Organoids are self-organizing, self-renewing three-dimensional cellular structures that resemble organs in structure and function. They can be derived from adult stem cells, embryonic stem cells, or ...induced pluripotent stem cells. They contain most of the relevant cell types with a topology and cell-to-cell interactions resembling that of the in vivo tissue. The widespread and increasing adoption of organoid-based technologies in human biomedical research is testament to their enormous potential in basic, translational- and applied-research. In a similar fashion there appear to be ample possibilities for research applications of organoids from livestock and companion animals. Furthermore, organoids as in vitro models offer a great possibility to reduce the use of experimental animals. Here, we provide an overview of studies on organoids in livestock and companion animal species, with focus on the methods developed for organoids from a variety of tissues/organs from various animal species and on the applications in veterinary research. Current limitations, and ongoing research to address these limitations, are discussed. Further, we elaborate on a number of fields of research in animal nutrition, host-microbe interactions, animal breeding and genomics, and animal biotechnology, in which organoids may have great potential as an in vitro research tool.
Objective We sought to apply a standardized evaluation of ultrasound parameters for the prediction of placental invasion in a high-risk population. Study Design This was a retrospective review of ...gravidas with ≥1 prior cesarean delivery who received an ultrasound diagnosis of placenta previa or low-lying placenta in the third trimester at our institution from 1997 through 2011. Sonographic images were reviewed by an investigator blinded to pregnancy outcome and sonography reports. Parameters assessed included loss of retroplacental clear zone, irregularity and width of uterine-bladder interface, smallest myometrial thickness, presence of lacunar spaces, and bridging vessels. Diagnosis of placental invasion was based on histologic confirmation. Statistical analyses were performed using linear logistic regression and multiparametric analyses to generate a predictive equation evaluated using a receiver operating characteristic curve. Results Of 184 gravidas who met inclusion criteria, 54 (29%) had invasion confirmed on hysterectomy specimen. All sonographic parameters were associated with placental invasion ( P < .001). Constructing a receiver operating characteristic curve, the combination of smallest sagittal myometrial thickness, lacunae, and bridging vessels, in addition to number of cesarean deliveries and placental location, yielded an area under the curve of 0.87 (95% confidence interval, 0.80–0.95). Using logistic regression, a predictive equation was generated, termed the “Placenta Accreta Index.” Each parameter was weighted to create a 9-point scale in which a score of 0-9 provided a probability of invasion that ranged from 2–96%, respectively. Conclusion Assignment of the Placenta Accreta Index may be helpful in predicting individual patient risk for morbidly adherent placenta.
The nature of the neutrino is one of the major open questions in experimental nuclear and particle physics. The most sensitive known method to establish the Majorana nature of the neutrino is ...detection of the ultra-rare process of neutrinoless double beta decay. However, identification of one or a handful of decay events within a large mass of candidate isotope, without obfuscation by backgrounds is a formidable experimental challenge. One hypothetical method for achieving ultra- low-background neutrinoless double beta decay sensitivity is the detection of single
Ba ions produced in the decay of
Xe ("barium tagging"). To implement such a method, a single-ion-sensitive barium detector must be developed and demonstrated in bulk liquid or dry gaseous xenon. This paper reports on the development of two families of dry-phase barium chemosensor molecules for use in high pressure xenon gas detectors, synthesized specifically for this purpose. One particularly promising candidate, an anthracene substituted aza-18-crown-6 ether, is shown to respond in the dry phase with almost no intrinsic background from the unchelated state, and to be amenable to barium sensing through fluorescence microscopy. This interdisciplinary advance, paired with earlier work demonstrating sensitivity to single barium ions in solution, opens a new path toward single ion detection in high pressure xenon gas.
Longitudinal studies objectively evaluating changes in regional fat distribution of HIV-infected children assessed by whole body dual energy X-ray absorptiometry (DEXA) are scarce, whilst this ...long-term effect of HIV and antiretroviral therapy (cART) is an important issue in infected children in need for lifelong treatment.
We assessed regional fat distribution over time, measured with sequential DEXA-scans in HIV-infected children on cART in cohorts from South Africa (SA) and the Netherlands (NL), and in healthy controls (SA). Limb and trunk fat Z-scores were calculated with the lambda-mu-sigma (LMS) method. Multivariable linear regression models with mixed effects were used to investigate the effect of cART compounds on body fat distribution over time.
In total, 218 children underwent 445 DEXA assessments with a median follow-up of 3.5 years. Fat mass in all limbs was decreased in HIV-infected children compared to controls (arm fat Z-score: coefficient -0.4813; P = 0.006, leg fat Z-score: coefficient -0.4345; P = 0.013). In the HIV-infected group, stavudine treatment was associated with lower subcutaneous fat mass (arm fat Z-score: coefficient -0.5838; P = 0.001), with an additional cumulative exposure effect (arm fat Z-score: coefficient -0.0867; P = 0.003).
Our study shows that subcutaneous fat loss is still prevalent in HIV-infected children on cART, and is strongly associated with cumulative stavudine exposure. These results underline the need for early detection of subcutaneous fat loss and alternative treatment options for HIV-infected children globally.
Calcific aortic stenosis (CAS) is the most common valvular heart disease in older adults and has no effective preventive therapies. Genome-wide association studies (GWAS) can identify genes ...influencing disease and may help prioritize therapeutic targets for CAS.
We performed a GWAS and gene association study of 14 451 patients with CAS and 398 544 controls in the Million Veteran Program. Replication was performed in the Million Veteran Program, Penn Medicine Biobank, Mass General Brigham Biobank, BioVU, and BioMe, totaling 12 889 cases and 348 094 controls. Causal genes were prioritized from genome-wide significant variants using polygenic priority score gene localization, expression quantitative trait locus colocalization, and nearest gene methods. CAS genetic architecture was compared with that of atherosclerotic cardiovascular disease. Causal inference for cardiometabolic biomarkers in CAS was performed using Mendelian randomization and genome-wide significant loci were characterized further through phenome-wide association study.
We identified 23 genome-wide significant lead variants in our GWAS representing 17 unique genomic regions. Of the 23 lead variants, 14 were significant in replication, representing 11 unique genomic regions. Five replicated genomic regions were previously known risk loci for CAS (
) and 6 were novel (
). Two novel lead variants were associated in non-White individuals (
<0.05): rs12740374 (
) in Black and Hispanic individuals and rs1522387 (
) in Black individuals. Of the 14 replicated lead variants, only 2 (rs10455872
, rs12740374
) were also significant in atherosclerotic cardiovascular disease GWAS. In Mendelian randomization, lipoprotein(a) and low-density lipoprotein cholesterol were both associated with CAS, but the association between low-density lipoprotein cholesterol and CAS was attenuated when adjusting for lipoprotein(a). Phenome-wide association study highlighted varying degrees of pleiotropy, including between CAS and obesity at the
locus. However, the
locus remained associated with CAS after adjusting for body mass index and maintained a significant independent effect on CAS in mediation analysis.
We performed a multiancestry GWAS in CAS and identified 6 novel genomic regions in the disease. Secondary analyses highlighted the roles of lipid metabolism, inflammation, cellular senescence, and adiposity in the pathobiology of CAS and clarified the shared and differential genetic architectures of CAS with atherosclerotic cardiovascular diseases.
To evaluate the incidence of vaginal bleeding in women with placenta accreta according to gestational age at delivery.
This is a retrospective cohort study of women with prior cesarean delivery and ...persistent placenta previa delivered at our institution between December 1997 and December 2011. Diagnosis of invasion was based on hysterectomy performed for an abnormally adherent placenta with histologic confirmation. Suspicion for invasion was based on the impression of the attending physician at the time of ultrasonography. Records were reviewed to identify indication for delivery and estimated blood loss. Statistical analyses were performed using Student's t test, χ2 test, and Mantel-Haenszel and Jonckheere-Terpstra tests for trend.
Of 216 women with prior cesarean delivery and persistent previa, 65 (30%) required cesarean hysterectomy and had histologic confirmation of invasion. Urgent delivery for bleeding was performed in 20% of these pregnancies (13/65). Delivery for bleeding decreased significantly with advancing gestation (P=.001). In our series, 71% with accreta were delivered at 36 weeks of gestation or greater with delivery for bleeding in five (11%), and estimated blood loss was not increased in these pregnancies. Of 79 women with ultrasonographic suspicion for accreta, the incidence of vaginal bleeding prompting urgent delivery also decreased with advancing gestation (P<.001).
Likelihood of vaginal bleeding necessitating delivery declined with advancing gestation in pregnancies with placenta accreta as did blood loss. Most were delivered at 36 weeks of gestation or greater, nearly 90% in the absence of bleeding complications. Thus, although preterm delivery is an important consideration when placenta accreta is suspected, our findings support individualizing delivery planning.
Predicting Placenta Accreta Spectrum Happe, Sarah K.; Yule, Casey S.; Spong, Catherine Y. ...
Journal of ultrasound in medicine,
08/2021, Letnik:
40, Številka:
8
Journal Article
Recenzirano
Objectives
The placenta accreta spectrum (PAS) incidence has risen substantially over the past century, paralleling a rise in cesarean delivery (CD) rates. Prenatal diagnosis of PAS improves maternal ...outcomes. The Placenta Accreta Index (PAI) is a standardized approach to prenatal diagnosis of PAS incorporating clinical risk and ultrasound (US) findings suggestive of placental invasion. We sought to validate the PAI for prediction of PAS in pregnancies with prior CD.
Methods
This work was a retrospective cohort study of pregnancies with 1 or more prior CDs that received a US diagnosis of placenta previa or low‐lying placenta in the third trimester. Images of third‐trimester US with a complete placental evaluation were read by 2 blinded physicians, and the PAI was applied. Surgical outcomes and pathologic findings were reviewed. Placenta accreta spectrum was diagnosed if clinical evidence of invasion was seen at time of delivery or if any placental invasion was identified histologically. International Federation of Gynecology and Obstetrics criteria were used.
Results
A total of 194 women met inclusion criteria. Cesarean hysterectomy was performed in 92 (47%), CD in 97 (50%), and vaginal delivery in 5 (3%). Of those who underwent hysterectomy, PAS was histologically confirmed in 79 (85%) pregnancies. Of the remaining 13 who underwent hysterectomy, all met International Federation of Gynecology and Obstetrics grade 1 clinical criteria for PAS. With a threshold of greater than 4, the PAI has a sensitivity of 87%, specificity of 77%, positive predictive value of 72%, and negative predictive value of 90% for PAS diagnosis.
Conclusions
Contemporaneous application of the PAI, a standardized approach to US diagnosis, is useful in the prenatal prediction of PAS.
A common
gene polymorphism, rs35705950-T, is associated with idiopathic pulmonary fibrosis (IPF), but its role in severe acute respiratory syndrome coronavirus 2 infection and disease severity is ...unclear.
To assess whether rs35705950-T confers differential risk for clinical outcomes associated with coronavirus disease (COVID-19) infection among participants in the Million Veteran Program (MVP).
The
rs35705950-T allele was directly genotyped among MVP participants; clinical events and comorbidities were extracted from the electronic health records. Associations between the incidence or severity of COVID-19 and rs35705950-T were analyzed within each ancestry group in the MVP followed by transancestry meta-analysis. Replication and joint meta-analysis were conducted using summary statistics from the COVID-19 Host Genetics Initiative (HGI). Sensitivity analyses with adjustment for additional covariates (body mass index, Charlson comorbidity index, smoking, asbestosis, rheumatoid arthritis with interstitial lung disease, and IPF) and associations with post-COVID-19 pneumonia were performed in MVP subjects.
The rs35705950-T allele was associated with fewer COVID-19 hospitalizations in transancestry meta-analyses within the MVP (N
= 4,325; N
= 507,640; OR = 0.89 0.82-0.97;
= 6.86 × 10
) and joint meta-analyses with the HGI (N
= 13,320; N
= 1,508,841; OR, 0.90 0.86-0.95;
= 8.99 × 10
). The rs35705950-T allele was not associated with reduced COVID-19 positivity in transancestry meta-analysis within the MVP (N
= 19,168/N
= 492,854; OR, 0.98 0.95-1.01;
= 0.06) but was nominally significant (
< 0.05) in the joint meta-analysis with the HGI (N
= 44,820; N
= 1,775,827; OR, 0.97 0.95-1.00;
= 0.03). Associations were not observed with severe outcomes or mortality. Among individuals of European ancestry in the MVP, rs35705950-T was associated with fewer post-COVID-19 pneumonia events (OR, 0.82 0.72-0.93;
= 0.001).
The
variant rs35705950-T may confer protection in COVID-19 hospitalizations.
Objectives
To prospectively evaluate low implantation of the gestational sac and other first‐trimester ultrasound (US) parameters for prediction of placenta accreta spectrum (PAS).
Methods
Women with ...a diagnosis of low implantation on clinically indicated first‐trimester US underwent a transvaginal US examination at 10 to 13 weeks’ gestation to assess the trophoblast location, anechoic areas, bridging vessels, and smallest myometrial thickness (SMT). The placental location was evaluated in the second trimester, and serial US examinations were performed in cases of low placentation. Placenta accreta spectrum was based on clinical findings and confirmed by histologic results.
Results
Of 68 women, 40 (59%) had prior cesarean delivery (CD). Hysterectomy was performed in 8, all with prior CD. Of these, 7 (88%) had US suspicion of PAS. In 16 with prior CD and basalis overlying the internal os, 9 (56%) had second‐trimester placenta previa, and 7 of 9 (78%) underwent hysterectomy with pathologic confirmation of PAS. Of 28 without prior CD, there were no cases of persistent low placentation in the third trimester regardless of the trophoblast location. Ultrasound parameters associated with PAS were a smaller distance from the inferior trophoblastic border to the external os, disruption of the bladder‐serosal interface, bridging vessels, anechoic areas, and the SMT. In women with prior CD, use of the SMT in the sagittal plane yielded an area under the receiver operating characteristic curve of 0.96 (95% confidence interval, 0.91–1.00).
Conclusions
First‐trimester low implantation increases the risk of persistent placenta previa and PAS in women with prior CD. All parameters were associated with PAS, the most predictive being the SMT.
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