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1.
PLoS Negl Trop Dis ; 18(6): e0012256, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38870209

RESUMEN

The Aedes aegypti cadherin-like protein (Aae-Cad) and the membrane-bound alkaline phosphatase (Aae-mALP) are membrane proteins identified as putative receptors for the larvicidal Cry toxins produced by Bacillus thuringiensis subsp. israelensis bacteria. Cry toxins are the most used toxins in the control of different agricultural pest and mosquitos. Despite the relevance of Aae-Cad and Aae-mALP as possible toxin-receptors in mosquitoes, previous efforts to establish a clear functional connection among them and Cry toxins activity have been relatively limited. In this study, we used CRISPR-Cas9 to generate knockout (KO) mutations of Aae-Cad and Aae-mALP. The Aae-mALP KO was successfully generated, in contrast to the Aae-Cad KO which was obtained only in females. The female-linked genotype was due to the proximity of aae-cad gene to the sex-determining loci (M:m). Both A. aegypti KO mutant populations were viable and their insect-development was not affected, although a tendency on lower egg hatching rate was observed. Bioassays were performed to assess the effects of these KO mutations on the susceptibility of A. aegypti to Cry toxins, showing that the Aae-Cad female KO or Aae-mALP KO mutations did not significantly alter the susceptibility of A. aegypti larvae to the mosquitocidal Cry toxins, including Cry11Aa, Cry11Ba, Cry4Ba, and Cry4Aa. These findings suggest that besides the potential participation of Aae-Cad and Aae-mALP as Cry toxin receptors in A. aegypti, additional midgut membrane proteins are involved in the mode of action of these insecticidal toxins.


Asunto(s)
Aedes , Fosfatasa Alcalina , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas , Sistemas CRISPR-Cas , Cadherinas , Endotoxinas , Proteínas Hemolisinas , Animales , Aedes/genética , Aedes/efectos de los fármacos , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/genética , Proteínas Hemolisinas/genética , Proteínas Hemolisinas/metabolismo , Endotoxinas/genética , Endotoxinas/metabolismo , Femenino , Cadherinas/genética , Cadherinas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo , Resistencia a los Insecticidas/genética , Técnicas de Inactivación de Genes , Larva/genética , Larva/crecimiento & desarrollo , Bacillus thuringiensis/genética , Bacillus thuringiensis/metabolismo , Masculino , Insecticidas/farmacología
2.
PEC Innov ; 4: 100291, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38872981

RESUMEN

Objective: To assess the Behavioral Intention Predictive Framework's utility in explaining variation in cancer patients' strong behavioral intention (SBI) to use LEAPS (Listen, Educate, Assess, Partner, Support) communication skills after viewing training videos. Methods: Ninety-eight patients were enrolled through anonymized online platforms to view LEAPS training videos, complete background and communication questionnaires and report their SBI to use LEAPS skills. Results: On average, patients indicated SBI to use 6 of 13 skills and 46% of patients expressed SBI across individual skills. The framework explained 27.7% of the adjusted variance in SBI with significant predictors of frequent past use of LEAPS-related shared decision-making behaviors, poor emotional health, being rarely accompanied to visits and positive ratings of narrative videos. Finally, 21.7% of the adjusted variance in problem communication was explained by infrequent use of LEAPS-related information behaviors, patient accompaniment of another adult and positive narrative scores. Conclusion: Patients SBI to use multiple LEAPS skills and past problem communication were explained by framework predictors. Innovation: Despite theoretical and empirical evidence that behavioral intention significantly predicts behavior, it has not been studied in patient communication research. Application of the novel framework to LEAPS training videos contributes an innovative address of this research gap.

3.
One Health ; 18: 100758, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38846705

RESUMEN

The Philippines faces a complex and interconnected web of human, animal, and environmental health issues, including zoonotic and reverse zoonotic diseases, antimicrobial resistance, food insecurity and contamination, and threats from environmental degradation. This paper examines these issues, existing interventions, and their implementation challenges. The overall framework used to analyze the level of operationalization of the One Health approach is the Multi-sectoral One Health Coordination Framework developed by the World Health Organization, Food and Agriculture Organization, and the World Organization for Animal Health. A two-step process was conducted: literature review, followed by consultations with government and non-government stakeholders across national, subnational, and local levels. There has been significant progress in laying the foundation for collaboration between the human, animal, and environmental sectors. These are demonstrated by the presence of structures and systems, including inter-agency task forces, emergency response plans and mechanisms, and a network for health human resources. However, these are eclipsed by challenges, including the limited governance mechanisms within inter-agency committees, fragmented risk assessment and surveillance, untapped opportunities for joint investigation and response, insufficient resources for capacity-building, and absence of comprehensive risk communication and community engagement initiatives. These challenges highlight the importance of promoting multi-sectoral governance and ensuring resource allocation and sharing. Joint activities across risk assessment, surveillance, investigation, and response are critical in ensuring a proactive and holistic approach to addressing threats. A well-capacitated interdisciplinary workforce, not only capable of managing these hazards but also empowering communities to protect themselves, is necessary in ensuring innovation and collaboration on health risks at the human-animal-environment interface. In light of the multifaceted challenges faced by the Philippines, the One Health approach emerges as a vital strategy. By addressing governance issues, enhancing coordination, and bolstering resource allocation, the country can better protect the health and well-being of its people, animals, and ecosystems.

4.
J Nephrol ; 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38837003

RESUMEN

BACKGROUND: Kidney failure in young people is often unexplained and a significant proportion will have an underlying genetic diagnosis. National Health Service England pioneered a comprehensive genomic testing service for such circumstances accessible to clinicians working outside of genetics. This is the first review of patients using this novel service since October 2021, following its introduction into clinical practice. METHODS: The 'Unexplained Young-Onset End-Stage Renal Disease' (test-code R257) gene panel uses targeted next generation sequencing to analyse 175 genes associated with renal disease in patients under 36 years of age. All tests undertaken between October 2021 and February 2022 were reviewed. Phenotypic data were extracted from request forms and referring clinicians contacted where additional details were required. RESULTS: Seventy-one patients underwent R257 testing over the study period. Among them, 23/71 patients (32%) were confirmed to have a genetic diagnosis and 2/71 (3%) had a genetically suggestive variant. Nephronophthisis and Alport syndrome were the most common conditions identified, (4/23 (17%) with pathogenic variants in NPHP1 and 4/23 (17%) with pathogenic variants in COL4A3/COL4A4). Positive predictors of a genetic diagnosis included a family history of renal disease (60% of positive cases) and extra-renal disease manifestations (48% of positive cases). CONCLUSION: This is the first study to evaluate the R257 gene panel in unexplained young-onset kidney failure, freely accessible to patients meeting testing criteria in England. A genetic diagnosis was identified in 32% of patients. This study highlights the essential and expanding role that genomic testing has for children and families affected by renal disease today.

5.
bioRxiv ; 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38854025

RESUMEN

Pulmonary arterial hypertension (PAH) is characterized by obliterative vascular remodeling of the small pulmonary arteries (PA) and progressive increase in pulmonary vascular resistance (PVR) leading to right ventricular (RV) failure. Although several drugs are approved for the treatment of PAH, mortality remains high. Accumulating evidence supports a pathological function of integrins in vessel remodeling, which are gaining renewed interest as drug targets. However, their role in PAH remains largely unexplored. We found that the arginine-glycine-aspartate (RGD)-binding integrin α5ß1 is upregulated in PA endothelial cells (PAEC) and PA smooth muscle cells (PASMC) from PAH patients and remodeled PAs from animal models. Blockade of the integrin α5ß1 or depletion of the α5 subunit resulted in mitotic defects and inhibition of the pro-proliferative and apoptosis-resistant phenotype of PAH cells. Using a novel small molecule integrin inhibitor and neutralizing antibodies, we demonstrated that α5ß1 integrin blockade attenuates pulmonary vascular remodeling and improves hemodynamics and RV function in multiple preclinical models. Our results provide converging evidence to consider α5ß1 integrin inhibition as a promising therapy for pulmonary hypertension. One sentence summary: The α5ß1 integrin plays a crucial role in pulmonary vascular remodeling.

6.
Ann Intern Med ; 177(6): 768-781, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38739921

RESUMEN

BACKGROUND: Whether circulating sex hormones modulate mortality and cardiovascular disease (CVD) risk in aging men is controversial. PURPOSE: To clarify associations of sex hormones with these outcomes. DATA SOURCES: Systematic literature review to July 2019, with bridge searches to March 2024. STUDY SELECTION: Prospective cohort studies of community-dwelling men with sex steroids measured using mass spectrometry and at least 5 years of follow-up. DATA EXTRACTION: Independent variables were testosterone, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), dihydrotestosterone (DHT), and estradiol concentrations. Primary outcomes were all-cause mortality, CVD death, and incident CVD events. Covariates included age, body mass index, marital status, alcohol consumption, smoking, physical activity, hypertension, diabetes, creatinine concentration, ratio of total to high-density lipoprotein cholesterol, and lipid medication use. DATA SYNTHESIS: Nine studies provided individual participant data (IPD) (255 830 participant-years). Eleven studies provided summary estimates (n = 24 109). Two-stage random-effects IPD meta-analyses found that men with baseline testosterone concentrations below 7.4 nmol/L (<213 ng/dL), LH concentrations above 10 IU/L, or estradiol concentrations below 5.1 pmol/L had higher all-cause mortality, and those with testosterone concentrations below 5.3 nmol/L (<153 ng/dL) had higher CVD mortality risk. Lower SHBG concentration was associated with lower all-cause mortality (median for quintile 1 [Q1] vs. Q5, 20.6 vs. 68.3 nmol/L; adjusted hazard ratio [HR], 0.85 [95% CI, 0.77 to 0.95]) and lower CVD mortality (adjusted HR, 0.81 [CI, 0.65 to 1.00]). Men with lower baseline DHT concentrations had higher risk for all-cause mortality (median for Q1 vs. Q5, 0.69 vs. 2.45 nmol/L; adjusted HR, 1.19 [CI, 1.08 to 1.30]) and CVD mortality (adjusted HR, 1.29 [CI, 1.03 to 1.61]), and risk also increased with DHT concentrations above 2.45 nmol/L. Men with DHT concentrations below 0.59 nmol/L had increased risk for incident CVD events. LIMITATIONS: Observational study design, heterogeneity among studies, and imputation of missing data. CONCLUSION: Men with low testosterone, high LH, or very low estradiol concentrations had increased all-cause mortality. SHBG concentration was positively associated and DHT concentration was nonlinearly associated with all-cause and CVD mortality. PRIMARY FUNDING SOURCE: Medical Research Future Fund, Government of Western Australia, and Lawley Pharmaceuticals. (PROSPERO: CRD42019139668).


Asunto(s)
Enfermedades Cardiovasculares , Causas de Muerte , Dihidrotestosterona , Estradiol , Hormona Luteinizante , Globulina de Unión a Hormona Sexual , Testosterona , Humanos , Masculino , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/sangre , Testosterona/sangre , Globulina de Unión a Hormona Sexual/análisis , Globulina de Unión a Hormona Sexual/metabolismo , Estradiol/sangre , Hormona Luteinizante/sangre , Dihidrotestosterona/sangre , Incidencia , Factores de Riesgo , Anciano , Persona de Mediana Edad
7.
Foods ; 13(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38790740

RESUMEN

Despite the rapid and dynamic evolution of research into dietary polyphenols, there is still a knowledge gap regarding their bioaccessibility since it could be influenced by the chemical and nutritional compositions of the food matrix. This study aimed to describe the impact of food thickeners (xanthan gum, guar gum, ß-glucan, pectin) on the bioactivity of flavonoids from saffron floral by-products in model beverages before and after thermal processing. The different beverage formulas were characterized in terms of polyphenolic composition using HPLC-DAD-ESI-MSn and rheological properties. The impact of food thickeners and thermal processing on the inhibition of digestive enzymes was also determined. The model beverages mainly presented glycosylated flavonols (of kaempferol, quercetin, and isorhamnetin), with a reduced content in some heat-treated samples. The inhibitory effect on α-amylase was only detected in heat-treated beverages, showing the formulation without any thickener to have the greatest inhibitory effect. Finally, the presence of saffron floral by-products in the beverages showed a tendency to decrease the flow consistency index (K) and an increase in the flow behavior index (n), most probably driven by the aggregation of phenolics with thickeners. Therefore, this research provides new insights into the development of flavonoid-rich beverages in order to ensure that they exert the expected beneficial effects after their ingestion.

8.
Stem Cell Reports ; 19(6): 859-876, 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38788724

RESUMEN

Hepatocyte nuclear factor 1B (HNF1B) encodes a transcription factor expressed in developing human kidney epithelia. Heterozygous HNF1B mutations are the commonest monogenic cause of dysplastic kidney malformations (DKMs). To understand their pathobiology, we generated heterozygous HNF1B mutant kidney organoids from CRISPR-Cas9 gene-edited human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) reprogrammed from a family with HNF1B-associated DKMs. Mutant organoids contained enlarged malformed tubules displaying deregulated cell turnover. Numerous genes implicated in Mendelian kidney tubulopathies were downregulated, and mutant tubules resisted the cyclic AMP (cAMP)-mediated dilatation seen in controls. Bulk and single-cell RNA sequencing (scRNA-seq) analyses indicated abnormal Wingless/Integrated (WNT), calcium, and glutamatergic pathways, the latter hitherto unstudied in developing kidneys. Glutamate ionotropic receptor kainate type subunit 3 (GRIK3) was upregulated in malformed mutant nephron tubules and prominent in HNF1B mutant fetal human dysplastic kidney epithelia. These results reveal morphological, molecular, and physiological roles for HNF1B in human kidney tubule differentiation and morphogenesis illuminating the developmental origin of mutant-HNF1B-causing kidney disease.


Asunto(s)
Factor Nuclear 1-beta del Hepatocito , Células Madre Pluripotentes Inducidas , Organoides , Humanos , Factor Nuclear 1-beta del Hepatocito/genética , Factor Nuclear 1-beta del Hepatocito/metabolismo , Organoides/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Diferenciación Celular/genética , Heterocigoto , Túbulos Renales/patología , Túbulos Renales/metabolismo , Mutación , Riñón/patología , Riñón/metabolismo , Riñón/anomalías , Sistemas CRISPR-Cas , Células Madre Pluripotentes/metabolismo , Edición Génica
9.
Nat Commun ; 15(1): 2359, 2024 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-38504097

RESUMEN

Genetic mechanisms of blood pressure (BP) regulation remain poorly defined. Using kidney-specific epigenomic annotations and 3D genome information we generated and validated gene expression prediction models for the purpose of transcriptome-wide association studies in 700 human kidneys. We identified 889 kidney genes associated with BP of which 399 were prioritised as contributors to BP regulation. Imputation of kidney proteome and microRNAome uncovered 97 renal proteins and 11 miRNAs associated with BP. Integration with plasma proteomics and metabolomics illuminated circulating levels of myo-inositol, 4-guanidinobutanoate and angiotensinogen as downstream effectors of several kidney BP genes (SLC5A11, AGMAT, AGT, respectively). We showed that genetically determined reduction in renal expression may mimic the effects of rare loss-of-function variants on kidney mRNA/protein and lead to an increase in BP (e.g., ENPEP). We demonstrated a strong correlation (r = 0.81) in expression of protein-coding genes between cells harvested from urine and the kidney highlighting a diagnostic potential of urinary cell transcriptomics. We uncovered adenylyl cyclase activators as a repurposing opportunity for hypertension and illustrated examples of BP-elevating effects of anticancer drugs (e.g. tubulin polymerisation inhibitors). Collectively, our studies provide new biological insights into genetic regulation of BP with potential to drive clinical translation in hypertension.


Asunto(s)
Hipertensión , Proteoma , Humanos , Presión Sanguínea/genética , Proteoma/genética , Proteoma/metabolismo , Transcriptoma/genética , Multiómica , Hipertensión/metabolismo , Riñón/metabolismo , Proteínas de Transporte de Sodio-Glucosa/genética , Proteínas de Transporte de Sodio-Glucosa/metabolismo
10.
Colorectal Dis ; 26(5): 916-925, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38467575

RESUMEN

AIM: The optimal management of patients with clinical complete response after neoadjuvant treatment for rectal cancer is controversial. The aim of this study is to compare the morbidity between patients with locally advanced rectal cancer who have had a pathological complete response (pCR) or not after neoadjuvant chemoradiotherapy (NCRT) and total mesorectal excision (TME). The study hypothesis was that pCR may impact the surgical complication rate. METHOD: A retrospective cohort study was conducted of a prospectively maintained database in Australia and New Zealand, the Binational Colorectal Cancer Audit, that identified patients with locally advanced rectal cancer (<15 cm from anal verge) from 1 January 2007 to 31 December 2019. Patients were included if they had locally advanced rectal cancer and had undergone NCRT and proceeded to surgical resection. RESULTS: There were 4584 patients who satisfied the inclusion criteria, 65% being male. The mean age was 63 years and 11% had a pCR (ypT0N0). TME with anastomosis was performed in 67.8% of patients, and the majority of the cohort received long-course radiotherapy (81.7%). Both major and minor complications were higher in the TME without anastomosis group (17.3% vs. 14.7% and 30.6% vs. 20.8%, respectively), and the 30-day mortality was 1.31%. In the TME with anastomosis group, pCR did not contribute to higher rates of surgical complications, but male gender (p < 0.0012), age (p < 0.0001), preoperative N stage (p = 0.0092) and American Society of Anesthesologists (ASA) score ≥3 (p < 0.0002) did. In addition, pCR had no significant effect (p = 0.44) but male gender (p = 0.0047) and interval to surgery (p = 0.015) contributed to higher rates of anastomotic leak. In the TME without anastomosis cohort, the only variable that contributed to higher rates of complications was ASA score ≥3 (p = 0.033). CONCLUSION: Patients undergoing TME dissection for rectal cancer following NCRT showed no difference in complications whether they had achieved pCR or not.


Asunto(s)
Terapia Neoadyuvante , Complicaciones Posoperatorias , Proctectomía , Neoplasias del Recto , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/cirugía , Neoplasias del Recto/terapia , Masculino , Femenino , Persona de Mediana Edad , Terapia Neoadyuvante/estadística & datos numéricos , Estudios Retrospectivos , Anciano , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Proctectomía/efectos adversos , Australia/epidemiología , Nueva Zelanda/epidemiología , Resultado del Tratamiento , Anastomosis Quirúrgica/efectos adversos , Recto/cirugía , Quimioradioterapia Adyuvante/estadística & datos numéricos
11.
Patient Educ Couns ; 123: 108176, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38422948

RESUMEN

OBJECTIVE: The study objective is to evaluate an adaptation of the LEAPS skill framework for cancer care partners (CPs) focusing on autonomy enhancing skills and assessed by strong behavioral intention (SBI) to use these skills METHOD: Cancer CPs were recruited through public platforms to view and rate 4 LEAPS cancer-specific narratives and 52 skill demonstration videos, indicate SBI to use demonstrated skills and provide information on skill-related measures. RESULTS: Half of CPs expressed SBI to use an average of 6.5 of 13 LEAPS skills which did not vary by LEAPS communication domains or examples used to demonstrate skills. Significant predictors of SBI include positive ratings of program narratives and past use of LEAPS-related behaviors in the communication domain of shared decision making (SDM). CONCLUSION: CPs indicated SBIs to use multiple autonomy enhancing skills and positively rated program videos after exposure to the brief LEAPS training program. PRACTICE IMPLICATIONS: The brevity of the LEAPS training videos make it possible for users to view an individual cancer-specific narrative and 13 skill demonstrations in roughly 6 min. This ultra-brief training can benefit care partners and the patients they accompany by increasing the likelihood that autonomy enhancing skills are used during accompanied visits.


Asunto(s)
Intención , Neoplasias , Humanos , Cuidadores , Comunicación , Toma de Decisiones Conjunta , Narración , Neoplasias/terapia
12.
Plants (Basel) ; 13(1)2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38202437

RESUMEN

De novo regeneration of Cannabis sativa L. (cannabis) using tissue culture techniques remains unreliable and infrequent. Conventional methods for the regeneration and transformation of cannabis have not achieved the reliability and replicability that need to be integrated into research and breeding programs. Protoplast systems are effective for gene expression studies and transformation and genome-editing technologies and open the possibility of somatic hybridization to create interspecific hybrids. To date, leaf-derived protoplasts have been isolated for transient gene expression studies, but protoplast-to-plant regeneration has not been reported. The present study aims to evaluate the efficacy of using a callus culture system as an abundant tissue source for protoplast isolation and lays the groundwork for a protoplast-to-plant regeneration system. Using hypocotyl-derived callus cultures, which are known to have relatively greater regenerative potential, the efficacy of protoplast isolation and initial cell division were assessed. In this study, the effect of 2-aminoindane-2-phosphonic acid (AIP), a competitive inhibitor of phenylalanine ammonia lyase (PAL), in callus culture media and the effect of subculture frequency on protoplast yield were assessed. This study found that inclusion of AIP at 1 mM resulted in a 334% increase in protoplast yield compared with AIP-free medium, representing the first known use of AIP in cannabis tissue culture. Inclusion of AIP led to a 28% decrease in total soluble phenolics and 52% decrease in tissue browning compared with the control medium. Lastly, a two-phase culture system for protoplast regeneration was tested. At a concentration of 2.0 × 105 protoplasts per mL, cell wall reconstitution and cell division were observed, providing one of the first know reports of cell division from cannabis protoplasts and setting the stage for the future development of a protoplast-to-plant regeneration system.

13.
Plant Reprod ; 2024 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-38218931

RESUMEN

KEY MESSAGE: Presented here are model Yang cycle, ethylene biosynthesis and signaling pathways in Cannabis sativa. C. sativa floral transcriptomes were used to predict putative ethylene-related genes involved in sexual plasticity in the species. Sexual plasticity is a phenomenon, wherein organisms possess the ability to alter their phenotypic sex in response to environmental and physiological stimuli, without modifying their sex chromosomes. Cannabis sativa L., a medically valuable plant species, exhibits sexual plasticity when subjected to specific chemicals that influence ethylene biosynthesis and signaling. Nevertheless, the precise contribution of ethylene-related genes (ERGs) to sexual plasticity in cannabis remains unexplored. The current study employed Arabidopsis thaliana L. as a model organism to conduct gene orthology analysis and reconstruct the Yang Cycle, ethylene biosynthesis, and ethylene signaling pathways in C. sativa. Additionally, two transcriptomic datasets comprising male, female, and chemically induced male flowers were examined to identify expression patterns in ERGs associated with sexual determination and sexual plasticity. These ERGs involved in sexual plasticity were categorized into two distinct expression patterns: floral organ concordant (FOC) and unique (uERG). Furthermore, a third expression pattern, termed karyotype concordant (KC) expression, was proposed, which plays a role in sex determination. The study revealed that CsERGs associated with sexual plasticity are dispersed throughout the genome and are not limited to the sex chromosomes, indicating a widespread regulation of sexual plasticity in C. sativa.

14.
Prenat Diagn ; 44(2): 187-195, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38056891

RESUMEN

OBJECTIVE: Determine the incremental yield of prenatal exome sequencing (PES) over chromosome microarray (CMA) and/or karyotype for urinary tract malformations (UTMs). METHOD: A prospective cohort study encompassing data from the English Genomic Medicine Service North Thames Laboratory Hub for fetuses with bilateral echogenic kidneys (BEKs) was combined with data from a systematic review. MEDLINE, EMBASE, Web of Science, MedRxiv and GreyLit were searched from 01/2010-02/2023 for studies reporting on the yield of PES over CMA or karyotype in fetuses with UTMs. Pooled incremental yield was determined using a random effects model. PROSPERO CRD42023364544. RESULTS: Fourteen studies (410 cases) were included. The incremental yield for multisystem UTMs, any isolated UTMs, and BEKs was 31% [95% CI, 18%-46%; I2  = 78%], 16% [95% CI, 6%-26%; I2  = 80%] and 51% [95% CI, 27%-75%; I2  = 34%]. The most common clinical diseases and syndromes identified, based on the variant genes detected, were Bardet-Biedl syndrome (BBS genes), dominant and recessive polycystic kidney diseases (PKD1, PKD2 and PKHD1) and renal cysts and diabetes syndrome (HNF1B). CONCLUSION: There was a notable incremental genetic diagnostic yield when PES was applied to multisystem UTMs and BEKs. There was a modest incremental yield when this technique was used for UTMs other than BEKs.


Asunto(s)
Riñón , Enfermedades Renales Poliquísticas , Humanos , Embarazo , Femenino , Estudios de Cohortes , Estudios Prospectivos , Cariotipificación , Riñón/diagnóstico por imagen , Riñón/anomalías
15.
Zoo Biol ; 43(1): 32-41, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37721178

RESUMEN

Captive cheetahs are prone to unusual diseases which may be attributed to their high muscle meat, collagen deficient captive diet. Glycine is a simple amino acid that is abundant in collagen rich tissues and has many physiological functions, specifically in collagen synthesis and in the conjugation of detrimental by-products produced during gut bacterial fermentation. Therefore, the aim of this study was to investigate the effect of a 4 week glycine supplementation on the body measurements, haematology and serum blood parameters of 10 captive cheetahs using a randomised controlled cross-over design. This approach has not yet been used to investigate the effect of diet in captive cheetahs. Cheetahs were randomly assigned to a control diet (horse meat only) or a glycine diet (30 g glycine per 1 kg meat) for 4 weeks before being crossed over. Blood was collected at baseline and after each intervention. The glycine diet resulted in a decreased serum albumin, alkaline phosphatase and total calcium concentration and increases in eosinophils and basophils counts compared to the control diet. Body weight also decreased on the glycine diet which may be due to increased ß-oxidation and fat loss. This was the first study to investigate the effect of glycine supplementation, which resulted in slight body and blood changes, in captive cheetahs using a cross-over design and this approach should be utilised for future dietary studies.


Asunto(s)
Acinonyx , Animales , Acinonyx/fisiología , Glicina/farmacología , Animales de Zoológico/fisiología , Suplementos Dietéticos , Colágeno
16.
Artículo en Inglés | MEDLINE | ID: mdl-38054369

RESUMEN

There is a regulatory need for crop development dates to assess current default values used within chemical exposure assessments as well as to justify refinements within risk assessments. However, a readily available pan-European crop phenology database covering key FOrum for the Co-ordination of pesticide fate models and their USe (FOCUS) crops and scenarios to meet this need is not currently available. Therefore, we describe the development of a harmonized, pan-European, CropLife Europe Crop Development Database (C2D2), that is fully aligned with this regulatory requirement utilizing efficacy trials data generated for regulatory submissions when registering plant protection products under Regulation (EU)1107/2009. Evaluation of C2D2 against an independent data set showed good agreement for equivalent time periods, crop growth stages, and geographical regions. We illustrate how this database can be used to evaluate existing default crop development dates mandated by regulatory agencies for use within exposure assessments. Despite the large data set compiled and the geographical coverage of C2D2, not all FOCUSsw/gw scenarios have sufficient data to facilitate comparison, with less significant scenarios, like FOCUSgw Porto, being underrepresented. For those scenarios with sufficient data, clear differences between C2D2 and crop development dates assumed in the FOCUS modeling framework (using the AppDate tool) are often indicated over many growth stages, suggesting that amendment of the existing representation of crop development within the risk assessment process may be required. C2D2 is freely available under a Creative Commons license to facilitate innovation in exposure science to allow for more accurate and realistic risk assessment leading to enhanced crop and environmental protection. Integr Environ Assess Manag 2023;00:1-15. © 2023 CropLife Europe (Corteva Agriscience) and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

17.
Opt Lett ; 48(21): 5783-5786, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37910758

RESUMEN

Experiments in photonics, laser optics, and quantum technology require low-loss, thermal, and mechanical stability. While photonic integrated circuits on monolithic chips achieve interferometric stability, important nanophotonic material systems suffer from propagation loss, thermal drift, and noise that prevent, for example, precise frequency stabilization of resonators. Here we show that tantalum pentoxide (Ta2O5) on insulator micro-ring resonators combine quality factors beyond 1.8 Mio with vanishing temperature-dependent wavelength shift in a relevant 70 K to 90 K temperature range. Our Ta2O5-on-SiO2 devices will thus enable athermal operation at liquid nitrogen temperatures, paving the way for ultra-stable low-cost resonators, as desired for wavelength division multiplexing, on chip frequency stabilization and low-noise optical frequency comb generation.

18.
Sci Rep ; 13(1): 20120, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37978310

RESUMEN

The NECTAR instrument provides access to thermal and fast neutrons which are suitable for non-destructive inspection of large and dense objects. Scintillators are used in combination with a camera system for radiography and tomography. Gamma-rays are produced as inevitable by-products of the neutron production. Furthermore, these gamma-rays are highly directional due to their constraint to the same beam-line geometry and come with similar divergence as the neutrons. We demonstrate how these gamma-rays, previously treated as beam contamination can be used as a complementary probe. While difficult to shield, it is possible to utilize them by using gamma sensitive scintillator screens in place of the neutron sensitive scintillators, viewed by the same camera based detector system. The combination of multiple probes often provides complementary information that can result in a better contrast or insight into the sample composition, for a broader range of materials and applications. Hence dual-mode imaging, combining thermal/cold neutrons with X-ray imaging has been developed at many neutron facilities. With X-rays limited in penetration of dense materials to millimeters only, we present a multimodal imaging technique that is capable of penetrating cm-sized objects using thermal to fast neutrons with the addition of gamma-rays by changing the combination of scintillator and beam filter used at the NECTAR instrument.

20.
Food Res Int ; 173(Pt 2): 113409, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37803750

RESUMEN

Phenolic compounds are known inhibitors of starch digestion through binding with α-amylase. However, a growing body of research shows that phenolic-starch interactions at the molecular level may interfere with this inhibition potential. In this study, we evaluated the effect of Gallic Acid (GA) as a model phenolic compound on starch digestion kinetics carried out in vitro in a Rapid ViscoAnalyzer (RVA). The results showed that when GA was added before cooking of starch in order to promote starch-GA complexation, the rate of digestion of starch was similar to that of starch alone, and faster than when GA was added after cooking of starch. The results demonstrated that when GA was introduced after cooking of starch, GA inhibited α-amylase strongly and that inhibition increased with starch paste viscosity only for potato and wheat starches. No correlation was found between starch molecular characteristics and the inhibiting capacity of GA at different starch concentrations. However, the apparent influence of starch chain length distribution suggested that physical effects (such as the absorption of GA at the surface of the starch paste) may play a role in the capacity of GA to inhibit α-amylase.


Asunto(s)
Ácido Gálico , Almidón , Almidón/química , Ácido Gálico/farmacología , Digestión , alfa-Amilasas/metabolismo , Fenómenos Químicos
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