recognized that barriers to communication can make initiating discussions around sexual concerns in routine practice difficult. Health care professionals need to routinely initiate conversations, effectively engage with patients, and assess needs in order to provide essential support. One proposed method that could support health care professionals to do this involves the use of prompts or structured frameworks to guide conversations. OBJECTIVE: This study aimed to assess feasibility, acceptability, and satisfaction with the tablet-based Engagement, Assessment, Support, and Sign-posting (EASSi) tool designed to facilitate and structure sexual well-being discussions in routine prostate cancer care. METHODS: Health care professionals (n=8) used the EASSi tool during 89 posttreatment appointments. Quantitative data were recorded based on program usage and surveys completed by health care professionals and patients. Qualitative data exploring perceptions on use of the tool were gathered using semistructured interviews with all health care professionals (n=8) and a sample of patients (n=10). RESULTS: Surveys were completed by health care professionals immediately following each appointment (n=89, 100%). Postal surveys were returned by 59 patients (66%). Health care professionals and patients reported that the tool helped facilitate discussions (81/89, 91% and 50/59, 85%, respectively) and that information provided was relevant (82/89, 92% and 50/59, 85%, respectively). The mean conversation duration was 6.01 minutes (SD 2.91). Qualitative synthesis identified the tool's ability to initiate and structure discussions, improve the "depth" of conversations, and normalize sexual concerns. CONCLUSIONS: The EASSi tool was appropriate and acceptable for use in practice and provided a flexible approach to facilitate routine brief conversations and deliver essential sexual well-being support. Further work will be conducted to evaluate the effectiveness of using the tablet-based tool in prostate cancer care settings.