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1.
Metabolomics ; 20(4): 66, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886248

RESUMO

The coral holobiont is underpinned by complex metabolic exchanges between different symbiotic partners, which are impacted by environmental stressors. The chemical diversity of the compounds produced by the holobiont is high and includes primary and secondary metabolites, as well as volatiles. However, metabolites and volatiles have only been characterised in isolation so far. Here, we applied a paired metabolomic-volatilomic approach to characterise holistically the chemical response of the holobiont under stress. Montipora mollis fragments were subjected to high-light stress (8-fold higher than the controls) for 30 min. Photosystem II (PSII) photochemical efficiency values were 7-fold higher in control versus treatment corals immediately following high-light exposure, but returned to pre-stress levels after 30 min of recovery. Under high-light stress, we identified an increase in carbohydrates (> 5-fold increase in arabinose and fructose) and saturated fatty acids (7-fold increase in myristic and oleic acid), together with a decrease in fatty acid derivatives in both metabolites and volatiles (e.g., 80% decrease in oleamide and nonanal), and other antioxidants (~ 85% decrease in sorbitol and galactitol). These changes suggest short-term light stress induces oxidative stress. Correlation analysis between volatiles and metabolites identified positive links between sorbitol, galactitol, six other metabolites and 11 volatiles, with four of these compounds previously identified as antioxidants. This suggests that these 19 compounds may be related and share similar functions. Taken together, our findings demonstrate how paired metabolomics-volatilomics may illuminate broader metabolic shifts occurring under stress and identify linkages between uncharacterised compounds to putatively determine their functions.


Assuntos
Antozoários , Luz , Metabolômica , Estresse Fisiológico , Animais , Antozoários/metabolismo , Metabolômica/métodos , Compostos Orgânicos Voláteis/metabolismo , Compostos Orgânicos Voláteis/análise , Complexo de Proteína do Fotossistema II/metabolismo
2.
Prev Med ; 185: 108050, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38906276

RESUMO

PURPOSE: Prevention efforts are critical to avoid the negative consequences of substance use in adolescents. This study aimed to examine national trends and sociodemographic differences in adolescents' participation in school-based substance use prevention (SUP) education, community-based SUP programs, as well as family conversations about substance use. METHODS: Publicly available data for adolescents aged 12-17 from the annual cross-sectional surveys of the National Survey on Drug Use and Health 2011-2019 were analyzed. RESULTS: Across the survey years, up to 74.9%, 12.2%, and 58.1% of adolescents reported having participated in school-based SUP education, community-based SUP programs, and family conversations about the danger of substance use in the past-year, respectively. From 2011 to 2019, statistically significant decreases were observed in adolescents' participation in school-based SUP education (OR = 0.97, 95% CI: 0.96, 0.98, p < 0.001) and community-based SUP programs (OR = 0.98, 95% CI: 0.97, 0.99, p < 0.001). Meanwhile, no significant changes were observed in adolescents' participation in family conversations about the dangers of substance use. Overall, lower levels of participation in school-based and community-based SUP programs were found in adolescents aged 16-17. Adolescents living in rural areas showed lower levels of participation in school-based SUP programs and family conversations about SUP. Racial/ethnic minority adolescents overall were less likely to participate in conversations with parents about SUP than Whites. CONCLUSIONS: Further development and implementation of developmentally appropriate, gender-specific, culturally sensitive, and contextually informed SUP programs at school, community, and family levels are needed.

3.
Cryobiology ; 116: 104909, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38763350

RESUMO

We studied the impact of modulating cholesterol levels in zebrafish sperm plasma membranes using cholesterol-loaded methyl-ß-cyclodextrin (CLC) and unloaded methyl-ß-cyclodextrin (MßC). Zebrafish sperm were treated with these substances before cryopreservation, and post-thaw sperm motility and in vitro fertilization (IVF) rates were compared between treated and untreated samples. Our findings indicate that adding cholesterol to sperm membranes increases post-thaw motility, motile cell count, and motile cell survival within a 0.5-4.0 mg per 1.2 × 108 cell concentration range. Conversely, depleting cholesterol using MßC at 1.0 and 2.0 mg per 1.2 × 108 cells reduced these parameters. On average, all CLC-treated sperm samples produced a 15 % higher IVF rate compared to untreated sperm. Including CLC in the extender before cryopreservation is beneficial for post-thaw sperm quantity and quality in zebrafish.

4.
Microorganisms ; 12(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38399721

RESUMO

The urgency of responding to climate change for corals necessitates the exploration of innovative methods to swiftly enhance our understanding of crucial processes. In this study, we employ an integrated chemical omics approach, combining elementomics, metabolomics, and volatilomics methodologies to unravel the biochemical pathways associated with the thermal response of the coral symbiont, Symbiodiniaceae Durusdinium trenchii. We outline the complimentary sampling approaches and discuss the standardised data corrections used to allow data integration and comparability. Our findings highlight the efficacy of individual methods in discerning differences in the biochemical response of D. trenchii under both control and stress-inducing temperatures. However, a deeper insight emerges when these methods are integrated, offering a more comprehensive understanding, particularly regarding oxidative stress pathways. Employing correlation network analysis enhanced the interpretation of volatile data, shedding light on the potential metabolic origins of volatiles with undescribed functions and presenting promising candidates for further exploration. Elementomics proves to be less straightforward to integrate, likely due to no net change in elements but rather elements being repurposed across compounds. The independent and integrated data from this study informs future omic profiling studies and recommends candidates for targeted research beyond Symbiodiniaceae biology. This study highlights the pivotal role of omic integration in advancing our knowledge, addressing critical gaps, and guiding future research directions in the context of climate change and coral reef preservation.

5.
J Am Pharm Assoc (2003) ; 64(1): 111-119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37940096

RESUMO

BACKGROUND: Pharmacy-based medication disposal programs is one approach to prevent diversion of unused prescription opioids. OBJECTIVE(S): The objective of this study was to assess the extent to which disposal programs have been implemented by retail pharmacies and identify determinants of implementation using the Consolidated Framework for Implementation Research. METHODS: A sequential mixed-method design was used to examine implementation of medication disposal programs at pharmacies in Pitt County, NC. We conducted environmental scans of all retail pharmacies that served community members (N = 31) to assess the extent to which disposal programs had been implemented. Then, we conducted interviews with pharmacists (n = 15; 48.4%) to identify determinants of implementation. The following pharmacy types were represented in the completed interviews: corporate chain (n = 10), small chain (n = 1), independently owned and operated (n = 1), medical (n = 2), and government (n = 1). RESULTS: We found that 32.3% of pharmacies (n = 10) had a medication disposal box and 12.9% (n = 4) had posted a flyer on medication disposal. Pharmacists perceived that patients benefit from disposal boxes and medication disposal is in their purview. Determinants of implementation included the cost of sustaining the intervention, polices of corporate and regional management, variable local control in the decision-making process to implement a disposal box, and experience with having a medication disposal box. CONCLUSION: Our findings highlight one way in which pharmacists can have a vital role in preventing diversion of opioid analgesics and associated consequences. There is a need to expand disposal boxes at pharmacies to increase community member accessibility and use. Future research is needed to determine the cost-effectiveness of expanding the scale of disposal box implementation in community pharmacies.


Assuntos
Serviços Comunitários de Farmácia , Farmácias , Humanos , North Carolina , Farmacêuticos , Prescrições , Analgésicos Opioides
6.
Plast Reconstr Surg Glob Open ; 11(9): e5231, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38152707

RESUMO

Background: Autologous breast reconstruction using a free deep inferior epigastric perforator (DIEP) flap is a complex procedure that requires a dedicated approach to achieve operative efficiency. We analyzed data for DIEP flaps at a single center over 15 years to identify factors contributing to operative efficiency. Methods: A single-center, retrospective cohort analysis was performed of consecutive patients undergoing autologous breast reconstruction using DIEP free flaps between January 1, 2005, and December 31, 2019. Data were abstracted a priori from electronic medical records. Analysis was conducted by a medical statistician. Results: Analysis of 416 unilateral and 320 bilateral cases (1056 flaps) demonstrated reduction in operative times from 2005 to 2019 (11.7-8.2 hours for bilateral and 8.4-6.2 hours for unilateral, P < 0.000). On regression analysis, factors significantly correlating with reduced operative times include the use of venous couplers (P < 0.000), and the internal mammary versus the thoracodorsal recipient vessels (P < 0.000). Individual surgeon experience correlated with reduced OR times. Post-operative length of stay decreased significantly, without an increase in 30-day readmission or emergency presentations. Flap failure occurred in two cases. Flap take-back rate was 2% (n = 23) with no change between 2005 and 2019. Conclusions: Operative times for breast reconstruction have decreased significantly at this center over 15 years. The introduction of venous couplers, use of the internal mammary system, and year of surgery significantly correlated with decreased operative times. Surgeon experience and a shift in surgical workflow for DIEP flap reconstruction likely contributed to the latter finding.

7.
Sci Rep ; 13(1): 20724, 2023 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007500

RESUMO

Symbiodiniaceae form associations with extra- and intracellular bacterial symbionts, both in culture and in symbiosis with corals. Bacterial associates can regulate Symbiodiniaceae fitness in terms of growth, calcification and photophysiology. However, the influence of these bacteria on interactive stressors, such as temperature and light, which are known to influence Symbiodiniaceae physiology, remains unclear. Here, we examined the photophysiological response of two Symbiodiniaceae species (Symbiodinium microadriaticum and Breviolum minutum) cultured under acute temperature and light stress with specific bacterial partners from their microbiome (Labrenzia (Roseibium) alexandrii, Marinobacter adhaerens or Muricauda aquimarina). Overall, bacterial presence positively impacted Symbiodiniaceae core photosynthetic health (photosystem II [PSII] quantum yield) and photoprotective capacity (non-photochemical quenching; NPQ) compared to cultures with all extracellular bacteria removed, although specific benefits were variable across Symbiodiniaceae genera and growth phase. Symbiodiniaceae co-cultured with M. aquimarina displayed an inverse NPQ response under high temperatures and light, and those with L. alexandrii demonstrated a lowered threshold for induction of NPQ, potentially through the provision of antioxidant compounds such as zeaxanthin (produced by Muricauda spp.) and dimethylsulfoniopropionate (DMSP; produced by this strain of L. alexandrii). Our co-culture approach empirically demonstrates the benefits bacteria can deliver to Symbiodiniaceae photochemical performance, providing evidence that bacterial associates can play important functional roles for Symbiodiniaceae.


Assuntos
Antozoários , Dinoflagellida , Animais , Antozoários/fisiologia , Fotossíntese , Temperatura , Bactérias , Complexo de Proteína do Fotossistema II , Dinoflagellida/fisiologia , Simbiose
8.
Support Care Cancer ; 31(12): 726, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38012345

RESUMO

Head and neck cancer (HNC) treatment often consists of major surgery followed by adjuvant therapy, which can result in treatment-related side effects, decreased physical function, and diminished quality of life. Perioperative nutrition interventions and early mobilization improve recovery after HNC treatment. However, there are few studies on prehabilitation that include exercise within the HNC surgical care pathway. We have designed a multiphasic exercise prehabilitation intervention for HNC patients undergoing surgical resection with free flap reconstruction. We will use a hybrid effectiveness-implementation study design guided by the RE-AIM framework to address the following objectives: (1) to evaluate intervention benefits through physical function and patient-reported outcome assessments; (2) to determine the safety and feasibility of the prehabilitation intervention; (3) to evaluate the implementation of exercise within the HNC surgical care pathway; and (4) to establish a post-operative screening and referral pathway to exercise oncology resources. The results of this study will provide evidence for the benefits and costs of a multiphasic exercise prehabilitation intervention embedded within the HNC surgical care pathway. This paper describes the study protocol design, multiphasic exercise prehabilitation intervention, planned analyses, and dissemination of findings. Trial registration: https://clinicaltrials.gov/NCT04598087.


Assuntos
Terapia por Exercício , Neoplasias de Cabeça e Pescoço , Humanos , Terapia por Exercício/métodos , Neoplasias de Cabeça e Pescoço/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Exercício Pré-Operatório , Qualidade de Vida
9.
J Vis Exp ; (200)2023 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-37902324

RESUMO

Gas chromatography-mass spectrometry (GC-MS)-based approaches have proven to be powerful for elucidating the metabolic basis of the cnidarian-dinoflagellate symbiosis and how coral responds to stress (i.e., during temperature-induced bleaching). Steady-state metabolite profiling of the coral holobiont, which comprises the cnidarian host and its associated microbes (Symbiodiniaceae and other protists, bacteria, archaea, fungi, and viruses), has been successfully applied under ambient and stress conditions to characterize the holistic metabolic status of the coral. However, to answer questions surrounding the symbiotic interactions, it is necessary to analyze the metabolite profiles of the coral host and its algal symbionts independently, which can only be achieved by physical separation and isolation of the tissues, followed by independent extraction and analysis. While the application of metabolomics is relatively new to the coral field, the sustained efforts of research groups have resulted in the development of robust methods for analyzing metabolites in corals, including the separation of the coral host tissue and algal symbionts. This paper presents a step-by-step guide for holobiont separation and the extraction of metabolites for GC-MS analysis, including key optimization steps for consideration. We demonstrate how, once analyzed independently, the combined metabolite profile of the two fractions (coral and Symbiodiniaceae) is similar to the profile of the whole (holobiont), but by separating the tissues, we can also obtain key information about the metabolism of and interactions between the two partners that cannot be obtained from the whole alone.


Assuntos
Antozoários , Animais , Antozoários/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Metabolômica/métodos , Bactérias , Temperatura , Simbiose , Recifes de Corais
10.
Nat Commun ; 14(1): 6864, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891154

RESUMO

Bacteria are key contributors to microalgae resource acquisition, competitive performance, and functional diversity, but their potential metabolic interactions with coral microalgal endosymbionts (Symbiodiniaceae) have been largely overlooked. Here, we show that altering the bacterial composition of two widespread Symbiodiniaceae species, during their free-living stage, results in a significant shift in their cellular metabolism. Indeed, the abundance of monosaccharides and the key phytohormone indole-3-acetic acid (IAA) were correlated with the presence of specific bacteria, including members of the Labrenzia (Roseibium) and Marinobacter genera. Single-cell stable isotope tracking revealed that these two bacterial genera are involved in reciprocal exchanges of carbon and nitrogen with Symbiodiniaceae. We identified the provision of IAA by Labrenzia and Marinobacter, and this metabolite caused a significant growth enhancement of Symbiodiniaceae. By unravelling these interkingdom interactions, our work demonstrates how specific bacterial associates fundamentally govern Symbiodiniaceae fitness.


Assuntos
Antozoários , Dinoflagellida , Rhodobacteraceae , Animais , Antozoários/microbiologia , Reguladores de Crescimento de Plantas , Recifes de Corais , Simbiose
11.
Int J Mol Sci ; 24(18)2023 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-37762542

RESUMO

Chronic Kidney Disease (CKD) and Cardiovascular Disease (CVD) are two devastating diseases that may occur in nondiabetics or individuals with diabetes and, when combined, it is referred to as cardiorenal disease. The impact of cardiorenal disease on society, the economy and the healthcare system is enormous. Although there are numerous therapies for cardiorenal disease, one therapy showing a great deal of promise is sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The SGLT family member, SGLT2, is often implicated in the pathogenesis of a range of diseases, and the dysregulation of the activity of SGLT2 markedly effects the transport of glucose and sodium across the luminal membrane of renal cells. Inhibitors of SGLT2 were developed based on the antidiabetic action initiated by inhibiting renal glucose reabsorption, thereby increasing glucosuria. Of great medical significance, large-scale clinical trials utilizing a range of SGLT2 inhibitors have demonstrated both metabolic and biochemical benefits via numerous novel mechanisms, such as sympathoinhibition, which will be discussed in this review. In summary, SGLT2 inhibitors clearly exert cardio-renal protection in people with and without diabetes in both preclinical and clinical settings. This exciting class of inhibitors improve hyperglycemia, high blood pressure, hyperlipidemia and diabetic retinopathy via multiple mechanisms, of which many are yet to be elucidated.


Assuntos
Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Rim/metabolismo , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
12.
JAMA Otolaryngol Head Neck Surg ; 149(9): 796-802, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37471080

RESUMO

Importance: Head and neck oncological resection and reconstruction is a complex process that requires multidisciplinary collaboration and prolonged operative time. Numerous factors are associated with operative time, including a surgeon's experience, team familiarity, and the use of new technologies. It is paramount to evaluate the contribution of these factors and modalities on operative time to facilitate broad adoption of the most effective modalities and reduce complications associated with prolonged operative time. Objective: To examine the association of head and neck cancer resection and reconstruction interventions with operative time. Design, Setting, and Participants: This large cohort study included all patients who underwent head and neck oncologic resection and free flap-based reconstruction in Calgary (Alberta, Canada) between January 1, 2007, and March 31, 2020. Data were analyzed between November 2021 and May2022. Interventions: The interventions that were implemented in the program were classified into team-based strategies and the introduction of new technology. Team-based strategies included introducing a standardized operative team, treatment centralization in a single institution, and introducing a microsurgery fellowship program. New technologies included use of venous coupler anastomosis and virtual surgical planning. Main Outcomes and Measures: The primary outcome was mean operative time difference before and after the implementation of each modality. Secondary outcomes included returns to the operating room within 30 days, reasons for reoperation, returns to the emergency department or readmissions to hospital within 30 days, and 2-year and 5-year disease-specific survival. Multivariate regression analyses were performed to examine the association of each modality with operative time. Results: A total of 578 patients (179 women [30.9%]; mean [SD] age, 60.8 [12.9] years) undergoing 590 procedures met inclusion criteria. During the study period, operative time progressively decreased and reached a 32% reduction during the final years of the study. A significant reduction was observed in mean operative time following the introduction of each intervention. However, a multivariate analysis revealed that team-based strategies, including the use of a standardized nursing team, treatment centralization, and a fellowship program, were significantly associated with a reduction in operative time. Conclusions: The results of this cohort study suggest that among patients with head and neck cancer, use of team-based strategies was associated with significant decreases in operative time without an increase in complications.


Assuntos
Retalhos de Tecido Biológico , Neoplasias de Cabeça e Pescoço , Humanos , Feminino , Pessoa de Meia-Idade , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/complicações
13.
iScience ; 26(8): 107260, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37520739

RESUMO

Sodium glucose cotransporters (SGLTs) are transport proteins that are expressed throughout the body. Inhibition of SGLTs is a relatively novel therapeutic strategy to improve glycemic control and has been shown to promote cardiorenal benefits. Dual SGLT1/2 inhibitors (SGLT1/2i) such as sotagliflozin target both SGLT1 and 2 proteins. Sotagliflozin or vehicle was administered to diabetic Akimba mice for 8 weeks at a dose of 25 mg/kg/day. Urine glucose levels, water consumption, and body weight were measured weekly. Serum, kidney, pancreas, and brain tissue were harvested under terminal anesthesia. Tissues were assessed using immunohistochemistry or ELISA techniques. Treatment with sotagliflozin promoted multiple metabolic benefits in diabetic Akimba mice resulting in decreased blood glucose and improved polydipsia. Sotagliflozin also prevented mortalities associated with diabetes. Our data suggests that there is the possibility that combined SGLT1/2i may be superior to SGLT2i in controlling glucose homeostasis and provides protection of multiple organs affected by diabetes.

14.
Front Biosci (Landmark Ed) ; 28(4): 83, 2023 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-37114550

RESUMO

BACKGROUND: Diabetic retinopathy (DR) is a leading cause of end-stage blindness globally and is arguably one of the most disabling complications of both Type 1 and Type 2 diabetes. Sodium Glucose Cotransporter-2 (SGLT2) inhibitors have now been successfully introduced to clinical medicine and exert multiple beneficial effects in diabetic patients. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may alleviate the progression of DR. Therefore, we aimed to compare the effectiveness of two clinically available SGLT2 inhibitors, Empagliflozin and Canagliflozin, on the progression of Retinopathy and DR using well-characterised mouse models, Kimba and Akimba, respectively. METHODS: Empagliflozin, Canagliflozin (25 mg/kg/day) or vehicle was administered to 10-week-old mice via drinking water for 8-weeks. Urine glucose levels were measured to ascertain SGLT2 inhibition promoted glucose excretion. Weekly body weight and water intake measurements were obtained. After 8-weeks of treatment, body weight, daily water intake, fasting blood glucose levels were measured and eye tissue was harvested. The retinal vasculature was assessed using immunofluorescence. RESULTS: Empagliflozin treated Akimba mice exhibited metabolic benefits suggested by healthy body weight gain and significantly reduced fasting blood glucose levels. Treatment with Empagliflozin reduced retinal vascular lesions in both Kimba and Akimba mice. Canagliflozin improved body weight gain, reduced blood glucose levels in Akimba mice, and reduced the development of retinal vascular lesions in Kimba mice. CONCLUSIONS: Our data demonstrates that Empagliflozin has future potential as a therapeutic for Retinopathy and DR and should now be considered for human trials.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Retinianas , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Camundongos , Animais , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/uso terapêutico , Glicemia/metabolismo , Hipoglicemiantes , Glucose , Peso Corporal
15.
Int J Nurs Sci ; 10(2): 158-166, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37095850

RESUMO

This paper identifies key factors rooted in the systemic failings of the long-term care sector amongst four high income countries during the COVID-19 pandemic. The goal is to offer practice and policy solutions to prevent future tragedies. Based on data from Australia, Canada, Spain and the United States, the findings support evidence-based recommendations at macro, meso and micro levels of practice and policy intervention. Key macro recommendations include improving funding, transparency, accountability and health system integration; and promoting not-for-profit and government-run long-term care facilities. The meso recommendation involves moving from warehouses to "green houses." The micro recommendations emphasize mandating recommended staffing levels and skill mix; providing infection prevention and control training; establishing well-being and mental health supports for residents and staff; building evidence-based practice cultures; ensuring ongoing education for staff and nursing students; and fully integrating care partners, such as families or friends, into the healthcare team. Enacting these recommendations will improve residents' safety and quality of life, families' peace of mind, and staff retention and work satisfaction.

16.
Biomedicines ; 11(3)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36979798

RESUMO

Hyperactivation of the sympathetic nervous system (SNS) has been demonstrated in various conditions including obesity, hypertension and type 2 diabetes. Elevated levels of the major neurotransmitter of the SNS, norepinephrine (NE), is a cardinal feature of these conditions. Increased levels of the sodium glucose cotransporter 1 (SGLT1) protein have been shown to occur in the parotid and submandibular glands of hypertensive rodents compared to normotensive controls. However, there was a need to examine SGLT1 expression in other tissues, such as the kidneys. Whether NE may directly affect SGLT1 protein expression has not yet been investigated, although such a link has been shown for sodium glucose cotransporter 2 (SGLT2). Hence, we aimed to determine (i) whether our murine model of neurogenic hypertension displays elevated renal SGLT1 expression and (ii) whether NE may directly promote elevations of SGLT1 in human proximal tubule (HK2) cells. We did indeed demonstrate that in vivo, in our mouse model of neurogenic hypertension, hyperactivation of the SNS promotes SGLT1 expression in the kidneys. In subsequent in vitro experiments in HK2 cells, we found that NE increased SGLT1 protein expression and translocation as assessed by both specific immunohistochemistry and/or a specific SGLT1 ELISA. Additionally, NE promoted a significant elevation in interleukin-6 (IL-6) levels which resulted in the promotion of SGLT1 expression and proliferation in HK2 cells. Our findings suggest that the SNS upregulates SGLT1 protein expression levels with potential adverse consequences for cardiometabolic control. SGLT1 inhibition may therefore provide a useful therapeutic target in conditions characterized by increased SNS activity, such as chronic kidney disease.

17.
Proc Biol Sci ; 290(1992): 20221877, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36750192

RESUMO

Anthropogenic stressors continue to escalate worldwide, driving unprecedented declines in reef environmental conditions and coral health. One approach to better understand how corals can function in the future is to examine coral populations that thrive within present day naturally extreme habitats. We applied untargeted metabolomics (gas chromatography-mass spectrometry (GC-MS)) to contrast metabolite profiles of Pocillopora acuta colonies from hot, acidic and deoxygenated mangrove environments versus those from adjacent reefs. Under ambient temperatures, P. acuta predominantly associated with endosymbionts of the genera Cladocopium (reef) or Durusdinium (mangrove), exhibiting elevated metabolism in mangrove through energy-generating and biosynthesis pathways compared to reef populations. Under transient heat stress, P. acuta endosymbiont associations were unchanged. Reef corals bleached and exhibited extensive shifts in symbiont metabolic profiles (whereas host metabolite profiles were unchanged). By contrast, mangrove populations did not bleach and solely the host metabolite profiles were altered, including cellular responses in inter-partner signalling, antioxidant capacity and energy storage. Thus mangrove P. acuta populations resist periodically high-temperature exposure via association with thermally tolerant endosymbionts coupled with host metabolic plasticity. Our findings highlight specific metabolites that may be biomarkers of heat tolerance, providing novel insight into adaptive coral resilience to elevated temperatures.


Assuntos
Antozoários , Dinoflagellida , Termotolerância , Animais , Antozoários/fisiologia , Recifes de Corais , Simbiose , Resposta ao Choque Térmico , Dinoflagellida/fisiologia
18.
PeerJ ; 10: e14176, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36345483

RESUMO

Coral reefs are declining worldwide primarily because of bleaching and subsequent mortality resulting from thermal stress. Currently, extensive efforts to engage in more holistic research and restoration endeavors have considerably expanded the techniques applied to examine coral samples. Despite such advances, coral bleaching and restoration studies are often conducted within a specific disciplinary focus, where specimens are collected, preserved, and archived in ways that are not always conducive to further downstream analyses by specialists in other disciplines. This approach may prevent the full utilization of unexpended specimens, leading to siloed research, duplicative efforts, unnecessary loss of additional corals to research endeavors, and overall increased costs. A recent US National Science Foundation-sponsored workshop set out to consolidate our collective knowledge across the disciplines of Omics, Physiology, and Microscopy and Imaging regarding the methods used for coral sample collection, preservation, and archiving. Here, we highlight knowledge gaps and propose some simple steps for collecting, preserving, and archiving coral-bleaching specimens that can increase the impact of individual coral bleaching and restoration studies, as well as foster additional analyses and future discoveries through collaboration. Rapid freezing of samples in liquid nitrogen or placing at -80 °C to -20 °C is optimal for most Omics and Physiology studies with a few exceptions; however, freezing samples removes the potential for many Microscopy and Imaging-based analyses due to the alteration of tissue integrity during freezing. For Microscopy and Imaging, samples are best stored in aldehydes. The use of sterile gloves and receptacles during collection supports the downstream analysis of host-associated bacterial and viral communities which are particularly germane to disease and restoration efforts. Across all disciplines, the use of aseptic techniques during collection, preservation, and archiving maximizes the research potential of coral specimens and allows for the greatest number of possible downstream analyses.


Assuntos
Antozoários , Branqueamento de Corais , Animais , Recifes de Corais , Antozoários/microbiologia
19.
Zebrafish ; 19(6): 241-244, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36318811

RESUMO

Severely skewed sex ratios in zebrafish stocks can pose significant hurdles for line propagation and sperm cryopreservation. To overcome female-biased sex ratios in stocks derived from imported sperm samples, the Zebrafish International Resource Center has implemented routine supplementation of larval food with 17α-methyltestosterone to skew gonadal sex differentiation toward masculinization. Resulting stocks averaged 80% males.


Assuntos
Metiltestosterona , Peixe-Zebra , Masculino , Feminino , Animais , Metiltestosterona/farmacologia , Sêmen , Gônadas , Diferenciação Sexual
20.
Curr Oncol ; 29(8): 5942-5954, 2022 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-36005207

RESUMO

Head and neck cancer (HNC) surgical patients experience a high symptom burden. Multiphasic exercise prehabilitation has the potential to improve patient outcomes, and to implement it into the care pathway, the perspectives of patients and healthcare providers (HCPs) must be considered. The purpose of this study was thus to gather feedback from HNC surgical patients and HCPs on building exercise into the standard HNC surgical care pathway. Methods: Semi-structured interviews were conducted with patients and HCPs as part of a feasibility study assessing patient-reported outcomes, physical function, and in-hospital mobilization. Interview questions included satisfaction with study recruitment, assessment completion, impact on clinical workflow (HCPs), and perceptions of a future multiphasic exercise prehabilitation program. This study followed an interpretive description methodology. Results: Ten patients and ten HCPs participated in this study. Four themes were identified: (1) acceptability and necessity of assessments, (2) the value of exercise, (3) the components of an ideal exercise program, and (4) factors to support implementation. Conclusion: These findings highlight the value of exercise across the HNC surgical timeline from both the patient and the HCP perspective. Results have informed the implementation of a multiphasic exercise prehabilitation trial in HNC surgical patients.


Assuntos
Neoplasias de Cabeça e Pescoço , Exercício Pré-Operatório , Procedimentos Clínicos , Neoplasias de Cabeça e Pescoço/cirurgia , Pessoal de Saúde , Humanos , Pesquisa Qualitativa
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