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1.
J Pediatr Surg ; : 161766, 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39271309

RESUMO

BACKGROUND: Institutions lack consensus on the management of patients with congenital diaphragmatic hernia (CDH) who are repaired on extracorporeal membrane oxygenation (ECMO). Our study aimed to evaluate risk factors associated with bleeding complications in patients with CDH repaired on ECMO. METHODS: A single-institution retrospective review evaluated all patients with CDH who underwent on-ECMO repair between January 2005 and December 2023. A significant bleeding complication post-repair was defined as bleeding necessitating re-operation. The association between preoperative factors and bleeding complications was evaluated. RESULTS: Forty-six patients were included. Bleeding complications developed in 11/46 (24%) patients. Birthweight (2.5 vs. 3.2 kg, p = 0.02), platelet count <100/mm3 (64% vs. 29%, p = 0.04), elevated blood urea nitrogen (BUN; 24.5 vs. 17.5 mg/dL, p = 0.05), and older age at repair (8 vs. 5 days, p = 0.04) were associated with bleeding. In univariate analysis, patients with platelets under 100/mm3 were more likely to develop a bleeding complication (OR = 4.4, p = 0.04). Patients who experienced a significant bleeding event experienced increased ECMO days (12 vs. 7 days, p < 0.01), ventilator days (31 vs. 18 days, p < 0.05), and lower survival to discharge (36% vs. 74%, p = 0.03). CONCLUSION: Among CDH patients undergoing repair on ECMO, those with lower birth weight, platelet counts under 100/mm3, elevated BUN, and older age at repair had an increased risk of a significant bleeding complication, resulting in more ECMO and ventilator days and higher mortality. Patients undergoing on-ECMO repair should have platelet count transfused to greater than 100/mm3. Patients at high risk for bleeding may benefit from early repair on ECMO. LEVEL OF EVIDENCE: Level III.

2.
Trials ; 25(1): 86, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38273319

RESUMO

BACKGROUND: Lower respiratory tract infections (LRTIs) are among the most frequent infections and a significant contributor to inappropriate antibiotic prescription. Currently, no single diagnostic tool can reliably identify bacterial pneumonia. We thus evaluate a multimodal approach based on a clinical score, lung ultrasound (LUS), and the inflammatory biomarker, procalcitonin (PCT) to guide prescription of antibiotics. LUS outperforms chest X-ray in the identification of pneumonia, while PCT is known to be elevated in bacterial and/or severe infections. We propose a trial to test their synergistic potential in reducing antibiotic prescription while preserving patient safety in emergency departments (ED). METHODS: The PLUS-IS-LESS study is a pragmatic, stepped-wedge cluster-randomized, clinical trial conducted in 10 Swiss EDs. It assesses the PLUS algorithm, which combines a clinical prediction score, LUS, PCT, and a clinical severity score to guide antibiotics among adults with LRTIs, compared with usual care. The co-primary endpoints are the proportion of patients prescribed antibiotics and the proportion of patients with clinical failure by day 28. Secondary endpoints include measurement of change in quality of life, length of hospital stay, antibiotic-related side effects, barriers and facilitators to the implementation of the algorithm, cost-effectiveness of the intervention, and identification of patterns of pneumonia in LUS using machine learning. DISCUSSION: The PLUS algorithm aims to optimize prescription of antibiotics through improved diagnostic performance and maximization of physician adherence, while ensuring safety. It is based on previously validated tests and does therefore not expose participants to unforeseeable risks. Cluster randomization prevents cross-contamination between study groups, as physicians are not exposed to the intervention during or before the control period. The stepped-wedge implementation of the intervention allows effect calculation from both between- and within-cluster comparisons, which enhances statistical power and allows smaller sample size than a parallel cluster design. Moreover, it enables the training of all centers for the intervention, simplifying implementation if the results prove successful. The PLUS algorithm has the potential to improve the identification of LRTIs that would benefit from antibiotics. When scaled, the expected reduction in the proportion of antibiotics prescribed has the potential to not only decrease side effects and costs but also mitigate antibiotic resistance. TRIAL REGISTRATION: This study was registered on July 19, 2022, on the ClinicalTrials.gov registry using reference number: NCT05463406. TRIAL STATUS: Recruitment started on December 5, 2022, and will be completed on November 3, 2024. Current protocol version is version 3.0, dated April 3, 2023.


Assuntos
Pneumonia , Infecções Respiratórias , Adulto , Humanos , Pró-Calcitonina , Qualidade de Vida , Suíça , Infecções Respiratórias/diagnóstico por imagem , Infecções Respiratórias/tratamento farmacológico , Pneumonia/diagnóstico por imagem , Pneumonia/tratamento farmacológico , Pulmão/diagnóstico por imagem , Antibacterianos/efeitos adversos , Ultrassonografia , Serviço Hospitalar de Emergência , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
J Plast Reconstr Aesthet Surg ; 88: 425-435, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38091684

RESUMO

A real-time 3D Telemedicine system - leveraging Microsoft's Holoportation™ communication technology - enabled an international multidisciplinary team meeting (MDT) to consult with complex reconstructive patients before, during, and after an overseas surgical collaboration. METHODS: A proof-of-concept international 3D MDT clinic took place in November 2022, between the Canniesburn Plastic Surgery Unit, UK, and the National Reconstructive Plastic Surgery and Burns Centre, Korle Bu Teaching Hospital, Ghana. The 3D system was utilised 1) previsit to assess patients and enable logistical planning, 2) on-site in Ghana to further allow patients to see themselves and proposed operations in 3D, and 3) post visit to debrief the team and patients. RESULTS: Four Ghana patients were followed through their patient journey (mandibular ameloblastoma, sarcoma thigh, maxillary tumour, sarcoma back). Thirteen participants (four patients, four Ghana clinicians, and five UK clinicians) completed feedback on the 3D MDT. Outcome measures were rated highly with satisfaction 84.31/100, perceived benefit 4.54/5, overall quality 127.3/147 (Telehealth Usability Questionnaire), and usability 83.2/100 (System Usability Scale). These data show close alignment with that previously published on high-income countries. CONCLUSIONS: This novel technology has the potential to enhance the delivery of overseas surgical visits to low-to-middle-income countries, by improving planning, informed discussion with patients, expert consensus on complex cases, and fostering engagement with professionals who may be thousands of miles away. This is the first demonstration that real-time 3D Telemedicine can both work, and enhance care within an international MDT clinic, and may thus enable change in the approach to overseas surgical collaborations.


Assuntos
Neoplasias Maxilares , Sarcoma , Telemedicina , Humanos , Gana , Hospitais de Ensino
4.
Front Oncol ; 13: 1278004, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38146508

RESUMO

BRCA1 is involved in the Fanconi anaemia (FA) pathway, which coordinates repair of DNA interstrand cross-links. FA is a rare genetic disorder characterised by bone marrow failure, cancer predisposition and congenital abnormalities, caused by biallelic mutations affecting proteins in the FA pathway. Germline monoallelic pathogenic BRCA1 mutations are known to be associated with hereditary breast/ovarian cancer, however biallelic mutations of BRCA1 were long predicted to be incompatible with embryonic viability, hence BRCA1 was not considered to be a canonical FA gene. Despite this, several patients with biallelic pathogenic BRCA1 mutations and FA-like phenotypes have been identified - defining a new FA type (FA-S) and designating BRCA1 as an FA gene. This report presents a scoping review of the cases of biallelic BRCA1 mutations identified to date, discusses the functional effects of the mutations identified, and proposes a phenotypic spectrum of BRCA1 mutations based upon available clinical and genetic data. We report that this FA-S cohort phenotype includes short stature, microcephaly, facial dysmorphisms, hypo/hyperpigmented lesions, intellectual disability, chromosomal sensitivity to crosslinking agents and predisposition to breast/ovarian cancer and/or childhood cancers, with some patients exhibiting sensitivity to chemotherapy. Unlike most other types of FA, FA-S patients lack bone marrow failure.

5.
Nucleic Acids Res ; 51(21): 11584-11599, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-37843099

RESUMO

Hypoxia is a common feature of solid tumors and is associated with poor patient prognosis, therapy resistance and metastasis. Radiobiological hypoxia (<0.1% O2) is one of the few physiologically relevant stresses that activates both the replication stress/DNA damage response and the unfolded protein response. Recently, we found that hypoxia also leads to the robust accumulation of R-loops, which led us to question here both the mechanism and consequence of hypoxia-induced R-loops. Interestingly, we found that the mechanism of R-loop accumulation in hypoxia is dependent on non-DNA damaging levels of reactive oxygen species. We show that hypoxia-induced R-loops play a critical role in the transcriptional stress response, evidenced by the repression of ribosomal RNA synthesis and the translocation of nucleolin from the nucleolus into the nucleoplasm. Upon depletion of R-loops, we observed a rescue of both rRNA transcription and nucleolin translocation in hypoxia. Mechanistically, R-loops accumulate on the rDNA in hypoxia and promote the deposition of heterochromatic H3K9me2 which leads to the inhibition of Pol I-mediated transcription of rRNA. These data highlight a novel mechanistic insight into the hypoxia-induced transcriptional stress response through the ROS-R-loop-H3K9me2 axis. Overall, this study highlights the contribution of transcriptional stress to hypoxia-mediated tumorigenesis.


Assuntos
Estruturas R-Loop , Espécies Reativas de Oxigênio , Transcrição Gênica , Hipóxia Tumoral , Humanos , DNA Ribossômico/genética , DNA Ribossômico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , RNA Polimerase I/metabolismo
6.
J Plast Reconstr Aesthet Surg ; 83: 221-232, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37285775

RESUMO

Vascularised periosteal flaps may increase the union rates in recalcitrant long bone non-union. The fibula-periosteal chimeric flap utilises the periosteum raised on an independent periosteal vessel. This allows the periosteum to be inset freely around the osteotomy site, thereby facilitating bone consolidation. PATIENTS AND METHODS: Ten patients underwent fibula-periosteal chimeric flaps (2016-2022) at the Canniesburn Plastic Surgery Unit, UK. Preceding non-union 18.6 months, with mean bone gap of 7.5 cm. Patients underwent preoperative CT angiography to identify the periosteal branches. A case-control approach was used. Patients acted as their own controls, with one osteotomy covered by the chimeric periosteal flap and one without, although in two patients both the osteotomies were covered using a long periosteal flap. RESULTS: A chimeric periosteal flap was used in 12 of the 20 osteotomy sites. Periosteal flap osteotomies had a primary union rate of 100% (11/11) versus those without flaps at 28.6% (2/7) (p = 0.0025). Union occurred in the chimeric periosteal flaps at 8.5 months versus 16.75 months in the control group (p = 0.023). One case was excluded from primary analysis due to recurrent mycetoma. The number needed to treat = 2, indicating that 2 patients would require a chimeric periosteal flap to avoid one non-union. Survival curves with a hazard ratio of 4.1 were observed, equating to a 4 times higher chance of union with periosteal flaps (log-rank p = 0.0016). CONCLUSIONS: The chimeric fibula-periosteal flap may increase the consolidation rates in difficult cases of recalcitrant non-union. This elegant modification of the fibula flap uses periosteum that is normally discarded, and this adds to the accumulating data supporting the use of vascularised periosteal flaps in non-union.


Assuntos
Fíbula , Procedimentos de Cirurgia Plástica , Humanos , Periósteo/cirurgia , Retalhos Cirúrgicos/cirurgia , Osteotomia , Transplante Ósseo
7.
J Plast Reconstr Aesthet Surg ; 87: 479-490, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36890078

RESUMO

BACKGROUND: The COVID pandemic brought the need for more realistic remote consultations into focus. 2D Telemedicine solutions fail to replicate the fluency or authenticity of in-person consultations. This research reports on an international collaboration on the participatory development and first validated clinical use of a novel, real-time 360-degree 3D Telemedicine system worldwide. The development of the system - leveraging Microsoft's Holoportation™ communication technology - commenced at the Canniesburn Plastic Surgery Unit, Glasgow, in March 2020. METHODS: The research followed the VR CORE guidelines on the development of digital health trials, placing patients at the heart of the development process. This consisted of three separate studies - a clinician feedback study (23 clinicians, Nov-Dec 2020), a patient feedback study (26 patients, Jul-Oct 2021), and a cohort study focusing on safety and reliability (40 patients, Oct 2021-Mar 2022). "Lose, Keep, and Change" feedback prompts were used to engage patients in the development process and guide incremental improvements. RESULTS: Participatory testing demonstrated improved patient metrics with 3D in comparison to 2D Telemedicine, including validated measures of satisfaction (p<0.0001), realism or 'presence' (Single Item Presence scale, p<0.0001), and quality (Telehealth Usability Questionnaire, p = 0.0002). The safety and clinical concordance (95%) of 3D Telemedicine with a face-to-face consultation were equivalent or exceeded estimates for 2D Telemedicine. CONCLUSIONS: One of the ultimate goals of telemedicine is for the quality of remote consultations to get closer to the experience of face-to-face consultations. These data provide the first evidence that Holoportation™ communication technology brings 3D Telemedicine closer to this goal than a 2D equivalent.


Assuntos
COVID-19 , Consulta Remota , Telemedicina , Humanos , Estudos de Coortes , Reprodutibilidade dos Testes , COVID-19/epidemiologia
8.
Nucleic Acids Res ; 51(13): 6509-6527, 2023 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-36940725

RESUMO

Telomere maintenance is a hallmark of malignant cells and allows cancers to divide indefinitely. In some cancers, this is achieved through the alternative lengthening of telomeres (ALT) pathway. Whilst loss of ATRX is a near universal feature of ALT-cancers, it is insufficient in isolation. As such, other cellular events must be necessary - but the exact nature of the secondary events has remained elusive. Here, we report that trapping of proteins (such as TOP1, TOP2A and PARP1) on DNA leads to ALT induction in cells lacking ATRX. We demonstrate that protein-trapping chemotherapeutic agents, such as etoposide, camptothecin and talazoparib, induce ALT markers specifically in ATRX-null cells. Further, we show that treatment with G4-stabilising drugs cause an increase in trapped TOP2A levels which leads to ALT induction in ATRX-null cells. This process is MUS81-endonuclease and break-induced replication dependent, suggesting that protein trapping leads to replication fork stalling, with these forks being aberrantly processed in the absence of ATRX. Finally, we show ALT-positive cells harbour a higher load of genome-wide trapped proteins, such as TOP1, and knockdown of TOP1 reduced ALT activity. Taken together, these findings suggest that protein trapping is a fundamental driving force behind ALT-biology in ATRX-deficient malignancies.


A key feature of all cancer cells is their ability to divide indefinitely, and this is dependent on circumvention of telomere shortening through induction of a telomere maintenance mechanism, such as the telomerase-independent, Alternative Lengthening of Telomeres (ALT) pathway. The ALT pathway is characterised by loss of the ATRX chromatin remodeler. The current study provides evidence that, in the absence of ATRX, increased trapping of proteins on DNA leads to replication fork stalling and collapse. At telomeres, this leads to ALT pathway activity. These results help to better understand ALT tumours and might, eventually, be instrumental in developing new therapeutic strategies.


Assuntos
Neoplasias , Telômero , Humanos , DNA , Neoplasias/genética , Telomerase/genética , Telômero/genética , Telômero/metabolismo , Homeostase do Telômero , Proteína Nuclear Ligada ao X/genética , Proteína Nuclear Ligada ao X/metabolismo
9.
Am J Clin Nutr ; 117(2): 252-265, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36811563

RESUMO

BACKGROUND: Dietary components that impact the gut microbiota may beneficially affect cardiometabolic health, possibly by altered bile acid metabolism. However, impacts of these foods on postprandial bile acids, gut microbiota, and cardiometabolic risk markers are unclear. OBJECTIVES: The aim of this study was to determine the chronic effects of probiotics, oats, and apples on postprandial bile acids, gut microbiota, and cardiometabolic health biomarkers. METHODS: Using an acute within chronic parallel design, 61 volunteers (mean ± SD: age 52 ± 12 y; BMI 24.8 ± 3.4 kg/m2) were randomly assigned to consume 40 g cornflakes (control), 40 g oats or 2 Renetta Canada apples each with 2 placebo capsules per day or 40 g cornflakes with 2 Lactobacillus reuteri capsules (>5 × 109 CFU) per day, for 8 wk. Fasting and postprandial serum/plasma bile acids and cardiometabolic health biomarkers, fecal bile acids, and gut microbiota composition were determined. RESULTS: At week 0, oats and apples significantly decreased postprandial serum insulin [area under the curve (AUC): 25.6 (17.4, 33.8) and 23.4 (15.4, 31.4) vs. 42.0 (33.7, 50.2) pmol/L × min and incremental AUC (iAUC): 17.8 (11.6, 24.0) and 13.7 (7.7, 19.8) vs. 29.6 (23.3, 35.8) pmol/L × min] and C-peptide responses [AUC: 599 (514, 684) and 550 (467, 632) vs. 750 (665, 835) ng/mL × min], whereas non-esterified fatty acids were increased [AUC 135 (117, 153) vs. 86.3 (67.9, 105) and iAUC 96.2 (78.8, 114) vs. 60 (42.1, 77.9) mmol/L × min] after the apples vs. control (P ≤ 0.05). Postprandial unconjugated [AUC: predicted means (95% CI) 1469 (1101, 1837) vs. 363 (-28, 754) µmol/L × min and iAUC: 923 (682, 1165) vs. 22.0 (-235, 279) µmol/L × min)] and hydrophobic [iAUC: 1210 (911, 1510) vs. 487 (168, 806) µmol/L × min] bile acid responses were increased after 8 wk probiotic intervention vs. control (P ≤ 0.049). None of the interventions modulated the gut microbiota. CONCLUSIONS: These results support beneficial effects of apples and oats on postprandial glycemia and the ability of the probiotic Lactobacillus reuteri to modulate postprandial plasma bile acid profiles compared with control (cornflakes), with no relationship evident between circulating bile acids and cardiometabolic health biomarkers.


Assuntos
Doenças Cardiovasculares , Malus , Probióticos , Humanos , Adulto , Pessoa de Meia-Idade , Avena/metabolismo , Ácidos e Sais Biliares , Biomarcadores , Doenças Cardiovasculares/prevenção & controle , Período Pós-Prandial/fisiologia , Glicemia/metabolismo , Insulina
10.
Acta Neurochir (Wien) ; 165(9): 2473-2478, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36625909

RESUMO

Supplementary motor area (SMA) syndrome is characterised by transient disturbance in volitional movement and speech production which classically occurs after injury to the medial premotor area. We present two cases of SMA syndrome following isolated surgical injury to the frontal aslant tract (FAT) with the SMA intact. The first case occurred after resection of a left frontal operculum tumour. The second case occurred after a transcortical approach to a ventricular neurocytoma. The clinical picture and fMRI activation patterns during recovery were typical for SMA syndrome and support the theory that the FAT is a critical bundle in the SMA complex function.


Assuntos
Córtex Motor , Humanos , Córtex Motor/diagnóstico por imagem , Córtex Motor/cirurgia , Imagem de Tensor de Difusão , Imageamento por Ressonância Magnética , Fala/fisiologia
11.
Nutrients ; 14(9)2022 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-35565746

RESUMO

Culinary education programs are generally designed to improve participants' food and cooking skills, with or without consideration to influencing diet quality or health. No published methods exist to guide food and cooking skills' content priorities within culinary education programs that target improved diet quality and health. To address this gap, an international team of cooking and nutrition education experts developed the Cooking Education (Cook-EdTM) matrix. International food-based dietary guidelines were reviewed to determine common food groups. A six-section matrix was drafted including skill focus points for: (1) Kitchen safety, (2) Food safety, (3) General food skills, (4) Food group specific food skills, (5) General cooking skills, (6) Food group specific cooking skills. A modified e-Delphi method with three consultation rounds was used to reach consensus on the Cook-EdTM matrix structure, skill focus points included, and their order. The final Cook-EdTM matrix includes 117 skill focus points. The matrix guides program providers in selecting the most suitable skills to consider for their programs to improve dietary and health outcomes, while considering available resources, participant needs, and sustainable nutrition principles. Users can adapt the Cook-EdTM matrix to regional food-based dietary guidelines and food cultures.


Assuntos
Culinária , Terapia Nutricional , Dieta , Alimentos , Educação em Saúde , Humanos
12.
Ophthalmic Plast Reconstr Surg ; 38(6): 563-566, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35550483

RESUMO

AIMS: To estimate the proportion of de novo lacrimal gland pleomorphic adenomas (PAs) and carcinomas expleomorphic adenomas (CEPAs), together with age at presentation and first symptom. Conjectural models of tumor growth are considered. METHODS: Retrospective review of patients with orbital lobe PA or CEPA. The presenting age was examined for conformation to a Gaussian distribution and the cumulative distribution function derived for both tumor types. The risk of CEPA with age was estimated by logistic regression. RESULTS: About one-sixth (27/172; 16%) of these primary orbital lobe tumors were CEPAs, with 145 PAs (76/145 male; 52%) and 27 CEPAs (12/27 male; 44%). The mean presenting age for PAs was 48.3 years (median 47.7; range 11-84 years) and 57.7 years for CEPAs (median 61.2, range 27-91 years) ( p = 0.0062), and the standard deviations for each group are almost identical (16.3 for PAs, 15.9 for CEPAs; p = 0.92). Five (3.4%) PAs and 1 (3.7%) CEPA were asymptomatic: otherwise, the median symptom duration was 24 months for both PAs and CEPAs ( U test: p = 0.65). The odds of CEPA rises significantly with age, increasing 1.04-fold annually ( p = 0.0079). CONCLUSION: The almost identical measures of dispersion for the presenting ages of PA and CEPA suggests that, once malignant transformation occurs, there might be a relatively constant period before it is evident. CEPAs present about a decade after PAs, this unexpectedly later presentation for the malignancy possibly being explained by a gradual replacement of the PA by the newly arising carcinoma within the preceding benign tumor.


Assuntos
Adenoma Pleomorfo , Carcinoma , Neoplasias Oculares , Doenças do Aparelho Lacrimal , Aparelho Lacrimal , Neoplasias Orbitárias , Neoplasias das Glândulas Salivares , Humanos , Masculino , Pessoa de Meia-Idade , Aparelho Lacrimal/patologia , Doenças do Aparelho Lacrimal/diagnóstico , Doenças do Aparelho Lacrimal/patologia , Adenoma Pleomorfo/diagnóstico , Adenoma Pleomorfo/patologia , Neoplasias Oculares/diagnóstico , Neoplasias Oculares/patologia , Carcinoma/patologia , Neoplasias Orbitárias/patologia
13.
Indian J Surg ; 84(Suppl 1): 306-310, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34539123

RESUMO

Over the last 20 years, surgical training in the United Kingdom (UK) has changed dramatically. There have been considerable efforts towards creating a programme that delivers the highest standard of training while maintaining patient safety. However, the journey to improve the quality of training has faced several hurdles and challenges. Recruitment processes, junior doctor contracts, flexible working hours and equality and diversity have all been under the spotlight in recent times. These issues, alongside the extended surgical team and the increasingly recognised importance of trainee wellbeing, mean that postgraduate surgical training is extremely topical. Alongside this, as technology has evolved, this has been incorporated into all aspects of training, from recruitment to simulated training opportunities and postgraduate examinations. The coronavirus (COVID-19) pandemic has brought technology and simulation to the forefront in an attempt to compensate for reduced operative exposure and experience, and has transformed the way that we learn and work. In this article, we reflect on the UK surgical trainee experience and discuss areas of success as well as highlighting potential areas for improvement going forward.

14.
Nutr Res Rev ; 35(2): 161-180, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-33926590

RESUMO

Beneficial effects of probiotic, prebiotic and polyphenol-rich interventions on fasting lipid profiles have been reported, with changes in the gut microbiota composition believed to play an important role in lipid regulation. Primary bile acids, which are involved in the digestion of fats and cholesterol metabolism, can be converted by the gut microbiota to secondary bile acids, some species of which are less well reabsorbed and consequently may be excreted in the stool. This can lead to increased hepatic bile acid neo-synthesis, resulting in a net loss of circulating low-density lipoprotein. Bile acids may therefore provide a link between the gut microbiota and cardiovascular health. This narrative review presents an overview of bile acid metabolism and the role of probiotics, prebiotics and polyphenol-rich foods in modulating circulating cardiovascular disease (CVD) risk markers and bile acids. Although findings from human studies are inconsistent, there is growing evidence for associations between these dietary components and improved lipid CVD risk markers, attributed to modulation of the gut microbiota and bile acid metabolism. These include increased bile acid neo-synthesis, due to bile sequestering action, bile salt metabolising activity and effects of short-chain fatty acids generated through bacterial fermentation of fibres. Animal studies have demonstrated effects on the FXR/FGF-15 axis and hepatic genes involved in bile acid synthesis (CYP7A1) and cholesterol synthesis (SREBP and HMGR). Further human studies are needed to determine the relationship between diet and bile acid metabolism and whether circulating bile acids can be utilised as a potential CVD risk biomarker.


Assuntos
Doenças Cardiovasculares , Microbioma Gastrointestinal , Probióticos , Animais , Humanos , Prebióticos , Microbioma Gastrointestinal/fisiologia , Ácidos e Sais Biliares , Polifenóis/farmacologia , Colesterol/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Lipídeos/farmacologia
16.
PLoS Genet ; 17(3): e1009443, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33739972

RESUMO

Most epigenome-wide association studies (EWAS) quantify DNA methylation (DNAm) in peripheral tissues such as whole blood to identify positions in the genome where variation is statistically associated with a trait or exposure. As whole blood comprises a mix of cell types, it is unclear whether trait-associated DNAm variation is specific to an individual cellular population. We collected three peripheral tissues (whole blood, buccal epithelial and nasal epithelial cells) from thirty individuals. Whole blood samples were subsequently processed using fluorescence-activated cell sorting (FACS) to purify five constituent cell-types (monocytes, granulocytes, CD4+ T cells, CD8+ T cells, and B cells). DNAm was profiled in all eight sample-types from each individual using the Illumina EPIC array. We identified significant differences in both the level and variability of DNAm between different sample types, and DNAm data-derived estimates of age and smoking were found to differ dramatically across sample types from the same individual. We found that for the majority of loci variation in DNAm in individual blood cell types was only weakly predictive of variance in DNAm measured in whole blood, although the proportion of variance explained was greater than that explained by either buccal or nasal epithelial samples. Covariation across sample types was much higher for DNAm sites influenced by genetic factors. Overall, we observe that DNAm variation in whole blood is additively influenced by a combination of the major blood cell types. For a subset of sites, however, variable DNAm detected in whole blood can be attributed to variation in a single blood cell type providing potential mechanistic insight about EWAS findings. Our results suggest that associations between whole blood DNAm and traits or exposures reflect differences in multiple cell types and our data will facilitate the interpretation of findings in epigenetic epidemiology.


Assuntos
Metilação de DNA , Epigênese Genética , Epigenômica , Epidemiologia Molecular , Células Sanguíneas , Epigenômica/métodos , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Especificidade de Órgãos/genética , Transcriptoma
18.
Rev Med Suisse ; 16(714): 2169-2171, 2020 Nov 11.
Artigo em Francês | MEDLINE | ID: mdl-33174699

RESUMO

Deprescribing, in order to reduce both polypharmacy and the use of potentially inappropriate medications, remains a challenge, especially in nursing homes. Healthcare professionals perceive residents of these homes as wary of change and reluctant to take part in such endeavours. The results of two studies, one qualitative and the other quantitative, show that, on the contrary, nursing home residents and their relatives would be ready to consider a treatment reduction, provided that time is invested to explain the expected benefits of such changes.


Déprescrire pour réduire l'usage de médicaments inappropriés et, plus généralement, diminuer la polymédication reste un défi, en particulier chez les résidents d'établissements médico-sociaux. Les professionnels de la santé actifs en institution perçoivent cette population comme réticente au changement et peu encline à s'engager dans une telle démarche. Pourtant, les résultats de trois études, les deux premières qualitatives, la dernière quantitative, indiquent que ces résidents, ainsi que leurs proches, seraient prêts à tester une réduction de leur traitement, pour autant que l'on prenne le temps de discuter avec eux des bénéfices potentiels.


Assuntos
Atitude Frente a Saúde , Desprescrições , Família/psicologia , Pessoal de Saúde/psicologia , Casas de Saúde , Pacientes/psicologia , Humanos , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados
19.
Sante Publique ; Vol. 32(1): 19-28, 2020 Jun 18.
Artigo em Francês | MEDLINE | ID: mdl-32706223

RESUMO

Purpose of research: The objective of this article is to investigate, from the perspective of patients, the disruptions of the biographical trajectories induced by chronic low back pain and the impact of a multidisciplinary rehabilitation program on their reconstruction. METHODS: Based on an interdisciplinary qualitative research, we investigated the experience of 20 participants with chronic low back pain following a three-week rehabilitation program at the hospital. Semi-directive interviews were conducted before and after inclusion in the program. RESULTS: Although affecting each person in a singular way, chronic low back pain induces biographical linearity disruptions related to the apparition of pain, and the disruption of daily and professional activities. For the majority of participants, the rehabilitation program provided a repairative space to restore continuity between past, present and future life. Whether or not there is a significant improvement in pain, most participants report benefits that give them the feeling of getting back to normality. Nevertheless, they identify those more for the domestic, family, and social spheres than at the professional level, effects remaining moderate to mitigated in that area. CONCLUSIONS: The rehabilitation program influences the dynamics of biographical trajectories and promotes a return to what is perceived as normality. By providing individuals with theoretical and practical tools and increasing their functional capacities, it promotes autonomous pain and problem management. Immediate effects are seen as restorative for domestic, family and social activities, but remain limited on the professional level.


Assuntos
Dor Crônica/reabilitação , Dor Lombar/reabilitação , Humanos , Avaliação de Programas e Projetos de Saúde , Pesquisa Qualitativa , Procedimentos de Cirurgia Plástica , Ruptura Espontânea/cirurgia
20.
Pharmacy (Basel) ; 8(1)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046022

RESUMO

Background: Polypharmacy and the use of potentially inappropriate medications are frequent safety issues among nursing home (NH) residents. Deprescribing can significantly reduce the number of drugs used, medication costs, and mortality. This qualitative study sought to understand and compare the perceptions and practices of nurses, pharmacists, and physicians regarding deprescribing in Swiss NHs, referring to an implementation approach on three levels of action: the individual, the institution, and the healthcare system. Methods: Two focus groups were held with 21 participants: one focus group with 11 pharmacists, another with 10 nurses and six semi-structured interviews with physicians were conducted and focused on their individual experience and practices. They were audiotaped and fully transcribed, and a content analysis was performed using to MAXQDA (Ver 12) software. Results: (1) At an individual level, physicians were concerned by consequences of deprescribing in terms of safety. Nurses were closest to residents and stressed the importance of finding the right time, creating a bond of trust before deprescribing and considering the purpose of the stay in the NH. Pharmacists relied on structured guides for deprescribing, which led their reflection and practice. All professionals saw the complexity of the clinical situations, as well as residents' and relatives' fears of interruption of care. (2) At an institutional level, the professionals stressed the lack of time to discuss patients' health and treatment, while pre-existing interprofessional collaboration, specifically, quality circles, seemed useful tools to create common knowledge. In order to reduce prescriptions, better coordination between physicians, nurses, pharmacists and specialists seemed crucial. (3) At the health system level, funding still needs to be provided to consolidate the process, go beyond organisational constraints and ensure deprescribing serves the patient's wellbeing above all. Conclusions: At the individual level of implementation, the different healthcare professionals expressed specific concerns about deprescribing, depending on their defined role in NHs. Their perspective about the different levers to promote deprescribing at institutional and healthcare system levels converge towards interprofessional collaboration supported by the healthcare system. Specific funding and incentives are therefore needed to support a sustainable interprofessional team.

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