Prenatal alcohol exposure is associated with changes in placental gene co-expression networks.

Alcohol consumption during pregnancy can result in a range of adverse postnatal outcomes among exposed children. However, identifying at-risk children is challenging given the difficulty to confirm prenatal alcohol exposure and the lack of early diagnostic tools. Placental surveys present an important opportunity to uncover early biomarkers to identify those at risk. Here, we report the first transcriptome-wide evaluation to comprehensively evaluate human placental pathways altered by fetal alcohol exposure. In a prospective longitudinal birth cohort in Cape Town, South Africa, we performed bulk tissue RNAseq in placenta samples from 32 women reporting heavy drinking during pregnancy and 30 abstainers/light drinkers. Weighted gene co-expression network analysis (WGCNA) and differential gene expression analysis were performed to assess associations between fetal alcohol exposure and placental gene expression patterns at a network-wide and single gene level, respectively. The results revealed altered expression in genes related to erythropoiesis and angiogenesis, which are implicated in established postnatal phenotypes related to alcohol exposure, including disruptions in iron homeostasis, growth, and neurodevelopment. The reported findings provide insights into the molecular pathways affected by prenatal alcohol exposure and highlight the potential of placental biomarkers for detecting and understanding the effects of alcohol on fetal development.

RNA-seq analysis reveals prenatal alcohol exposure is associated with placental inflammatory cells and gene expression.

BACKGROUND: Fetal alcohol spectrum disorders (FASD) are the most common preventable cause of birth defects and neurodevelopmental disorders worldwide. The placenta is the crucial interface between mother and fetus. Prenatal alcohol exposure (PAE) has been shown to alter placental structure and expression of genes in bulk placental tissue samples, but prior studies have not examined effects on placental cell-type composition or taken cell-type into consideration in transcriptome analyses. METHODS: We leveraged an existent placenta single-cell RNA-seq dataset to perform cell-type deconvolution of bulk placental RNA-seq data from 35 heavy drinking pregnant women and 33 controls in a prospective birth cohort in Cape Town, South Africa. We used bivariate analyses and multivariable adjusted linear regression models to assess the relation of PAE on inferred placental cell-type proportions. We also examined differential expression of inflammatory response genes and PAE, using multivariable adjusted linear models. RESULTS: Deconvolution analyses showed heterogeneous placenta cell-type composition in which stromal (27 %), endothelial (26 %) and cytotrophoblasts (18 %) were the predominant cell-types. PAE around conception was associated with a higher proportion of Hofbauer cells (B = 0.51, p = 0.035) in linear models adjusted for maternal age, infant sex, and gestational age. Among the 652 inflammatory genes examined, 35 were differential expressed in alcohol exposed placentas (FDR p < 0.05). CONCLUSIONS: Our findings suggest that heavy alcohol exposure during pregnancy can influence the proportion of fetal placental villi macrophages (Hofbauer cells) and increased expression of inflammatory genes. Future studies are needed to further characterize these effects and to assess the potential functional roles of placental inflammation in FASD.

Assessing the efficacy and mechanisms of glycol-contaminated water treatment through floating treatment wetlands.

The growing concerns surrounding water pollution and the degradation of ecosystems worldwide have led to an increased use of nature-based solutions (NbSs). This study assessed the feasibility of using floating treatment wetlands (FTWs) as an NbS to treat propylene glycol-contaminated water and quantitatively investigated different removal pathways. With an environmentally relevant concentration of propylene glycol (1,250 mg/L), FTWs containing Acorus calamus and mixed species demonstrated the highest average glycol mass removal efficacy (99%), followed by Carex acutiformis (98%), Juncus effusus (93%), and the control group without plants (10%) after 1 week. Additional mesocosm-scale experiments with varying FTW configurations, including surface coverage to reduce evaporation and photodegradation processes, and the addition of antibiotics to inhibit microbial activity, were conducted to quantify glycol removal pathways. Mass balance analysis results revealed that microbial biodegradation (33.3-39.7%) and plant uptake (37.9-45.2%) were the primary pathways for glycol removal. Only 15.5-19.5% of the glycol removal via evaporation and photodegradation was accounted in this study, which may be attributed to the mesocosm experimental setup (static water and no wind). Aligned with the broader discussion regarding biodiversity improvements and carbon storage capacity, this study demonstrated that FTWs are an environmentally friendly and effective NbS for addressing glycol-contaminated water.

Effects of prenatal pesticide exposure on the fetal brain and placenta transcriptomes in a rodent model.

Organophosphate and pyrethroid pesticides are among the most extensively used insecticides worldwide. Prenatal exposures to both classes of pesticides have been linked to a wide range of neurobehavioral deficits in the offspring. The placenta is a neuroendocrine organ and the crucial regulator of the intrauterine environment; early-life toxicant exposures could impact neurobehavior by disrupting placental processes. Female C57BL/6 J mice were exposed via oral gavage to an organophosphate, chlorpyrifos (CPF) at 5 mg/kg, a pyrethroid, deltamethrin (DM), at 3 mg/kg, or vehicle only control (CTL). Exposure began two weeks before breeding and continued every three days until euthanasia at gestational day 17. The transcriptomes of fetal brain (CTL n = 18, CPF n = 6, DM n = 8) and placenta (CTL n = 19, CPF n = 16, DM n = 12) were obtained through RNA sequencing, and resulting data was evaluated using weighted gene co-expression networks, differential expression, and pathway analyses. Fourteen brain gene co-expression modules were identified; CPF exposure disrupted the module related to ribosome and oxidative phosphorylation, whereas DM disrupted the modules related to extracellular matrix and calcium signaling. In the placenta, network analyses revealed 12 gene co-expression modules. While CPF exposure disrupted modules related to endocytosis, Notch and Mapk signaling, DM exposure dysregulated modules linked to spliceosome, lysosome and Mapk signaling pathways. Overall, in both tissues, CPF exposure impacted oxidative phosphorylation, while DM was linked to genes involved in spliceosome and cell cycle. The transcription factor Max involved in cell proliferation was overexpressed by both pesticides in both tissues. In summary, gestational exposure to two different classes of pesticide can induce similar pathway-level transcriptome changes in the placenta and the brain; further studies should investigate if these changes are linked to neurobehavioral impairments.

The American Student Placements in Rehabilitation Engineering Program (ASPIRE).

Background: American Student Placements and Internships in Rehabilitation Engineering is founded on the principal of sparking the interest in a new generation of rehabilitation engineering scientists to transform the lives of older adults and people with disabilities. Each year a minimum of 10 students were enrolled.Methods: The internship runs for 10 weeks and activities center on developing excitement about technology and engineering and understanding the principles and processes of conducting rehabilitation engineering research. This was accomplished by student participation in 1) rehabilitation engineering research projects; 2) educational research training, and 3) professional activities with clinical and engineering faculty, staff, and graduate students. Of the 162 participants, 53% were women and 47% men. 23% of participants were from minority or underrepresented groups, and 18% identified as having a disability.Results: From post-internship follow-up efforts, 65% of program participants went on to pursue or have graduated with advanced degrees, 27% of whom are engineers from underrepresented groups. Of those students that are working post-baccalaureate, 70% are engineers working in a biomedical/technology field. In the past 3 years, 92% of students stated that the program met or exceeded their expectations, while 100% of the 2018 group felt that their expectations were met.Conclusion: The American Student Placements and Internships in Rehabilitation Engineering program has demonstrated efficacy in preparing undergraduate students for future academic work and employment.Implications for RehabilitationCreative researchers and designers will lead the way in advancing accessibility standards and engineering for people with disabilities.The ASPIRE program increases excitement for and interest in the fields of rehabilitation engineering among undergraduate students to positively influence academic and professional careers.Students enrolled in the ASPIRE program actively participated in a real multidisciplinary project supervised by professor mentors. This led students to take a problem-based approach in their professional development.The ASPIRE program stimulates rehabilitation engineering in students' mindset and promotes inclusive academic environments and communities.Rehabilitation engineering is not a mainstream discipline, but the ASPIRE program indicates that there are benefits to student education, including participatory action engineering, that need to continue gain momentum until rehabilitation engineering is a mainstream discipline or a core component of engineering education.We must move beyond a "survival of the fittest" mentality. A "survival of the fittest" model places a disproportionate burden on groups that are underrepresented in science and engineering, and thereby postpones the day on which the demographics of science and engineering are comparable to that of society as a whole.The ASPIRE program needs to be replicated at various institutions around the world.

Accessible machining for people who use wheelchairs.

Despite the Americans with Disabilities Act mandate for reasonable accommodations, wheelchair users are often placed in the role of observer and note-taker when learning machining and fabrication skills due to a lack of accessibility. The focus of this case study report is to identify and develop reasonable accommodations for wheelchair users in an academic machine shop environment to address accessibility limitations of original equipment manufacturer (OEM) machines. Individual wheelchair users working and learning within the Human Engineering Research Laboratories (HERL) were observed and interviewed about their experiences using the machine shop equipment without modifications, followed by further observations after accommodations were implemented.

Impact of Cardiac Resynchronization Therapy on Daily Physical Activity in Heart Failure Patients.

PURPOSE: Cardiac resynchronization therapy (CRT) has emerged as a beneficial therapy for heart failure (HF) patients. It has been shown to enhance cardiac pump function and increase exercise capacity in patients with HF who display wide QRS complex on their electrocardiogram. To date, few studies have assessed daily physical activity (PA) in CRT patients. The objective of this pilot study was to assess the impact of CRT on the physical function and daily PA of HF patients who met the standard indications for CRT implantation. METHODS: The daily PA of 18 CRT patients was measured using a SenseWear Armband for ∼3 d. Daily PA measurements included steps/d and time spent sedentary (≤1.5 metabolic equivalent tasks), in light PA (1.6-2.9 metabolic equivalent tasks), and in moderate-vigorous PA (≥3 metabolic equivalent tasks). To assess exercise capacity, a 6-min walk test was performed pre- and post-CRT. RESULTS: There was no significant change in the 6-min walk test distance from pre- to post-CRT (383 ± 99 m at baseline vs 402 ± 104 m post-CRT). There was a decrease in total steps/d from 3405 ± 2334 pre-CRT to 2553 ± 1692 post-CRT (P = .017). Furthermore, no significant changes were observed pre- to post-CRT with regard to the additional PA assessments. CONCLUSIONS: Our patients exhibited a sedentary lifestyle pre- and post-CRT. These findings underscore the need for a cardiac rehabilitation program that encourages post-CRT patients to decrease sedentary time.

Cardiac work-up protocol for liver transplant candidates: experience from a single liver transplant centre.

BACKGROUND: Ischemic cardiac events can cause significant morbidity and mortality postliver transplantation; however, no validated protocols to screen patients before transplantation exist. OBJECTIVES: To report the introduction of a noninvasive cardiac screening protocol used at the Liver Unit, University of Calgary (Calgary, Alberta); to determine whether the protocol decreases use of coronary angiograms; and to compare cardiac outcomes using the new protocol with an appropriately matched historical control group. METHODS: A new cardiac screening protocol was introduced into the program in 2005, which uses perfusion scintigraphy to screen high-risk cardiac patients, reserving coronary angiograms for abnormal results. Transplanted patients screened using this protocol were compared with matched historical controls. Electronic charts were reviewed for cardiac outcomes intra- and postliver transplantation. RESULTS: A total of 396 patients were screened between April 2005 and February 2009. Eighty-two were transplanted by February 2009 and included in the study. Eighty-one patients were successfully matched according to age, sex, cardiac history and presence of diabetes. Twelve of 82 (14.6%) and 11 of 81 (13.6%) in the study and control groups, respectively, underwent coronary angiograms (P=0.85). Coronary artery disease was found in six of 12 (50.0%) study patients and three of 11 (27.3%) control patients who underwent coronary angiography (P=0.27). The mean (± SD) length of the follow-up period was 1.87±0.91 years and 4.45±1.89 years in the study and control groups, respectively. One of 81 in the control group and zero of 82 in the study group experienced an acute coronary syndrome event postoperatively. CONCLUSIONS: Coronary events are infrequent in liver transplant recipients. The described protocol is an effective method of coronary artery disease screening before liver transplant but does not reduce the number of cardiac investigations performed.

Impact of AV conduction disorders on SafeR mode performance.

PURPOSE: CAN-SAVE R is a Canadian multicenter study that compares the effects of a new pacing mode algorithm designed to minimize right ventricular (V) pacing versus DDD mode with a long atrioventricular (AV) delay in a general population of pacemaker (PM) recipients. STUDY PARTICIPANTS: Patients with permanent atrial fibrillation (AF) or high-degree AV block (AVB) were excluded. We present preliminary data collected in 208 patients (mean age=71 +/- 11 years, 68% men), for the 2-month baseline period during which all PM were programmed in the new pacing mode. The pacing indications were sinus node disease (SND) without AVB in 39%, AVB without SND in 30%, SND and AVB in 16%, and miscellaneous in 15% of patients. RESULTS: The mean percent V pacing in the overall population was 9.5 +/- 23.8% (range=0-100%, median <1%), ranging between 0.5 +/- 1.5% (median=0) in patients without AVB and 18.7 +/- 31.2% in patients (median = 1) with AVB. Adverse events potentially related to the new pacing mode were observed in two patients with AVB. CONCLUSIONS: A new pacing mode was effective and safe in a general population of PM recipients without permanent AVB and was associated with an overall <1% median V pacing. CAN-SAVE R will compare the long-term effects of the new pacing mode with DDD with a long AV delay on clinical outcomes and cardiac function.

Using NANDA, NIC, and NOC (NNN) language for clinical reasoning with the Outcome-Present State-Test (OPT) model.

PURPOSE: To analyze the degree to which standardized nursing language was used by baccalaureate nursing students completing Outcome-Present State-Test (OPT) model worksheets in a clinical practicum. METHODS. A scoring instrument was developed and 100 worksheets were retrospectively analyzed. FINDINGS: NANDA nursing diagnoses were correctly stated in 92% of the OPT models. Nursing Outcomes Classification (NOC) outcomes were explicitly stated in 22%, and implied in 72%. Interventions matched appropriate Nursing Interventions Classification (NIC) activities in 61%. CONCLUSIONS: NANDA, NIC, and NOC (NNN) language was used inconsistently by students in this sample. IMPLICATIONS FOR PRACTICE: If NNN language is to advance nursing knowledge, its promotion, representation in curriculum development, and active use is necessary. Educational research is needed on the facilitators and barriers to NNN language use.

Intention-to-treat analysis: who is in? Who is out?

To assess whether the term "intention to treat" (ITT) predicts inclusion of all randomized subjects in the analysis, we reviewed 100 randomly selected reports of randomized trials that mentioned analysis by ITT. Only 42 of 100 reports included all randomized subjects in the ITT analysis. We could not determine which categories of participants were excluded from the ITT analysis in 13 trials. The most common categories of excluded subjects were patients who, after randomization, received no follow-up (16/100), received no treatment (14/100), or were found not to meet study entry criteria (12/100). We could determine the number of participants in the ITT analysis for 92 studies. Nineteen of the 92 studies excluded more than 5% of randomized participants, and 10 excluded more than 10%. There is considerable variation in how researchers define and apply the principle of intention to treat.

A comparison of textual and echoic prompts on the acquisition of intraverbal behavior in a six-year-old boy with autism.

A comparison of textual and echoic prompts was conducted to determine which form of prompts was more effective for teaching intraverbal behavior to a 6-year-old boy with autism. A multiple baseline design across three sets of questions measured (a) the number of full-sentence target answers, (b) partial answers that made sense, and (c) partial answers that did not make sense, or no response, to direct questions asked. A fading procedure using either scripted textual or scripted echoic prompts was employed to evoke the child's correct answers. Although both forms of prompts were effective, results indicated that textual prompts were much more effective. These findings suggest that textual prompts may be effective in teaching complex skills to children with autism.