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1.
Environ Microbiol ; 26(3): e16587, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38454741

RESUMO

To comprehensively evaluate the impact of agricultural management practices on soil productivity, it is imperative to conduct a thorough analysis of soil bacterial ecology. Deep-banding nutrient-rich amendments is a soil management practice that aims to improve plant growth and soil structure by addressing the plant-growth constraints posed by dense-clay subsoils. However, the response of bacterial communities to deep-banded amendments has not been thoroughly studied. To address this knowledge gap, we conducted a controlled-environment column experiment to examine the effects of different types of soil amendments (poultry litter, wheat straw + chemical fertiliser and chemical fertiliser alone) on bacterial taxonomic composition in simulated dense-clay subsoils. We evaluated the bacterial taxonomic and ecological group composition in soils beside and below the amendment using 16S rRNA amplicon sequencing and robust statistical methods. Our results indicate that deep-banded amendments alter bacterial communities through direct and indirect mechanisms. All amendments directly facilitated a shift in bacterial communities in the absence of growing wheat. However, a combination of amendments with growing wheat led to a more pronounced bacterial community shift which was distinct from and eclipsed the direct impact of the amendments and plants alone. This indirect mechanism was evidenced to be mediated primarily by plant growth and hypothesised to result from an enhancement in wheat root distribution, density and rhizodeposition changes. Therefore, we propose that subsoil amendments regardless of type facilitated an expansion in the rhizosphere which engineered a substantial plant-mediated bacterial community response within the simulated dense-clay subsoils. Overall, our findings highlight the importance of considering the complex and synergistic interactions between soil physicochemical properties, plant growth and bacterial communities when assessing agricultural management strategies for improving soil and plant productivity.


Assuntos
Microbiota , Microbiota/genética , Argila , Rizosfera , Fertilizantes , RNA Ribossômico 16S/genética , Microbiologia do Solo , Solo/química , Plantas/genética , Bactérias , Triticum/microbiologia
2.
J Subst Use Addict Treat ; 162: 209358, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38548060

RESUMO

INTRODUCTION: Compared to the general U.S. adolescent population, young people involved in the juvenile justice system are at greater risk of experiencing substance use (SU) issues. There are critical opportunities across the juvenile justice continuum, at points of interface with community-based treatment services, to screen and assess for SU issues, identify unmet treatment needs, and refer those in need to treatment. The treatment referral process is, however, complex, and contingent on a seamless nexus between juvenile justice operations and the wider treatment provider landscape. Given the lack of successful SU referrals among justice-involved youth and the variable referral rates across jurisdictions, this study's aim is to provide a qualitative, explanatory understanding of the conditions that together contribute to successful referring practices. METHODS: The study is based on an analysis of a qualitative dataset comprising focus group data with probation and community-based behavioral health treatment staff working in 31 sites in 6 different states as part of the clustered randomized trial of an organizational change intervention known as JJ-TRIALS (Juvenile Justice Translational Research on Interventions for Adolescents in the Legal System). The data contain respondents' narratives on the achievements, successes, and challenges with implementing the intervention. The data were analyzed through a combination of strategies to identify the conditions that both facilitate and impede referral processes between probation offices and community-based SU treatment providers. RESULTS: Participants across sites discussed the positive impacts that the JJ-TRIALS intervention had on their improved ability to communicate, collaborate, and collect data. From the interviews, seven main conditions were observed to contribute to successful SU treatment referral practices: (1) communication (inter-organizational); (2) collaboration; (3) data-driven practices; (4) family engagement; (5) institutionalized policy and referral documentation; (6) efficient referral policies and procedures; and (7) suitable and accessible system of treatment providers. CONCLUSION: Findings highlight the value of a holistic understanding of successful treatment referrals for justice-involved youth and help inform research and practice efforts to identify and measure the many dimensions of referral-making at the interface of juvenile probation and behavioral health services.

3.
bioRxiv ; 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38405789

RESUMO

Progesterone production by the corpus luteum is fundamental for establishing and maintaining pregnancy. The pituitary gonadotropin luteinizing hormone (LH) is recognized as the primary stimulus for luteal formation and progesterone synthesis, regardless of species. Previous studies demonstrated an elevation in abundance of genes related to glucose and lipid metabolism during the follicular to luteal transition. However, the metabolic phenotype of these highly steroidogenic cells has not been studied. Herein, we determined acute metabolic changes induced by LH in primary luteal cells and defined pathways required for progesterone synthesis. Untargeted metabolomics analysis revealed that LH induces rapid changes in vital metabolic pathways, including glycolysis, tricarboxylic acid (TCA) cycle, pentose phosphate pathway, de novo lipogenesis, and hydrolysis of phospholipids. LH stimulated glucose uptake, enhanced glycolysis, and flux of [U- 13 C 6 ]-labeled glucose-derived carbons into metabolic branches associated with adenosine 5'-triphosphate (ATP) and NADH/NADPH production, synthesis of nucleotides, proteins, and lipids, glycosylation of proteins or lipids, and redox homeostasis. Selective use of small molecule inhibitors targeting the most significantly changed pathways, such as glycolysis, TCA cycle, and lipogenesis, uncovered cellular metabolic routes required for LH-stimulated steroidogenesis. Furthermore, LH via the protein kinase A (PKA) pathway triggered post- translational modification of acetyl-CoA carboxylase alpha (ACACA) and ATP citrate lyase (ACLY), enzymes involved in de novo synthesis of fatty acids. Inhibition of ACLY and fatty acid transport into mitochondria reduced LH-stimulated ATP, cAMP production, PKA activation, and progesterone synthesis. Taken together, these findings reveal novel hormone-sensitive metabolic pathways essential for maintaining LHCGR/PKA signaling and steroidogenesis in ovarian luteal cells. Significance: The establishment and maintenance of pregnancy require a well-developed corpus luteum, an endocrine gland within the ovary that produces progesterone. Although there is increased awareness of intracellular signaling events initiating the massive production of progesterone during the reproductive cycle and pregnancy, there are critical gaps in our knowledge of the metabolic and lipidomic pathways required for initiating and maintaining luteal progesterone synthesis. Here, we describe rapid, hormonally triggered metabolic pathways, and define metabolic targets crucial for progesterone synthesis by ovarian steroidogenic cells. Understanding hormonal control of metabolic pathways may help elucidate approaches for improving ovarian function and successful reproduction or identifying metabolic targets for developing nonhormonal contraceptives.

4.
Cell Death Dis ; 15(1): 31, 2024 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212315

RESUMO

Maternal obesity increases the risk of childhood obesity and programs the offspring to develop metabolic syndrome later in their life. Palmitate is the predominant saturated free fatty acid (FFA) that is transported across the placenta to the fetus. We have recently shown that saturated FFA in the maternal circulation as a result of increased adipose tissue lipolysis in third trimester of pregnancy induces trophoblast lipoapoptosis. Here, we hypothesized that palmitate induces integrated stress response by activating mitogen-activated protein kinases (MAPKs), endoplasmic reticulum (ER) stress and granular stress and lipoapoptosis in trophoblasts. Choriocarcinoma-derived third-trimester placental trophoblast-like cells (JEG-3 and JAR) referred as trophoblasts were exposed to various concentrations of palmitate (PA). Apoptosis was assessed by nuclear morphological changes and caspase 3/7 activity. Immunoblot and immunofluorescence analysis was performed to measure the activation of MAPKs, ER stress and granular stress response pathways. Trophoblasts exposed to pathophysiological concentrations of PA showed a concentration-dependent increase in trophoblast lipoapoptosis. PA induces a caspase-dependent trophoblast lipoapoptosis. Further, PA induces MAPK activation (JNK and ERK) via phosphorylation, and activation of ER stress as evidenced by an increased phosphorylation eIF2α & IRE1α. PA also induces the activation of stress granules formation. Two pro-apoptotic transcriptional mediators of PA-induced trophoblast lipoapoptosis, CHOP and FoxO3 have increased nuclear translocation. Mechanistically, PA-induced JNK is critical for trophoblast lipoapoptosis. However, PA-induced activation of ERK and stress granule formation were shown to be cell survival signals to combat subcellular stress due to PA exposure. In conclusion, PA induces the activation of integrated stress responses, among which small molecule inhibition of JNK demonstrated that activation of JNK is critical for PA-induced trophoblast lipoapoptosis and small molecule activation of stress granule formation significantly prevents PA-induced trophoblast lipoapoptosis.


Assuntos
Palmitatos , Obesidade Infantil , Criança , Feminino , Humanos , Gravidez , Palmitatos/farmacologia , Palmitatos/metabolismo , Linhagem Celular Tumoral , Endorribonucleases , Placenta/metabolismo , Proteínas Serina-Treonina Quinases , Apoptose , Proteínas Quinases Ativadas por Mitógeno , Estresse do Retículo Endoplasmático , Trofoblastos/metabolismo
5.
Police Pract Res ; 24(6): 728-734, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37981953

RESUMO

Cities have been experimenting with less police-centered models for responding to people experiencing mental health crises. Ten focus groups were conducted with Philadelphia police officers to understand their experiences encountering mental health distress in the community and their perspectives on a new co-deployment initiative. There was general consensus that conventional police-centered responses to mental health concerns are often problematic. However, perspectives varied on the value of co-deployment and the general feasibility of reducing police involvement. This variation is traced to different notions of what constitutes a mental health crisis, whether crises are prospectively identifiable, how dangerousness is assessed, and whether civilian co-response partners will effectively complete key response activities. Bringing greater understanding and consensus to these issues is essential to healthier and more effective responses to mental health crises.

6.
Int J Colorectal Dis ; 38(1): 264, 2023 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-37932486

RESUMO

PURPOSES: To compare the risk of anastomotic leak (AL) between Ethicon manual circular staplers (two-row) versus Medtronic EEA™ circular stapler with Tri-Staple™ technology (three-row) and between Medtronic EEA™ circular stapler with DST™ Series technology (two-row) versus Tri-Staple™ technology. METHODS: A retrospective cohort study was conducted in adult patients who underwent a left-sided colorectal surgery 2019-2022 in U.S. Premier Healthcare Database to assess the risk of AL within 30 days post-index procedure. The study devices were Ethicon manual circular staplers, Medtronic EEA™ circular stapler with DST™ technology, and Medtronic EEA™ circular stapler with Tri-Staple™ technology. RESULTS: Across 447 hospitals, the cumulative incidences (95% confidence intervals [CI]) of AL within 30 days post-index procedure were 7.78% (6.91-8.74%) among 8337 patients in the Ethicon manual circular stapler cohort, 7.54% (6.87-8.27%) among 7928 patients in the Medtronic EEA™ circular stapler with DST™ technology cohort, and 8.19% (6.57-10.07%) among 1306 patients in the Medtronic EEA™ circular stapler with Tri-Staple™ technology cohort. Comparative analyses revealed no difference comparing Ethicon manual circular staplers with Medtronic EEA™ circular staplers with Tri-Staple™ technology (risk ratio [RR], 0.72; 95% CI, 0.52-1.01) or comparing Medtronic EEA™ circular staplers with DST™ technology to Tri-Staple™ technology (RR, 0.75; 95% CI, 0.53-1.06). CONCLUSION: In this analysis of a large cohort of patients undergoing a left-sided colorectal surgery from a U.S. hospital database, the risk of AL observed with manual two-row circular staplers was similar to that seen with three-row devices. This study affirms the safety of manual two-row circular staplers in colorectal anastomosis.


Assuntos
Fístula Anastomótica , Neoplasias Colorretais , Adulto , Humanos , Fístula Anastomótica/etiologia , Estudos de Coortes , Grampeadores Cirúrgicos/efeitos adversos , Estudos Retrospectivos , Anastomose Cirúrgica/efeitos adversos , Neoplasias Colorretais/cirurgia , Grampeamento Cirúrgico/efeitos adversos
7.
Animals (Basel) ; 13(20)2023 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-37894013

RESUMO

The process of follicle maturation leading to ovulation is a key milestone in female fertility. It is known that circulating lipids and cytokines play a role in the follicle's ability to go through follicular maturation and the ovulatory processes. However, the specific mechanisms are not well understood. We posit that dysregulation of granulosa cells influences the ovarian environment, which tries to adapt by changing released lipids and cytokines to achieve follicular maturation. Eleven non-lactating adult females underwent estrus synchronization with two injections of PGF2α 14 days apart. Daily blood samples were collected for 28 days to monitor steroid hormone production after the second injection. To understand the potential impacts of lipids and cytokines during ovulation, a low-dose FSH stimulation (FSHLow) was performed after resynchronization of cows, and daily blood samples were collected for 14 days to monitor steroid hormone production until ovariectomies. The lipidomic analysis demonstrated increased circulating diacylglycerides and triacylglycerides during the mid-luteal phase and after FSHLow treatment. Cholesteryl esters decreased in circulation but increased in follicular fluid (FF) after FSHLow. Increased circulating concentrations of TNFα and reduced CXCL9 were observed in response to FSHLow. Therefore, specific circulating lipids and cytokines may serve as markers of normal follicle maturation.

8.
Infect Immun ; 91(11): e0009723, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37830823

RESUMO

Enterotoxigenic Escherichia coli (ETEC) is a leading cause of bacterial diarrhea with the potential to cause long-term gastrointestinal (GI) dysfunction. Preventative treatments for ETEC-induced diarrhea exist, yet the effects of these treatments on GI commensals in healthy individuals are unclear. Whether administration of a prophylactic preventative treatment for ETEC-induced diarrhea causes specific shifts in gut microbial populations in controlled environments is also unknown. Here, we studied the effects of a hyperimmune bovine colostrum (IMM-124E) used in the manufacture of Travelan (AUST L 106709) on GI bacteria in healthy C57BL/6 mice. Using next-generation sequencing, we aimed to test the onset and magnitude of potential changes to the mouse gut microbiome in response to the antidiarrheagenic hyperimmune bovine colostrum product, rich in immunoglobulins against select ETEC strains (Travelan, Immuron Ltd). We show that in mice administered colostrum containing lipopolysaccharide (LPS) antibodies, there was an increased abundance of potentially gut-beneficial bacteria, such as Akkermansia and Desulfovibrio, without disrupting the underlying ecology of the GI tract. Compared to controls, there was no difference in overall weight gain, body or cecal weights, or small intestine length following LPS antibody colostrum supplementation. Overall, dietary supplementation with colostrum containing LPS antibodies produced subtle alterations in the gut bacterial composition of mice. Primarily, Travelan LPS antibody treatment decreased the ratio of Firmicutes/Bacteroidetes in gut microbial populations in unchallenged healthy mice. Further studies are required to examine the effect of Travelan LPS antibody treatment to engineer the microbiome in a diseased state and during recovery.


Assuntos
Escherichia coli Enterotoxigênica , Infecções por Escherichia coli , Microbioma Gastrointestinal , Feminino , Gravidez , Camundongos , Animais , Bovinos , Lipopolissacarídeos , Imunoglobulina G , Colostro , Camundongos Endogâmicos C57BL , Fatores Imunológicos , Diarreia/microbiologia , Infecções por Escherichia coli/prevenção & controle
9.
Women Birth ; 36(6): 529-537, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37423802

RESUMO

PROBLEM: There is limited data regarding dose and duration of nitrous oxide use by women in peripartum care. Experiences of using nitrous in Australian settings have not previously been explored BACKGROUND: More than 1:2 women use nitrous oxide analgesia during labour and birth, despite this, there are limited published data on nitrous oxide use for labour or procedural analgesia in Australia. AIM: To explore the use of nitrous oxide during labour and birth or procedural care. METHODS: A two-phased sequential design was used; clinical audit (n = 183) and cross-sectional survey (n = 137) approaches supported data collection. Quantitative data were analysed using descriptive and inferential statistics, qualitative data underwent content analysis. FINDINGS: Nitrous oxide was used by primiparous and multiparous women evenly. Duration of labour-use ranged from < 15 min (10.9%) to > 5 h (10.8%), with equal representation between > 50% concentration (43%) and < 50% (43%). At audit, 75% found nitrous useful; postpartum maternal satisfaction scores remained high, mean indicators were 75%. More multiparous women found nitrous oxide useful than primiparous (95%vs80%,p = 0.009). There was no association between perceived usefulness and whether women were in spontaneous, augmented or induced labour; regardless of concentrations reached. Three key themes described women's perspectives of physical and psycho-emotional effects and challenges. DISCUSSION: Nitrous oxide plays an important role in the provision of analgesia during procedural or labour and birth care. Service provision, parent and professional education, and future service design will benefit from these novel findings confirming the utility and acceptability of nitrous oxide use in contemporary maternity care.

10.
Sci Immunol ; 8(85): eadg0033, 2023 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-37506197

RESUMO

Type I interferons (IFN-I) are critical mediators of innate control of viral infections but also drive the recruitment of inflammatory cells to sites of infection, a key feature of severe coronavirus disease 2019. Here, IFN-I signaling was modulated in rhesus macaques (RMs) before and during acute SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection using a mutated IFN-α2 (IFN-modulator; IFNmod), which has previously been shown to reduce the binding and signaling of endogenous IFN-I. IFNmod treatment in uninfected RMs was observed to induce a modest up-regulation of only antiviral IFN-stimulated genes (ISGs); however, in SARS-CoV-2-infected RMs, IFNmod reduced both antiviral and inflammatory ISGs. IFNmod treatment resulted in a potent reduction in SARS-CoV-2 viral loads both in vitro in Calu-3 cells and in vivo in bronchoalveolar lavage (BAL), upper airways, lung, and hilar lymph nodes of RMs. Furthermore, in SARS-CoV-2-infected RMs, IFNmod treatment potently reduced inflammatory cytokines, chemokines, and CD163+ MRC1- inflammatory macrophages in BAL and expression of Siglec-1 on circulating monocytes. In the lung, IFNmod also reduced pathogenesis and attenuated pathways of inflammasome activation and stress response during acute SARS-CoV-2 infection. Using an intervention targeting both IFN-α and IFN-ß pathways, this study shows that, whereas early IFN-I restrains SARS-CoV-2 replication, uncontrolled IFN-I signaling critically contributes to SARS-CoV-2 inflammation and pathogenesis in the moderate disease model of RMs.


Assuntos
COVID-19 , Interferon Tipo I , Animais , Interferon Tipo I/farmacologia , SARS-CoV-2 , Macaca mulatta , Replicação Viral , Antivirais/farmacologia , Antivirais/uso terapêutico , Inflamação/tratamento farmacológico
11.
Biol Reprod ; 109(3): 367-380, 2023 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-37283496

RESUMO

Cyclic regression of the ovarian corpus luteum, the endocrine gland responsible for progesterone production, involves rapid matrix remodeling. Despite fibroblasts in other systems being known for producing and maintaining extracellular matrix, little is known about fibroblasts in the functional or regressing corpus luteum. Vast transcriptomic changes occur in the regressing corpus luteum, among which are reduced levels of vascular endothelial growth factor A (VEGFA) and increased expression of fibroblast growth factor 2 (FGF2) after 4 and 12 h of induced regression, when progesterone is declining and the microvasculature is destabilizing. We hypothesized that FGF2 activates luteal fibroblasts. Analysis of transcriptomic changes during induced luteal regression revealed elevations in markers of fibroblast activation and fibrosis, including fibroblast activation protein (FAP), serpin family E member 1 (SERPINE1), and secreted phosphoprotein 1 (SPP1). To test our hypothesis, we treated bovine luteal fibroblasts with FGF2 to measure downstream signaling, type 1 collagen production, and proliferation. We observed rapid and robust phosphorylation of various signaling pathways involved in proliferation, such as ERK, AKT, and STAT1. From our longer-term treatments, we determined that FGF2 has a concentration-dependent collagen-inducing effect, and that FGF2 acts as a mitogen for luteal fibroblasts. FGF2-induced proliferation was greatly blunted by inhibition of AKT or STAT1 signaling. Our results suggest that luteal fibroblasts are responsive to factors that are released by the regressing bovine corpus luteum, an insight into the contribution of fibroblasts to the microenvironment in the regressing corpus luteum.


Assuntos
Fator 2 de Crescimento de Fibroblastos , Progesterona , Animais , Bovinos , Feminino , Proliferação de Células , Colágeno/metabolismo , Corpo Lúteo/metabolismo , Dinoprosta/metabolismo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibroblastos/metabolismo , Luteólise , Progesterona/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
12.
Access Microbiol ; 5(5): acmi000419, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37323944

RESUMO

The use of bacterial spores in probiotics over viable loads of bacteria has many advantages, including the durability of spores, which allows spore-based probiotics to effectively traverse the various biochemical barriers present in the gastrointestinal tract. However, the majority of spore-based probiotics developed currently aim to treat adults, and there is a litany of differences between the adult and infant intestinal systems, including the immaturity and low microbial species diversity observed within the intestines of infants. These differences are only further exacerbated in premature infants with necrotizing enterocolitis (NEC) and indicates that what may be appropriate for an adult or even a healthy full-term infant may not be suited for an unhealthy premature infant. Complications from using spore-based probiotics for premature infants with NEC may involve the spores remaining dormant and adhering to the intestinal epithelia, the out-competing of commensal bacteria by spores, and most importantly the innate antibiotic resistance of spores. Also, the ability of Bacillus subtilis to produce spores under duress may result in less B. subtilis perishing within the intestines and releasing membrane branched-chain fatty acids. The isolate B. subtilis BG01-4TM is a proprietary strain developed by Vernx Biotechnology through accumulating mutations within the BG01-4TM genome in a serial batch culture. Strain BG01-4TM was provided as a non-spore-forming B. subtilis , but a positive sporulation status for BG01-4TM was confirmed through in vitro testing and suggested that selection for the sporulation defective genes could occur within an environment that would select against sporulation. The durability of key sporulation genes was ratified in this study, as the ability of BG01-4TM to produce spores was not eliminated by the attempts to select against sporulation genes in BG01-4TM by the epigenetic factors of high glucose and low pH. However, a variation in the genes in isolate BG01-4-8 involved in the regulation of sporulation is believed to have occurred during the mutation selection from the parent strain BG01-4TM. An alteration in selected sporulation regulation genes is expected to have occurred from BG01-4TM to BG01-4-8, with BG01-4-8 producing spores within 24 h, ~48 h quicker than BG01-4TM.

13.
Heart Rhythm O2 ; 4(5): 291-297, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37323995

RESUMO

Background: Catheter ablation is recommended for the treatment of symptomatic atrial fibrillation (AF) refractory to medical therapy. Objective: The study sought to examine racial/ethnic and sex differences in complications and AF/atrial flutter (AFL)-related acute healthcare utilization following catheter ablation for AF. Methods: We performed a retrospective analysis using data from the Centers for Medicare and Medicaid Services Medicare Standard Analytical Files (October 1, 2014, to September 30, 2019) among patients ≥65 years of age with AF who underwent catheter ablation for rhythm control. The risk of any complication within 30 days and AF/AFL-related acute healthcare utilization within 1 year of ablation by race, ethnicity, and sex were assessed using multivariable Cox regression modeling. Results: We identified 95,394 patients for analysis of postablation complications and 68,408 patients for analysis of AF/AFL-related acute healthcare utilization. Both cohorts were ∼95% White and 52% male. Female patients had a slightly elevated risk of complications compared with male patients (adjusted hazard ratio [aHR] 1.07, 95% confidence interval [CI] 1.03-1.12). Black (aHR 0.78, 95% CI 0.77-1.00) and Asian (aHR 0.67, 95% CI 0.50-0.89) patients had lower utilization compared with White patients. Specifically, Asian men (aHR 0.58, 95% CI 0.38-0.91) had lower utilization compared with White men. Conclusion: Differences in safety and healthcare utilization after catheter ablation for AF were observed by race/ethnicity and sex groups. Underrepresented racial and ethnic groups with AF had a lower risk of AF/AFL-related acute healthcare utilization postablation.

14.
Sci Immunol ; 8(88): eadg7015, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37191508

RESUMO

Omicron SARS-CoV-2 variants escape vaccine-induced neutralizing antibodies and cause nearly all current COVID-19 cases. Here, we compared the efficacy of three booster vaccines against Omicron BA.5 challenge in rhesus macaques: mRNA-1273, the Novavax ancestral spike protein vaccine (NVX-CoV2373), or Omicron BA.1 spike protein version (NVX-CoV2515). All three booster vaccines induced a strong BA.1 cross-reactive binding antibody and changed immunoglobulin G (Ig) dominance from IgG1 to IgG4 in the serum. All three booster vaccines also induced strong and comparable neutralizing antibody responses against multiple variants of concern, including BA.5 and BQ.1.1, along with long-lived plasma cells in the bone marrow. The ratio of BA.1 to WA-1 spike-specific antibody-secreting cells in the blood was higher in NVX-CoV2515 animals compared with NVX-CoV2373 animals, suggesting a better recall of BA.1-specific memory B cells by the BA.1 spike-specific vaccine compared with the ancestral spike-specific vaccine. Further, all three booster vaccines induced low levels of spike-specific CD4 but not CD8 T cell responses in the blood. After challenge with SARS-CoV-2 BA.5 variant, all three vaccines showed strong protection in the lungs and controlled virus replication in the nasopharynx. In addition, both Novavax vaccines blunted viral replication in nasopharynx at day 2. The protection against SARS-CoV-2 BA.5 infection in the upper respiratory airways correlated with binding, neutralizing, and ADNP activities of the serum antibody. These data have important implications for COVID-19 vaccine development, because vaccines that lower nasopharyngeal virus may help to reduce transmission.


Assuntos
Vacina de mRNA-1273 contra 2019-nCoV , COVID-19 , Animais , Humanos , Vacinas contra COVID-19 , COVID-19/prevenção & controle , Macaca mulatta , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética , Imunoglobulina G
15.
Life Sci Alliance ; 6(7)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37188480

RESUMO

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2α elicits increased intracellular reactive oxygen species and promotes receptor-mediated activation of PINK-Parkin mitophagy. These findings place the mitochondrium as a novel target in response to luteolytic mediator, PGF2α. Understanding intracellular processes occurring during early luteolysis may serve as a target for improving fertility.


Assuntos
Dinoprosta , Dinâmica Mitocondrial , Feminino , Bovinos , Animais , Dinoprosta/farmacologia , Dinoprosta/metabolismo , Mitofagia , Corpo Lúteo/metabolismo , Transdução de Sinais , Mamíferos/metabolismo
16.
Psychiatr Serv ; 74(11): 1163-1170, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37070262

RESUMO

The overrepresentation of people with serious mental illnesses in the criminal legal system has spurred the development of crisis response models to improve or reduce police response to a mental health crisis. However, limited research has explored preferences for crisis response, and no research in the United States has examined the responses desired by mental health care clients or their family members. This study aimed to understand the experiences of people with serious mental illnesses interacting with police and to learn about their preferences for crisis response models. The authors interviewed 50 clients with serious mental illnesses and a history of arrest who were enrolled in a randomized controlled trial of a police-mental health linkage system, as well as 18 of their family members and friends. Data were coded with deductive and inductive approaches and were grouped into larger themes. Clients and family or friends described needing a calm environment and empathy during a crisis. They selected a nonpolice response as their first choice and response from a crisis intervention team as their last choice among four options, highlighting the importance of trained responders and past negative interactions with police. However, they also noted concerns about safety and the shortcomings of a nonpolice response. These findings build understanding about clients' and family members' preferences for crisis response and highlight concerns that are relevant for policy makers.


Assuntos
Transtornos Mentais , Serviços de Saúde Mental , Humanos , Estados Unidos , Transtornos Mentais/terapia , Saúde Mental , Amigos , Intervenção em Crise , Polícia
17.
Health Justice ; 11(1): 20, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37014478

RESUMO

BACKGROUND: People with mental illnesses are disproportionately entangled in the criminal legal system. Historically, this involvement has resulted from minor offending, often accompanied by misdemeanor charges. In recent years, policymakers have worked to reduce the footprint of the criminal legal system. This paper seeks to better understand how misdemeanor systems intervene in the lives of people with mental illnesses. METHODS: System mapping exercises were conducted with misdemeanor system stakeholders from the jurisdictions of Atlanta, Chicago, Manhattan, and Philadelphia. Narrative detail on decision-making and case processing, both generally and in relation to specific types of behavior, including trespassing, retail theft/shoplifting, and simple assault, were coded and analyzed for thematic patterns. Based on the qualitative analysis, this paper offers a conceptual diagram of contexts shaping misdemeanor system interventions among people with mental illnesses. RESULTS: All four sites have been engaged in efforts to reduce the use of misdemeanor charges both generally and in relation to people with mental illnesses. Decision-makers across all sites experience contexts that shape how, when, and where they intervene, which are: (1) law and policy environments; (2) location of the behavior; (3) expectations of stakeholders; (4) knowledge of mental illnesses; and (5) access to community resources. Law and policy environments expand or constrain opportunities for diversion. The location of offending is relevant to who has a stake in the behavior, and what demands they have. Clinical, experiential, and system-level knowledge of mental illnesses inform a chain of decisions about what to do. The capacity to address mental health needs is contingent on access to social services, including housing. CONCLUSION: People making decisions along the criminal legal continuum are critical to illuminating the dynamic, inter-related contexts that facilitate and frustrate attempts to address defendants' mental health needs while balancing considerations of public safety. Multi-sector, scenario-based or case study exercises could help identify concrete ways of improving each of the contexts that surround whole-of-system decisions.

18.
Parkinsonism Relat Disord ; 109: 105346, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36966051

RESUMO

INTRODUCTION: Deep brain stimulation (DBS) is an effective treatment for Parkinson's disease (PD), but its efficacy is tied to DBS programming, which is often time consuming and burdensome for patients, caregivers, and clinicians. Our aim is to test whether the Mobile Application for PD DBS (MAP DBS), a clinical decision support system, can improve programming. METHODS: We conducted an open-label, 1:1 randomized, controlled, multicenter clinical trial comparing six months of SOC standard of care (SOC) to six months of MAP DBS-aided programming. We enrolled patients between 30 and 80 years old who received DBS to treat idiopathic PD at six expert centers across the United States. The primary outcome was time spent DBS programming and secondary outcomes measured changes in motor symptoms, caregiver strain and medication requirements. RESULTS: We found a significant reduction in initial visit time (SOC: 43.8 ± 28.9 min n = 37, MAP DBS: 27.4 ± 13.0 min n = 35, p = 0.001). We did not find a significant difference in total programming time between the groups over the 6-month study duration. MAP DBS-aided patients experienced a significantly larger reduction in UPDRS III on-medication scores (-7.0 ± 7.9) compared to SOC (-2.7 ± 6.9, p = 0.01) at six months. CONCLUSION: MAP DBS was well tolerated and improves key aspects of DBS programming time and clinical efficacy.


Assuntos
Estimulação Encefálica Profunda , Aplicativos Móveis , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Doença de Parkinson/complicações , Resultado do Tratamento
19.
J Med Primatol ; 52(2): 108-120, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36744630

RESUMO

BACKGROUND: Compatible pair housing of macaques in research settings increases species-typical behaviors and facilitates beneficial social buffering. It is not yet established whether these benefits are maintained after intrafacility transfer and domestic quarantine, which are two stressors that can lead to behavioral and clinical abnormalities. METHODS: We evaluated 40 adolescent male rhesus macaques who were single- or pair-housed immediately following an intrafacility transfer. We measured behavior, fecal cortisol, body weight, and diarrhea occurrence. Body weight and diarrhea occurrence were also retrospectively analyzed in an additional 120 adolescent rhesus who underwent a similar transfer. RESULTS AND CONCLUSIONS: Pair-housed macaques exhibited less of some undesirable behaviors (e.g., self-clasping) and experienced less diarrhea than single-housed subjects; however, no significant differences in cortisol levels or alopecia measures were found. The demonstrated beneficial effects of pair housing for rhesus macaques following intrafacility transfer and adjustment suggest pairing upon arrival at a new facility will bolster animal welfare.


Assuntos
Hidrocortisona , Quarentena , Animais , Masculino , Macaca mulatta , Quarentena/veterinária , Estudos Retrospectivos , Abrigo para Animais , Comportamento Social , Comportamento Animal
20.
Insects ; 14(1)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36662023

RESUMO

Certain crops depend upon pollination services for fruit set, and, of these, almonds are of high value for Australia. Stressors, such as diseases, parasites, pesticides, and nutrition, can contribute to honey bee Apis mellifera L. colony decline, thereby reducing bee activity and pollination efficiency. In Australia, field studies are required to monitor honey bee health and to ascertain whether factors associated with colony decline are impacting hives. We monitored honey bee colonies during and after pollination services of almond. Video surveillance technology was used to quantify bee activity, and bee-collected pollen was periodically tested for pesticide residues. Plant species diversity was also assessed using DNA metabarcoding of the pollen. Results showed that bee activity increased in almond but not in bushland. Residues detected included four fungicides, although the quantities were of low risk of oral toxicity to bees. Floral diversity was lower in the pollen collected by bees from almonds compared to bushland. However, diversity was higher at the onset and conclusion of the almond bloom, suggesting that bees foraged more widely when availability was low. Our findings suggest that commercial almond orchards may sustain healthier bee colonies compared to bushland in early spring, although the magnitude of the benefit is likely landscape-dependent.

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