Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 229
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Cell ; 166(2): 343-357, 2016 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-27374334

RESUMEN

Cells benefit from silencing foreign genetic elements but must simultaneously avoid inactivating endogenous genes. Although chromatin modifications and RNAs contribute to maintenance of silenced states, the establishment of silenced regions will inevitably reflect underlying DNA sequence and/or structure. Here, we demonstrate that a pervasive non-coding DNA feature in Caenorhabditis elegans, characterized by 10-base pair periodic An/Tn-clusters (PATCs), can license transgenes for germline expression within repressive chromatin domains. Transgenes containing natural or synthetic PATCs are resistant to position effect variegation and stochastic silencing in the germline. Among endogenous genes, intron length and PATC-character undergo dramatic changes as orthologs move from active to repressive chromatin over evolutionary time, indicating a dynamic character to the An/Tn periodicity. We propose that PATCs form the basis of a cellular immune system, identifying certain endogenous genes in heterochromatic contexts as privileged while foreign DNA can be suppressed with no requirement for a cellular memory of prior exposure.


Asunto(s)
Caenorhabditis elegans/metabolismo , ADN Intergénico/metabolismo , Silenciador del Gen , Animales , Composición de Base , Caenorhabditis elegans/genética , Cromatina , Elementos Transponibles de ADN , ADN Viral/genética , Células Germinativas/metabolismo , Intrones , Regiones Promotoras Genéticas , ARN sin Sentido/metabolismo , ARN Mensajero/metabolismo , Transgenes
2.
Development ; 149(16)2022 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-35876680

RESUMEN

Despite the prominent role of endo-siRNAs in transposon silencing, their expression is not limited to these 'nonself' DNA elements. Transcripts of protein-coding genes ('self' DNA) in some cases also produce endo-siRNAs in yeast, plants and animals. How cells distinguish these two populations of siRNAs to prevent unwanted silencing of active genes in animals is not well understood. To address this question, we inserted various self-gene or gfp fragments into an LTR retrotransposon that produces abundant siRNAs and examined the propensity of these gene fragments to produce ectopic siRNAs in the Caenorhabditis elegans germline. We found that fragments of germline genes are generally protected from production of ectopic siRNAs. This phenomenon, which we termed 'target-directed suppression of siRNA production' (or siRNA suppression), is dependent on the germline expression of target mRNA and requires germline P-granule components. We found that siRNA suppression can also occur in naturally produced endo-siRNAs. We suggest that siRNA suppression plays an important role in regulating siRNA expression and preventing self-genes from aberrant epigenetic silencing. This article has an associated 'The people behind the papers' interview.


Asunto(s)
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Animales , Caenorhabditis elegans/genética , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Células Germinativas/metabolismo , Humanos , Interferencia de ARN , ARN Bicatenario/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo
3.
Nat Methods ; 19(2): 187-194, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35115715

RESUMEN

Single-guide RNAs can target exogenous CRISPR-Cas proteins to unique DNA locations, enabling genetic tools that are efficient, specific and scalable. Here we show that short synthetic guide Piwi-interacting RNAs (piRNAs) (21-nucleotide sg-piRNAs) expressed from extrachromosomal transgenes can, analogously, reprogram the endogenous piRNA pathway for gene-specific silencing in the hermaphrodite germline, sperm and embryos of Caenorhabditis elegans. piRNA-mediated interference ('piRNAi') is more efficient than RNAi and can be multiplexed, and auxin-mediated degradation of the piRNA-specific Argonaute PRG-1 allows conditional gene silencing. Target-specific silencing results in decreased messenger RNA levels, amplification of secondary small interfering RNAs and repressive chromatin modifications. Short (300 base pairs) piRNAi transgenes amplified from arrayed oligonucleotide pools also induce silencing, potentially making piRNAi highly scalable. We show that piRNAi can induce transgenerational epigenetic silencing of two endogenous genes (him-5 and him-8). Silencing is inherited for four to six generations after target-specific sg-piRNAs are lost, whereas depleting PRG-1 leads to essentially permanent epigenetic silencing.


Asunto(s)
Animales Modificados Genéticamente/genética , Caenorhabditis elegans/genética , Silenciador del Gen , Interferencia de ARN , ARN Interferente Pequeño/genética , Animales , Proteínas Argonautas/genética , Caenorhabditis elegans/embriología , Proteínas de Caenorhabditis elegans/genética , Proteínas de Ciclo Celular/genética , Embrión no Mamífero , Epigénesis Genética , Femenino , Masculino
4.
Hum Reprod ; 39(2): 303-309, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38140699

RESUMEN

Fertility restoration using autologous testicular tissue transplantation is relevant for infertile men surviving from childhood cancer and, possibly, in men with absent or incomplete spermatogenesis resulting in the lack of spermatozoa in the ejaculate (non-obstructive azoospermia, NOA). Currently, testicular tissue from pre-pubertal boys extracted before treatment with gonadotoxic cancer therapy can be cryopreserved with good survival of spermatogonial stem cells. However, strategies for fertility restoration, after successful cancer treatment, are still experimental and no clinical methods have yet been developed. Similarly, no clinically available treatments can help men with NOA to become biological fathers after failed attempts of testicular surgical sperm retrieval. We present a case of a 31-year-old man with NOA who had three pieces of testis tissue (each ∼2 × 4 × 2 mm3) extracted and cryopreserved in relation to performing microdissection testicular sperm extraction (mTESE). Approximately 2 years after mTESE, the thawed tissue pieces were engrafted in surgically created pockets bilaterally under the scrotal skin. Follow-up was performed after 2, 4, and 6 months with assessment of reproductive hormones and ultrasound of the scrotum. After 6 months, all engrafted tissue was extracted and microscopically analyzed for the presence of spermatozoa. Furthermore, parts of the extracted tissue were analyzed histologically and by immunohistochemical analysis. Active blood flow in the engrafted tissue was demonstrated by doppler ultrasound after 6 months. No spermatozoa were found in the extracted tissue. Histological and immunohistochemical analysis demonstrated graft survival with intact clear tubules and normal cell organization. Sertoli cells and spermatocytes with normal morphology were located near the basement membrane. MAGE-A and VASA positive spermatogonia/spermatocytes were detected together with SOX9 positive Sertoli cells. Spermatocytes and/or Sertoli cells positive for γH2AX was also detected. In summary, following autologous grafting of frozen-thawed testis tissue under the scrotal skin in a man with NOA, we demonstrated graft survival after 6 months. No mature spermatozoa were detected; however, this is likely due to the pre-existing spermatogenic failure.


Asunto(s)
Azoospermia , Testículo , Adulto , Humanos , Masculino , Niño , Testículo/patología , Semen , Espermatozoides/patología , Espermatogonias , Células de Sertoli , Azoospermia/cirugía , Azoospermia/patología , Recuperación de la Esperma
5.
BJU Int ; 133(6): 742-751, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38348547

RESUMEN

OBJECTIVE: To explore how the use of the ProPep® Nerve Monitoring System (ProPep Surgical, Austin, TX, USA) for intraoperative specific sparing of the pudendal nerve fibres influences postoperative functional outcomes after unilateral nerve-sparing (UNS) or non-nerve-sparing (NNS) robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: We randomised 100 men undergoing UNS or NNS RARP to ProPep nerve monitoring during RARP (intervention) or standard of care RARP (control). Functional outcomes were assessed at 3, 6, and 12 months using the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), the International Prostate Symptom Score, the Danish Prostate Symptom Score, the International Index of Erectile Function, the Erection Hardness Scale, and 24-h pad tests. The primary outcome was the difference in ICIQ-SF score between the groups at 12 months. Secondary outcomes included differences in the remaining outcome measures and continence rates at all time points. Continence was defined as the use of no pads and the answer 'Never' to the question: 'How often do you experience urinary incontinence?' or a urine loss of <8 g on the 24-h pad test. RESULTS: A total of 82 patients were included in the per-protocol analysis at 12 months with 41 in each group. At 12 months the mean ICIQ-SF scores were 5.37 (95% confidence interval [CI] 3.71-7.03) and 5.66 (95% CI 4.05-7.27) for the intervention and control groups, respectively (P = 0.8). There were no statistically significant differences in any of the remaining outcomes. However, the continence rate was higher in the intervention group at 6 months (63% vs 44%, P = 0.09). CONCLUSIONS: Intraoperative nerve monitoring did not result in better functional outcomes following UNS or NNS RARP. Larger studies are needed to explore if ProPep can reduce the time to continence after RARP.


Asunto(s)
Prostatectomía , Neoplasias de la Próstata , Nervio Pudendo , Procedimientos Quirúrgicos Robotizados , Incontinencia Urinaria , Humanos , Prostatectomía/métodos , Prostatectomía/efectos adversos , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/cirugía , Anciano , Procedimientos Quirúrgicos Robotizados/efectos adversos , Resultado del Tratamiento , Incontinencia Urinaria/etiología , Incontinencia Urinaria/prevención & control , Tratamientos Conservadores del Órgano/métodos , Próstata/inervación , Próstata/cirugía , Disfunción Eréctil/etiología , Disfunción Eréctil/prevención & control , Monitoreo Intraoperatorio/métodos , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Recuperación de la Función
6.
World J Urol ; 42(1): 359, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38811395

RESUMEN

PURPOSE: Platelet-rich plasma (PRP) as a regenerative therapy has gained interest in the field of andrology for the treatment of erectile dysfunction (ED) and Peyronie's disease (PD). This systematic review aims to critically evaluate the current evidence on the use of PRP for these conditions. METHODS: We performed a systematic literature search according to the PRISMA guidelines using PubMed and Scopus databases in December 2023. Studies were included if they evaluated the effect of PRP therapy for ED or PD in humans. RESULTS: We identified 164 articles, 17 of which were included, consisting of 11 studies on ED, 5 studies on PD, and 1 study on both. We included four randomized controlled trials, 11 prospective cohort studies, and three retrospective cohort studies including a total of 1099 patients. The studies on ED and PD generally showed small to moderate benefits with mild and transient side effects and no major adverse events were reported. General limitations included variations in PRP protocols, small sample sizes, short follow-up periods, and lack of control groups except in the three randomized trials on ED and the one on PD. CONCLUSION: The literature on PRP therapy in andrology is limited and difficult to interpret due to variations in protocols and methodological drawbacks. Further research is necessary to determine the optimal preparation and treatment protocols for PRP therapy and clarify its effectiveness in andrology.


Asunto(s)
Disfunción Eréctil , Induración Peniana , Plasma Rico en Plaquetas , Humanos , Induración Peniana/terapia , Masculino , Disfunción Eréctil/terapia
7.
Acta Anaesthesiol Scand ; 68(1): 137-143, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37743099

RESUMEN

Mobilisation difficulties, due to muscle weakness, and urinary retention are common reasons for prolonged admission following hip and knee arthroplasty procedures. Whether spinal anaesthesia is detrimental to early mobilisation is controversial. Previous studies have reported differences in post-operative recovery between spinal anaesthesia and general anaesthesia; however, up-to-date comparisons in fast-track setups are needed. Our randomized, single-blinded, multi-centre, clinical trials aim to compare the post-operative recovery after total hip (THA), total knee (TKA), and unicompartmental knee arthroplasties (UKA) respectively when using either spinal anaesthesia (SA) or general anaesthesia (GA) in a fast-track setup. Included patients (74 THA, 74 TKA, and 74 UKA patients) are randomized (1:1) to receive either SA (2 mL 0.5% Bupivacaine) or GA (Induction: Propofol 1.0-2.0 mg/kg iv with Remifentanil 3-5 mcg/kg iv. Infusion: Propofol 3-5 mg/kg/h and Remifentanil 0.5 mcg/kg/min iv). Patients undergo standard primary unilateral hip and knee arthroplasty procedures in an optimized fast-track setup with intraoperative local infiltrative analgesia in TKA and UKA, post-operative multimodal opioid sparing analgesia, immediate mobilisation with full weightbearing, no drains and in-hospital only thromboprophylaxis. Data will be collected on the day of surgery and until patients are discharged. The primary outcome is the ability to be safely mobilised during a 5-m walking test within 6 h of surgery. Secondary outcomes include fulfilment of discharge criteria, post-operative pain, dizziness, and nausea as well as patient reported recovery and opioid related side effects. Data will also be gathered on all hospital contacts within 30-days of surgery. This study will offer insights into advantages and disadvantages of anaesthetic methods used in fast-track arthroplasty surgery.


Asunto(s)
Anestesia Raquidea , Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Propofol , Tromboembolia Venosa , Humanos , Anestesia Raquidea/métodos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Remifentanilo , Analgésicos Opioides , Anticoagulantes , Tromboembolia Venosa/etiología , Anestesia General/métodos , Artroplastia de Reemplazo de Cadera/efectos adversos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto
8.
J Med Internet Res ; 26: e47278, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602748

RESUMEN

BACKGROUND: The digitalization of public and health sectors worldwide is fundamentally changing health systems. With the implementation of digital health services in health institutions, a focus on digital health literacy and the use of digital health services have become more evident. In Denmark, public institutions use digital tools for different purposes, aiming to create a universal public digital sector for everyone. However, this digitalization risks reducing equity in health and further marginalizing citizens who are disadvantaged. Therefore, more knowledge is needed regarding patients' digital practices and experiences with digital health services. OBJECTIVE: This study aims to examine digital practices and experiences with public digital health services and digital tools from the perspective of patients in the neurology field and address the following research questions: (1) How do patients use digital services and digital tools? (2) How do they experience them? METHODS: We used a qualitative design with a hermeneutic approach. We conducted 31 semistructured interviews with patients who were hospitalized or formerly hospitalized at the department of neurology in a hospital in Denmark. The interviews were audio recorded and subsequently transcribed. The text from each transcribed interview was analyzed using manifest content analysis. RESULTS: The analysis provided insights into 4 different categories regarding digital practices and experiences of using digital tools and services in health care systems: social resources as a digital lifeline, possessing the necessary capabilities, big feelings as facilitators or barriers, and life without digital tools. Our findings show that digital tools were experienced differently, and specific conditions were important for the possibility of engaging in digital practices, including having access to social resources; possessing physical, cognitive, and communicative capabilities; and feeling motivated, secure, and comfortable. These prerequisites were necessary for participants to have positive experiences using digital tools in the health care system. Those who did not have these prerequisites experienced challenges and, in some cases, felt left out. CONCLUSIONS: Experiences with digital practices and digital health services are complex and multifaceted. Engagement in digital practices for the examined population requires access to continuous assistance from their social network. If patients do not meet requirements, digital health services can be experienced as exclusionary and a source of concern. Physical, cognitive, and communicative difficulties might make it impossible to use digital tools or create more challenges. To ensure that digitalization does not create inequities in health, it is necessary for developers and institutions to be aware of the differences in digital health literacy, focus on simplifying communication with patients and next of kin, and find flexible solutions for citizens who are disadvantaged.


Asunto(s)
Concienciación , Salud Digital , Humanos , Investigación Cualitativa , Hermenéutica , Comunicación
9.
J Electrocardiol ; 84: 129-136, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38663227

RESUMEN

BACKGROUND: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time. METHODS: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population. We regressed ECG markers with the presence of diabetes and the duration of clinical diabetes, respectively, adjusted for sex, age, body mass index, smoking, heart rate, diabetes medication, renal function, hypertension, and myocardial infarction. RESULTS: We matched 988 people with type 2 diabetes (332, 34% females) with as many controls. Heart rate was 8 bpm higher (p < 0.001) in people with vs. without type 2 diabetes, but the difference declined with increasing diabetes duration. For most depolarization markers, the difference between people with and without type 2 diabetes increased progressively with diabetes duration. On average, R-wave amplitude was 6 mm lower in lead V5 (p < 0.001), P-wave duration was 5 ms shorter (p < 0.001) and QRS duration was 3 ms (p = 0.03). Among repolarization markers, T-wave amplitude (measured in V5) was lower in patients with type 2 diabetes (1 mm lower, p < 0.001) and the QRS-T angle was 10 degrees wider (p = 0.002). We observed no association between diabetes duration and repolarization markers. CONCLUSIONS: Type 2 diabetes was independently associated with electrocardiographic depolarization and repolarization changes. Differences in depolarization markers, but not repolarization markers, increased with increasing diabetes duration.


Asunto(s)
Diabetes Mellitus Tipo 2 , Electrocardiografía , Humanos , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Anciano , Sensibilidad y Especificidad , Biomarcadores/sangre , Reproducibilidad de los Resultados , Frecuencia Cardíaca
10.
Euro Surveill ; 29(7)2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38362625

RESUMEN

A surge in gonorrhoea in Denmark has occurred since 2022, a 46% increase from 2021. National surveillance, leveraging mandatory reporting and epidemiological data, highlights three distinct clades linked to heterosexual transmission. Despite the rise, these exhibit high susceptibility, contrasting MSM-associated strains. Geographical hotspots and age-specific patterns further illuminate transmission dynamics. The combination of genomic and epidemiological data provides novel insights into the evolving landscape of gonorrhoea, indicating potential shifts in infection dynamics and transmissibility.


Asunto(s)
Gonorrea , Humanos , Antibacterianos/uso terapéutico , Dinamarca/epidemiología , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Heterosexualidad , Neisseria gonorrhoeae/genética
11.
Acta Orthop ; 95: 147-151, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38393295

RESUMEN

BACKGROUND AND PURPOSE: The overall potential pool of day-case candidates on a national level in hip and knee arthroplasty is unknown. We aimed to estimate the proportion of hip and knee arthroplasty patients eligible for day-case surgery based on contemporary widely used criteria and determine whether there has been a change in the proportion of eligible patients over time and, secondarily, to investigate the proportion of eligible patients discharged on the day of surgery. METHODS: Based on data from the Danish National Patient Register, we identified all patients undergoing primary unilateral hip or knee arthroplasty from January 2010 to March 2020. Using a modification of day-case eligibility criteria proposed by a national multicenter collaboration, we sorted patients into either day-case eligible or ineligible. A day-case procedure was defined as discharge on the day of surgery. RESULTS: We included patients comprising a total of 166,730 primary total hip (THA), total knee (TKA), and unicompartmental knee arthroplasty (UKA). 48% (95% confidence interval [CI] 48-49) were eligible for day-case surgery, with a decline from 50% (CI 49-51) in 2010 to 46% (CI 46-47) eligible in 2019. More UKA patients were day-case eligible (55%, CI 54-56) than THA (47%, CI 47-48) and TKA patients (49%, CI 48-49). A maximum of 8.0% (CI 7.4-8.5) of eligible patients were discharged on the day of surgery in 2019. CONCLUSION: 48% of the Danish hip and knee arthroplasty patients were potential day-case candidates, with a small decline in eligibility from 50% in 2010 to 46% in 2019. Day of surgery discharge among day-case eligible patients peaked at 8% in 2019. Thus, the potential for more day-case surgery seems large.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Humanos , Procedimientos Quirúrgicos Ambulatorios , Artroplastia de Reemplazo de Cadera/métodos , Artroplastia de Reemplazo de Rodilla/métodos , Extremidad Inferior , Alta del Paciente , Sistema de Registros
12.
Acta Orthop ; 95: 219-224, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715473

RESUMEN

BACKGROUND AND PURPOSE: Length of hospital stay after hip and knee arthroplasty is about 1 day in Denmark with few patients discharged on the day of surgery. Hence, a protocol for multicenter implementation of discharge on day of surgery has been instituted. We aimed to describe the implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting. METHODS: We performed a prospective multicenter study from 7 public hospitals across Denmark. Patients were screened using well-defined in- and exclusion criteria and were discharged on day of surgery when fulfilling functional discharge criteria. The study period was from September 2022 to February 2023 with variable start of implementation. Data from the same centers in a 6-month period before the COVID pandemic from July 2019 to December 2019 was used for baseline control. RESULTS: Of 2,756 primary hip and knee arthroplasties, 37% (95% confidence interval [CI] 35-39) were eligible (range 21-50% in centers) and 52% (range 24-62%) of these were discharged on day of surgery. 21% (CI 20-23) of all patients (eligible and non-eligible) were discharged on day of surgery with a range of 10-31% within centers. This was an additional 15% (CI 13-17, P < 0.001) compared with patients discharged in the control period (6% in 2019). CONCLUSION: We found it possible to perform outpatient hip and knee replacement in 21% of patients in a public healthcare setting, probably to be increased with further center experience.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Artroplastia de Reemplazo de Cadera/métodos , Estudios Prospectivos , Dinamarca , Femenino , Masculino , Anciano , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Procedimientos Quirúrgicos Ambulatorios , Tiempo de Internación , Alta del Paciente , Hospitales Públicos/estadística & datos numéricos , Anciano de 80 o más Años
13.
BMC Genomics ; 24(1): 213, 2023 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-37095447

RESUMEN

BACKGROUND: Understanding the mechanisms underlining forage production and its biomass nutritive quality at the omics level is crucial for boosting the output of high-quality dry matter per unit of land. Despite the advent of multiple omics integration for the study of biological systems in major crops, investigations on forage species are still scarce. RESULTS: Our results identified substantial changes in gene co-expression and metabolite-metabolite network topologies as a result of genetic perturbation by hybridizing L. perenne with another species within the genus (L. multiflorum) relative to across genera (F. pratensis). However, conserved hub genes and hub metabolomic features were detected between pedigree classes, some of which were highly heritable and displayed one or more significant edges with agronomic traits in a weighted omics-phenotype network. In spite of tagging relevant biological molecules as, for example, the light-induced rice 1 (LIR1), hub features were not necessarily better explanatory variables for omics-assisted prediction than features stochastically sampled and all available regressors. CONCLUSIONS: The utilization of computational techniques for the reconstruction of co-expression networks facilitates the identification of key omic features that serve as central nodes and demonstrate correlation with the manifestation of observed traits. Our results also indicate a robust association between early multi-omic traits measured in a greenhouse setting and phenotypic traits evaluated under field conditions.


Asunto(s)
Oryza , Poaceae , Multiómica , Fenotipo , Metabolómica
14.
Int J Obes (Lond) ; 47(11): 1143-1151, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37653071

RESUMEN

BACKGROUND/OBJECTIVES: After Roux-en-Y gastric bypass (RYGB) a subset of patients never obtain excess BMI loss (EBMIL) > 50% and are categorized as having primary weight loss (WL) failure. We hypothesized that postprandial concentrations of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) would be lower in patients with primary WL failure compared with patients with successfully maintained WL. Furthermore, that inhibition of gut hormone secretions would increase ad libitum food intake less in patients with primary WL failure. SUBJECTS/METHODS: Twenty women with primary WL failure (LowEBMIL < 50%) were individually matched to twenty women with successful WL (HighEBMIL > 60%) on age, preoperative BMI and time from RYGB. On separate days performed in a random order, patient-blinded subcutaneous injections of octreotide or saline (placebo) were followed by a fixed breakfast and an ad libitum lunch with blood sampling for appetite regulating hormones and Visual-Analogue-Scale (VAS)-scoring of hunger/satiety. Furthermore, participants underwent gene variant analysis for GLP-1, PYY and their receptors, indirect calorimetry, dual-energy X-ray absorptiometry (DXA)-scans, 4-days at-home food registration and 14-days step counting. RESULTS: On placebo days, postprandial GLP-1, PYY and cholecystokinin (CCK) concentrations were similar between groups after breakfast. Fasting ghrelin was lower in LowEBMIL, but the postprandial suppression was similar. LowEBMIL had lower satiety VAS-scores and less suppression of hunger VAS-scores. Gene variants did not differ between groups. Octreotide diminished GLP-1, PYY, CCK and ghrelin concentrations in both groups. Octreotide did not affect ad libitum food intake in LowEBMIL (-1% [-13, 12], mean [95%CI]), while food intake increased in HighEBMIL (+23% [2,44]). CONCLUSIONS: Primary WL failure after RYGB was not characterized by impaired secretions of appetite regulating gut hormones. Interestingly, inhibition of gut hormone secretions with octreotide only increased food intake in patients with successful WL post-RYGB. Thus, an impaired central anorectic response to gut hormones may contribute to primary WL failure after RYGB.


Asunto(s)
Derivación Gástrica , Hormonas Gastrointestinales , Humanos , Femenino , Ghrelina , Octreótido/farmacología , Péptido YY , Péptido 1 Similar al Glucagón , Colecistoquinina , Ingestión de Alimentos , Pérdida de Peso/fisiología
15.
Malar J ; 22(1): 285, 2023 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-37752504

RESUMEN

BACKGROUND: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has revolutionized identification of bacteria and is becoming available in an increasing number of laboratories in malaria-endemic countries. The purpose of this proof-of-concept study was to explore the potential of MALDI-TOF as a diagnostic tool for direct detection and quantification of Plasmodium falciparum in human blood. METHODS: Three different P. falciparum strains (3D7, HB3 and IT4) were cultured and synchronized following standard protocols. Ring-stages were diluted in fresh blood group 0 blood drawn in EDTA from healthy subjects to mimic clinical samples. Samples were treated with saponin and washed in PBS to concentrate protein material. Samples were analysed using a Microflex LT MALDI-TOF and resulting mass spectra were compared using FlexAnalysis software. RESULTS: More than 10 peaks specific for P. falciparum were identified. The identified peaks were consistent among the three genetically unrelated strains. Identification was possible in clinically relevant concentrations of 0.1% infected red blood cells, and a close relationship between peak intensity and the percentage of infected red blood cells was seen. CONCLUSION: The findings indicate that the method has the potential to detect and quantify P. falciparum at clinically relevant infection intensities and provides proof-of-concept for MALDI-TOF-based diagnosis of human malaria. Further research is needed to include other Plasmodium spp., wildtype parasite isolates and to increase sensitivity. MALDI-TOF may be a useful tool for mass-screening purposes and for diagnosis of malaria in settings where it is readily available.


Asunto(s)
Malaria Falciparum , Plasmodium falciparum , Humanos , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción/métodos , Prueba de Estudio Conceptual , Malaria Falciparum/diagnóstico , Rayos Láser
16.
Clin Chem Lab Med ; 61(9): 1590-1596, 2023 08 28.
Artículo en Inglés | MEDLINE | ID: mdl-36971447

RESUMEN

OBJECTIVES: We evaluated the long-term stability of thyroid peroxidase antibody (anti-TPO). METHODS: In the Danish General Suburban Population Study (GESUS), serum samples were biobanked at -80 °C during 2010-2013. In a paired design with 70 subjects, we compared anti-TPO (30-198 U/mL) measured on fresh serum on Kryptor Classic in 2010-2011 (anti-TPOfresh) with anti-TPO remeasured on frozen serum (anti-TPOfrozen) on Kryptor Compact Plus in 2022. Both instruments used the same reagents and the anti-TPOn automated immunofluorescent assay, which was calibrated against the international standard NIBSC 66/387, based on the Time Resolved Amplified Cryptate Emission (TRACE) technology from BRAHMS. Values greater than 60 U/mL are regarded as positive in Denmark with this assay. Statistical comparisons included Bland-Altman, Passing-Bablok regression, and Kappa statistic. RESULTS: The mean follow-up time was 11.9 years (SD: 0.43). For anti-TPOfrozen vs. anti-TPOfresh, the line of equality was within the confidence interval of the absolute mean difference [5.71 (-0.32; 11.7) U/mL] and the average percentage deviation [+2.22% (-3.89%; +8.34%)]. The average percentage deviation of 2.22% did not exceed analytical variability. Passing-Bablok regression revealed both a statistically significant systematic and proportional difference: Anti-TPOfrozen=-22.6 + 1.22*(anti-TPOfresh). Frozen samples were correctly classified as positive in 64/70 (91.4%; Kappa=71.8%). CONCLUSIONS: Anti-TPO serum samples in the range 30-198 U/mL were stable after 12-years of storage at -80 °C with an estimated nonsignificant average percentage deviation of +2.22%. This comparison is based on Kryptor Classic and Kryptor Compact Plus, which used identical assays, reagents, and calibrator, but for which the agreement in the range 30-198 U/mL is unclarified.


Asunto(s)
Autoanticuerpos , Yoduro Peroxidasa , Humanos , Población Suburbana , Dinamarca
17.
Euro Surveill ; 28(26)2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37382884

RESUMEN

A highly virulent sub-lineage of the Streptococcus pyogenes M1 clone has been rapidly expanding throughout Denmark since late 2022 and now accounts for 30% of the new invasive group A streptococcal infections. We aimed to investigate whether a shift in variant composition can account for the high incidence rates observed over winter 2022/23, or if these are better explained by the impact of COVID-19-related restrictions on population immunity and carriage of group A Streptococcus.


Asunto(s)
COVID-19 , Infecciones Estreptocócicas , Humanos , Streptococcus pyogenes/genética , Estaciones del Año , Infecciones Estreptocócicas/epidemiología , Dinamarca/epidemiología
18.
J Arthroplasty ; 38(2): 252-258.e2, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36096272

RESUMEN

BACKGROUND: In this study, we examined the association between obesity and patient-reported outcome measures after medial unicompartmental knee arthroplasty (MUKA), assessed through score changes, Patient Acceptable Symptom State (PASS), and minimal important change (MIC). Second, the association between obesity and early readmissions was examined. METHODS: A total of 450 MUKAs (mean body mass index [BMI] 30.3, range, 19.6-53.1), performed from February 2016 to December 2020, were grouped using BMI: <30, 30-34.9, and >34.9. Oxford Knee Score (OKS), Forgotten Joint Score (FJS), and Activity and Participation Questionnaire (APQ) were assessed preoperatively and at 3, 12, and 24 months, postoperatively. The 12-month PASS and MIC were also assessed, defining PASS as OKS = 30, MIC-OKS as change in OKS = 8, and MIC-FJS as change in FJS = 14. RESULTS: No significant differences in OKS change were found between BMI groups. After 12 months, patients who had a BMI of 30-34.9 had lower change in FJS (estimate -8.1, 95% CI -14.9 to -1.4) and were less likely to reach PASS (odds ratio 0.4, 95% CI 0.2-0.7) as well as MIC-FJS (odds ratio 0.5, 95% CI 0.2-0.9). Both obese groups had lower change in APQ after 12 months. Differences in 90-day readmission rates were nonsignificant between groups. CONCLUSION: Our findings of no differences in OKS improvement between BMI groups and achieving MIC for BMI > 34.9 suggest good improvements in obese patients despite lower preoperative scores, supporting contemporary indications for MUKA. Lower APQ development and achievement of 12-month PASS may be used when addressing expectations of recovery.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/etiología , Obesidad/cirugía , Medición de Resultados Informados por el Paciente , Índice de Masa Corporal , Resultado del Tratamiento
19.
Acta Orthop ; 94: 178-184, 2023 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-37074191

RESUMEN

BACKGROUND AND PURPOSE: No previous studies have investigated the use of day-case arthroplasty in Denmark on a national scale. We investigated the frequency of day-case surgery in total hip (THA), total knee (TKA), and unicompartmental knee arthroplasty (UKA) from 2010 to 2020 in Denmark. PATIENTS AND METHODS: Primary unilateral THAs, TKAs, and UKAs performed for osteoarthritis were identified in the Danish National Patient Register using procedural and diagnosis codes. Day-case surgery was defined as discharge on the day of surgery. 90-day readmissions were defined as any overnight admissions following discharge. RESULTS: From 2010 to 2020 Danish surgical centers performed 86,070 THAs, 70,323 TKAs, and 10,440 UKAs. From 2010 to 2014, less than 0.5% of THAs and TKAs were day-case procedures. They increased to 5.4% (95% confidence interval [CI] 4.9-5.8) of THAs and 2.8% (CI 2.4-3.2) of TKAs in 2019. From 2010 to 2014, 11% of UKAs were day-case procedures, but they increased to 20% (CI 18-22) in 2019. This increase was driven by a few surgical centers (3-7 centers). In 2010, readmission rates within 90 days of surgery were 10% after THAs and 11% after TKAs, and 9.4% for both THAs and TKAs in 2019. Readmission rates after UKA fluctuated between 4% and 7%. CONCLUSION: From 2010 to 2020 the use of day-case surgery in THA, TKA, and UKA increased in Denmark, driven by only a few centers. During the same period readmissions did not increase.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Osteoartritis de la Rodilla/epidemiología , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico , Articulación de la Rodilla/cirugía , Hospitalización , Dinamarca/epidemiología
20.
Acta Orthop ; 94: 516-522, 2023 10 13.
Artículo en Inglés | MEDLINE | ID: mdl-37831058

RESUMEN

BACKGROUND AND PURPOSE: Day-case hip and knee arthroplasty has gained in popularity, but there are conflicting results regarding readmissions. We aimed to investigate differences in 30- and 90-day readmission rates between day-case patients and patients with a single overnight stay following primary total hip arthroplasty (THA), total knee arthroplasty (TKA), and unicompartmental knee arthroplasty (UKA). PATIENTS AND METHODS: We identified day-case (DC) and overnight (ON) THA, TKA, and UKA patients, operated on between 2010 and 2020, from the Danish National Patient Register. Day-case surgery was defined as discharge on the day of surgery. Overnight readmissions within 30 or 90 days of surgery were considered readmissions. We compared readmission rates between DC and ON patients within arthroplasty types using logistic regression adjusted for patient characteristics and year of surgery. We included 29,486 THAs (1,353 DC and 28,133 ON), 15,116 TKAs (617 DC and 14,499 ON), and 6,440 UKAs (1,528 DC and 4,914 ON). RESULTS: The 30-day readmission rates were: DC-THA 4.4% vs. ON-THA 4.4% (adjusted odds-ratio [aOR] 1.2, 95% confidence interval [CI] 0.91-1.6), DC-TKA 4.7% vs. ON-TKA 4.4% (aOR 1.1, CI 0.69-1.5), and DC-UKA 3.0% vs. ON-UKA 3.0% (aOR 1.1, CI 0.78-1.5). Similarly, no significant differences were present between DC and ON THA, TKA, and UKA regarding 90-day readmissions or time to readmission. CONCLUSION: We found no differences in readmission rates between day-case THA, TKA, and UKA patients and patients with a single overnight stay.


Asunto(s)
Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Readmisión del Paciente , Complicaciones Posoperatorias , Artroplastia de Reemplazo de Cadera/efectos adversos , Alta del Paciente , Tiempo de Internación , Factores de Riesgo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA