High-resolution anatomical imaging of the fetal brain with a reduced field of view using outer volume suppression.

PURPOSE: To achieve high-resolution fetal brain anatomical imaging without introducing image artifacts by reducing the FOV, and to demonstrate improved image quality compared to conventional full-FOV fetal brain imaging. METHODS: Reduced FOV was achieved by applying outer volume suppression (OVS) pulses immediately prior to standard single-shot fast spin echo (SSFSE) imaging. In the OVS preparation, a saturation RF pulse followed by a gradient spoiler was repeated three times with optimized flip-angle weightings and a variable spoiler scheme to enhance signal suppression. Simulations and phantom and in-vivo experiments were performed to evaluate OVS performance. In-vivo high-resolution SSFSE images acquired using the proposed approach were compared with conventional and high-resolution SSFSE images with a full FOV, using image quality scores assessed by neuroradiologists and calculated image metrics. RESULTS: Excellent signal suppression in the saturation bands was confirmed in phantom and in-vivo experiments. High-resolution SSFSE images with a reduced FOV acquired using OVS demonstrated the improved depiction of brain structures without significant motion and blurring artifacts. The proposed method showed the highest image quality scores in the criteria of sharpness, contrast, and artifact and was selected as the best method based on overall image quality. The calculated image sharpness and tissue contrast ratio were also the highest with the proposed method. CONCLUSION: High-resolution fetal brain anatomical images acquired using a reduced FOV with OVS demonstrated improved image quality both qualitatively and quantitatively, suggesting the potential for enhanced diagnostic accuracy in detecting fetal brain abnormalities in utero.

Teaching module for obesity bias education: incorporating comprehensive competencies and innovative techniques.

BACKGROUND: The majority of the United States population is overweight or obese, and obesity bias is frequently reported by patients. Obesity bias is associated with adverse health outcomes, even independent of body weight. Primary care residents are often sources of obesity bias towards patients with weight, yet education regarding obesity bias is significantly lacking in most family medicine residency teaching curricula. The aim of this study is to describe an innovative web-based module on obesity bias and discuss its impact in family medicine residents. METHODS: The e-module was developed by an interprofessional team of health care students and faculty. It consisted of a 15-minute video containing five clinical vignettes that depicted instances of explicit and implicit obesity bias in a patient-centered medical home (PCMH) model. Family medicine residents viewed the e-module as part of a dedicated one-hour didactic on obesity bias. Surveys were administered prior to and following the viewing of the e-module. They assessed previous education on obesity care, comfort in working with patients with obesity, residents' understanding of their own biases in working with this population, and the anticipated impact of the module on future patient care. RESULTS: A total of 83 residents from three family medicine residency programs viewed the e-module and 56 completed both the pre and post survey. There was a significant improvement in residents' comfort in working with patients with obesity as well as their understanding of their own biases. CONCLUSION: This teaching e-module is a short, interactive, web-based educational intervention that is free and open-sourced. The first-person patient perspective allows learners to better understand the patient's point of view and its PCMH setting illustrates interactions with a variety of healthcare professionals. It was engaging and well received by family medicine residents. This module can begin the conversation around obesity bias, leading to improved patient care.

Outcomes of a US-Sino family medicine leadership program.

BACKGROUND AND OBJECTIVES: The purpose of this study was to determine the outcomes of a two- week US-Sino Family Medicine Leadership Symposium for medical educators from China and how participants have integrated their learning into their teaching and practice of medicine. METHODS: Teaching topics emphasized principles of family medicine, teaching methods, assessment, and curriculum development. Each cohort received a wide range of practical, didactic and hands-on learning experiences. Online surveys were distributed anonymously to participants from the 2013-2019 cohorts to assess learner opinion and learner behavior change as a result of the leadership symposium. Quantitative measures assessed their level of integration of the topics into teaching and clinical practice and their satisfaction in the areas of teaching and leadership. They were also asked to provide qualitative feedback regarding incorporation of the content into their work. RESULTS: The survey response rate was 47.6% (39/82). Respondents stated that they incorporated topics such as basic interviewing skills and information on the patient-centered medical home into their teaching in China. The most applied clinical skills they were able to incorporate into their clinical environment in China included: Breaking Bad News, Simulations Sessions with practice, One-Minute Preceptor, and Interprofessional Education. CONCLUSIONS: Results indicate that participants have demonstrated behavior changes that have led to the incorporation of the content into teaching and clinical practice. We demonstrated effectiveness of the curriculum in cultivating the teaching and practice of family medicine. The program appears to be a positive experience that has led to embracement of the roles as trainer and leader. 100% of the participants who completed the survey felt that the program improved patient confidence in their ability as a family doctor. Future assessment on barriers to their progress as teachers and leaders in family medicine would be helpful to explore.

Comprehensive Obesity Education for Family Medicine Residents.

BACKGROUND: Family medicine residents receive limited education on obesity management and obesity bias. Weight stigmatization is prevalent in primary care providers and trainees, and early mitigation is critical to optimize patient-centered care. Recent Provider Competencies for the Prevention and Management of Obesity include obesity bias. This report is intended to fill a current gap in obesity education for family medicine residents. METHODS: An interprofessional obesity teaching half day for family medicine residents incorporated the Provider Competencies and focused on five modules that addressed complexities of obesity and its clinical management. The obesity bias module focused on both explicit and implicit bias, assessment of implicit bias, preferential language usage, and mitigation strategies. An obesity-simulation empathy suit was available, and a public health expert described successful obesity care in a patient-centered medical home. Family medicine residents were surveyed prior to, immediately after the half-day of obesity teaching, and 15 months later. RESULTS: Survey results indicated 39.3% of residents had no previous biopsychosocial obesity education. Residents believed the content moderately (68.8%) or mostly (12.5%) impacted their approach to working with patients with obesity. Residents' comfort in working with patients with obesity as well as their perceived understanding of their own biases increased immediately after the intervention and was sustained 15 months later. CONCLUSIONS: Our results suggest that a half day of obesity teaching can have a positive and sustained impact on family medicine residents. Additionally, this educational experience allowed for greater individual awareness building and insight regarding implicit bias. Such education for family medicine residents fills an identified gap in obesity education.

The Use of Ultrasound as a Potential Adjunct to Cell-Free Fetal DNA Screening for Aneuploidy at Weill Cornell Medical College, New York, USA.

Objective To evaluate the utility of ultrasound in identifying fetuses with uncommon chromosomal abnormalities that would be considered not detectable by cell-free fetal deoxyribonucleic acid (cfDNA). Study Design We performed a retrospective study of fetuses with chromosomal abnormalities that would be undetectable by cfDNA, who underwent an 11- to 14-week ultrasound from 2006 to 2016. Results There were 43 pregnancies included. First-trimester ultrasound revealed a fetal abnormality in 19 (44.2%) cases, of which 13 (30.2%) had a thickened nuchal translucency. There were an additional four fetuses with second-trimester sonographic abnormalities. Overall, 23 (53.5%) fetuses were found to have a major anomaly diagnosed by ultrasound. The rate of first-trimester sonographic abnormalities varied widely based on category of chromosomal abnormalities with high rates seen with triploidy (87.5%) and autosomal trisomy (80%) and lower rates seen with structurally abnormal chromosomes (33.3%), trisomy mosaicism (27.3%), other forms of mosaicism (11.1%), and deletions or duplications (25.0%), p < 0.001. Conclusion The majority of fetuses with uncommon chromosomal abnormalities in our cohort had major sonographic anomalies. The use of first-trimester ultrasound with nuchal translucency measurement may offer utility in identifying fetuses with risk of aneuploidy that would not be detectable with cfDNA.

The composition of the vaginal microbiome in first trimester pregnant women influences the level of autophagy and stress in vaginal epithelial cells.

Epithelial cells lining the vagina are major components of genital tract immunity. The influence of the vaginal microbiome on properties of host epithelial cells is largely unexplored. We evaluated whether differences in the most abundant lactobacilli species or bacterial genera in the vagina of first trimester pregnant women were associated with variations in the extent of stress and autophagy in vaginal epithelial cells. Vaginal swabs from 154 first trimester pregnant women were analyzed for bacterial composition by amplification and sequencing of the V1-V3 region of bacterial 16S rRNA genes. Vaginal epithelial cells were lysed and autophagy quantitated by measurement of p62. Intracellular levels of the inducible 70kDa heat shock protein (hsp70), an indicator of cell stress and an autophagy inhibitor, were determined. When Lactobacillus crispatus was the most abundant member of the vaginal microbiota, epithelial p62 and hsp70 levels were lowest as compared to when other bacterial taxa were most abundant. The highest concentrations of p62 and hsp70 were associated with Streptococcus and Bifidobacterium abundance. The p62 level associated with Gardnerella abundance was lower than that observed when lactobacilli other than L. crispatus were most abundant. In conclusion, in the first trimester of pregnancy the abundance of different bacterial taxa is associated with variations in autophagy and magnitude of the stress response in vaginal epithelial cells.

Influence of Pregnancy History on the Vaginal Microbiome of Pregnant Women in their First Trimester.

Pregnancy permanently alters maternal anatomy, physiology and immunity. We evaluated if the vaginal microbiome differed between women with a first or subsequent conception. Relative abundance of bacteria in the vaginal microbiome in first trimester pregnant women, 52 with their first known conception, 26 with a prior spontaneous or induced abortion but no deliveries and 77 with at least one prior birth, was determined by classifying DNA sequences from the V1-V3 region of bacterial 16 S rRNA genes. Lactobacillus crispatus was the numerically most abundant bacterium in 76.4% of women with a first conception, 50.0% with only a prior spontaneous or scheduled abortion and 22.2% with a prior birth (p ≤ 0.01). L. iners was the most abundant bacterium in 3.8% of women with a first conception as compared to 19.2% (p = 0.03) and 20.8% (p = 0.03) in those with a prior abortion or birth, respectively. Gardnerella as the most abundant bacterial genus increased from 3.8% in women with a first conception to 15.4% and 14.3% in those with a prior abortion or birth, respectively (p > 0.05). L. iners dominance was also associated with a history of spontaneous abortion (p ≤ 0.02). The composition of the vaginal microbiome and its influence on pregnancy outcome varies with pregnancy history.

First trimester cystic hygroma: does early detection matter?

OBJECTIVE: To describe the association of abnormal outcomes with fetal cystic hygroma detected when crown-rump length measures less than 45 mm, and to compare them to outcomes among fetuses with cystic hygroma detected when crown-rump length measures 45-84 mm. METHODS: We performed a retrospective cohort study of fetuses with first trimester nuchal cystic hygroma from 2005 to 2015. RESULTS: A total of 212 fetuses were included. Abnormal karyotype was found in 20 of 46 (43.4%) fetuses with cystic hygroma detected when crown-rump length measured below 45 mm, compared to 108 of 148 (73%) fetuses with cystic hygroma detected at crown-rump lengths of 45-84 mm (p = 0.001). There were no differences in rates of major structural anomaly (27% vs 36%; p = 0.53) or pregnancy loss (23% vs 7%; p = 0.22) among fetuses with normal karyotype. Those with cystic hygroma diagnosed at crown-rump lengths below 45 mm were more likely to have a normal neonatal outcome compared to cases diagnosed with crown-rump lengths of 45-84 mm (25% vs 11%; p = 0.02). CONCLUSION: Cystic hygroma detected when crown-rump length measures below 45 mm have lower rates of chromosomal abnormalities and a higher proportion of normal birth outcomes when compared to those detected later in the first trimester. © 2016 John Wiley & Sons, Ltd.

Group B streptococcus alters properties of vaginal epithelial cells in pregnant women.

BACKGROUND: Group B streptococcus (GBS) infection in pregnancy is a major cause of maternal and neonatal morbidity. An understanding of the mechanisms responsible for GBS persistence in the genital tract, as well as recognition of host defenses employed to combat its presence, are crucial to our efforts to reduce maternal GBS colonization and prevent the acquisition of neonatal infections. However, alterations in vaginal immunity in response to GBS colonization in pregnant women remain incompletely defined. Whether GBS modulates autophagy, a major host defense mechanism and contributor to the control of intracellular microbial infections, also remains unclear. OBJECTIVE: We sought to identify differences in the extent of autophagy as well as in the concentration of biomarkers previously shown to be involved in vaginal innate immunity between GBS-positive and GBS-negative pregnant women. STUDY DESIGN: We performed a prospective cohort study of healthy pregnant women, who had vaginal secretions obtained at 35-37 weeks of gestation, just prior to the standard GBS rectovaginal sample collection. The contents of the swabs were released into tubes containing 1 mL of sterile phosphate-buffered saline. Samples were centrifuged, and supernatant and cell pellet fractions were collected and stored separately at -80°C until used for analysis. Epithelial cells were then lysed, and the extent of autophagy was determined by measuring the residual level of p62 remaining in the cytoplasm. p62 is a protein that is consumed during autophagy, and so its concentration detectable in the cytoplasm is inversely related to the extent of autophagy induction. The intracellular level of the inducible 70-kDa heat shock protein (hsp70), an inhibitor of autophagy, was also measured. The cell-free fraction was assayed for D- and L-lactic acid, neutrophil gelatinase-associated lipocalin, extracellular matrix metalloproteinase inducer (EMMPRIN), matrix metalloproteinase (MMP)-8, alpha amylase, hyaluronan, and total protein. Laboratory personnel were blinded to all clinical data. RESULTS: There were 145 women included in the study, of which 45 (31%) were culture-positive for GBS. Vaginal cells from GBS-positive women had elevated intracellular levels of p62 (2.1 vs 0.7 pg/mL, P < .01) and hsp70 (16.9 vs 9.6 ng/mL, P = .03) as compared to GBS-negative women. The p62 and hsp70 levels were highly correlated in both groups of subjects (P < .01). In vaginal fluid, concentrations of neutrophil gelatinase-associated lipocalin (1.1 vs 0.7 ng/µg total protein, P = .01), MMP-8 (21.9 vs 11.1 pg/µg total protein, P = .01), and extracellular MMP inducer (8.8 vs 7.2 pg/µg total protein, P = .03) were highest in GBS-positive women. There were no differences in the concentrations of D- and L-lactic acid, alpha amylase, or hyaluronan between the 2 groups of women. CONCLUSION: The inhibition of autophagy in vaginal epithelial cells by GBS-induced hsp70 production is associated with its persistence. Concurrently, alterations in components known to influence vaginal bacterial colonization or facilitate microbial passage to the upper genital tract also occur in relation to GBS carriage.

Predictors of Health-Related Quality of Life After Bariatric Surgery.

BACKGROUND: Bariatric surgery is typically associated with improvement in health-related quality of life (HRQoL). However, recent reports are conflicting, and the aim of this study was to determine factors that would be predictive for long-term outcomes after bariatric procedures. METHODS: One thousand five hundred and seventy-three patients at one Midwestern academic medical center who underwent any type of bariatric surgery were sent the SF-36 survey. Three hundred and fifty completed surveys collected over a 3-month period were returned. Multivariate analysis was conducted. RESULTS: The physical and mental component scores were significantly lower than the norm population mean. Age at time of surgery, pre-surgical body mass index (BMI) and duration since surgery were negatively related to HRQoL. CONCLUSIONS: Improvements in HRQoL following bariatric surgery do not appear to be sustained over the long term. Older patients and those with high pre-surgical obesity do not appear to have the same benefits in HRQoL over time.

Obesity bias in primary care providers.

BACKGROUND AND OBJECTIVES: At the forefront of the obesity epidemic, obesity bias is an under-recognized and widely prevalent barrier to optimal care of the obese patient, even among primary care professionals. Recommendations for the reduction of obesity bias include increasing provider awareness about the complex etiology of obesity and the difficulties obtaining sustainable weight loss. METHODS: Obesity bias was measured in primary care professionals (n=233) participating in a continuing education program, using the Anti-Fat Attitudes Questionnaire (AFAQ). Three sub-factors, "Fear of Fat," "Willpower," and "Dislike," were evaluated. Participants were divided into three primary care experience groups: least experienced (0--9 years, n=67), moderately experienced (10--19 years, n=49), and most experienced (20+ years, n=98). "Fear of Fat" and "Willpower" components were found to be more prevalent than "Dislike"; however, scores on the "Dislike" subscale were highest and significantly more prevalent in the group with the most experience. RESULTS: Results indicated that more experienced primary care professionals reported greater bias toward obese people than less experienced colleagues. CONCLUSIONS: Ongoing continuing education that recognizes the wide prevalence of obesity, encourages respect for people of size, and mitigates obesity stigma should be promoted for all providers, particularly those who have been in practice for many years.

First-trimester cystic hygroma: relationship of nuchal translucency thickness and outcomes.

OBJECTIVE: To estimate the relationship between nuchal translucency thickness and abnormal karyotype, major congenital anomaly, perinatal loss, and composite abnormal outcome in fetuses with first-trimester nuchal cystic hygroma. METHODS: We performed a retrospective cohort study of first-trimester fetuses with ultrasound-diagnosed nuchal cystic hygroma collected over a 10-year period. RESULTS: There were 944 first-trimester fetuses with nuchal cystic hygroma. A karyotype abnormality occurred in 54.9% (400 of 729) of fetuses. A major congenital anomaly occurred in 28.8% (61 of 212) of fetuses with a normal karyotype. Perinatal loss occurred in 39% (115 of 295) of fetuses not electively terminated. Overall, an abnormal outcome occurred in 86.6% (543 of 627) of fetuses. After adjusting for potential confounders, every 1-mm increase in nuchal translucency thickness increased the odds of an abnormal karyotype by 44% (adjusted odds ratio [OR] 1.44, 95% confidence interval [CI] 1.29-1.60, P<.001), the odds of major congenital anomaly by 26% (adjusted OR 1.26, 95% CI, 1.08-1.47, P=.003), the odds of perinatal loss by 47% (adjusted OR 1.47, 95% CI 1.07-2.02, P=.019), and the odds of a composite abnormal outcome by 77% (adjusted OR 1.77, 95% CI 1.15-2.74, P=.01). CONCLUSION: First-trimester nuchal cystic hygroma is associated with high rates of karyotype abnormality, major congenital anomaly, perinatal loss, and abnormal outcome. As the thickness of the nuchal translucency increases, the odds of abnormal karyotype, major congenital anomaly, perinatal loss, and abnormal outcome increase.

Assessing genetic polymorphisms using DNA extracted from cells present in saliva samples.

BACKGROUND: Technical advances following the Human Genome Project revealed that high-quality and -quantity DNA may be obtained from whole saliva samples. However, usability of previously collected samples and the effects of environmental conditions on the samples during collection have not been assessed in detail. In five studies we document the effects of sample volume, handling and storage conditions, type of collection device, and oral sampling location, on quantity, quality, and genetic assessment of DNA extracted from cells present in saliva. METHODS: Saliva samples were collected from ten adults in each study. Saliva volumes from .10-1.0 ml, different saliva collection devices, sampling locations in the mouth, room temperature storage, and multiple freeze-thaw cycles were tested. One representative single nucleotide polymorphism (SNP) in the catechol-0-methyltransferase gene (COMT rs4680) and one representative variable number of tandem repeats (VNTR) in the serotonin transporter gene (5-HTTLPR: serotonin transporter linked polymorphic region) were selected for genetic analyses. RESULTS: The smallest tested whole saliva volume of .10 ml yielded, on average, 1.43 ± .77 µg DNA and gave accurate genotype calls in both genetic analyses. The usage of collection devices reduced the amount of DNA extracted from the saliva filtrates compared to the whole saliva sample, as 54-92% of the DNA was retained on the device. An "adhered cell" extraction enabled recovery of this DNA and provided good quality and quantity DNA. The DNA from both the saliva filtrates and the adhered cell recovery provided accurate genotype calls. The effects of storage at room temperature (up to 5 days), repeated freeze-thaw cycles (up to 6 cycles), and oral sampling location on DNA extraction and on genetic analysis from saliva were negligible. CONCLUSIONS: Whole saliva samples with volumes of at least .10 ml were sufficient to extract good quality and quantity DNA. Using 10 ng of DNA per genotyping reaction, the obtained samples can be used for more than one hundred candidate gene assays. When saliva is collected with an absorbent device, most of the nucleic acid content remains in the device, therefore it is advisable to collect the device separately for later genetic analyses.