Assessing efficacy of day 3 embryo time-lapse algorithms retrospectively: impacts of dataset type and confounding factors

This study investigated the efficacy of four published day 3 embryo time-lapse algorithms based on different types of datasets (known implantation data [KID] and single embryo transfer [SET]), and the confounding effect of female age and conventional embryo morphology. Four algorithms were retrospectively applied to three types of datasets generated at Fertility North between February 2013 and December 2014: (a) KID dataset (n?=?270), (b) a subset of SET (n?=?144, end-point?=?implantation), and (c) SET (n?=?144, end-point?=?live birth), respectively. All four algorithms showed progressively reduced predictive power (expressed as area under the receiver operating characteristics curve and 95% confidence interval [CI]) after application to the three datasets (a–c): Liu (0.762 [0.701–0.824] vs. 0.724 [0.641–0.807] vs. 0.707 [0.620–0.793]), KIDScore (0.614 [0.539–0.688] vs. 0.548 [0.451–0.645] vs. 0.536 [0.434–0.637]), Meseguer (0.585 [0.508–0.663] vs. 0.56 [0.462–0.658] vs. 0.549 [0.445–0.652]), and Basile (0.582 [0.505–0.659] vs. 0.519 [0.421–0.618] vs. 0.509 [0.406–0.612]). Furthermore, using KID dataset, the association (expressed as odds ratio and 95% CI) between time-lapse algorithms and implantation outcomes lost statistical significance after adjusting for conventional embryo morphology and female age in 3 of the 4 algorithms (KIDScore 1.832 [1.118–3.004] vs. 1.063 [0.659–1.715], Meseguer 1.150 [1.021–1.295] vs. 1.122 [0.981–1.284] and Basile 1.122 [1.008–1.249] vs. 1.038 [0.919–1.172]). In conclusion, SET is a preferred dataset to KID when developing or validating time-lapse algorithms, and day 3 conventional embryo morphology and female age should be considered as confounding factors.     

Unusual persistent primitive trigeminal artery with a superior duplicated basilar system

A 67-year-old patient who presented with a right cerebellar hemorrhage underwent vascular workup for suspicion of underlying vascular anomalies. A diagnostic cerebral angiogram demonstrated a duplicated basilar system fed solely by a persistent primitive trigeminal artery. The findings proved to be incidental and unrelated to the patient’s hemorrhage. These developmental abnormalities are consistent with embryological development.     

Anatomy and White Matter Connections of the Superior Frontal Gyrus

The superior frontal gyrus (SFG) is an important region implicated in a variety of tasks including motor movement, working memory, resting-state, and cognitive control. A detailed understanding of the subcortical white matter of the SFG could improve postoperative morbidity related to surgery around this gyrus. Through DSI-based fiber tractography validated by gross anatomical dissection, we characterized the fiber tracts of the SFG based on their relationships to other well-known neuroanatomic structures. Diffusion imaging from the Human Connectome Project from 10 healthy adult subjects was used for fiber tractography. We evaluated the SFG as a whole based on its connectivity with other regions. All tracts were mapped in both hemispheres, and a lateralization index was calculated based on resultant tract volumes. Ten cadaveric dissections were then performed using a modified Klingler technique to delineate the location of major tracts integrated within the SFG. We identified four major SFG connections: the frontal aslant tract connecting to the inferior frontal gyrus; the inferior fronto-occipital fasciculus connecting to the cuneus, lingual gyrus, and superior parietal lobule; the cingulum connecting to the precuneus and parahippocampal gyrus/uncus; and a callosal fiber bundle connecting the SFG bilaterally. The functional networks of the SFG involve a complex series of white matter tracts integrated within the gyrus, including the FAT, IFOF, cingulum, and callosal fibers. Postsurgical outcomes related to this region may be better understood in the context of the fiber-bundle anatomy highlighted in this study. Clin. Anat. 33:823–832, 2020. © 2019 Wiley Periodicals, Inc.     

Attachment-related psychodynamics

Because there has been relatively little communication and cross-fertilization between the two major lines of research on adult attachment, one based on coded narrative assessments of defensive processes, the other on simple self-reports of ‘attachment style’ in close relationships, we here explain and review recent work based on a combination of self-report and other kinds of method, including behavioral observations and unconscious priming techniques. The review indicates that considerable progress has been made in testing central hypotheses derived from attachment theory and in exploring unconscious, psychodynamic processes related to affect-regulation and attachment-system activation. The combination of self-report assessment of attachment style and experimental manipulation of other theoretically pertinent variables allows researchers to test causal hypotheses. We present a model of normative and individual-difference processes related to attachment and identify areas in which further research is needed and likely to be successful. One long-range goal is to create a more complete theory of personality built on attachment theory and other object relations theories.     

The Association of Respiratory Symptoms and Indoor Housing Conditions Among Migrant Farmworkers in Eastern North Carolina

Farm labor housing has been described as among the worst in the nation, oftentimes with poor and unsanitary indoor living conditions. The objective of this study was to evaluate the association between indoor environmental risk factors and respiratory health among migrant farmworker occupants (N = 352) living in employer-provided housing. A cross-sectional sample of adult Latino male farm laborers were administered a questionnaire to identify the prevalence of major respiratory symptoms. Self-reported and independent observations were made to evaluate environmental respiratory risk factors and indoor housing conditions, including but not limited to, the presence of cockroaches, rodents, pesticides, and visible signs of mold. Spirometry was performed to evaluate lung function using FEV₁ (forced expiratory volume in 1 second), FVC (forced vital capacity), and FEV₁ /FVC ratio. Bivariate analysis was applied to evaluate associations between respiratory symptoms and selected indoor environmental risk factors. Findings for respiratory health included prevalence of wheeze (11.4%), coughing up phlegm (17.3%), tightness of chest (16.8%), and runny or stuffy nose (34.4%). Respiratory risks identified inside the dwellings included the use of pesticides or bug sprays for cockroaches (31.5%), rat or mouse poison (19.5%), visible signs of water damage in the bathroom (22.5%), and mold in the sleeping room (11.1%). Spirometry values were normal for most occupants, although statistically significant associations were found between mold and coughing up phlegm when not having a cold (P = .0262); presence of mold and asthma (P = .0084); pesticides used in the home and tightness of chest (P = .0001); and use of tobacco and coughing up phlegm (P = .0131). Although causal inference can be difficult to establish from a cross-sectional study, findings from this study represents suggestive evidence that indoor environmental risk factors may be contributory factors for respiratory health problems among this vulnerable workgroup population.     

Identification of a novel selective serotonin reuptake inhibitor by coupling monoamine transporter-based virtual screening and rational molecular hybridization

Ligand virtual screening (VS) using the vestibular binding pocket of a 3-D monoamine transporter (MAT) computational model followed by in vitro pharmacology led to the identification of a human serotonin transporter (hSERT) inhibitor with modest affinity (hSERT K(i) = 284 nM). Structural comparison of this VS-elucidated compound, denoted MI-17, to known SERT ligands led to the rational design and synthesis of DJLDU-3-79, a molecular hybrid of MI-17 and dual SERT/5-HT(1A) receptor antagonist SSA-426. Relative to MI-17, DJLDU-3-79 displayed 7-fold improvement in hSERT binding affinity and a 3-fold increase in [(3)H]-serotonin uptake inhibition potency at hSERT/HEK cells. This hybrid compound displayed a hSERT:hDAT selectivity ratio of 50:1, and a hSERT:hNET (human norepinephrine transporter) ratio of >200:1. In mice, DJLDU-3-79 decreased immobility in the tail suspension test comparable to the SSRI fluvoxamine, suggesting that DJLDU-3-79 may possess antidepressant properties. This proof of concept study highlights MAT virtual screening as a powerful tool for identifying novel inhibitor chemotypes and chemical fragments for rational inhibitor design.