Corrigendum: Maternal serum iron status, hepcidin and interleukin-6 levels in women with preeclampsia.

[This corrects the article DOI: 10.3389/fphys.2023.1049994.].

Understanding the genetic mechanisms and cognitive impairments in Down syndrome: towards a holistic approach.

The most common genetic cause of intellectual disability is Down syndrome (DS), trisomy 21. It commonly results from three copies of human chromosome 21 (HC21). There are no mutations or deletions involved in DS. Instead, the phenotype is caused by altered transcription of the genes on HC21. These transcriptional variations are responsible for a myriad of symptoms affecting every organ system. A very debilitating aspect of DS is intellectual disability (ID). Although tremendous advances have been made to try and understand the underlying mechanisms of ID, there is a lack of a unified, holistic view to defining the cause and managing the cognitive impairments. In this literature review, we discuss the mechanisms of neuronal over-inhibition, abnormal morphology, and other genetic factors in contributing to the development of ID in DS patients and to gain a holistic understanding of ID in DS patients. We also highlight potential therapeutic approaches to improve the quality of life of DS patients.

Targeting mGluR group III for the treatment of neurodegenerative diseases.

Glutamate, an excitatory neurotransmitter, is essential for neuronal function, and it acts on ionotropic or metabotropic glutamate receptors (mGluRs). A disturbance in glutamatergic signaling is a hallmark of many neurodegenerative diseases. Developing disease-modifying treatments for neurodegenerative diseases targeting glutamate receptors is a promising avenue. The understudied group III mGluR 4, 6-8 are commonly found in the presynaptic membrane, and their activation inhibits glutamate release. Thus, targeted mGluRs therapies could aid in treating neurodegenerative diseases. This review describes group III mGluRs and their pharmacological ligands in the context of amyotrophic lateral sclerosis, Parkinson's, Alzheimer's, and Huntington's diseases. Attempts to evaluate the efficacy of these drugs in clinical trials are also discussed. Despite a growing list of group III mGluR-specific pharmacological ligands, research on the use of these drugs in neurodegenerative diseases is limited, except for Parkinson's disease. Future efforts should focus on delineating the contribution of group III mGluR to neurodegeneration and developing novel ligands with superior efficacy and a favorable side effect profile for the treatment of neurodegenerative diseases.

Antibody-directed extracellular proximity biotinylation reveals that Contactin-1 regulates axo-axonic innervation of axon initial segments.

Axon initial segment (AIS) cell surface proteins mediate key biological processes in neurons including action potential initiation and axo-axonic synapse formation. However, few AIS cell surface proteins have been identified. Here, we use antibody-directed proximity biotinylation to define the cell surface proteins in close proximity to the AIS cell adhesion molecule Neurofascin. To determine the distributions of the identified proteins, we use CRISPR-mediated genome editing for insertion of epitope tags in the endogenous proteins. We identify Contactin-1 (Cntn1) as an AIS cell surface protein. Cntn1 is enriched at the AIS through interactions with Neurofascin and NrCAM. We further show that Cntn1 contributes to assembly of the AIS extracellular matrix, and regulates AIS axo-axonic innervation by inhibitory basket cells in the cerebellum and inhibitory chandelier cells in the cortex.

Iron deficiency and thyroid dysfunction among sudanese women in first trimester of pregnancy: a cross-sectional study.

BACKGROUND: Pregnant women are more susceptible to iron deficiency (ID), and it can lead to several maternal and perinatal adverse effects. There are some published data on the effect of ID on thyroid function, but none of the studies were conducted in sub-Saharan African countries including Sudan. This study was conducted to investigate association between ID (ferritin < 15 µg/L) and thyroid functions [thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4)] among Sudanese women in the first trimester of pregnancy. METHOD: A cross-sectional study was conducted in Saad Abuelela Maternity Hospital, Sudan. Obstetric/sociodemographic characteristics were gathered through questionnaires. Hemoglobin, serum ferritin, TSH, FT3, and FT4 were measured in all pregnant women. Continuous variables were compared with either independent sample t-test if they were normally distributed, or with Mann-Whitney U- test if they were not-normally distributed. Spearman correlations were performed between the continuous variables. RESULTS: In total, 127 pregnant women with mean [standard deviation (SD)] age of 27.0 (5.5) years and gestational age of 10.5 (3.0) weeks, respectively, were enrolled in this study. Forty-seven (37.0%) of these 127 women had ID. While the median [interquartile range (IQR)] of the parity, TSH, and FT3 were not different between women with ID and women without ID, the median (IQR) of FT4 was significantly lower in women with ID compared with women without ID [1.020 (0.910‒1.120) vs. 1.095 (0.990‒1.217) pmol, P = 0.014]. Serum ferritin was inversely correlated with FT3, (r = -0.225, P = 0.011). There was no significant correlation between serum ferritin, TSH, and FT4. CONCLUSIONS: Iron deficiency was common during the first trimester of pregnancy and was associated with thyroid dysfunctions. Therefore, ID should be evaluated to avoid thyroid dysfunction.

Applications of advances in mRNA-based platforms as therapeutics and diagnostics in reproductive technologies.

The recent COVID-19 pandemic led to many drastic changes in not only society, law, economics, but also in science and medicine, marking for the first time when drug regulatory authorities cleared for use mRNA-based vaccines in the fight against this outbreak. However, while indeed representing a novel application of such technology in the context of vaccination medicine, introducing RNA into cells to produce resultant molecules (proteins, antibodies, etc.) is not a novel principle. It has been common practice to introduce/inject mRNA into oocytes and embryos to inhibit, induce, and identify several factors in a research context, while such aspects have also been proposed as potential therapeutic and diagnostic applications to combat infertility in humans. Herein, we describe key areas where mRNA-based platforms have thus far represented potential areas of clinical applications, describing the advantages and limitations of such applications. Finally, we also discuss how recent advances in mRNA-based platforms, driven by the recent pandemic, may stand to benefit the treatment of infertility in humans. We also present brief future directions as to how we could utilise recent and current advancements to enhance RNA therapeutics within reproductive biology, specifically with relation to oocyte and embryo delivery.

Homocysteine levels, H-Hypertension, and the MTHFR C677T genotypes: A complex interaction.

Background and objectives: High homocysteine levels are associated with increased risk of hypertension and stroke. Homocysteine is metabolized by the methylenetetrahydrofolate reductase (MTHFR). We aimed to investigate the levels of homocysteine and their association with hypertension, stroke, and antihypertensive medication usage in patients with different MTHFR C677T genotypes. Methods and results: Genotype frequency of MTHFR polymorphism was performed, and plasma homocysteine levels were measured in 2,640 adult Lebanese patients. Hypertension, history of stroke, and list of medications were documented, among other clinical and demographic parameters. The TT mutant genotype and the T mutant allele of MTHFR were more prevalent in hyperhomocysteinemia (HHcy) and H-hypertensive (H-HTN, defined as hypertension with hyperhomocysteinemia) patients when compared to non-HHcy subjects and non H-HTN patients respectively. Homocysteine levels were significantly higher in hypertensive patients specifically among those on diuretics. A higher level of homocysteine was found in hypertensive patients with the MTHFR T allele compared to patients carrying the C allele. Among the T allele carriers, the average plasma homocysteine level was 13.3 ± 0.193 µmol/L for hypertensive subjects compared to 11.9 ± 0.173 µmol/L (non-hypertensives). Furthermore, homocysteine levels significantly correlated with stroke risk in patients with the T alleles. Conclusions: We found an association of homocysteine with hypertension, hypertensive medication, and stroke risk among patients with the MTHFR T allele and the TT genotype. The association of diuretics therapy with higher homocysteine levels calls for routine measurements and therapeutic control of homocysteine in patients on diuretic, to improve health-related outcomes.

Antigen Unmasking Is Required to Clinically Assess Levels and Localisation Patterns of Phospholipase C Zeta in Human Sperm.

Mammalian oocyte activation is initiated by intracellular calcium (Ca2+) oscillations, driven by the testis-specific phospholipase C zeta (PLCζ). Sperm PLCζ analysis represents a diagnostic measure of sperm fertilisation capacity. The application of antigen unmasking/retrieval (AUM) generally enhanced the visualisation efficacy of PLCζ in mammalian sperm, but differentially affected the PLCζ profiles in sperm from different human males. It is unclear whether AUM affects the diagnosis of PLCζ in human sperm. Herein, we examined whether the application of AUM affected the correlation of PLCζ profiles with sperm parameters and fertilisation capacity. PLCζ fluorescence levels and localisation patterns were examined within the sperm of males undergoing fertility treatment (55 patients aged 29-53) using immunofluorescence in the absence/presence of AUM. The changes in PLCζ profiles following AUM were examined in relation to sperm health and fertilisation outcome. AUM enhanced the observable levels and specific localisation patterns of PLCζ in relation to both optimal sperm parameters and fertilisation outcome, without which significant differences were not observed. The extent of the change in levels and localisation ratios of PLCζ was also affected to a larger degree in terms of the optimal parameters of sperm fertility and fertilisation capacity by AUM. Collectively, AUM was essential to accurately assesses PLCζ in human sperm in both scientific and clinical contexts.

Spatio-temporal variation of the microbial community of the coast of Lebanon in response to petroleum hydrocarbon pollution.

In this study, the coast of Lebanon was analyzed for the dynamic changes in sediment microbial communities in response to a major petroleum oil spill and tar contamination that occurred in the summer of 2021. Spatio-temporal variations in the microbial structure along the shores of Lebanon were assessed in comparison to baseline microbial structure determined in 2017. Microbial community structure and diversity were determined using Illumina MiSeq technology and DADA2 pipeline. The results show a significant diversity of microbial populations along the Lebanese shore, and a significant change in the sediment microbial structure within four years. Namely, Woeseia, Blastopirellula, and Muriicola were identified in sediment samples collected in year 2017, while a higher microbial diversity was observed in 2021 with Woeseia, Halogranum, Bacillus, and Vibrio prevailing in beach sediments. In addition, the results demonstrate a significant correlation between certain hydrocarbon degraders, such as Marinobacter and Vibrio, and measured hydrocarbon concentrations.

Fostering formative assessment: teachers' perception, practice and challenges of implementation in four Sudanese medical schools, a mixed-method study.

Formative assessment (assessment for learning) enhances learning (especially deep learning) by using feedback as a central tool. However, implementing it properly faces many challenges. We aimed to describe the perception of medical teachers towards FA, their practice, challenges of implementing FA and present applicable solutions. A mixed-method, explanatory approach study was applied by administering a validated questionnaire to 190 medical teachers in four medical schools in Sudan. The obtained results were further studied using the Delphi method. Quantitative analysis revealed that medical teachers perceived their grasping of the concept of FAs and their ability to differentiate formative from summative assessments as very well (83.7%) and (77.4%), respectively. However, in contradiction to the former results, it was noteworthy that (41%) of them mistakenly perceived FA as an approach conducted for purposes of grading and certification. The qualitative study defined the challenges into two main themes: lack of understanding of formative assessment and lack of resources. Medical teachers' development and resource allocation were the main recommendations. We conclude that there is misunderstanding and malpractice in implementing formative assessment attributed to the lack of understanding of FA as well as the lack of resources. We as well present suggested solutions derived from the perception of the medical teachers in the study and evolved around three approaches: faculty development, managing the curriculum by allocating time and resources for FA, and advocacy among stakeholders.

Functional foods and their impact on health.

Functional foods play an important role in maintaining a healthy lifestyle and reducing the risk factors of various diseases. Most foods have a functional element which is responsible for improving the healthy state. All food substances such as fruits, vegetables, cereals, meat, fish, dairy contain functional ingredients. A wide range of naturally occurring substances from plant and animal sources having active components which play a role in physiological actions deserve attention for their optimal use in maintaining health. The market for functional food is keep on expanding, and the global market is projected to reach a value of at least 91 billion USD soon. Overwhelming evidence from preclinical (in vitro and in vivo) and clinical studies have shown that intake of functional foods could have an impact on the prevention of chronic diseases, especially cancer, cardiovascular diseases, gastrointestinal tract disorders and neurological diseases. Extensive research needs to be done to determine the potential health benefits for the proper application of these foods to improve health state and combat chronic disease progression. The aim of this review is to conduct a thorough literature survey, to understand the various classification of functional foods and their health benefits.

Maternal serum iron status, hepcidin and interleukin-6 levels in women with preeclampsia.

Introduction: Preeclampsia can lead to a number of adverse maternal and perinatal effects. The association between iron status [serum iron, ferritin and total iron-binding capacity (TIBC)], unsaturated iron-binding capacity, hepcidin, interleukin-6 (IL-6) levels and preeclampsia is not fully understood. Objective: To assess the levels of iron status, hepcidin and interleukin-6 in women with preeclampsia compared with healthy pregnant women. Method: A case-control study (60 women were recruited in each group) was conducted at Saad Abuelela Maternity Hospital in Khartoum, Sudan. Sociodemographic and clinical data were gathered through a questionnaire. The levels of iron status, hepcidin and IL-6 were measured using applicable methods. Results: There was no significant difference in the median [interquartile range (IQR)] of age, parity or body mass index between the two groups. Moreover, the median (IQR) of the iron status, hepcidin and interleukin-6 did not differ between women with preeclampsia and healthy controls. There were no significant correlations between haemoglobin, hepcidin and IL-6. There were also no significant correlations between serum iron, serum ferritin, hepcidin and IL-6. However, there was a significant positive correlation between hepcidin and IL-6 (r = 0.393, p = 0.002). Conclusion: In this study, women with preeclampsia had levels of iron status, hepcidin and IL-6 similar to those observed in healthy pregnant women. There was no significant correlation between iron status, hepcidin and IL-6.

The Therapeutic and Diagnostic Potential of Phospholipase C Zeta, Oocyte Activation, and Calcium in Treating Human Infertility.

Oocyte activation, a fundamental event during mammalian fertilisation, is initiated by concerted intracellular patterns of calcium (Ca2+) release, termed Ca2+ oscillations, predominantly driven by testis-specific phospholipase C zeta (PLCζ). Ca2+ exerts a pivotal role in not just regulating oocyte activation and driving fertilisation, but also in influencing the quality of embryogenesis. In humans, a failure of Ca2+ release, or defects in related mechanisms, have been reported to result in infertility. Furthermore, mutations in the PLCζ gene and abnormalities in sperm PLCζ protein and RNA, have been strongly associated with forms of male infertility where oocyte activation is deficient. Concurrently, specific patterns and profiles of PLCζ in human sperm have been linked to parameters of semen quality, suggesting the potential for PLCζ as a powerful target for both therapeutics and diagnostics of human fertility. However, further to PLCζ and given the strong role played by Ca2+ in fertilisation, targets down- and up-stream of this process may also present a significantly similar level of promise. Herein, we systematically summarise recent advancements and controversies in the field to update expanding clinical associations between Ca2+-release, PLCζ, oocyte activation and human fertility. We discuss how such associations may potentially underlie defective embryogenesis and recurrent implantation failure following fertility treatments, alongside potential diagnostic and therapeutic avenues presented by oocyte activation for the diagnosis and treatment of human infertility.

A multi-country phase 2 study to evaluate the suitcase lab for rapid detection of SARS-CoV-2 in seven Sub-Saharan African countries: Lessons from the field.

BACKGROUND: The COVID-19 pandemic led to severe health systems collapse, as well as logistics and supply delivery shortages across sectors. Delivery of PCR related healthcare supplies continue to be hindered. There is the need for a rapid and accessible SARS-CoV-2 molecular detection method in low resource settings. OBJECTIVES: To validate a novel isothermal amplification method for rapid detection of SARS-CoV-2 across seven sub-Sharan African countries. STUDY DESIGN: In this multi-country phase 2 diagnostic study, 3,231 clinical samples in seven African sites were tested with two reverse transcription Recombinase-Aided Amplification (RT-RAA) assays (based on SARS-CoV-2 Nucleocapsid (N) gene and RNA-dependent RNA polymerase (RdRP) gene). The test was performed in a mobile suitcase laboratory within 15 min. All results were compared to a real-time RT-PCR assay. Extraction kits based on silica gel or magnetic beads were applied. RESULTS: Four sites demonstrated good to excellent agreement, while three sites showed fair to moderate results. The RdRP gene assay exhibited an overall PPV of 0.92 and a NPV of 0.88. The N gene assay exhibited an overall PPV of 0.93 and a NPV 0.88. The sensitivity of both RT-RAA assays varied depending on the sample Ct values. When comparing sensitivity between sites, values differed considerably. For high viral load samples, the RT-RAA assay sensitivity ranges were between 60.5 and 100% (RdRP assay) and 25 and 98.6 (N assay). CONCLUSION: Overall, the RdRP based RT-RAA test showed the best assay accuracy. This study highlights the challenges of implementing rapid molecular assays in field conditions. Factors that are important for successful deployment across countries include the implementation of standardized operation procedures, in-person continuous training for staff, and enhanced quality control measures.

Genetic Variants in PHACTR1 & LPL Mediate Restenosis Risk in Coronary Artery Patients.

Background and Objective: Coronary artery disease (CAD) is a major cause of death worldwide. Revascularization via stent placement or coronary artery bypass grafting (CABG) are standard treatments for CAD. Despite a high success rate, these approaches are associated with long-term failure due to restenosis. Risk factors associated with restenosis were investigated using a case-control association study design. Methods: Five thousand two hundred and forty-two patients were enrolled in this study and were assigned as follows: Stenosis Group: 3570 patients with CAD >50% without a prior stent or CABG (1394 genotyped), and Restenosis Group: 1672 patients with CAD >50% and prior stent deployment or CABG (705 genotyped). Binomial regression models were applied to investigate the association of restenosis with diabetes, hypertension, and dyslipidemia. The genetic association with restenosis was conducted using PLINK 1.9. Results: Dyslipidemia is a major risk factor (Odds Ratio (OR) = 2.14, P-value <0.0001) for restenosis particularly among men (OR = 2.32, P < 0.0001), while type 2 diabetes (T2D) was associated with an increased risk of restenosis in women (OR = 1.36, P = 0.01). The rs9349379 (PHACTR1) and rs264 (LPL) were associated with an increased risk of restenosis in our patients. PHACTR1 variant was associated with increased risk of restenosis mainly in women and in diabetic patients, while the LPL variant was associated with increased risk of restenosis in men. Conclusion: The rs9349379 in PHACTR1 gene is significantly associated with restenosis, this association is more pronounced in women and in diabetic patients. The rs264 in LPL gene was associated with increased risk of restenosis in male patients.

Association of Maternal Anemia and Cesarean Delivery: A Systematic Review and Meta-Analysis.

Anaemia during pregnancy is associated with an increased incidence of caesarean delivery (CD). This study was conducted to explore the association between CD and maternal anaemia. The PubMed/MEDLINE, Cochrane, Google, Google Scholar and ScienceDirect databases were searched for relevant studies on this topic. The assessment and review were conducted with the Joanna Briggs Institute Meta-Analysis of Statistics Assessment and Review Instrument. The studies were assessed using the modified Newcastle−Ottawa quality assessment scale. Data were collected in an Excel sheet, and the 'meta' package of the R 4.0.3 software was used for statistical analysis. Fourteen studies that enrolled 336,128 pregnant women were included in the meta-analysis. Women with anaemia were found to be at a higher risk for CD (OR = 1.63, 95% CI = 1.23−2.17). As heterogeneity was detected in the studies, the random-effects model was used for the pooled meta-analysis (Q = 96.7, p < 0.001). In the subgroup analysis, anaemic women were found to be at higher risk for CD in studies from both low-middle-income (7) and high-income countries (7). In meta-regression analysis, none of the investigated covariates were associated with the pooled OR of CD. This evidence demonstrates with a moderate level of certainty that anaemic pregnant women are more likely to have CD than non-anaemic pregnant women.

Elevated Lp(a) Levels Correlate with Severe and Multiple Coronary Artery Stenotic Lesions.

Backgrounds and Aims: The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim of this study is to investigate the correlation of high Lp(a) levels with the degree of coronary artery stenosis. Methods: Two hundred and sixty-eight patients were enrolled for this study. Patients who underwent coronary artery angiography and who had Lp(a) measurements available were included in this study. Binomial logistic regressions were applied to investigate the association between Lp(a) and stenosis in the four major coronary arteries. The effect of LDL and HDL Cholesterol on modulating the association of Lp(a) with coronary artery disease (CAD) was also evaluated. Multinomial regression analysis was applied to assess the association of Lp(a) with the different degrees of stenosis in the four major coronary arteries. Results: Our analyses showed that Lp(a) is a risk factor for CAD and this risk is significantly apparent in patients with HDL-cholesterol ≥35 mg/dL and in non-obese patients. A large proportion of the study patients with elevated Lp(a) levels had CAD even when exhibiting high HDL serum levels. Increased HDL with low Lp(a) serum levels were the least correlated with stenosis. A significantly higher levels of Lp(a) were found in patients with >50% stenosis in at least two major coronary vessels arguing for pronounced and multiple stenotic lesions. Finally, the derived variant (rs1084651) of the LPA gene was significantly associated with CAD. Conclusion: Our study highlights the importance of Lp(a) levels as an independent biological marker of severe and multiple coronary artery stenosis.

Association of Selenium Levels with Preeclampsia: A Systematic Review and Meta-analysis.

Several observational studies have shown inconclusive findings on the association between selenium levels and preeclampsia. This systematic review and meta-analysis was conducted to clarify the association between selenium levels and preeclampsia. The databases PubMed, Google Scholar, ScienceDirect, and the Cochrane Library were searched for studies which investigated selenium levels with preeclampsia and which were published up to April 2022. The overall standardized mean differences (SMD) of selenium levels between cases and controls were measured. Sensitivity analysis, reporting bias, subgroup analysis, and meta-regression were performed for the estimate. The meta-analysis was calculated using the "meta" package in the open-source software R. A total of 26 studies with 1855 preeclampsia cases compared with 3728 healthy pregnant controls were included. The level of selenium was significantly lower in cases of preeclampsia compared with the controls [SMD = - 0.85; 95% confidence interval (CI): (- 1.46, - 0.25); P = < 0.01). As there was significant heterogeneity [I2 = 96%, Cochran's Q = 620.47; P = < 0.01], the random effects model was used. A stratified meta-analysis revealed that selenium levels were significantly lower in the cases compared with the controls among pregnant women from the African continent [SMD = - 1.15 (- 1.65, - 0.65); P = < 0.01]. Likewise, the same pattern was observed among women from middle- and low-income countries [SMD = - 1.32 (- 2.22, - 0.42); P = < 0.01]. None of the investigated factors (Modified Newcastle-Ottawa Scale quality score, year of publication, and sample size) showed significant association with the selenium SMD. The level of certainty of this evidence is "low certainty," as calculated by the GRADEpro GDT online tool. This meta-analysis with low level of evidence certainty revealed that low selenium level is associated significantly with preeclampsia. This pattern is also observed in women from the African continent and women from low- or middle-income countries. Further studies with different prospective designs and detailed patient characteristics are needed to consolidate this evidence.