Malate dehydrogenase in parasitic protozoans: roles in metabolism and potential therapeutic applications.

The role of malate dehydrogenase (MDH) in the metabolism of various medically significant protozoan parasites is reviewed. MDH is an NADH-dependent oxidoreductase that catalyzes interconversion between oxaloacetate and malate, provides metabolic intermediates for both catabolic and anabolic pathways, and can contribute to NAD+/NADH balance in multiple cellular compartments. MDH is present in nearly all organisms; isoforms of MDH from apicomplexans (Plasmodium falciparum, Toxoplasma gondii, Cryptosporidium spp.), trypanosomatids (Trypanosoma brucei, T. cruzi) and anaerobic protozoans (Trichomonas vaginalis, Giardia duodenalis) are presented here. Many parasitic species have complex life cycles and depend on the environment of their hosts for carbon sources and other nutrients. Metabolic plasticity is crucial to parasite transition between host environments; thus, the regulation of metabolic processes is an important area to explore for therapeutic intervention. Common themes in protozoan parasite metabolism include emphasis on glycolytic catabolism, substrate-level phosphorylation, non-traditional uses of common pathways like tricarboxylic acid cycle and adapted or reduced mitochondria-like organelles. We describe the roles of MDH isoforms in these pathways, discuss unusual structural or functional features of these isoforms relevant to activity or drug targeting, and review current studies exploring the therapeutic potential of MDH and related genes. These studies show that MDH activity has important roles in many metabolic pathways, and thus in the metabolic transitions of protozoan parasites needed for success as pathogens.

Is a Higher Amniotic Fluid Viral Load Associated with a Greater Risk of Fetal Injury in Congenital Cytomegalovirus Infection-A Systematic Review and Meta-Analysis.

Background: Numerous studies have aimed to predict prenatal and neonatal outcomes for pregnancies complicated by congenital cytomegalovirus (CMV). Presently, assessing CMV severity prenatally relies largely on fetal imaging. A controversy exists regarding CMV viral load (VL) and its association with fetal and neonatal sequelae. Objective: To perform a systematic review and meta-analysis investigating the association between CMV DNA VL in amniotic fluid and fetal and neonatal outcomes in pregnancies with congenital CMV. Results: All cohort, case-control and observational studies that compared outcomes of fetuses with congenital CMV and provided information on individual patient CMV VL quantified in copies per milliliter (c/mL) from inception to January 2023 were included, with no geographical or language restrictions. A total of 1251 citations were reviewed with eight studies meeting inclusion criteria and included in meta-analysis. Affected pregnancies had a higher VL in the amniotic fluid compared to those unaffected with a mean difference of 2.2e+7 (range 1.5e+7 to 2.8e+7). In subgroup analysis, the VL was significantly higher in the fetuses, with imaging findings related to CMV compared to asymptomatic fetuses with a mean difference of 4.1e+7 (95% CI 2.8e+7-5.4e+7). However, among babies with congenital CMV, the VL was not significantly different between symptomatic and asymptomatic babies. Conclusions: Amniotic fluid CMV VL is associated with fetal sequalae in congenital CMV, with a higher VL conferring a greater risk for prenatal injury.

Using augmented reality in molecular case studies to enhance biomolecular structure-function explorations in undergraduate classrooms.

Molecular case studies (MCSs) are open educational resources that use a storytelling approach to engage students in biomolecular structure-function explorations, at the interface of biology and chemistry. Although MCSs are developed for a particular target audience with specific learning goals, they are suitable for implementation in multiple disciplinary course contexts. Detailed teaching notes included in the case study help instructors plan and prepare for their implementation in diverse contexts. A newly developed MCS was simultaneously implemented in a biochemistry and a molecular parasitology course at two different institutions. Instructors participating in this cross-institutional and multidisciplinary implementation collaboratively identified the need for quick and effective ways to bridge the gap between the MCS authors' vision and the implementing instructor's interpretation of the case-related molecular structure-function discussions. Augmented reality (AR) is an interactive and engaging experience that has been used effectively in teaching molecular sciences. Its accessibility and ease-of-use with smart devices (e.g., phones and tablets) make it an attractive option for expediting and improving both instructor preparation and classroom implementation of MCSs. In this work, we report the incorporation of ready-to-use AR objects as checkpoints in the MCS. Interacting with these AR objects facilitated instructor preparation, reduced students' cognitive load, and provided clear expectations for their learning. Based on our classroom observations, we propose that the incorporation of AR in MCSs can facilitate its successful implementation, improve the classroom experience for educators and students, and make MCSs more broadly accessible in diverse curricular settings.

Evaluating the validity of ChatGPT responses on common obstetric issues: Potential clinical applications and implications.

OBJECTIVE: To evaluate the quality of ChatGPT responses to common issues in obstetrics and assess its ability to provide reliable responses to pregnant individuals. The study aimed to examine the responses based on expert opinions using predetermined criteria, including "accuracy," "completeness," and "safety." METHODS: We curated 15 common and potentially clinically significant questions that pregnant women are asking. Two native English-speaking women were asked to reframe the questions in their own words, and we employed the ChatGPT language model to generate responses to the questions. To evaluate the accuracy, completeness, and safety of the ChatGPT's generated responses, we developed a questionnaire with a scale of 1 to 5 that obstetrics and gynecology experts from different countries were invited to rate accordingly. The ratings were analyzed to evaluate the average level of agreement and percentage of positive ratings (≥4) for each criterion. RESULTS: Of the 42 experts invited, 20 responded to the questionnaire. The combined score for all responses yielded a mean rating of 4, with 75% of responses receiving a positive rating (≥4). While examining specific criteria, the ChatGPT responses were better for the accuracy criterion, with a mean rating of 4.2 and 80% of the questions received a positive rating. The responses scored less for the completeness criterion, with a mean rating of 3.8 and 46.7% of questions received a positive rating. For safety, the mean rating was 3.9 and 53.3% of questions received a positive rating. There was no response with an average negative rating below three. CONCLUSION: This study demonstrates promising results regarding potential use of ChatGPT's in providing accurate responses to obstetric clinical questions posed by pregnant women. However, it is crucial to exercise caution when addressing inquiries concerning the safety of the fetus or the mother.

The association between discordant umbilical arterial resistance in growth-restricted fetuses and adverse outcomes.

BACKGROUND: Assessing the umbilical artery pulsatility index via Doppler measurements plays a crucial role in evaluating fetal growth impairment. OBJECTIVE: This study aimed to investigate perinatal outcomes associated with discordant pulsatility indices of umbilical arteries in fetuses with growth restriction. STUDY DESIGN: In this retrospective cohort study, all singleton pregnancies were included if their estimated fetal weight and/or abdominal circumference fell below the 10th percentile for gestational age (2017-2022). Eligible cases included singleton pregnancies with concurrent sampling of both umbilical arteries within 14 days of birth at the ultrasound evaluation closest to delivery. The exclusion criteria included births before 22 weeks of gestation, evidence of absent or reverse end-diastolic flow in either umbilical artery, and known fetal genetic or structural anomalies. The study compared cases with discordant umbilical artery pulsatility index values (defined as 1 umbilical artery pulsatility index at ≤95th percentile and the other umbilical artery pulsatility index at >95th percentile for gestational age) to pregnancies where both umbilical artery pulsatility indices had normal pulsatility index values and those with both umbilical arteries displaying abnormal pulsatility index values. The primary outcome assessed was the occurrence of composite adverse neonatal outcomes. Multivariable logistic regressions were performed, adjusting for relevant covariates. RESULTS: The study encompassed 1014 patients, including 194 patients (19.1%) with discordant umbilical artery pulsatility index values among those who had both umbilical arteries sampled close to delivery, 671 patients (66.2%) with both umbilical arteries having normal pulsatility index values, and 149 patients (14.7%) with both umbilical arteries exhibiting abnormal values. Pregnancies with discordant umbilical artery pulsatility index values displayed compromised sonographic parameters compared with those with both umbilical arteries showing normal pulsatility index values. Similarly, the number of abnormal umbilical artery pulsatility index values was associated with adverse perinatal outcomes in a dose-response manner. Cases with 1 abnormal (discordant) umbilical artery pulsatility index value showed favorable sonographic parameters and perinatal outcomes compared with cases with both abnormal umbilical artery pulsatility index values, and cases with both abnormal umbilical artery pulsatility index values showed worse sonographic parameters and perinatal outcomes compared with cases with discordant UA PI values. Multivariate analysis revealed that discordant umbilical artery pulsatility indices were significantly and independently associated with composite adverse perinatal outcomes, with an adjusted odds ratio of 1.75 (95% confidence interval, 1.24-2.47; P = .002). CONCLUSION: Evaluating the resistance indices of both umbilical arteries may provide useful data and assist in assessing adverse perinatal outcomes among fetuses with growth restriction.

miRNA profiling of esophageal adenocarcinoma using transcriptome analysis.

Esophageal adenocarcinoma (EAC) occurs following a series of histological changes through epithelial-mesenchymal transition (EMT). A variable expression of normal and aberrant genes in the tissue can contribute to the development of EAC through the activation or inhibition of critical molecular signaling pathways. Gene expression is regulated by various regulatory factors, including transcription factors and microRNAs (miRs). The exact profile of miRs associated with the pathogenesis of EAC is largely unknown, though some candidate miRNAs have been reported in the literature. To identify the unique miR profile associated with EAC, we compared normal esophageal tissue to EAC tissue using bulk RNA sequencing. RNA sequence data was verified using qPCR of 18 selected genes. Fourteen were confirmed as being upregulated, which include CDH11, PCOLCE, SULF1, GJA4, LUM, CDH6, GNA12, F2RL2, CTSZ, TYROBP, and KDELR3 as well as the downregulation of UGT1A1. We then conducted Ingenuity Pathway Analysis (IPA) to analyze for novel miR-gene relationships through Causal Network Analysis and Upstream Regulator Analysis. We identified 46 miRs that were aberrantly expressed in EAC compared to control tissues. In EAC tissues, seven miRs were associated with activated networks, while 39 miRs were associated with inhibited networks. The miR-gene relationships identified provide novel insights into potentially oncogenic molecular pathways and genes associated with carcinogenesis in esophageal tissue. Our results revealed a distinct miR profile associated with dysregulated genes. The miRs and genes identified in this study may be used in the future as biomarkers and serve as potential therapeutic targets in EAC.

Identification of genetic variants affecting reproduction traits in Vrindavani cattle.

Genome-wide association studies (GWAS) are one of the best ways to look into the connection between single-nucleotide polymorphisms (SNPs) and the phenotypic performance. This study aimed to identify the genetic variants that significantly affect the important reproduction traits in Vrindavani cattle using genome-wide SNP chip array data. In this study, 96 randomly chosen Vrindavani cows were genotyped using the Illumina Bovine50K BeadChip platform. A linear regression model of the genome-wide association study was fitted in the PLINK program between genome-wide SNP markers and reproduction traits, including age at first calving (AFC), inter-calving period (ICP), dry days (DD), and service period (SP) across the first three lactations. Information on different QTLs and genes, overlapping or adjacent to genomic coordinates of significant SNPs, was also mined from relevant databases in order to identify the biological pathways associated with reproductive traits in bovine. The Bonferroni correction resulted in total 39 SNP markers present on different chromosomes being identified that significantly affected the variation in AFC (6 SNPs), ICP (7 SNPs), DD (9 SNPs), and SP (17 SNPs). Novel potential candidate genes associated with reproductive traits that were identified using the GWAS methodology included UMPS, ITGB5, ADAM2, UPK1B, TEX55, bta-mir-708, TMPO, TDRD5, MAPRE2, PTER, AP3B1, DPP8, PLAT, TXN2, NDUFAF1, TGFA, DTNA, RSU1, KCNQ1, ADAM32, and CHST8. The significant SNPs and genes associated with the reproductive traits and the enriched genes may be exploited as candidate biomarkers in animal improvement programs, especially for improved reproduction performance in bovines.

An idea to explore: Augmented reality and LEGO® brick modeling in the biochemistry and cell biology classroom-two tactile ways to teach biomolecular structure-Function.

We present here two accessible ways for enhanced understanding of complex biological structures and their function in undergraduate Biology and Biochemistry classrooms. These methods can be applied for in-class instruction as well as for remote lessons, as they are cheap, easily available and easy to implement. LEGO® bricks and MERGE CUBE based augmented reality can be applied to make three-dimensional representation for any structure available on PDB. We envisage these techniques to be useful for students when visualizing simple stereochemical problems or complex pathway interactions.

A Picture is Worth 1000 Words: Teaching Science Communication with Graphical Abstract Assignments.

An important part of scientific training in undergraduate curriculum involves teaching students how to effectively communicate in science. Scientific writing and oral presentations are important parts of most science classes. The same cannot be said about a new and emerging aspect of many recent scientific articles: graphical abstracts. In recent years, many scientific journals have adopted graphical abstracts as a way to capture both the scientific audience and increase visibility on social media platforms. Graphical abstracts are becoming the norm for many journals; however, there is no equivalent training in undergraduate classes that teaches students the intricate skills of efficient graphical design. In this paper, we share our course design and discuss how students can be taught to design better experiments and excel in communicating their research findings through graphical abstracts.

Optimizing Transfer of Postcesarean Patients to Postoperative Ward Through a Quality Improvement (QI) Project: Curtailing Delays, Improving Care.

BACKGROUND AND OBJECTIVES: Close monitoring of patients in the first 2 hours after cesarean delivery (CD) is crucial. Delays in shifting of the post-CD patients led to a chaotic environment in the postoperative ward, suboptimal monitoring, and inadequate nursing care. Our aim was to increase the percentage of post-CD patients shifted from transfer trolley to bed within 10 minutes of arrival in the postoperative ward from a baseline of 64% to 100%, and to maintain that rate for more than 3 weeks. METHODS: A quality improvement team including physicians, nurses, and workers was constituted. Problem analysis revealed lack of communication among the caregivers as the main cause of delay. The percentage of post-CD patients shifted from trolley to bed within 10 minutes of being wheeled into the postoperative ward out of the total number of post-CD patients transferred from the operation theater to the postoperative ward was taken as the outcome indicator for the project. Multiple Plan-Do-Study-Act cycles based on the Point of Care Quality Improvement methodology were undertaken to achieve the target. Main interventions were: 1) written information of patient being transferred to operation theater for CD sent to the postoperative ward; 2) stationing of a duty doctor in the postoperative ward; and 3) keeping a buffer of 1 vacant bed in the postoperative ward. The data were plotted weekly as a dynamic time series chart and signals of change were observed. RESULTS: Eighty-three percent (172 out of 206) of women were shifted in time by 3 weeks. After Plan-Do-Study-Act 4, the percentages kept improving leading to a median shift from 85.6% to 100% after 10 weeks post-initiation of the project. Sustainment was confirmed by continuing observations for 6 more weeks to ensure that the changed protocol was assimilated in the system. We found that all women were shifted within 10 minutes of their arrival in postoperative ward from trolley to bed. CONCLUSION: Providing high-quality care to patients must be a priority for all health care providers. High-quality care is timely, efficient, evidence based, and patient-centric. Delays in transfer of postoperative patients to the monitoring area can be detrimental. The point of Care Quality Improvement methodology is useful and effective in solving complex problems by understanding and fixing the various contributory factors one by one. Reorganization of processes and available manpower without any extra investment in terms of infrastructure and resources is pivotal for long term success of a quality improvement project.

Comparison of circulating maternal placenta growth factor levels and sonographic evaluation of patients with abnormal first trimester screening analytes.

OBJECTIVE: To evaluate the role of mid-trimester placental growth factor (PlGF) in patients with abnormal circulating levels of first-trimester biomarkers. METHODS: Retrospective cohort study including singleton pregnancies complicated by abnormal first-trimester biomarkers (2017-2020). Pregnancies complicated with chromosomal/structural anomalies were excluded. All patients had ultrasound imaging including uterine artery Doppler combined with measurement of maternal circulating PlGF. Sonographic findings, maternal and perinatal outcomes, and placental histopathology were compared between pregnancies with normal and low (<10th percentile for gestational age) PlGF levels. The diagnostic accuracy of PlGF for the prediction of specific placental-mediated complications was compared with the uterine artery Doppler assessment and additional sonographic findings. RESULTS: Seventy-one pregnancies were assessed, of which 35 (49.3%) had low PlGF levels. Maternal sociodemographic characteristics, nulliparity, and aspirin consumption were comparable. In comparison with patients with normal PlGF levels, individuals with low PlGF levels had a higher rate of fetal growth restriction (EFW <3rd centile; 42.9% vs. 8.3%, p = 0.001), preterm-preeclampsia (22.9% vs. 0%, p = 0.002), preterm delivery <34 weeks (54.3% vs. 8.3%, p < 0.001) and maternal vascular malperfusion placental pathology (72.7% vs. 21.7%, p < 0.001) following delivery. Adjusting for uterine artery Doppler and fetal biometry status, mid-trimester low PlGF remained significantly associated with these placental-mediated complications. The predictive capacity of PlGF outperformed ultrasound imaging with only minimal diagnostic improvement when ultrasound information was combined with PlGF status. CONCLUSION: In pregnancies with unexplained abnormal first-trimester biomarkers, mid-trimester PlGF outperformed a comprehensive ultrasound assessment in the identification of a subset of patients destined to develop placental dysfunction. This blood test may be an alternative initial approach in this context, especially where access to specialist care is more geographically challenging.

Allele mining in gene encoding fc fragment of IgG receptor, transporter, alpha (FCGRT) and association of nucleotide variants with passive transfer of immunity in neonatal buffalo calves.

BACKGROUND: Neonatal Fc receptors (FcRn) mediate the transcytosis of IgG present in colostrum across absorptive gut epithelium of newborn calves. FcRn receptor is a heterodimer composed of two polypeptides encoded by FCGRT (Fc fragment of IgG Receptor Transporter neonatal) and B2M (Beta 2 microglobulin) genes. Polymorphism in FCGRT gene may have a bearing on absorption of colostral immunoglobulins by neonatal buffalo calves, thereby affecting their immune status and susceptibility to diseases. The primary aim of our study was to mine alleles and single nucleotide polymorphs in the FCGRT gene and determine their association with the levels of IgG in serum of neonatal buffalo calves. METHODS AND RESULTS: On the basis of serum IgG levels estimated by indirect ELISA in 80 newborn calves, 20 calves each with highest and lowest IgG concentration were selected to study polymorphism in the FCGRT gene. The exonic regions of this gene were amplified in nine fragments which were subjected to PCR-SSCP to detect variations followed by the sequencing of variants to locate the SNPs. A total of nine SNPs (7 in introns and 2 in exons) were detected in four polymorphic fragments. Association study based on Odds ratios (ORs) with 95% Confidence Interval (CIs) established that the SNP G40T in fragment 3 has a significant (P < 0.05) bearing on IgG level in serum of neonatal buffalo calves. CONCLUSION: Genetic variation in FCGRT gene in buffalo calves was found to be associated with their serum IgG levels in neonatal stage which may have implications in calf survival and growth vis-à-vis inadequate transfer of passive immunity.

Hemodynamic functional connectivity optimization of frequency EEG microstates enables attention LSTM framework to classify distinct temporal cortical communications of different cognitive tasks.

Temporal analysis of global cortical communication of cognitive tasks in coarse EEG information is still challenging due to the underlying complex neural mechanisms. This study proposes an attention-based time-series deep learning framework that processes fMRI functional connectivity optimized quasi-stable frequency microstates for classifying distinct temporal cortical communications of the cognitive task. Seventy volunteers were subjected to visual target detection tasks, and their electroencephalogram (EEG) and functional MRI (fMRI) were acquired simultaneously. At first, the acquired EEG information was preprocessed and bandpass to delta, theta, alpha, beta, and gamma bands and then subjected to quasi-stable frequency-microstate estimation. Subsequently, time-series elicitation of each frequency microstates is optimized with graph theory measures of simultaneously eliciting fMRI functional connectivity between frontal, parietal, and temporal cortices. The distinct neural mechanisms associated with each optimized frequency-microstate were analyzed using microstate-informed fMRI. Finally, these optimized, quasi-stable frequency microstates were employed to train and validate the attention-based Long Short-Term Memory (LSTM) time-series architecture for classifying distinct temporal cortical communications of the target from other cognitive tasks. The temporal, sliding input sampling windows were chosen between 180 to 750 ms/segment based on the stability of transition probabilities of the optimized microstates. The results revealed 12 distinct frequency microstates capable of deciphering target detections' temporal cortical communications from other task engagements. Particularly, fMRI functional connectivity measures of target engagement were observed significantly correlated with the right-diagonal delta (r = 0.31), anterior-posterior theta (r = 0.35), left-right theta (r = - 0.32), alpha (r = - 0.31) microstates. Further, neuro-vascular information of microstate-informed fMRI analysis revealed the association of delta/theta and alpha/beta microstates with cortical communications and local neural processing, respectively. The classification accuracies of the attention-based LSTM were higher than the traditional LSTM architectures, particularly the frameworks that sampled the EEG data with a temporal width of 300 ms/segment. In conclusion, the study demonstrates reliable temporal classifications of global cortical communication of distinct tasks using an attention-based LSTM utilizing fMRI functional connectivity optimized quasi-stable frequency microstates.

Timing of cesarean delivery in women with uncomplicated placenta previa.

OBJECTIVE: The optimal timing of an elective cesarean delivery for uncomplicated placenta previa remains controversial. Although the present guidelines recommend an elective cesarean delivery between 360/7 and 376/7 weeks of gestation, data supporting this recommendation does not differentiate in outcomes between elective and emergent delivery, or between women with and without ante-partum hemorrhage. Recommendations regarding optimal timing of delivery are based on the risks and benefits associated with delivery at a certain gestational week, compared with a reference of 38 weeks. Therefore, the aim of this paper was to assess the maternal and neonatal adverse outcomes associated with elective delivery at different gestational weeks from 360/7 to 386/7 weeks compared with expectant management in women with uncomplicated placenta previa. METHODS: A retrospective cohort study in a single tertiary medical center of 251 women with a diagnosis of uncomplicated placenta previa, who delivered between 360/7 and 386/7 weeks of gestation, who delivered at our center between Jan 2011 and Dec 2019. Maternal and neonatal outcomes at each gestational week were compared with expectant management. RESULTS: At 360/7-366/7 weeks, the rate of composite maternal adverse outcome was similar for elective delivery and expectant management (10.5% vs 7.7%, p = .68). Similarly, at 370/7-376/7 the rate of composite maternal adverse outcome was comparable for elective cesarean delivery and expectant management (7.2% vs 6.4%, p = .54). Maternal bleeding was the main indication of an urgent cesarean delivery, and account for 86% of urgent cesarean delivery at 360/7-366/7, 76.4% of urgent cesarean delivery at 370/7-376/7, and for 70.6% of all urgent cesarean delivery at 380/7-386/7 weeks. This group of women who were delivered due to maternal bleeding had a history of maternal bleeding during 2nd and/or 3rd trimester in 75-92.3% of cases. Composite adverse neonatal outcome was similar for elective cesarean delivery at each gestational age compared with expectant management. The risk for lower 5-min APGAR score and hypoglycemia was higher for newborns that were delivered electively a 36th weeks of gestation compared with expectant management. CONCLUSION: Our study suggests that the optimal time of delivery for women with an uncomplicated placenta previa is between 380/7 and 386/7 weeks of gestation, especially in women without ante-partum bleeding.

Insights from Client Experience with Injection Medroxyprogesterone Acetate (MPA) in India: Lessons from the Field.

Background: The injectable contraceptives have been recently added to the contraceptive basket of Government of India under the National Family Welfare program with the aim to reduce the unmet need of contraception in the country. The present study has been conducted to analyse the continuation rates and concerns among the acceptors of injection MPA. Materials and Methods: The present study was an ambispective observational study conducted in the out-patient department of family welfare division at a tertiary care hospital in New Delhi over a period of 6 months. The study enrolled 483 acceptors of injection MPA who were interviewed in person or telephonically, and a proforma was filled which included the demographic profile, obstetric history of the women, source of information about injection and its timing, number of doses received, side effects experienced and the compliance status. The data obtained was subjected to statistical analysis. Results: The mean age of the studied population was 28.44 ± 4.73 years and average parity was 2. It was found that injection MPA was initiated in the interval period in 304 women (63.3%), post-abortal in 124 (25.8%), and postnatal in 52 (10.8%). The source of information about the injection for most women was health workers (83.5%). Most women (74.3%) were pleased with the injection and showed their willingness to continue, and 67.7% were continuing with the injection at the time of interview. Menstrual irregularity was the most common side effect observed in 48.5% women. Conclusion: The present study showed a good continuation rate of injection MPA for the Indian population. The coverage for this excellent contraceptive modality can be enhanced further if more efforts to disseminate awareness about this method are made. Menstrual irregularity is the most common side effect causing discontinuation which can be mitigated to a significant extent with an effective pre-administration counseling.