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Co-treatment of the enzyme inhibitors with the CB1R inhibitor AM 251 confirmed the involvement of CB1R in motor neuron branching. Disruption of FAAH or MAGL reduced larval swimming activity, and AM251 attenuated the JZL195 and URB597 induced locomotor changes, but not the effects of JZL184. Together, these findings indicate that inhibition of FAAH, or augmentation of AEA acting through CB1R during early development may be responsible for locomotor deficiencies.

This article reviews recent literature on the use of SNOMED CT as an extension of Lee et al's 2014 review on the same topic. The Lee et al's article covered literature published from 2001-2012, and the scope of this review was 2013-2020.

In line with Lee et al's methods, we searched the PubMed and Embase databases and identified 1002 articles for review, including studies from January 2013 to September 2020. The retrieved articles were categorized and analyzed according to SNOMED CT focus categories (ie, indeterminate, theoretical, pre-development, implementation, and evaluation/commodity), usage categories (eg, illustrate terminology systems theory, prospective content coverage, used to classify or code in a study, retrieve or analyze patient data, etc.), medical domains, and countries.

After applying inclusion and exclusion criteria, 622 articles were selected for final review. Compared to the papers published between 2001 and 2012, papers published between 2013 and 2020 revealed an increase in more mature usage of SNOMED CT, and the number of papers classified in the "implementation" and "evaluation/commodity" focus categories expanded. When analyzed by decade, papers in the "pre-development," "implementation," and "evaluation/commodity" categories were much more numerous in 2011-2020 than in 2001-2010, increasing from 169 to 293, 30 to 138, and 3 to 65, respectively.

Published papers in more mature usage categories have substantially increased since 2012. From 2013 to present, SNOMED CT has been increasingly implemented in more practical settings. Future research should concentrate on addressing whether SNOMED CT influences improvement in patient care.

Published papers in more mature usage categories have substantially increased since 2012. From 2013 to present, SNOMED CT has been increasingly implemented in more practical settings. Future research should concentrate on addressing whether SNOMED CT influences improvement in patient care.There has been increased excitement around the use of machine learning (ML) and artificial intelligence (AI) in dermatology for the diagnosis of skin cancers and assessment of other dermatologic conditions. Glesatinib As these technologies continue to expand, it is essential to ensure they do not create or widen sex- and gender-based disparities in care. While desirable bias may result from the explicit inclusion of sex or gender in diagnostic criteria of diseases with gender-based differences, undesirable biases can result from usage of datasets with an underrepresentation of certain groups. We believe that sex and gender differences should be taken into consideration in ML/AI algorithms in dermatology because there are important differences in the epidemiology and clinical presentation of dermatologic conditions including skin cancers, sex-specific cancers, and autoimmune conditions. We present recommendations for ensuring sex and gender equity in the development of ML/AI tools in dermatology to increase desirable bias and avoid undesirable bias.The nuclear lamina supports many functions, including maintaining nuclear structure and gene expression control, and correct spatio-temporal assembly is vital to meet these activities. Recently, multiple lamina systems have been described that, despite independent evolutionary origins, share analogous functions. In trypanosomatids the two known lamina proteins, NUP-1 and NUP-2, have molecular masses of 450 and 170 kDa, respectively, which demands a distinct architecture from the ∼60 kDa lamin-based system of metazoa and other lineages. To uncover organizational principles for the trypanosome lamina we generated NUP-1 deletion mutants to identify domains and their arrangements responsible for oligomerization. We found that both the N- and C-termini act as interaction hubs, and that perturbation of these interactions impacts additional components of the lamina and nuclear envelope. Furthermore, the assembly of NUP-1 terminal domains suggests intrinsic organizational capacity. Remarkably, there is little impact on silencing of telomeric variant surface glycoprotein genes. We suggest that both terminal domains of NUP-1 have roles in assembling the trypanosome lamina and propose a novel architecture based on a hub-and-spoke configuration.Repressor element 1-silencing transcription factor (REST) plays a crucial role in the differentiation of neural progenitor cells (NPCs). C-terminal domain small phosphatases (CTDSPs) are REST effector proteins that reduce RNA polymerase II activity on genes required for neurogenesis. miR-26b regulates neurogenesis in zebrafish by targeting ctdsp2 mRNA, but the molecular events triggered by this microRNA (miR) remain unknown. Here, we show in a murine embryonic stem cell differentiation paradigm that inactivation of miR-26 family members disrupts the formation of neurons and astroglia and arrests neurogenesis at the neural progenitor level. Furthermore, we show that miR-26 directly targets Rest, thereby inducing the expression of a large set of REST complex-repressed neuronal genes, including miRs required for induction of the neuronal gene expression program. Our data identify the miR-26 family as the trigger of a self-amplifying system required for neural differentiation that acts upstream of REST-controlled miRs.

Maternal micronutrient status is critical for child growth and nutrition. It is unclear whether maternal multiple micronutrient supplementation (MMS) during pregnancy and lactation improves child growth and prevents child morbidity.

This study aimed to determine the effects of prenatal and postnatal maternal MMS on child growth and morbidity. In this double-blind, randomized-controlled trial, 8428 HIV-negative pregnant women were enrolled from Dar es Salaam, Tanzania, between 2001 and 2004. From pregnancy (12-27 weeks of gestation) through to 6 weeks postpartum, participants were randomized to receive daily oral MMS or placebo. All women received daily iron and folic acid during pregnancy. From 6 weeks postpartum through to 18 months postpartum, 3100 women were re-randomized to MMS or placebo. Child-growth measures, haemoglobin concentrations and infectious morbidities were assessed longitudinally from birth to ≤18 months.

Prenatal MMS led to modest increases in weight-for-age z-scores (mean difference 0.050; 95% confidence interval 0.002, 0.099; p = 0.04) and length-for-age z-score (mean difference 0.062; 95% confidence interval 0.013, 0.111; p = 0.01) during the first 6 months of life but not thereafter. Prenatal or postnatal MMS did not have benefits for other child outcomes.

Whereas maternal MMS is a proven strategy to prevent adverse birth outcomes, other approaches may also need to be considered to curb the high burdens of child morbidity and growth faltering.

Whereas maternal MMS is a proven strategy to prevent adverse birth outcomes, other approaches may also need to be considered to curb the high burdens of child morbidity and growth faltering.

Due to the strong association between ankylosing spondylitis and Human Leukocyte Antigen (HLA)-B27, accurate identification of HLA-B27 is important in the diagnosis of patients with suspected spondyloarthritides. For this study, we compared a high-resolution HLA-B typing method to the clinical flow cytometry and allele-specific PCR melting assays to determine clinical benefits of high-resolution testing.

Residual clinical samples submitted for HLA-B27 testing by flow cytometry were tested by single-locus HLA-B genotyping using next-generation sequencing (NGS), and PCR with melting curve analysis, currently used as a reflex test for indeterminate flow cytometry results.

Fifty out of the 51 samples (98%) positive by flow cytometry confirmed as HLA-B27 positive by PCR melting assay and by NGS. The sample that did not confirm was genotyped as HLA-B*0702. All the samples negative by flow cytometry were confirmed as HLA-B27 negative by both PCR melting assay and NGS. For the group that was indeterminate by flow cytometry, 84.5% (n = 49) typed as positive for HLA-B27, while 15.5% (n = 9) were negative for HLA-B27 but positive for HLA-B*0702. NGS was the only method able to distinguish between pathogenic and nonpathogenic HLA-B27 variants, in contrast to the flow cytometry or the PCR melting assays.

Single-locus NGS is superior to flow cytometry and PCR melting assay for the unambiguous identification of HLA-B27 variants, and uniquely able to distinguish between pathogenic and nonpathogenic B27 alleles. Due to its high accuracy, it may be a feasible superior alternative to flow cytometry and traditional molecular methods for clinical HLA-B27 testing.

Single-locus NGS is superior to flow cytometry and PCR melting assay for the unambiguous identification of HLA-B27 variants, and uniquely able to distinguish between pathogenic and nonpathogenic B27 alleles. Due to its high accuracy, it may be a feasible superior alternative to flow cytometry and traditional molecular methods for clinical HLA-B27 testing.

The aim of the present study was to examine the effect that the introduction of Doppler ultrasound in obstetric care has had on fetal death in Norway. One mechanism by which Doppler ultrasound may reduce fetal death may be through the increased use of Caesarean delivery. Therefore, we also examined the effect that the use of Doppler ultrasound has had on the use of Caesarean delivery.

The Medical Birth Registry of Norway provided detailed medical information for ∼1.2 million deliveries from 1990 to 2014. Information about the year of introduction of Doppler ultrasound was collected directly from the maternity units, using a questionnaire. The data were analysed using a hospital fixed-effects regression model with fetal death as the outcome measure. The key independent variable was the introduction of Doppler ultrasound at each maternity ward. Hospital-specific trends and risk factors of the mother for fetal death were included as covariates.

For pre-term deliveries, the introduction of Doppler ultrasound contributed to a reduction in fetal death of ∼30% and to an increase in planned Caesarean section of ∼15%. There were no effects for emergency Caesarean sections or inductions pre-term. The introduction of Doppler ultrasound had no effect on fetal death or Caesarean section for term deliveries.

The introduction of Doppler ultrasound during the 1990s and 2000s made a significant contribution to the decline in the number of pre-term fetal deaths in Norway. Increased use of Caesarean section may have contributed to this reduction.

The introduction of Doppler ultrasound during the 1990s and 2000s made a significant contribution to the decline in the number of pre-term fetal deaths in Norway. Increased use of Caesarean section may have contributed to this reduction.