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1.
Int J Circumpolar Health ; 83(1): 2392406, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39151145

RESUMEN

Gastrointestinal function plays a pivotal role in nutrient absorption and overall digestive health. Abnormal gastric emptying is closely linked to type 2 diabetes, impacting blood glucose regulation and causing gastrointestinal symptoms. This study aims to investigate and compare segmental transit times, motility indices, and micromilieu between Greenlandic Inuit and Danish individuals with and without type 2 diabetes. We included forty-four Greenlandic Inuit, twenty-three of whom had type 2 diabetes, and age and gender-matched Danish individuals. Segmental transit time, motility, and luminal environment were measured using the SmartPill®. Greenlandic controls displayed shorter gastric emptying time (GET) (163 min), higher gastric median pH (2.0 pH) and duodenal median contractions (18.2 mm Hg) compared to Greenlanders with type 2 diabetes (GET: 235 min, pH:1.9, median duodenal contraction 18.4 mm Hg) and Danish controls (GET: 190, pH:1.2 median duodenal contraction 17.5 mmHg). Despite similar anti-diabetic management efforts, variations in gastrointestinal physiology were evident, highlighting the complexity of diabetes and its interaction with ethnicity, suggesting potential dietary or even genetic influences, emphasising the necessity for personalised diabetes management approaches. Finally, the study opens possibilities for future research, encouraging investigations into the underlying mechanisms linking genetics, diet, and gastric physiology, as an understanding of factors can lead to more effective, tailored strategies for diabetes care and improved digestive health in diverse populations.


Asunto(s)
Diabetes Mellitus Tipo 2 , Vaciamiento Gástrico , Motilidad Gastrointestinal , Inuk , Humanos , Diabetes Mellitus Tipo 2/etnología , Diabetes Mellitus Tipo 2/fisiopatología , Groenlandia/epidemiología , Dinamarca/epidemiología , Femenino , Masculino , Persona de Mediana Edad , Vaciamiento Gástrico/fisiología , Motilidad Gastrointestinal/fisiología , Adulto , Anciano , Duodeno
2.
CJC Open ; 6(7): 884-892, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39026619

RESUMEN

Background: Atrial fibrillation (AF) increases the risk of conditions such as ischemic stroke, dementia, and heart failure, and early detection is crucial. In Greenland, ischemic strokes are common, and the prevalences of AF risk factors are increasing. Studies based on 30-second electrocardiograms (ECGs) and diagnosis codes so far have indicated either a low prevalence of AF or a prevalence comparable to that in other Western countries, such as Denmark. However, using short, single-point ECGs may underestimate the true prevalence, as especially paroxysmal AF can be missed. With this study, we aim to estimate the prevalence of AF using 3-5-day continuous Holter recordings among people in Nuuk, the capital of Greenland. Methods: In this cross-sectional study, we estimated the prevalence of AF among the population aged ≥ 50 years in Greenland's capital, Nuuk. We used an ePatch to record continuous ECGs for 3-5 days, and questionnaires to assess demographic data, comorbidities, medication, symptoms, and risk factors for AF. Results: Of 226 participants (62% women), 21 (33% women) had either self-reported AF, AF on the recording, or both, equivalent to a prevalence of 9.3% (confidence interval [CI] 5.8-13.9). The age-stratified prevalence was 7.2% (CI 2.7-15.1) among those aged 50-59 years; 8.8% (CI 4.1-16.1) among those aged 60-69 years; and 18.2% (CI 7.0-35.5) among those aged ≥ 70 years. Conclusions: This study provides a novel insight into AF prevalence in Nuuk, emphasizing the potential underestimation in previous studies. Continuous ECG monitoring revealed a higher prevalence, especially among the younger age groups, urging a reevaluation of diagnostic practices in this unique population.


Contexte: La fibrillation auriculaire augmente le risque d'accidents vasculaires cérébraux (AVC) ischémiques, de démence et d'insuffisance cardiaque. Il est donc essentiel de la dépister rapidement. Au Groenland, les AVC ischémiques sont fréquents, et la prévalence des facteurs de risque de fibrillation auriculaire est à la hausse. Les études reposant sur des électrocardiogrammes (ECG) de 30 secondes et des codes de diagnostic ont jusqu'à présent révélé une faible prévalence de la fibrillation auriculaire ou une prévalence comparable à celle d'autres pays occidentaux, comme le Danemark. Cependant, l'utilisation d'ECG courts à un moment fixe dans le temps peut sous-estimer la prévalence réelle, car la fibrillation auriculaire paroxystique, en particulier, peut passer inaperçue. Cette étude a pour but d'estimer la prévalence de la fibrillation auriculaire en utilisant des enregistrements Holter continus de trois à cinq jours chez des habitants de Nuuk, la capitale du Groenland. Méthodologie: Dans cette étude transversale, nous avons estimé la prévalence de la fibrillation auriculaire dans la population de ≥ 50 ans de Nuuk, la capitale du Groenland. Nous avons utilisé un timbre électronique pour enregistrer des ECG en continu pendant trois à cinq jours, ainsi que des questionnaires pour recueillir les données démographiques et consigner les maladies concomitantes, les médicaments, les symptômes et les facteurs de risque de fibrillation auriculaire. Résultats: Sur 226 participants (dont 62 % étaient des femmes), 21 (33 % de femmes) présentaient, soit une fibrillation auriculaire autodéclarée, soit une fibrillation auriculaire selon l'enregistrement, soit les deux, ce qui correspond à une prévalence de 9,3 % (intervalle de confiance [IC] : 5,8 à 13,9). La prévalence stratifiée en fonction de l'âge était de 7,2 % (IC : 2,7 à 15,1) chez les 50 à 59 ans, de 8,8 % (IC : 4,1 à 16,1) chez les 60 à 69 ans et de 18,2 % (IC : 7,0 à 35,5) chez les 70 ans et plus. Conclusions: Cette étude fournit de nouveaux renseignements sur la prévalence de la fibrillation auriculaire à Nuuk et souligne la prévalence potentiellement sous-estimée dans les études précédentes. La surveillance continue de l'ECG a révélé une prévalence plus élevée, en particulier dans les tranches d'âge plus jeunes, ce qui incite à réévaluer les pratiques de diagnostic utilisées dans cette population particulière.

3.
J Anim Ecol ; 93(8): 1003-1021, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38864368

RESUMEN

Terrestrial invertebrates are highly important for the decomposition of dung from large mammals. Mammal dung has been present in many of Earth's ecosystems for millions of years, enabling the evolution of a broad diversity of dung-associated invertebrates that process various components of the dung. Today, large herbivorous mammals are increasingly introduced to ecosystems with the aim of restoring the ecological functions formerly provided by their extinct counterparts. However, we still know little about the ecosystem functions and nutrient flows in these rewilded ecosystems, including the dynamics of dung decomposition. In fact, the succession of insect communities in dung is an area of limited research attention also outside a rewilding context. In this study, we use environmental DNA metabarcoding of dung from rewilded Galloway cattle in an experimental set-up to investigate invertebrate communities and functional dynamics over a time span of 53 days, starting from the time of deposition. We find a strong signal of successional change in community composition, including for the species that are directly dependent on dung as a resource. While several of these species were detected consistently across the sampling period, others appeared confined to either early or late successional stages. We believe that this is indicative of evolutionary adaptation to a highly dynamic resource, with species showing niche partitioning on a temporal scale. However, our results show consistently high species diversity within the functional groups that are directly dependent on dung. Our findings of such redundancy suggest functional stability of the dung-associated invertebrate community, with several species ready to fill vacant niches if other species disappear. Importantly, this might also buffer the ecosystem functions related to dung decomposition against environmental change. Interestingly, alpha diversity peaked after approximately 20-25 days in both meadow and pasture habitats, and did not decrease substantially during the experimental period, probably due to preservation of eDNA in the dung after the disappearance of visiting invertebrates, and from detection of tissue remains and cryptic life stages.


Asunto(s)
Artrópodos , Biodiversidad , Código de Barras del ADN Taxonómico , Heces , Animales , Bovinos/fisiología , Heces/química , Artrópodos/fisiología , ADN Ambiental/análisis , Ecosistema
4.
Int J Cardiol ; 408: 132137, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38705205

RESUMEN

BACKGROUND: Limited knowledge of antihypertensive treatment of the elderly potentially impedes effective strategies for hypertension management in this growing patient group. We aimed to investigate temporal trends for first-line drug choice for antihypertensive treatment and treatment continuity among patients ≥75 years from 2000 to 2021. METHODS: Using nationwide Danish registers, patients ≥75 years initiated for the first time on antihypertensive drugs: Angiotensin converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB), beta blockers (BB), calcium channel blockers (CCB), thiazides, or combinations, were identified. Patients with other indications than hypertension were excluded. Treatment continuity was described using claimed prescriptions the first 180 days following study entry. RESULTS: From 2000 to 2021, 170,769 patients (median age 80 years [interquartile range:77-84], 60.3% female) were included. From 2000 to 2003 to 2015-2021 the proportion of first-line drug choice increased for ACEi (8.7% to 14.9%), ARB (4.1% to 23.9%), and CCB (10.7% to 27.6%), decreased for thiazides (60.6% to 15.9%) and remained stable for BB (12.9% to 14.1%) and combinations (2.9% to 3.6%). For 157,457 patients alive after 180 days, discontinuation was highest among patients initiated on thiazides (28.3%) whereas most patients continued the same single drug regimen if they started on ACEi (55.2%), ARB (65.0%), BB (57.2%) or CCB (59.3%). CONCLUSIONS: From 2000 to 2021 thiazides have been replaced by ACEi, ARB and CCB. Thiazides had the lowest treatment continuity while ARB appeared preferred slightly over ACEi. Differences in adherence in relation to first-line drug choice may warrant scrutiny regarding recommendations for the elderly.


Asunto(s)
Antihipertensivos , Hipertensión , Sistema de Registros , Humanos , Femenino , Masculino , Anciano , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Antihipertensivos/uso terapéutico , Anciano de 80 o más Años , Estudios de Cohortes , Dinamarca/epidemiología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Continuidad de la Atención al Paciente/tendencias , Antagonistas de Receptores de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico
5.
Cell ; 187(17): 4444-4448, 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-38754422

RESUMEN

Environmental DNA (eDNA) has opened promising avenues for establishing standardized, cost-efficient monitoring of biodiversity. However, comprehensive and systematic implementation is urgently needed to address the current biodiversity crisis. Here, we envision a global eDNA biomonitoring scheme, which could potentially revolutionize the understanding and conservation of life on Earth.


Asunto(s)
Biodiversidad , ADN Ambiental , Monitoreo del Ambiente , ADN Ambiental/análisis , Monitoreo del Ambiente/métodos , Conservación de los Recursos Naturales/métodos , Humanos , Animales , Planeta Tierra
6.
Ugeskr Laeger ; 186(9)2024 02 26.
Artículo en Danés | MEDLINE | ID: mdl-38445323

RESUMEN

In his case report, a 74-year-old physically fit man was evaluated repeatedly for several years in the cardiology department due to dyspnoea on exertion (DOE). Several standard cardiac and pulmonary tests were performed but did not provide sufficient cause for the DOE. Lastly, the patient was evaluated with a cardiopulmonary exercise test (CPET) with simultaneous in- and expiratory gas sampling. The test revealed a low aerobic capacity due to chronotropic incompetence (CI), thus explaining the DOE. Subsequently, the patient was treated with a rate-responsive pacemaker. CPET-is an ideal test for diagnosing CI.


Asunto(s)
Prueba de Esfuerzo , Marcapaso Artificial , Masculino , Humanos , Anciano , Corazón , Disnea/diagnóstico , Disnea/etiología
7.
Med Phys ; 51(3): 2200-2209, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37929802

RESUMEN

BACKGROUND: The continued development of new radiotherapy techniques requires dosimetry systems that satisfy increasingly rigorous requirements, such as high sensitivity, wide dose range, and high spatial resolution. An emerging requirement is the ability to read out doses in three dimensions (3D) with high precision and spatial resolution. A few dosimetry systems with 3D capabilities are available, but their application in a clinical workflow is limited for various reasons, primarily originating from their chemical nature. The search for a 3D dosimetry system with potential for clinical implementation is thus ongoing. PURPOSE: To demonstrate the capabilities of a novel optically-stimulated-luminescence (OSL)-based 3D dosimetry system capable of measuring radiation doses in clinically relevant volumes. METHODS: A laser-based readout system was used to measure dose distributions delivered by both photons and protons, utilizing the OSL from a 50 × 50 × 50 $50\times 50\times 50$  mm 3 $^3$ YSO:Ce crystal. A homogeneous treatment plan consisting of two opposing photon fields was used to establish an inhomogeneity correction map of the crystal response and demonstrated the accuracy and precision of the system. The crystal was additionally irradiated with a photon treatment plan consisting of three overlapping 10 × 10 $10\times 10$  mm 2 $^2$ fields delivered from different angles, and a proton treatment plan consisting of four pencil beams with energies 90 MeV ( × 2 $\times 2$ ), 115 MeV, and 140 MeV. The system abilities were quantified by comparing the 3D-resolved measurements to Monte Carlo simulations. RESULTS: The dose map reproducibility of the system was found to be within 2% including both statistical and systematic errors. The measurements yielded integrated doses from a volume of 50 × 50 × 40 $50\times 50\times 40$  mm 3 $^3$ with voxel volumes of just 0.28 × 0.28 × 0.50 $0.28\times 0.28\times 0.50$  mm 3 $^3$ . An excellent agreement between the 3D-resolved measurements and the simulations was found for both photon- and proton-irradiation. CONCLUSIONS: The capabilities of the devised system for measuring clinically relevant fields of photons and proton pencil beams within a clinically relevant volume were demonstrated. The system poses as a promising candidate for clinical applications, and enables future research in the field of OSL-based tissue-equivalent 3D dosimetry.


Asunto(s)
Luminiscencia , Dosimetría con Luminiscencia Ópticamente Estimulada , Protones , Reproducibilidad de los Resultados , Radiometría/métodos
8.
HardwareX ; 16: e00491, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38034102

RESUMEN

Aerosol particles with rare specific properties act as nuclei for ice formation. The presence of ice nucleating particles in the atmosphere leads to heterogeneous freezing at warm temperatures and thus these particles play an important role in modulating microphysical properties of clouds. This work presents an ice nucleation cold stage instrument for measuring the concentration of ice nucleating particles in liquids. The cost is âˆ¼ $10 k including an external chiller. Using a lower cost heat sink reduces the cost to âˆ¼ $6 k. The instrument is suitable for studying ambient ice nucleating particle concentrations and laboratory-based process-level studies of ice nucleation. The design plans allow individuals to self-manufacture the cold-stage using 3D printing, off-the-shelf parts, and a handful of standard tools. Software to operate the instrument and analyze the data is also provided. The design is intended to be simple enough that a graduate student can build it as part of a course or thesis project. Costs are kept to a minimum to facilitate use in classroom demonstrations and laboratory classes.

10.
Nucleic Acids Res ; 51(17): e91, 2023 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-37572348

RESUMEN

Biological functions are orchestrated by intricate networks of interacting genetic elements. Predicting the interaction landscape remains a challenge for systems biology and new research tools allowing simple and rapid mapping of sequence to function are desirable. Here, we describe CRI-SPA, a method allowing the transfer of chromosomal genetic features from a CRI-SPA Donor strain to arrayed strains in large libraries of Saccharomyces cerevisiae. CRI-SPA is based on mating, CRISPR-Cas9-induced gene conversion, and Selective Ploidy Ablation. CRI-SPA can be massively parallelized with automation and can be executed within a week. We demonstrate the power of CRI-SPA by transferring four genes that enable betaxanthin production into each strain of the yeast knockout collection (≈4800 strains). Using this setup, we show that CRI-SPA is highly efficient and reproducible, and even allows marker-free transfer of genetic features. Moreover, we validate a set of CRI-SPA hits by showing that their phenotypes correlate strongly with the phenotypes of the corresponding mutant strains recreated by reverse genetic engineering. Hence, our results provide a genome-wide overview of the genetic requirements for betaxanthin production. We envision that the simplicity, speed, and reliability offered by CRI-SPA will make it a versatile tool to forward systems-level understanding of biological processes.


Asunto(s)
Edición Génica , Saccharomyces cerevisiae , Betaxantinas , Edición Génica/métodos , Reproducibilidad de los Resultados , Saccharomyces cerevisiae/genética
11.
Int J Cardiol Heart Vasc ; 47: 101219, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37576076

RESUMEN

Background: Sleep apnea (SA), a modifiable risk factor in - atrial fibrillation (AF), is associated with worse outcomes in AF. We aimed to assess the prevalence and severity of SA in patients with AF, and, subsequently, to assess the positive predictive value (PPV) of moderate to severe SA by a home-monitoring device in comparison to cardio-respiratory monitoring (CRM) in consecutive patients with AF. Methods: This cross-sectional study recruited unselected patients with AF without known SA from an out-patient clinic at Department of Cardiology, Herlev-Gentofte University Hospital. Participants underwent four consecutive nights of sleep-recording with the home-monitoring device NightOwl™ (NO). Moderate SA was defined as an Apnea-Hypopnea Index (AHI) of 15-29 and severe SA as ≥ 30 AHI. Participants with moderate to severe SA was offered CRM for validation of the diagnosis. Results: We included 126 patients with AF with a median age of 68 (interquartile range: 60-75) years, 42 (33 %) women, 70 (56 %) hypertension, 61 (48 %) hyperlipidemia and 49 (39 %) heart failure. NO detected severe SA in 36 (29 %) of patients with AF, moderate SA in 35 (28 %), mild SA in 45 (36 %) and no SA in 10 (8 %). Of 71 patients with moderate to severe SA by NO, 38 patients underwent CRM and the PPV of NO was 0.82 (31/38) to diagnose moderate SA and 0.92 (22/24) to diagnose severe SA by CRM. Conclusion: Moderate to severe SA by NO was highly prevalent in patients with AF without known SA. A home-monitoring device such as NO could be an easy and feasible SA screening tool in patients with AF.

12.
Obesity (Silver Spring) ; 31(7): 1953-1961, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37312268

RESUMEN

OBJECTIVE: Visceral fat mass (VFM) is a risk factor for cardiovascular diseases, type 2 diabetes mellitus, and malignancy; however, normative data are limited. The aim of this study was to provide reference data for VFM from a large, apparently healthy Caucasian adult population. METHODS: Volunteers aged 20 to 93 years from the Copenhagen City Heart Study had a standardized whole-body dual-energy x-ray absorptiometry scan performed using the iDXA (GE Lunar). Total and regional fat mass was measured. VFM was quantified using the CoreScan application. RESULTS: A total of 1277 participants were included (708 women, mean [SD], age: 56 [19] years, height: 1.66 [0.07] m, BMI: 24.64 [4.31] kg/m2 ; and 569 men, age: 57 [18] years, height: 1.80 [0.07] m, BMI: 25.99 [3.86] kg/m2 ). Increased VFM was positively correlated with age in both sexes. Men had significantly higher VFM in mass (g) after normalization to body size (m2 ) and total fat mass (p < 0.001). VFM increased more in women with high values of the android/gynoid ratio. CONCLUSIONS: Normative data of VFM from a large, healthy Danish cohort aged 20 to 93 years are presented. VFM increased with age in both sexes, but men had significantly higher VFM compared with women with the same BMI, body fat percentage, and fat mass index.


Asunto(s)
Diabetes Mellitus Tipo 2 , Adulto , Masculino , Humanos , Femenino , Persona de Mediana Edad , Diabetes Mellitus Tipo 2/metabolismo , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/metabolismo , Índice de Masa Corporal , Longevidad , Factores de Riesgo , Absorciometría de Fotón , Composición Corporal
13.
Neuropsychologia ; 188: 108602, 2023 09 09.
Artículo en Inglés | MEDLINE | ID: mdl-37270028

RESUMEN

Language is a key part of human cognition, essential for our well-being at all stages of our lives. Whereas many neurocognitive abilities decline with age, for language the picture is much less clear, and how exactly speech comprehension changes with ageing is still unknown. To investigate this, we employed magnetoencephalography (MEG) and recorded neuromagnetic brain responses to auditory linguistic stimuli in healthy participants of younger and older age using a passive task-free paradigm and a range of different linguistic stimulus contrasts, which enabled us to assess neural processing of spoken language at multiple levels (lexical, semantic, morphosyntactic). Using machine learning-based classification algorithms to scrutinise intertrial phase coherence of MEG responses in cortical source space, we found that patterns of oscillatory neural activity diverged between younger and older participants across several frequency bands (alpha, beta, gamma) for all tested linguistic information types. The results suggest multiple age-related changes in the brain's neurolinguistic circuits, which may be due to both healthy ageing in general and compensatory processes in particular.


Asunto(s)
Magnetoencefalografía , Percepción del Habla , Humanos , Magnetoencefalografía/métodos , Comprensión/fisiología , Habla , Encéfalo/fisiología , Lenguaje , Percepción del Habla/fisiología
14.
Clin Epidemiol ; 15: 483-491, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37128596

RESUMEN

Background/Aim: The Danish National Patient Registry (DNPR) provides unique epidemiological insight, but often lacks granular data. We propose a procedure-based definition of cancer status in patients with breast-, lung- and colorectal cancer, which can be applied to administrative health databases. New definitions of cancer status are needed as mortality and morbidity are closely linked to cancer status, yet most studies only use duration since cancer diagnosis as a severity marker. The aim of the study was to validate a new pragmatic definition. Methods: Medical journals of 600 patients, with breast-, lung- and colorectal cancer from the Department of Oncology at Herlev-Gentofte Hospital were retrospectively reviewed. We defined active cancer as a cancer diagnosis, not followed by a potentially curative procedure within 6 months of the diagnosis. The remaining patients were characterized as having non-active cancer. This dichotomization was then compared to a cancer status assessment based on treatment received and paraclinical test such as their first post-procedural control scan. Based on this comparison, we calculated the positive predictive value (PPV) of our definitions of active and non-active cancer. Results: The calculated PPVs for active breast-, lung- and colorectal cancer were 87% (CI 95%: 0.74-0.99), 91% (CI 95%: 0.87-0.96) and 82% (CI 95%: 0.73-0.91). The PPVs for non-active breast-, lung- and colorectal cancer were 95% (CI 95%: 0.92-0.99), 91% (CI 95%: 0.82-0.99) and 73% (CI 95%: 0.66-0.81), respectively. Conclusion: We found an overall high PPV for both active and non-active cancer across all three types of cancer.

16.
Adv Mater ; 35(36): e2301907, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37204117

RESUMEN

Modification of the electronic structure of quantum matter by ad atom deposition allows for directed fundamental design of electronic and magnetic properties. This concept is utilized in the present study in order to tune the surface electronic structure of magnetic topological insulators based on MnBi2 Te4 . The topological bands of these systems are typically strongly electron-doped and hybridized with a manifold of surface states that place the salient topological states out of reach of electron transport and practical applications. In this study, micro-focused angle-resolved photoemission spectroscopy (microARPES) provides direct access to the termination-dependent dispersion of MnBi2 Te4 and MnBi4 Te7 during in situ deposition of rubidium atoms. The resulting band structure changes are found to be highly complex, encompassing coverage-dependent ambipolar doping effects, removal of surface state hybridization, and the collapse of a surface state band gap. In addition, doping-dependent band bending is found to give rise to tunable quantum well states. This wide range of observed electronic structure modifications can provide new ways to exploit the topological states and the rich surface electronic structures of manganese bismuth tellurides.

17.
Cancer Discov ; 13(7): 1678-1695, 2023 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-37098965

RESUMEN

Inflammation is strongly associated with pancreatic ductal adenocarcinoma (PDAC), a highly lethal malignancy. Dysregulated RNA splicing factors have been widely reported in tumorigenesis, but their involvement in pancreatitis and PDAC is not well understood. Here, we report that the splicing factor SRSF1 is highly expressed in pancreatitis, PDAC precursor lesions, and tumors. Increased SRSF1 is sufficient to induce pancreatitis and accelerate KRASG12D-mediated PDAC. Mechanistically, SRSF1 activates MAPK signaling-partly by upregulating interleukin 1 receptor type 1 (IL1R1) through alternative-splicing-regulated mRNA stability. Additionally, SRSF1 protein is destabilized through a negative feedback mechanism in phenotypically normal epithelial cells expressing KRASG12D in mouse pancreas and in pancreas organoids acutely expressing KRASG12D, buffering MAPK signaling and maintaining pancreas cell homeostasis. This negative feedback regulation of SRSF1 is overcome by hyperactive MYC, facilitating PDAC tumorigenesis. Our findings implicate SRSF1 in the etiology of pancreatitis and PDAC, and point to SRSF1-misregulated alternative splicing as a potential therapeutic target. SIGNIFICANCE: We describe the regulation of splicing factor SRSF1 expression in the context of pancreas cell identity, plasticity, and inflammation. SRSF1 protein downregulation is involved in a negative feedback cellular response to KRASG12D expression, contributing to pancreas cell homeostasis. Conversely, upregulated SRSF1 promotes pancreatitis and accelerates KRASG12D-mediated tumorigenesis through enhanced IL1 and MAPK signaling. This article is highlighted in the In This Issue feature, p. 1501.


Asunto(s)
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Pancreatitis , Animales , Ratones , Empalme Alternativo , Carcinogénesis/genética , Carcinoma Ductal Pancreático/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Inflamación , Neoplasias Pancreáticas/patología , Pancreatitis/genética , Pancreatitis/complicaciones , Pancreatitis/patología , Factores de Empalme de ARN/genética , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismo , Humanos
18.
Life (Basel) ; 13(3)2023 Mar 03.
Artículo en Inglés | MEDLINE | ID: mdl-36983848

RESUMEN

Giant cell arteritis (GCA) is an ophthalmological emergency that can be difficult to diagnose and prompt treatment is vital. We investigated the sequential diagnostic value for patients with suspected GCA using three biochemical measures as they arrive to the clinician: first, platelet count, then C-reactive protein (CRP), and lastly, erythrocyte sedimentation rate (ESR). This retrospective cross-sectional study of consecutive patients with suspected GCA investigated platelet count, CRP, and ESR using diagnostic test accuracy statistics and odds ratios (ORs) in a sequential fashion. The diagnosis was established by experts at follow-up, considering clinical findings and tests including temporal artery biopsy. A total of 94 patients were included, of which 37 (40%) were diagnosed with GCA. Compared with those without GCA, patients with GCA had a higher platelet count (p < 0.001), CRP (p < 0.001), and ESR (p < 0.001). Platelet count demonstrated a low sensitivity (38%) and high specificity (88%); CRP, a high sensitivity (86%) and low specificity (56%); routine ESR, a high sensitivity (89%) and low specificity (47%); and age-adjusted ESR, a moderate sensitivity (65%) and moderate specificity (65%). Sequential analysis revealed that ESR did not provide additional value in evaluating risk of GCA. Initial biochemical evaluation can be based on platelet count and CRP, without waiting for ESR, which allows faster initial decision-making in GCA.

19.
Acta Trop ; 241: 106887, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36871618

RESUMEN

OBJECTIVE: In the 2020 UNAIDS HIV treatment goals, 90% of people living with HIV (PLHIV) should be diagnosed, 90% of these should receive antiretroviral treatment (ART) and 90% of these should be virally suppressed. We aimed to evaluate whether Guinea-Bissau fulfills the 2020 treatment goals for both for HIV-1 and HIV-2. DESIGN: By combining data from a general population survey, treatment records from HIV clinics across Guinea-Bissau and a biobank from patients attending the largest HIV clinics in Bissau, we estimated each column of the 90-90-90 cascade. METHOD: 2601 participated in the survey and were used to estimate the proportion of PLHIV who knew their HIV status and the proportion of PLHIV on ART. Answers given in the survey was verified with treatment records from HIV clinics. We measured viral load from biobank materials from HIV patients and estimated the proportion of virally suppressed PLHIV. RESULT: 19.1% of PLHIV indicated to be aware of their HIV status. Of these, 48.5% received ART, and 76.4% of these were virally suppressed. For HIV-1 and HIV-1/2 the results were 21.2%, 40.9% and 75.1%. For HIV-2 the results were 15.9%, 63.6% and 80.7%. 26.9% of all HIV-1 infected in the survey were virologically suppressed, indicating that a much higher number of HIV-1 infected were aware of their status and on treatment. CONCLUSION: Guinea-Bissau lags severely behind both the global and regional progress. Improvement in both testing and treating HIV is necessary to improve the quality of care.


Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , VIH-2 , Guinea Bissau/epidemiología , Antirretrovirales/uso terapéutico , Continuidad de la Atención al Paciente
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