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CONTEXT: Vitreoretinal large B- cell lymphoma (VR- LBCL) is a type of non- Hodgkin lymphoma confined to the eye and central nervous system (CNS). The clinical manifestations of intraocular lymphoma can precede, occur simultaneously with, or follow disease at CNS sites. It differs from other forms of extra-nodal lymphoma; in that it does not involve systemic sites other than CNS. OBJECTIVES: To analyse the clinical and pathological features, and treatment outcomes of a cohort of patients diagnosed with vitreoretinal lymphoma (VRL) in Royal Victoria Eye and Ear Hospital, Ireland between 2010 and 2024. METHOD: Retrospective review of medical records and pathology specimens of patients with ocular involvement in VR- LBCL over 14-year period and a review of the literature. RESULTS: Eight patients were included. All of them underwent pars plana vitrectomy and were confirmed to have VR- LBCL. The median age at diagnosis was 71 years. Three were men and five were women. Six had bilateral disease and two unilateral. Four of four patients had MYD88 L265P mutation present. Four patients showed a high interleukin-10 (IL-10) to interleukins-6 (IL-6) ratio in keeping with the diagnosis of VRL. Three patients had primary CNS lymphoma with subsequent eye involvement, despite systemic chemotherapy treatment. Of the five patients who presented with ocular lymphoma, two patients had CNS involvement after primary vitreoretinal lymphoma was diagnosed. Of those, one was initially treated with local intravitreal chemotherapy. Three patients had no CNS recurrence. At the time of this study, seven patients of eight are alive, four are disease free and two are on a first- line local chemotherapy treatment. One underwent treatment for CNS relapse. One patient died of the disease before commencing targeted therapy. CONCLUSION: This case series demonstrated excellent treatment outcomes for seven patients, alive at the time of the study. Both local radiotherapy and intravitreal chemotherapy achieved good ocular control with acceptable side effects and no significant difference in visual outcome. VRL is a difficult diagnosis and vitreous cytology should be prioritised in cases of vitritis unresponsive to treatment. Analysis of MYD88 L265P mutation and IL- 10: IL- 6 ratio >1 are useful adjuncts in the diagnosis of VR- LBCL, particularly in cases where limited vitreous material makes cytological evaluation challenging.
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Neoplasias da Retina , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias da Retina/patologia , Neoplasias da Retina/terapia , Neoplasias da Retina/genética , Idoso de 80 Anos ou mais , Corpo Vítreo/patologia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/genética , Linfoma Intraocular/patologia , Linfoma Intraocular/terapia , Linfoma Intraocular/genética , Linfoma Intraocular/diagnóstico , Vitrectomia , Neoplasias Oculares/patologia , Neoplasias Oculares/terapia , Neoplasias Oculares/genéticaRESUMO
BACKGROUND: For endovascular treatment of below-the-knee (BTK) peripheral artery disease (PAD), independently adjudicated real-world outcomes comparing non-stent (balloon angioplasty or PTA and adjunctive treatment) with or without a concomitant ipsilateral femoropopliteal (FP) artery intervention are scarce. METHODS: 1060 patients from the multicenter XLPAD Registry between 2006-2021 with non-stent based BTK PAD intervention are included. PRIMARY OUTCOME: 1-year incidence of major adverse limb events (MALE), a composite of all-cause death, any amputation, or clinically driven repeat revascularization. RESULTS: 566 patients underwent BTK and 494 BTKâ¯+â¯FP interventions; 72% men, with mean age 68.4 ± 10.9 years. Diabetes mellitus is more prevalent in BTK only group (76.5% vs. 69%, p=0.006). Mean Rutherford class 4.2 ± 1.18; chronic limb threatening ischemia is more frequent in the BTK group (55.3% vs. 49%, p=0.040). Moderate to severe calcification is higher in BTKâ¯+â¯FP (21.2% vs. 27.1%, p=0.024), so is lesion length (110.6 ± 77.3 vs. 135.4 ± 86.3 mm; p<0.001). Nearly, 81% lesions are treated with PTA. DCB (1.6% vs 14%, p<0.001) and atherectomy (38% vs. 58.5%; p<0.001) use is greater in BTKâ¯+â¯FP. Procedural success is higher in BTKâ¯+â¯FP group (86% vs. 91%, p=0.009), with amputation being the most common complication at 3.3% ≤30 days. One-year MALE (21.2% vs. 22.3%, p=0.675) and mortality (4.6% vs. 3.4%; p=0.3) are similar across BTK and BTKâ¯+â¯FP groups. CONCLUSION: Non-stent treatment for BTK PAD with concomitant FP intervention leads to high procedural success and similar rates of 1-year MALE compared with isolated BTK intervention. CONDENSED ABSTRACT: The vast majority of below-the-knee (BTK) peripheral artery disease (PAD) interventions are performed with balloon angioplasty. Presence of inflow femoropopliteal (FP) PAD in patients undergoing BTK interventions can affect the outcome of the procedure. This report explores the immediate procedural success and major adverse limb events at 1 year following balloon angioplasty treatment for isolated BTK and in those undergoing an additional FP PAD intervention.
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Raf protein kinases act as Ras-GTP sensing components of the ERK signal transduction pathway in animal cells, influencing cell proliferation, differentiation, and survival. In humans, somatic and germline mutations in the genes BRAF and RAF1 are associated with malignancies and developmental disorders. Recent studies shed light on the structure of activated Raf, a heterotetramer consisting of Raf and 14-3-3 dimers, and raised the possibility that a Raf C-terminal distal tail segment (DTS) regulates activation. We investigated the role of the DTS using the Caenorhabditis elegans, which has a single Raf ortholog termed lin-45 . We discovered that truncations removing the DTS strongly enhanced lin-45(S312A) , a weak gain-of-function allele equivalent to RAF1 mutations found in patients with Noonan Syndrome. We generated mutations to test three elements of the LIN-45 DTS, which we termed the active site binding sequence (ASBS), the KTP motif, and the aromatic cluster. In the context of lin-45(S312A), mutation of either the ASBS, KTP motif, or aromatic cluster enhanced activity. We used AlphaFold to predict DTS protein interactions for LIN-45, fly Raf, and human BRAF, within the activated heterotetramer complex. We propose distinct functions for the LIN-45 DTS elements: i) the ASBS binds the kinase active site as an inhibitor, ii) phosphorylation of the KTP motif modulates DTS-kinase domain interaction, and iii) the aromatic cluster anchors the DTS in an inhibitory conformation. This work establishes that the Raf/LIN-45 DTS negatively regulates signaling in C. elegans and provides a model for its function in other Raf proteins.
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OBJECTIVE: Limited prospective data exist about the impact of stimulant therapy for attention-deficit hyperactivity disorder (ADHD) during adolescence on the risk for later prescription drug misuse (PDM; i.e., of benzodiazepines, opioids, and stimulants). METHODS: National longitudinal multicohort panels (baseline cohort years 2005-2017) of U.S. 12th grade students (N=11,066; ages 17 and 18 years) from the Monitoring the Future study were surveyed via self-administered questionnaires and followed up biennially during young adulthood (ages 19-24). A multivariable analysis was used to assess whether adolescents' lifetime history of stimulant therapy for ADHD was associated with subsequent PDM. RESULTS: Overall, 9.9% of adolescents reported lifetime stimulant therapy for ADHD at ages 17 and 18. No significant differences were found in the adjusted odds of later incidence or prevalence of past-year PDM during young adulthood between adolescents with lifetime stimulant therapy and adolescents with no stimulant therapy. Over the 5-year follow-up, past-year PDM during young adulthood was most prevalent among adolescents who reported both stimulant therapy and prescription stimulant misuse (53.1%) and those who reported prescription stimulant misuse only (51.5%). Compared with adolescents in a control group without lifetime stimulant therapy or misuse, adolescents reporting prescription stimulant misuse had significantly higher adjusted odds of later incidence and prevalence of PDM during young adulthood. CONCLUSIONS: Adolescents' stimulant therapy for ADHD was not significantly associated with increased risk for later PDM during young adulthood. In contrast, adolescents' misuse of prescription stimulants strongly predicted later PDM. Monitoring adolescents for prescription stimulant misuse may help identify and mitigate the risk for future PDM.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Uso Indevido de Medicamentos sob Prescrição , Humanos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Adolescente , Estimulantes do Sistema Nervoso Central/uso terapêutico , Masculino , Feminino , Uso Indevido de Medicamentos sob Prescrição/estatística & dados numéricos , Adulto Jovem , Estudos Longitudinais , Estados Unidos/epidemiologia , AdultoRESUMO
BACKGROUND: Suicide, especially by firearm, remains a leading cause of death in military populations in the USA. Reducing access to firearms, especially during high risk times, may help prevent suicide and other forms of violence. The purpose of this study was to adapt a promising existing lethal means safety intervention (Project Safe Guard, PSG) for cross-cutting violence prevention and peer support in active-duty service communities using community engagement methods. METHODS: A two-pronged community-engaged research approach was employed, including the Community Translation (CT) process that engaged 15 Service Members from one installation to help adapt PSG successfully. In addition, qualitative data was collected from 40 active-duty service members and military violence prevention specialists through in-depth interviews and focus group discussions. RESULTS: Qualitative data and CT feedback led to site-specific PSG adaptations. Participants emphasized the importance of peer-to-peer discussions and highlighted resource allocation, leadership support, and stigma on firearm ownership as potential implementation challenges. CONCLUSIONS: Findings demonstrate the feasibility of community-engaged research to adapt lethal means safety interventions within military populations. PSG implementation should consider resource allocation, leadership support, and addressing stigma. This study has implications for future policies and standards for performing research on sensitive topics, particularly among military populations.
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Warm red-emitting praseodymium-doped LiSrVO4 phosphors were synthesized via solid-state reaction. The phase formation was verified using an X-ray diffraction study and the morphology was investigated using a scanning electron microscope study. The LiSrVO4 :Pr3+ phosphors emitted red light when exposed to ultraviolet light, indicating their possibility for use in warm white light-emitting diodes (WLEDs). Furthermore, the effect of charge compensators on the luminescence characteristics was addressed. The decay time was investigated using time-resolved photoluminescence. Furthermore, thermal quenching was analyzed through temperature-dependent photoluminescence spectra. Their sensitivity was calculated using temperature-dependent decay time analysis. The colour purity of the emitted light could be measured by photometric analysis. This comprehensive investigation provides a thorough understanding of the luminescence properties of phosphors for WLED applications.
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Luminescência , Luz Vermelha , Difração de Raios X , Raios Ultravioleta , TemperaturaRESUMO
BACKGROUND: Cold air plasma (CAP) can generate plasma-activated liquids (PALs) with high concentrations of reactive oxygen (ROS) and nitrogen species (RNS), e.g., nitrites, with antimicrobial properties. AIM: We investigated the concentrations of ROS and RNS in saline PAL. We assessed planktonic bacterial inactivation by PAL and the decontamination of contaminated cleaning cloths. METHODS: Phosphate-buffered saline (PBS) was treated with an air-driven CAP jet for 90 or 300 s to generate PAL. The ROS and RNS were measured using quantitative fluorescent (2,7-dichlorofluorescin diacetate) and colourimetric (Greiss) assays. Isolates of MRSA and Escherichia coli were incubated in PAL overnight and inactivation measured through colony forming unit (cfu) assays. Sections of cleaning cloths were incubated with MRSA and E. coli, and treated with PAL for 1 h. Bacterial inactivation was measured through resazurin reduction assays. RESULTS: Nitrites increased from 0.1 µM in untreated PBS to 49.1 µM and to 94.0 µM in 90- and 300-s CAP-treated PAL, respectively. ROS increased from 30 µM in untreated PBS to 75 µM and to 103 µM in 90- and 300-s CAP-treated PAL, respectively. 90-s PAL reduced MRSA and E. coli viability (P<0.05) and 300-s PAL resulted in more than a 7-log reduction of both. One-hour treatment of contaminated cleaning cloths in PAL resulted in a 55% and 73% reduction in viable MRSA and E. coli, respectively (P<0.05). CONCLUSION: Inactivation of planktonic bacteria correlated with ROS and RNS concentrations. PAL reduced bacteria contaminated cleaning cloths. PAL has potential as a hospital disinfectant, including cleaning cloths.
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Desinfecção , Escherichia coli , Humanos , Desinfecção/métodos , Nitritos , Espécies Reativas de Oxigênio , Bactérias , Antibacterianos/farmacologia , Atenção à SaúdeRESUMO
BACKGROUND: To assess whether age of onset and duration of stimulant therapy for attention-deficit/hyperactivity disorder (ADHD) are associated with cocaine, methamphetamine, and prescription stimulant misuse during adolescence. METHODS: Nationally representative samples of US 10th and 12th grade students (N = 150,395) from the Monitoring the Future study were surveyed via self-administered questionnaires from 16 annual surveys (2005-2020). RESULTS: An estimated 8.2% of youth received stimulant therapy for ADHD during their lifetime (n = 10,937). More than one in 10 of all youth reported past-year prescription stimulant misuse (10.4%)-past-year cocaine (4.4%) and methamphetamine (2.0%) use were less prevalent. Youth who initiated early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years) did not have significantly increased adjusted odds of cocaine or methamphetamine use relative to population controls (ie, non-ADHD and unmedicated ADHD youth). Youth who initiated late stimulant therapy for ADHD (≥10 years old) and for short duration (<1 year) had significantly higher odds of past-year cocaine or prescription stimulant misuse in adolescence than those initiating early stimulant therapy for ADHD (≤9 years old) and for long duration (≥6 years). Youth who initiated late stimulant therapy for ADHD (≥10 years) for short duration (<1 year) had significantly higher odds of past-year cocaine, methamphetamine, and prescription stimulant misuse versus population controls during adolescence. No differences in past-year cocaine, methamphetamine, and prescription stimulant misuse were found between individuals who only used non-stimulant therapy for ADHD relative to youth who initiated early stimulant therapy (≤9 years old) and for long duration (≥6 years). CONCLUSIONS: An inverse relationship was found between years of stimulant therapy and illicit and prescription stimulant misuse. Adolescents with later initiation and/or shorter duration of stimulant treatment for ADHD should be monitored for potential illicit and prescription stimulant misuse.
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Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Cocaína , Metanfetamina , Transtornos Relacionados ao Uso de Substâncias , Adolescente , Humanos , Criança , Metanfetamina/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Idade de Início , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Cocaína/efeitos adversos , Prescrições de MedicamentosRESUMO
Natural variation can provide important insights into the genetic and environmental factors that shape social behaviour and its evolution. The sweat bee, Lasioglossum baleicum, is a socially flexible bee capable of producing both solitary and eusocial nests. We demonstrate that within a single nesting aggregation, soil temperatures are a strong predictor of the social structure of nests. Sites with warmer temperatures in the spring have a higher frequency of social nests than cooler sites, perhaps because warmer temperatures provide a longer reproductive window for those nests. To identify the molecular correlates of this behavioural variation, we generated a de novo genome assembly for L. baleicum, and we used transcriptomic profiling to compare adults and developing offspring from eusocial and solitary nests. We find that adult, reproductive females have similar expression profiles regardless of social structure in the nest, but that there are strong differences between reproductive females and workers from social nests. We also find substantial differences in the transcriptomic profiles of stage-matched pupae from warmer, social-biased sites compared to cooler, solitary-biased sites. These transcriptional differences are strongly predictive of adult reproductive state, suggesting that the developmental environment may set the stage for adult behaviours in L. baleicum. Together, our results help to characterize the molecular mechanisms shaping variation in social behaviour and highlight a potential role of environmental tuning during development as a factor shaping adult behaviour and physiology in this socially flexible bee.
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The Epidemic-Pandemic Impacts Inventory (EPII) is a 92-item measure developed to assess tangible impacts of the pandemic including both negative (work, home, social, and health) and positive changes. The EPII has been used in a variety of studies, but a standard scoring system has not been determined. Parents of young children (N = 216) completed the EPII, Perceived Stress Scale, Parenting Stress Scale, Positive and Negative Affect Scale (PANAS-PA and PANAS-NA), and COVID-19 Stress Scale (CSS) online September 2021-May 2022. The EPII was scored in three ways represented in the literature to examine which scoring method accounted for the greatest amount of variance in parents' stress and mood, independent of demographic factors and CSS. Hierarchical linear regression results revealed that one EPII scoring method consistently accounted for the greatest amount of variance in each outcome variable (largest R2) compared to the other two scoring methods. Additionally, number of negative and positive pandemic impacts accounted for more variance (larger ß coefficient) in each outcome compared to demographic factors and CSS, with the exception that negative pandemic impacts were not associated with PANAS-PA. One method of scoring the EPII may maximize the measures' potential to account for variance in stress and mood among parents of young children. The EPII may be a valuable measure to include in studies examining the impact of the pandemic on parents' well-being even beyond the peak of the pandemic, as its association with stress and mood appears to be long-lasting and independent of demographic factors and COVID-19 stress. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
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COVID-19 , Pandemias , Criança , Humanos , Pré-Escolar , Pais , Poder Familiar , Afeto , COVID-19/epidemiologiaRESUMO
Objective: To describe four unique models of implementing Wastewater Based Surveillance (WBS) for SARS-CoV-2 in jails of graduated sizes and differing architectural designs. Methods: This study summarizes how jails of Cook County (Illinois, average daily population [ADP] 6000), Fulton County (Georgia, ADP 3000, Washington DC (ADP 1600) and Middlesex County (Massachusetts, ADP 875) initiated WBS between 2020 and 2023. Results: Positive signal for SARS-CoV-2 via WBS can herald new onset of infection in a previously uninfected housing unit of a jail. Challenges in implementing WBS included political will and realized value, funding, understanding of the building architecture, and the need for granularity in the findings. Conclusions: WBS has been effective for detecting outbreaks of SARS-CoV-2 in differing sized jails, both those with dorm-based and cell-based architectural design. Policy implications: Given its effectiveness in monitoring SARS-CoV-2, WBS provides a model for population-based surveillance in carceral facilities for future infectious disease outbreaks.
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Natural variation can provide important insights into the genetic and environmental factors that shape social behavior and its evolution. The sweat bee, Lasioglossum baleicum , is a socially flexible bee capable of producing both solitary and eusocial nests. We demonstrate that within a single nesting aggregation, soil temperatures are a strong predictor of the social structure of nests. Sites with warmer temperatures in the spring have a higher frequency of social nests than cooler sites, perhaps because warmer temperatures provide a longer reproductive window for those nests. To identify the molecular correlates of this behavioral variation, we generated a de novo genome assembly for L. baleicum , and we used transcriptomic profiling to compare adults and developing offspring from eusocial and solitary nests. We find that adult, reproductive females have similar expression profiles regardless of social structure in the nest, but that there are strong differences between reproductive females and workers from social nests. We also find substantial differences in the transcriptomic profiles of stage-matched pupae from warmer, social-biased sites compared to cooler, solitary-biased sites. These transcriptional differences are strongly predictive of adult reproductive state, suggesting that the developmental environment may set the stage for adult behaviors in L. baleicum . Together, our results help to characterize the molecular mechanisms shaping variation in social behavior and highlight a potential role of environmental tuning during development as a factor shaping adult behavior and physiology in this socially flexible bee.
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Signaling by the kinase cascade composed of Raf, MEK, and ERK is critical for animal development and is often inappropriately activated in human malignancies. We sought to identify factors that control signaling mediated by the Caenorhabditis elegans Raf ortholog LIN-45. A genetic screen showed that the degradation of LIN-45 required the E3/E4 ubiquitin ligase UFD-2. Both UFD-2 and its partner, the ATP-dependent segregase CDC-48, were required for the developmental regulation of LIN-45 protein abundance. We showed that UFD-2 acted in the same pathway as the E3 ubiquitin ligase SCFSEL-10 to decrease LIN-45 abundance in cells in which Raf-MEK-ERK signaling was most highly active. UFD-2 also reduced the protein abundance of activated LIN-45 carrying a mutation equivalent to the cancer-associated BRAF(V600E) variant. Our structure-function studies showed that the disruption of LIN-45 domains that mediate protein-protein interactions, including the conserved cysteine-rich domain and 14-3-3 binding motifs, were required for UFD-2-independent degradation of LIN-45. We propose a model in which UFD-2 and CDC-48 act downstream of SCFSEL-10 to remove LIN-45 from its protein interaction partners and facilitate proteasomal targeting and degradation. These findings imply that UFD-2 and CDC-48 may be important for Raf degradation during normal and oncogenic Ras and MAPK signaling in mammalian cells.
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Proteínas de Caenorhabditis elegans , Ubiquitina-Proteína Ligases , Animais , Humanos , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ciclo Celular , Mamíferos , Quinases de Proteína Quinase Ativadas por Mitógeno , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética , UbiquitinasRESUMO
INTRODUCTION: Many surgical procedures are prone to human error, particularly in the learning phase of skills acquisition. Task standardisation has been suggested as an approach to reducing errors, but it fails to account for the human factors associated with learning. Human reliability analysis (HRA) is a structured approach to assess human error during surgery. This study used HRA methodologies to examine skills acquisition associated with carpal tunnel decompression. METHODS: The individual steps or subtasks required to complete a carpal tunnel decompression were identified using hierarchical task analysis (HTA). The systematic human error reduction and prediction approach (SHERPA) was carried out by consensus of subject matter experts. This identified the potential human errors at each subgoal, the level of risk associated with each task and how these potential errors could be prevented. RESULTS: Carpal tunnel decompression was broken down into 46 subtasks, of which 21 (45%) were medium risk and 25 (55%) were low risk. Of the 46 subtasks, 4 (9%) were assigned high probability and 18 (39%) were assigned medium probability. High probability errors (>1/50 cases) included selecting incorrect tourniquet size, failure to infiltrate local anaesthetic in a proximal-to-distal direction and completion of the World Health Organization (WHO) surgical sign-out. Three (6%) of the subtasks were assigned high criticality, which included failure to aspirate before anaesthetic injection, whereas 21 (45%) were assigned medium criticality. Remedial strategies for each potential error were devised. CONCLUSIONS: The use of HRA techniques provides surgeons with a platform to identify critical steps that are prone to error. This approach may improve surgical training and enhance patient safety.
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Introduction: Preovulatory follicle response to the luteinizing hormone (LH) surge leads to metabolic, molecular, and functional changes in the oocyte and somatic follicular cells from the onset of estrus to ovulation. Follicular fluid contains metabolites, miRNAs, proteins, and hormones that are byproducts of follicular metabolism and support cellular processes of oocyte, cumulus, and granulosa constituents. Numerous studies have highlighted the importance of follicular fluid composition to support fertility, but critical gaps exist toward understanding dynamic modifications in the follicular fluid metabolome from estrous onset to ovulation. The hypothesis was that abundance of follicular fluid metabolites is dependent on follicle progression post LH surge and variability in follicular fluid metabolome profiles indicate key processes required for preparation of the follicle and oocyte for optimal fertility. The objective was to generate preovulatory follicular fluid metabolome profiles and discern differences in the metabolome of preovulatory follicular fluid samples collected at onset of estrus, 11 h post estrous onset, and 18 h post estrous onset. Methods: Estrus was synchronized in non-lactating Jersey cows (n=40) and follicular fluid was collected immediately after the first observed standing mount (hr 0) or at approximately h 11 or 18 after the first standing mount. Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry was performed on preovulatory follicular fluid samples (n = 9 collected at hr 0, 9 at h 11, and 10 at h 18) and a multiple linear model was performed to determine if time post estrous onset impacted metabolite abundance. Results: Metabolites influenced by time post estrous onset were tested for enrichment in KEGG pathways. Ninety metabolites were identified in follicular fluid samples. Twenty metabolites differed in abundance among timepoints post estrous onset (p ≤ 0.05). Pathways corresponding to amino acid and energy metabolism were enriched with metabolites impacted by time post estrous onset (FDR ≤ 0.10). Discussion: Results from the current study indicate early response to the LH surge to increase bioavailability of amino acids and metabolites used by the cumulus and granulosa cells for energy production and shuttled into the oocyte to support meiotic maturation. Such metabolites may later be used by the ovulatory follicle for protein production.
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BACKGROUND: Perpetuation of atrial fibrillation (AF) is rooted in derailment of molecular proteostasis pathways that cause electrical conduction disorders that drive AF. Emerging evidence indicates a role for long noncoding RNAs (lncRNAs) in the pathophysiology of cardiac diseases, including AF. OBJECTIVES: In the present study, the authors explored the association between 3 cardiac lncRNAs and the degree of electropathology. METHODS: Patients had paroxysmal AF (ParAF) (n = 59), persistent AF (PerAF) (n = 56), or normal sinus rhythm without a history of AF (SR) (n = 70). The relative expression levels of urothelial carcinoma-associated 1 (UCA1), OXCT1-AS1 (SARRAH), and the mitochondrial lncRNA uc022bqs.q (LIPCAR) were measured by means of quantitative reverse-transcription polymerase chain reaction in the right atrial appendage (RAA) or serum (or both). A selection of the patients was subjected to high-resolution epicardial mapping to evaluate electrophysiologic features during SR. RESULTS: The expression levels of SARRAH and LIPCAR were decreased in RAAs of all AF patients compared with SR. Also, in RAAs, UCA1 levels significantly correlated with the percentage of conduction block and delay, and inversely with conduction velocity, indicating that UCA1 levels in RAA reflect the degree of electrophysiologic disorders. Moreover, in serum samples, SARRAH and UCA1 levels were increased in the total AF group and ParAF patients compared with SR. CONCLUSIONS: LncRNAs SARRAH and LIPCAR are reduced in RAA of AF patients, and UCA1 levels correlate with electrophysiologic conduction abnormalities. Thus, RAA UCA1 levels may aid staging of electropathology severity and act as a patient-tailored bioelectrical fingerprint.
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Apêndice Atrial , Fibrilação Atrial , Carcinoma de Células de Transição , RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , Fibrilação Atrial/patologia , Carcinoma de Células de Transição/complicações , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/patologia , Doença do Sistema de Condução Cardíaco , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias da Bexiga Urinária/complicações , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologiaRESUMO
BACKGROUND: Platelet concentrates (PLT) can be manufactured using a combination of apheresis collection devices and suspension media (plasma or platelet additive solution (PAS)). It is unclear how platelet quality and hemostatic function differ across the current in-use manufacturing methods in the United States. The objective of this study was therefore to compare baseline function of PLT collected using different apheresis collection platforms and storage media. STUDY DESIGN AND METHODS: PLT were collected at two sites with identical protocols (N = 5 per site, N = 10 total per group) on the MCS® + 9000 (Haemonetics; "MCS"), the Trima Accel® 7 (Terumo; "Trima"), and the Amicus Cell Separator (Fresenius Kabi, "Amicus"). MCS PLT were collected into plasma while Trima and Amicus PLT were collected into plasma or PAS (Trima into Isoplate and Amicus into InterSol; yielding groups "TP", "TI" and "AP", "AI", respectively). PLT units were sampled 1 h after collection and assayed to compare cellular counts, biochemistry, and hemostatic function. RESULTS: Differences in biochemistry were most evident between plasma and PAS groups, as anticipated. MCS and TP had the highest clot strength as assessed by viscoelastometry. AI had the lowest thrombin generation capacity. Both TP and TI had the highest responses on platelet aggregometry. AI had the greatest number of microparticles. DISCUSSION: Platelet quality and function differ among collection platforms at baseline. MCS and Trima platelets overall appear to trend toward higher hemostatic function. Future investigations will assess how these differences change throughout storage, and if these in vitro measures are clinically relevant.
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Plaquetas , Hemostáticos , Humanos , Plaquetoferese/métodos , Separação Celular , Contagem de CélulasRESUMO
In butterflies and moths, male-killing endosymbionts are transmitted from infected females via their eggs, and the male progeny then perish. This means that successful transmission of the parasite relies on the successful mating of the host. Paradoxically, at the population level, parasite transmission also reduces the number of adult males present in the final population for infected females to mate with. Here we investigate if successful female mating when males are rare is indeed a likely rate-limiting step in the transmission of male-killing Spiroplasma in the African Monarch, Danaus chrysippus. In Lepidoptera, successful pairings are hallmarked by the transfer of a sperm-containing spermatophore from the male to the female during copulation. Conveniently, this spermatophore remains detectable within the female upon dissection, and thus, spermatophore counts can be used to assess the frequency of successful mating in the field. We used such spermatophore counts to examine if altered sex ratios in the D. chrysippus do indeed affect female mating success. We examined two different field sites in East Africa where males were often rare. Surprisingly, mated females carried an average of 1.5 spermatophores each, regardless of male frequency, and importantly, only 10-20% remained unmated. This suggests that infected females will still be able to mate in the face of either Spiroplasma-mediated male killing and/or fluctuations in adult sex ratio over the wet-dry season cycle. These observations may begin to explain how the male-killing mollicute can still be successfully transmitted in a population where males are rare.
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Sweat bees have repeatedly gained and lost eusociality, a transition from individual to group reproduction. Here we generate chromosome-length genome assemblies for 17 species and identify genomic signatures of evolutionary trade-offs associated with transitions between social and solitary living. Both young genes and regulatory regions show enrichment for these molecular patterns. We also identify loci that show evidence of complementary signals of positive and relaxed selection linked specifically to the convergent gains and losses of eusociality in sweat bees. This includes two pleiotropic proteins that bind and transport juvenile hormone (JH)-a key regulator of insect development and reproduction. We find that one of these proteins is primarily expressed in subperineurial glial cells that form the insect blood-brain barrier and that brain levels of JH vary by sociality. Our findings are consistent with a role of JH in modulating social behaviour and suggest that eusocial evolution was facilitated by alteration of the proteins that bind and transport JH, revealing how an ancestral developmental hormone may have been co-opted during one of life's major transitions. More broadly, our results highlight how evolutionary trade-offs have structured the molecular basis of eusociality in these bees and demonstrate how both directional selection and release from constraint can shape trait evolution.
Assuntos
Comportamento Social , Suor , Abelhas , Animais , Reprodução , FenótipoRESUMO
Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with higher substance use rates. Stimulant and non-stimulant pharmacotherapy improve adolescent ADHD, but their associations with prescription stimulant misuse (PSM), cocaine, and methamphetamine use are unclear. Using 2005-2020 US Monitoring the Future data, we investigated relationships between ADHD pharmacotherapy history and PSM, cocaine, or methamphetamine use. Methods: Secondary students (13-19 years) provided data on pharmacotherapy history (N = 199,560; 86.3% of total sample) between January 1, 2005 and May 31, 2020 in a cross-sectional multi-cohort study; weights assured a nationally representative sample. Participants were grouped by ADHD pharmacotherapy history: none (88.7%; principally non-ADHD controls); stimulant-only (5.8%); non-stimulant-only (3.3%); both stimulant and non-stimulant (2.1%). Outcomes were past-year PSM, cocaine, and methamphetamine use. Logistic regressions examined relationships between pharmacotherapy history and outcomes, controlling for sociodemographics, recent substance use, and stimulant treatment cessation. Findings: Past-year outcome rates were lowest in adolescents with no pharmacotherapy history: 4.7% for PSM [8310/174,561], 1.6% for cocaine [2858/174,688], and 0.7% for methamphetamine [1036/148,378]. A history of both stimulant and non-stimulant treatment was associated with the highest rates: 22.3% for PSM [940/4098], 10.4% for cocaine [450/4110], and 7.8% for methamphetamine [275/3427]. Adolescents who received monotherapy (stimulant- or non-stimulant-only) had intermediate rates, with no differences between monotherapy groups. Interpretation: While elevated PSM and illicit stimulant use rates are likely influenced by ADHD, our findings suggested adolescents with a history of both stimulant and non-stimulant pharmacotherapy are at highest risk for these stimulant outcomes. Adolescents receiving ADHD pharmacotherapy should be monitored for PSM and illicit stimulant use. Funding: National Institute on Drug Abuse/National Institutes of Health (USA) and Food and Drug Administration (USA).