Wastewater-based SARS-CoV-2 airport surveillance: key trends at the Cape Town International Airport.

Monitoring of SARS-CoV-2 RNA in wastewater has revealed the role of mobility in the transmission of coronavirus disease (COVID-19), and the surveillance of airport wastewater in cities across the world has demonstrated how travel entry points can give an indication of trends in transmission. This study undertook wastewater surveillance at the Cape Town International Airport (CTIA) to assess the use of a WBE approach to provide supplementary information on the presence of COVID-19 at a key air travel entry point in South Africa. Grab wastewater samples (n = 55) were collected from the CTIA wastewater pump station and analysed using quantitative real-time polymerase chain reaction (qRT-PCR) method. The study found a correlation between the wastewater data and clinical cases reported in the City of Cape Town during various time periods and during the peak of a COVID-19 wave. Highly elevated viral loads in the wastewater were observed at times there was increased mobility through the airport. The study also revealed elevated viral load levels at the airport despite the stricter restrictions and through the lower restrictions. The study findings indicate wastewater surveillance and airports can provide supplementary information to airport authorities to assess the impacts of imposed travel restrictions.

Delineating the Spread and Prevalence of SARS-CoV-2 Omicron Sublineages (BA.1-BA.5) and Deltacron Using Wastewater in the Western Cape, South Africa.

This study was one of the first to detect Omicron sublineages BA.4 and BA.5 in wastewater from South Africa. Spearman rank correlation analysis confirmed a strong positive correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral RNA in wastewater samples and clinical cases (r = 0.7749, P < .0001). SARS-CoV-2 viral load detected in wastewater, resulting from the Delta-driven third wave, was significantly higher than during the Omicron-driven fourth wave. Whole-genome sequencing confirmed presence of Omicron lineage defining mutations in wastewater with the first occurrence reported 23 November 2021 (BA.1 predominant). The variant spread rapidly, with prevalence of Omicron-positive wastewater samples rising to >80% by 10 January 2022 with BA.2 as the predominant sublineage by 10 March 2022, whilst on 18 April 2022 BA.4 and BA.5 were detected in selected wastewater sites. These findings demonstrate the value of wastewater-based epidemiology to monitor the spatiotemporal spread and potential origin of new Omicron sublineages.

Adiponectin as a Potential Biomarker for Pregnancy Disorders.

Adiponectin is an adipocyte-derived hormone that plays a critical role in energy homeostasis, mainly attributed to its insulin-sensitizing properties. Accumulating studies have reported that adiponectin concentrations are decreased during metabolic diseases, such as obesity and type 2 diabetes, with an emerging body of evidence providing support for its use as a biomarker for pregnancy complications. The identification of maternal factors that could predict the outcome of compromised pregnancies could act as valuable tools that allow the early recognition of high-risk pregnancies, facilitating close follow-up and prevention of pregnancy complications in mother and child. In this review we consider the role of adiponectin as a potential biomarker of disorders associated with pregnancy. We discuss common disorders associated with pregnancy (gestational diabetes mellitus, preeclampsia, preterm birth and abnormal intrauterine growth) and highlight studies that have investigated the potential of adiponectin to serve as biomarkers for these disorders. We conclude the review by recommending strategies to consider for future research.

Global DNA methylation profiling in peripheral blood cells of South African women with gestational diabetes mellitus.

Background/Objective: Recently, several studies have reported that DNA methylation changes in tissue are reflected in blood, sparking interest in the potential use of global DNA methylation as a biomarker for gestational diabetes mellitus (GDM). This study investigated whether global DNA methylation is associated with GDM in South African women. Methods: Global DNA methylation was quantified in peripheral blood cells of women with (n = 63) or without (n = 138) GDM using the MDQ1 Imprint® DNA Quantification Kit. Results: Global DNA methylation levels were not different between women with or without GDM and were not associated with fasting glucose or insulin concentrations. However, levels were 18% (p = 0.012) higher in obese compared to non-obese pregnant women and inversely correlated with serum adiponectin concentrations (p = 0.005). Discussion: Contrary to our hypothesis, global DNA methylation was not associated with GDM in our population. These preliminary findings suggest that despite being a robust marker of overall genomic methylation that offers opportunities as a biomarker, global DNA methylation profiling may not offer the resolution required to detect methylation differences in the peripheral blood cells of women with GDM. Moreover, global DNA methylation in peripheral blood cells may not reflect changes in placental tissue. Further studies in a larger sample are required to explore the candidacy of a more targeted approach using gene-specific methylation as a biomarker for GDM in our population.

Altered Genome-Wide DNA Methylation in Peripheral Blood of South African Women with Gestational Diabetes Mellitus.

Increasing evidence implicate altered DNA methylation in the pathophysiology of gestational diabetes mellitus (GDM). This exploratory study probed the association between GDM and peripheral blood DNA methylation patterns in South African women. Genome-wide DNA methylation profiling was conducted in women with (n = 12) or without (n = 12) GDM using the Illumina Infinium HumanMethylationEPIC BeadChip array. Functional analysis of differentially methylated genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. A total of 1046 CpG sites (associated with 939 genes) were differentially methylated between GDM and non-GDM groups. Enriched pathways included GDM-related pathways such as insulin resistance, glucose metabolism and inflammation. DNA methylation of the top five CpG loci showed distinct methylation patterns in GDM and non-GDM groups and was correlated with glucose concentrations. Of these, one CpG site mapped to the calmodulin-binding transcription activator 1 (CAMTA1) gene, which have been shown to regulate insulin production and secretion and may offer potential as an epigenetic biomarker in our population. Further validation using pyrosequencing and conducting longitudinal studies in large sample sizes and in different populations are required to investigate their candidacy as biomarkers of GDM.

Association between gestational diabetes and biomarkers: a role in diagnosis.

BACKGROUND: We investigated the association between markers of insulin resistance, chronic inflammation, and adipokines and GDM. METHODS: In our case-cohort study in Johannesburg we included women with GDM and controls. We tested the ability of biomarkers to identify women at high risk of GDM. RESULTS: Of the 262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p = 0.04) and had more clinical risk factors (p = 0.008). We found a significant difference in fasting insulin (p < 0.001), adiponectin (p = 0.046), HOMA (p < 0.001) and QUICKI (p < 0.001). HOMA (AUROC = 0.82) or QUICKI (AUROC = 0.82) improved the ability of risk factors to identify women at high risk of GDM. CONCLUSIONS: Insulin sensitivity markers are promising tools to identify women at high risk of GDM.

Molecular Biomarkers for Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a growing public health problem worldwide. The condition is associated with perinatal complications and an increased risk for future metabolic disease in both mothers and their offspring. In recent years, molecular biomarkers received considerable interest as screening tools for GDM. The purpose of this review is to provide an overview of the current status of single-nucleotide polymorphisms (SNPs), DNA methylation, and microRNAs as biomarkers for GDM. PubMed, Scopus, and Web of Science were searched for articles published between January 1990 and August 2018. The search terms included "gestational diabetes mellitus", "blood", "single-nucleotide polymorphism (SNP)", "DNA methylation", and "microRNAs", including corresponding synonyms and associated terms for each word. This review updates current knowledge of the candidacy of these molecular biomarkers for GDM with recommendations for future research avenues.

Connective tissue graft and tunnel or trapezoidal flap for the treatment of single maxillary gingival recessions: a randomized clinical trial.

BACKGROUND: Although ample evidence supports connective tissue graft (CTG) use for root coverage, there is need for research on recipient site preparation approaches. The purpose of this study was to compare the outcomes of trapezoidal coronally advanced flap (CAF) and coronally advanced tunnel flap (TUN) when used in conjunction with CTG. METHODS: Forty-two patients presenting 42 single maxillary, Miller Class I and II, gingival recession defects were randomly assigned to receive either CAF + CTG (N = 21) or TUN + CTG (N = 21). Clinical, patient-centred, and aesthetic outcomes were assessed. RESULTS: Six months postoperatively, both groups resulted in significant reduction in recession depth and increases in keratinized tissue thickness and width. CAF + CTG and TUN + CTG mean root coverage was 87.2 ± 27.1% and 77.4 ± 20.4% respectively (p = 0.02). Complete root coverage was achieved in 71.4% and 28.6% of defects treated with CAF + CTG and TUN + CTG respectively (p = 0.01). At 7 days postoperatively, TUN + CTG patients reported significantly less pain experience (p = 0.04). Both approaches reduced dentine hypersensitivity by approximately 85% (p < 0.05). Patient-based aesthetic evaluation indicated significant improvement for both groups. Although patient- and professional-based aesthetic assessments revealed no differences between groups, tissue texture was significantly better for TUN + CTG (p = 0.02). CONCLUSIONS: For root coverage of single maxillary recession defects, CAF + CTG was more effective than TUN + CTG (ClinicalTrial.org-NCT02814279).

Comparison of two power densities on the healing of palatal wounds after connective tissue graft removal: randomized clinical trial.

UNLABELLED: Connective tissue graft (CTG), which is considered to be among the best techniques for treating gingival recession, has presented stable long-term results. However, this technique causes morbidity and discomfort in the palatine region due to graft removal at that site. A previous study reports that photobiomodulation (PBM) using a dosage of 15 J/cm(2) may improve wound healing and the patient's postoperative comfort. However, no other studies in the literature provide the best application dosage or comparisons between protocols for this purpose. The aim of this study is to compare two power densities of PBM on the wound-healing process of the donor palatine area after CTG removal. In this study, 51 patients presenting buccal gingival recession were randomized into one of the following groups: group 1: CTG procedure for root coverage and PBM application at the donor site using a 60 J/cm(2) dose; group 2: CTG and PBM application using a 30 J/cm(2) dose; or group 3: CTG and sham application. The evaluated parameters were the wound remaining area (WRA), scar and tissue colorimetry (TC), tissue thickness (TT), and postoperative discomfort (D), evaluated at baseline and 7, 14, 45, 60, and 90 days after surgery. Group 1 presented statistically significant smaller wounds at day 7 (p > 0.05). None of the patients presented scars at the operated area, and all of the patients reported mild discomfort, with low consumption of analgesic pills. We concluded that the protocol of 60 J/cm(2) provided faster wound healing 7 days after removing the connective tissue graft for root coverage. TRIAL REGISTRATION: ClinicalTrial.org (NCT02580357) https://clinicaltrials.gov/ct2/show/NCT02580357 .

Connective tissue graft associated or not with low laser therapy to treat gingival recession: randomized clinical trial.

BACKGROUND: To evaluate the treatment of gingival recession with a connective tissue graft (CTG) alone or in combination with low-level laser therapy (CTG + L). METHODS: Forty patients presenting 40 Miller Class I and II gingival recessions were included. The defects were randomly assigned to receive either CTG (n = 20) or CTG + L (n = 20). A diode laser (660 nm) was applied to the test sites immediately after surgery and every other day for 7 days (eight applications). RESULTS: The mean percentage of root coverage was 91.9% for the test group and 89.48% for the control group after 6 months (p > 0.05). The test group presented more complete root coverage (n = 13, 65%) than the control group (n = 7, 35%) (p = 0.04). Dentine sensitivity decreased significantly after 6 months in both groups (p < 0.001). The two groups showed improvement in aesthetics at the end of treatment. CONCLUSIONS: Low-level laser therapy may increase the percentage of complete root coverage when associated with CTG.

Effect of GaAIAs low-level laser therapy on the healing of human palate mucosa after connective tissue graft harvesting: randomized clinical trial.

Among the available techniques to treat gingival recession, connective tissue graft (CTG) presents more foreseeability and better results in the long term. However, this technique causes morbidity and discomfort in the palatine region due to graft removal at that site. The aim of this clinical trial was to evaluate the influence of low-level laser therapy (LLLT) on the healing of the donor palatine area after CTG. Thirty-two patients presenting buccal gingival recession were selected and randomly assigned to receive LLLT irradiation (test group) or LLLT sham (control group) in the palatine area after connective graft removal. A diode laser (AsGaAl, 660 nm) was applied to test the sites immediately after surgery and every other day for 7 days. The evaluated parameters were wound remaining area (WRA), scar and tissue colorimetry (TC), tissue thickness (TT), and postoperative discomfort (D). These parameters were evaluated at baseline and 7, 14, 45, 60, and 90 days after surgery. Two-way repeated measures ANOVA was used for analysis. The test group presented statistically significant smaller wounds at days 14 and 45. None of the patients presented a scar at the operated area, and colorimetry analysis revealed that there was no statistically significant difference between groups (p > 0.05). Patients reported mild to moderate discomfort, with low consumption of analgesic pills. We concluded that LLLT irradiation can accelerate wound healing on palatine mucosa after connective tissue removal for root coverage techniques (ClinicalTrial.org NCT02239042).

Esthetic evaluation of different approaches to treat gingival recession associated with non-carious cervical lesion treatment: a 2-year follow-up.

PURPOSE: To evaluate the esthetic outcome of four different approaches to treat gingival recession, associated with non-carious cervical lesion (combined defects) and the possible roles of patient-related factors in this esthetic outcome. METHODS: 78 combined defects were previously treated by: coronally advanced flap (CAF), CAF plus cervical restoration using resin-modified glass-ionomer material (CAF+R), connective tissue graft (CTG) and CTG+R. After a follow-up of 2 years, esthetic evaluations were performed using a modification of the Root Coverage Esthetic Score (MRES) and Qualitative Cosmetic Evaluation (QCE). Additionally, regression analyses were performed to evaluate the influence of patient-related factors in the final esthetic outcome. RESULTS: The MRES showed that CAF and CTG had statistically significantly better results, when compared to the other groups (P < 0.05). Similarly, the QCE showed that CAF and CTG, along with CAF+R presented better results, and CTG+R showed the poorest esthetic outcome. Regression analyses showed that the overall gingival inflammation (full mouth bleeding index--FMBI) was negatively associated with CTG MRES score (P = 0.04 and R = -0.48). This means that the greater the FMBI during the study period, the lower the final esthetic score.

Gestational Diabetes and the Gut Microbiota: Fibre and Polyphenol Supplementation as a Therapeutic Strategy.

Gestational diabetes mellitus (GDM) is an escalating public health concern due to its association with short- and long-term adverse maternal and child health outcomes. Dysbiosis of microbiota within the gastrointestinal tract has been linked to the development of GDM. Modification of microbiota dysbiosis through dietary adjustments has attracted considerable attention as adjunct strategies to improve metabolic disease. Diets high in fibre and polyphenol content are associated with increased gut microbiota alpha diversity, reduced inflammation and oxidative processes and improved intestinal barrier function. This review explores the potential of fibre and polyphenol supplementation to prevent GDM by investigating their impact on gut microbiota composition and function.

The Maternal Microbiome and Gestational Diabetes Mellitus: Cause and Effect.

Gestational diabetes mellitus (GDM) is a growing public health concern that affects many pregnancies globally. The condition is associated with adverse maternal and neonatal outcomes including gestational hypertension, preeclampsia, placental abruption, preterm birth, stillbirth, and fetal growth restriction. In the long-term, mothers and children have an increased risk of developing metabolic diseases such as type 2 diabetes and cardiovascular disease. Accumulating evidence suggest that alterations in the maternal microbiome may play a role in the pathogenesis of GDM and adverse pregnancy outcomes. This review describes changes in the maternal microbiome during the physiological adaptations of pregnancy, GDM and adverse maternal and neonatal outcomes. Findings from this review highlight the importance of understanding the link between the maternal microbiome and GDM. Furthermore, new therapeutic approaches to prevent or better manage GDM are discussed. Further research and clinical trials are necessary to fully realize the therapeutic potential of the maternal microbiome and translate these findings into clinical practice.

Using Wastewater Surveillance to Compare COVID-19 Outbreaks during the Easter Holidays over a 2-Year Period in Cape Town, South Africa.

Wastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown to be an important approach to determine early outbreaks of infections. Wastewater-based epidemiology (WBE) is regarded as a complementary tool for monitoring SARS-CoV-2 trends in communities. In this study, the changes in the SARS-CoV-2 RNA levels in wastewater during Easter holidays in 2021 and 2022 in the City of Cape Town were monitored over nine weeks. Our findings showed a statistically significant difference in the SARS-CoV-2 RNA viral load between the study weeks over the Easter period in 2021 and 2022, except for study week 1 and 4. During the Easter week, 52% of the wastewater treatment plants moved from the lower (low viral RNA) category in 2021 to the higher (medium to very high viral RNA) categories in 2022. As a result, the median SARS-CoV-2 viral loads where higher during the Easter week in 2022 than Easter week in 2021 (p = 0.0052). Mixed-effects model showed an association between the SARS-CoV-2 RNA viral loads and Easter week over the Easter period in 2021 only (p < 0.01). The study highlights the potential of WBE to track outbreaks during the holiday period.

Pregnancy as an opportunity to prevent type 2 diabetes mellitus: FIGO Best Practice Advice.

Gestational diabetes (GDM) impacts approximately 17 million pregnancies worldwide. Women with a history of GDM have an 8-10-fold higher risk of developing type 2 diabetes and a 2-fold higher risk of developing cardiovascular disease (CVD) compared with women without prior GDM. Although it is possible to prevent and/or delay progression of GDM to type 2 diabetes, this is not widely undertaken. Considering the increasing global rates of type 2 diabetes and CVD in women, it is essential to utilize pregnancy as an opportunity to identify women at risk and initiate preventive intervention. This article reviews existing clinical guidelines for postpartum identification and management of women with previous GDM and identifies key recommendations for the prevention and/or delayed progression to type 2 diabetes for global clinical practice.

The role of maternal DNA methylation in pregnancies complicated by gestational diabetes.

Diabetes in pregnancy is associated with adverse pregnancy outcomes and poses a serious threat to the health of mother and child. Although the pathophysiological mechanisms that underlie the association between maternal diabetes and pregnancy complications have not yet been elucidated, it has been suggested that the frequency and severity of pregnancy complications are linked to the degree of hyperglycemia. Epigenetic mechanisms reflect gene-environment interactions and have emerged as key players in metabolic adaptation to pregnancy and the development of complications. DNA methylation, the best characterized epigenetic mechanism, has been reported to be dysregulated during various pregnancy complications, including pre-eclampsia, hypertension, diabetes, early pregnancy loss and preterm birth. The identification of altered DNA methylation patterns may serve to elucidate the pathophysiological mechanisms that underlie the different types of maternal diabetes during pregnancy. This review aims to provide a summary of existing knowledge on DNA methylation patterns in pregnancies complicated by pregestational type 1 (T1DM) and type 2 diabetes mellitus (T2DM), and gestational diabetes mellitus (GDM). Four databases, CINAHL, Scopus, PubMed and Google Scholar, were searched for studies on DNA methylation profiling in pregnancies complicated with diabetes. A total of 1985 articles were identified, of which 32 met the inclusion criteria and are included in this review. All studies profiled DNA methylation during GDM or impaired glucose tolerance (IGT), while no studies investigated T1DM or T2DM. We highlight the increased methylation of two genes, Hypoxia-inducible Factor-3α (HIF3α) and Peroxisome Proliferator-activated Receptor Gamma-coactivator-Alpha (PGC1-α), and the decreased methylation of one gene, Peroxisome Proliferator Activated Receptor Alpha (PPARα), in women with GDM compared to pregnant women with normoglycemia that were consistently methylated across diverse populations with varying pregnancy durations, and using different diagnostic criteria, methodologies and biological sources. These findings support the candidacy of these three differentially methylated genes as biomarkers for GDM. Furthermore, these genes may provide insight into the pathways that are epigenetically influenced during maternal diabetes and which should be prioritized and replicated in longitudinal studies and in larger populations to ensure their clinical applicability. Finally, we discuss the challenges and limitations of DNA methylation analysis, and the need for DNA methylation profiling to be conducted in different types of maternal diabetes in pregnancy.

Comparing the effects of tumor necrosis factor alpha, lipopolysaccharide and palmitic acid on lipid metabolism and inflammation in murine 3T3-L1 adipocytes.

AIMS: This study aimed to develop a model of dysregulated lipid metabolism and inflammation by treating 3T3-L1 adipocytes with tumor necrosis factor alpha (TNFα), lipopolysaccharide (LPS), and palmitic acid (PA) individually or in combination to assess their effects and mechanism of action. MAIN METHODS: Differentiated 3T3-L1 adipocytes were treated with TNFα (10 ng/mL), LPS (100 ng/mL), and PA (0.75 mM) individually or in combination for 24 h. Lipolysis, lipid content, inflammation, and the expression of lipid metabolism and inflammation genes were assessed by glycerol release quantification, Oil Red O staining, enzyme-linked immunosorbent assays, and quantitative reverse transcription-polymerase chain reaction, respectively. KEY FINDINGS: Exposure of 3T3-L1 adipocytes to TNFα stimulated lipolysis, reduced lipid accumulation, decreased adiponectin (ADIPOQ) secretion, and increased secretion of pro-inflammatory adipokines, monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), and interleukin 1 beta (IL-1ß). These changes were accompanied by decreased expression of lipid metabolism genes, increased expression of pro-inflammatory genes (MCP-1 and IL-6), and decreased expression of the anti-inflammatory gene, ADIPOQ. Exposure to LPS and PA, alone or in combination did not affect these parameters, while co-treatment with TNFα, LPS, and PA enhanced lipolysis and decreased ADIPOQ secretion compared to TNFα treatment. SIGNIFICANCE: Dysregulation of lipid metabolism and inflammation in 3T3-L1 adipocytes is attributed to TNFα rather than LPS and PA. We propose that exposing 3T3-L1 adipocytes to TNFα presents a suitable in vitro model of adipocyte dysfunction that closely resembles the complexity of obesity in vivo.

A Big Role for microRNAs in Gestational Diabetes Mellitus.

Maternal diabetes is associated with pregnancy complications and poses a serious health risk to both mother and child. Growing evidence suggests that pregnancy complications are more frequent and severe in pregnant women with pregestational type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) compared to women with gestational diabetes mellitus (GDM). Elucidating the pathophysiological mechanisms that underlie the different types of maternal diabetes may lead to targeted strategies to prevent or reduce pregnancy complications. In recent years, microRNAs (miRNAs), one of the most common epigenetic mechanisms, have emerged as key players in the pathophysiology of pregnancy-related disorders including diabetes. This review aims to provide an update on the status of miRNA profiling in pregnancies complicated by maternal diabetes. Four databases, Pubmed, Web of Science, EBSCOhost, and Scopus were searched to identify studies that profiled miRNAs during maternal diabetes. A total of 1800 articles were identified, of which 53 are included in this review. All studies profiled miRNAs during GDM, with no studies on miRNA profiling during pregestational T1DM and T2DM identified. Studies on GDM were mainly focused on the potential of miRNAs to serve as predictive or diagnostic biomarkers. This review highlights the lack of miRNA profiling in pregnancies complicated by T1DM and T2DM and identifies the need for miRNA profiling in all types of maternal diabetes. Such studies could contribute to our understanding of the mechanisms that link maternal diabetes type with pregnancy complications.

Coronavirus and Pregnancy: The Challenges of the 21st Century: A Review.

Despite many advances in medicine we are still faced with emerging pathogens. Pregnant women have been disproportionately affected by previous coronavirus outbreaks. The COVID-19 pandemic has not affected pregnant women as greatly as SARS-CoV and MERS, but has posed other challenges such as the need for quarantine and isolation, limited access to antenatal care, use of personal protective equipment (PPE), vaccine hesitancy and inequities in vaccine access and therapeutics between rich countries and the global south. This review will describe the impact of the significant coronaviruses on pregnancy, with special focus on the challenges being encountered by the SARS-CoV-2 global pandemic.