Magnetic Ionic Liquids: Current Achievements and Future Perspectives with a Focus on Computational Approaches.

Magnetic ionic liquids (MILs) stand out as a remarkable subclass of ionic liquids (ILs), combining the desirable features of traditional ILs with the unique ability to respond to external magnetic fields. The incorporation of paramagnetic species into their structures endows them with additional attractive features, including thermochromic behavior and luminescence. These exceptional properties position MILs as highly promising materials for diverse applications, such as gas capture, DNA extractions, and sensing technologies. The present Review synthesizes key experimental findings, offering insights into the structural, thermal, magnetic, and optical properties across various MIL families. Special emphasis is placed on unraveling the influence of different paramagnetic species on MILs' behavior and functionality. Additionally, the Review highlights recent advancements in computational approaches applied to MIL research. By leveraging molecular dynamics (MD) simulations and density functional theory (DFT) calculations, these computational techniques have provided invaluable insights into the underlying mechanisms governing MILs' behavior, facilitating accurate property predictions. In conclusion, this Review provides a comprehensive overview of the current state of research on MILs, showcasing their special properties and potential applications while highlighting the indispensable role of computational methods in unraveling the complexities of these intriguing materials. The Review concludes with a forward-looking perspective on the future directions of research in the field of magnetic ionic liquids.

Flexiplex: a versatile demultiplexer and search tool for omics data.

MOTIVATION: The process of analyzing high throughput sequencing data often requires the identification and extraction of specific target sequences. This could include tasks, such as identifying cellular barcodes and UMIs in single-cell data, and specific genetic variants for genotyping. However, existing tools, which perform these functions are often task-specific, such as only demultiplexing barcodes for a dedicated type of experiment, or are not tolerant to noise in the sequencing data. RESULTS: To overcome these limitations, we developed Flexiplex, a versatile and fast sequence searching and demultiplexing tool for omics data, which is based on the Levenshtein distance and thus allows imperfect matches. We demonstrate Flexiplex's application on three use cases, identifying cell-line-specific sequences in Illumina short-read single-cell data, and discovering and demultiplexing cellular barcodes from noisy long-read single-cell RNA-seq data. We show that Flexiplex achieves an excellent balance of accuracy and computational efficiency compared to leading task-specific tools. AVAILABILITY AND IMPLEMENTATION: Flexiplex is available at https://davidsongroup.github.io/flexiplex/.

Novel CDKL5 targets identified in human iPSC-derived neurons.

CDKL5 Deficiency Disorder (CDD) is a debilitating epileptic encephalopathy disorder affecting young children with no effective treatments. CDD is caused by pathogenic variants in Cyclin-Dependent Kinase-Like 5 (CDKL5), a protein kinase that regulates key phosphorylation events in neurons. For therapeutic intervention, it is essential to understand molecular pathways and phosphorylation targets of CDKL5. Using an unbiased phosphoproteomic approach we identified novel targets of CDKL5, including GTF2I, PPP1R35, GATAD2A and ZNF219 in human iPSC-derived neuronal cells. The phosphoserine residue in the target proteins lies in the CDKL5 consensus motif. We validated direct phosphorylation of GTF2I and PPP1R35 by CDKL5 using complementary approaches. GTF2I controls axon guidance, cell cycle and neurodevelopment by regulating expression of neuronal genes. PPP1R35 is critical for centriole elongation and cilia morphology, processes that are impaired in CDD. PPP1R35 interacts with CEP131, a known CDKL5 phospho-target. GATAD2A and ZNF219 belong to the Nucleosome Remodelling Deacetylase (NuRD) complex, which regulates neuronal activity-dependent genes and synaptic connectivity. In-depth knowledge of molecular pathways regulated by CDKL5 will allow a better understanding of druggable disease pathways to fast-track therapeutic development.

Dynamic gene expression and growth underlie cell-to-cell heterogeneity in Escherichia coli stress response.

Cell-to-cell heterogeneity in gene expression and growth can have critical functional consequences, such as determining whether individual bacteria survive or die following stress. Although phenotypic variability is well documented, the dynamics that underlie it are often unknown. This information is important because dramatically different outcomes can arise from gradual versus rapid changes in expression and growth. Using single-cell time-lapse microscopy, we measured the temporal expression of a suite of stress-response reporters in Escherichia coli, while simultaneously monitoring growth rate. In conditions without stress, we found several examples of pulsatile expression. Single-cell growth rates were often anticorrelated with reporter levels, with changes in growth preceding changes in expression. These dynamics have functional consequences, which we demonstrate by measuring survival after challenging cells with the antibiotic ciprofloxacin. Our results suggest that fluctuations in both gene expression and growth dynamics in stress-response networks have direct consequences on survival.

Elucidation of the mechanisms of fluconazole resistance and repurposing treatment options against urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt.

BACKGROUND: The incidence of fungal urinary tract infections (UTIs) has dramatically increased in the past decades, with Candida arising as the predominant etiological agent. Managing these infections poses a serious challenge to clinicians, especially with the emergence of fluconazole-resistant (FLC-R) Candida species. In this study, we aimed to determine the mechanisms of fluconazole resistance in urinary Candida spp. isolated from hospitalized patients in Alexandria, Egypt, assess the correlation between fluconazole resistance and virulence, and explore potential treatment options for UTIs caused by FLC-R Candida strains. RESULTS: Fluconazole susceptibility testing of 34 urinary Candida isolates indicated that 76.5% were FLC-R, with a higher prevalence of resistance recorded in non-albicans Candida spp. (88.9%) than in Candida albicans (62.5%). The calculated Spearman's correlation coefficients implied significant positive correlations between fluconazole minimum inhibitory concentrations and both biofilm formation and phospholipase production. Real-time PCR results revealed that most FLC-R isolates (60%) significantly overexpressed at least one efflux pump gene, while 42.3% significantly upregulated the ERG11 gene. The most prevalent mutation detected upon ERG11 sequencing was G464S, which is conclusively linked to fluconazole resistance. The five repurposed agents: amikacin, colistin, dexamethasone, ketorolac, and sulfamethoxazole demonstrated variable fluconazole-sensitizing activities in vitro, with amikacin, dexamethasone, and colistin being the most effective. However, the fluconazole/colistin combination produced a notable reduction (49.1%) in bladder bioburden, a 50% decrease in the inflammatory response, and tripled the median survival span relative to the untreated murine models. CONCLUSIONS: The fluconazole/colistin combination offers a promising treatment option for UTIs caused by FLC-R Candida, providing an alternative to the high-cost, tedious process of novel antifungal drug discovery in the battle against antifungal resistance.

Analyzing and modeling massive transfusion strategies and the role of fibrinogen-How much is the patient actually receiving?

BACKGROUND: Hemorrhage is a leading cause of preventable death in trauma, cardiac surgery, liver transplant, and childbirth. While emphasis on protocolization and ratio of blood product transfusion improves ability to treat hemorrhage rapidly, tools to facilitate understanding of the overall content of a specific transfusion strategy are lacking. Medical modeling can provide insights into where deficits in treatment could arise and key areas for clinical study. By using a transfusion model to gain insight into the aggregate content of massive transfusion protocols (MTPs), clinicians can optimize protocols and create opportunities for future studies of precision transfusion medicine in hemorrhage treatment. METHODS: The transfusion model describes the individual round and aggregate content provided by four rounds of MTP, illustrating that the total content of blood elements and coagulation factor changes over time, independent of the patient's condition. The configurable model calculates the aggregate hematocrit, platelet concentration, percent volume plasma, total grams and concentration of citrate, percent volume anticoagulant and additive solution, and concentration of clotting factors: fibrinogen, factor XIII, factor VIII, and von Willebrand factor, provided by the MTP strategy. RESULTS: Transfusion strategies based on a 1:1:1 or whole blood foundation provide between 13.7 and 17.2 L of blood products over four rounds. Content of strategies varies widely across all measurements based on base strategy and addition of concentrated sources of fibrinogen and other key clotting factors. DISCUSSION: Differences observed between modeled transfusion strategies provide key insights into potential opportunities to provide patients with precision transfusion strategy.

Has telemedicine come to fruition? Parents' and pediatricians' perceptions and preferences regarding telemedicine.

BACKGROUND: Telemedicine has increasingly become a viable option for patient care and may increase access to care. The aim of our study was to evaluate both parent and pediatrician perceptions, preferences, and acceptability regarding the use of different telemedicine modalities. METHODS: We conducted a cross-sectional survey of both parents and pediatricians in Geneva, Switzerland in 2021. The questionnaire focused on digital literacy, preferences, acceptability, advantages, and disadvantages regarding telemedicine (phone, email, video, and instant message). Descriptive statistics and comparisons of preferences and perceptions (Pearson Chi2 and logistic regression) were performed. RESULTS: Two hundred and twenty-two parents and 45 pediatricians participated. After face-to-face consultations, parents and pediatricians preferred the phone for simple medical advice, discussion of parameters, acute or chronic problems, and psychological support. Email was preferred for communication of results and prescription renewal. Main reasons for using telemedicine were avoiding travel and saving time. Disadvantages were lack of physical examination, technical problems, and unsuitability of the reason for consultation. CONCLUSIONS: Understanding the factors that influence acceptance and satisfaction with telemedicine is vital for its successful implementation. Convenience, quality of care, trust, strong pediatrician-parent relationships, technical reliability, user-friendliness, and privacy considerations play significant roles in shaping parent and pediatrician attitudes toward telemedicine. IMPACT: The COVID-19 pandemic spurred the expansion of the use of telemedicine in pediatric care. Few studies have addressed parent and pediatrician perceptions and preferences regarding telemedicine. Both parents and pediatricians consider certain telemedicine modalities (phone, email, video, and instant message) pertinent in only specific clinical situations. Advantages of telemedicine outweigh disadvantages with parents and pediatricians appreciating the increased access to care, time savings, and avoiding transport. However, the lack of a physical examination remains a significant disadvantage. Convenience, quality of care, trust, strong pediatrician-parent relationship, technical reliability, user-friendliness, and privacy considerations play significant roles in shaping attitudes towards telemedicine.

Frailty, but not cognitive impairment, improves mortality risk prediction among those with chronic kidney disease-a nationally representative study.

BACKGROUND: Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. METHODS: Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. RESULTS: Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment. CONCLUSIONS: Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.

Retrieval fluency inflates perceived preparation for difficult problems.

When faced with a difficult problem, people often rely on past experiences. While remembering clearly helps us reach solutions, can retrieval also lead to misperceptions of our abilities? In three experiments, participants encountered "worst case scenarios" they likely had never experienced and that would be difficult to navigate without extensive training (e.g., bitten by snake). Learning brief tips improved problem-solving performance later, but retrieval increased feelings of preparation by an even larger margin. This gap occurred regardless of whether people thought that tips came from an expert or another participant in the study, and it did not reflect mere familiarity with the problems themselves. Instead, our results suggest that the ease experienced while remembering, or retrieval fluency, inflated feelings of preparation.

Associations Between Gestational Weight Gain, Gestational Diabetes, and Childhood Obesity Incidence.

INTRODUCTION: Excessive maternal gestational weight gain (GWG) is strongly correlated with childhood obesity, yet how excess maternal weight gain and gestational diabetes mellitus (GDM) interact to affect early childhood obesity is poorly understood. The purpose of this study was to investigate whether overall and trimester-specific maternal GWG and GDM were associated with obesity in offspring by age 6 years. METHODS: A cohort of 10,335 maternal-child dyads was established from electronic health records. Maternal weights at conception and delivery were estimated from weight trajectory fits using functional principal components analysis. Kaplan-Meier curves and Cox regression, together with generalized raking, examined time-to-childhood-obesity. RESULTS: Obesity diagnosed prior to age 6 years was estimated at 19.7% (95% CI: 18.3, 21.1). Maternal weight gain during pregnancy was a strong predictor of early childhood obesity (p < 0.0001). The occurrence of early childhood obesity was lower among mothers with GDM compared with those without diabetes (adjusted hazard ratio = 0.58, p = 0.014). There was no interaction between maternal weight gain and GDM (p = 0.55). Higher weight gain during the first trimester was associated with lower risk of early childhood obesity (p = 0.0002) whereas higher weight gain during the second and third trimesters was associated with higher risk (p < 0.0001). DISCUSSION: Results indicated total and trimester-specific maternal weight gain was a strong predictor of early childhood obesity, though obesity risk by age 6 was lower for children of mothers with GDM. Additional research is needed to elucidate underlying mechanisms directly related to trimester-specific weight gain and GDM that impede or protect against obesity prevalence during early childhood.

Excessive maternal gestational weight gain (GWG) and gestational diabetes mellitus (GDM) have been linked to childhood obesity. Yet, research on how excessive total and trimester-specific GWG and GDM interact to affect early childhood obesity remains inconclusive. This study found that inadequate weight gain in the first trimester and excessive weight gain in the second and third trimester were associated with higher risks of childhood obesity by age 6. No significant interaction between maternal GWG and GDM was noted suggesting that these two important maternal conditions do not have a combined effect on the risk of early childhood obesity.

Timing matters when correcting fake news.

Countering misinformation can reduce belief in the moment, but corrective messages quickly fade from memory. We tested whether the longer-term impact of fact-checks depends on when people receive them. In two experiments (total N = 2,683), participants read true and false headlines taken from social media. In the treatment conditions, "true" and "false" tags appeared before, during, or after participants read each headline. Participants in a control condition received no information about veracity. One week later, participants in all conditions rated the same headlines' accuracy. Providing fact-checks after headlines (debunking) improved subsequent truth discernment more than providing the same information during (labeling) or before (prebunking) exposure. This finding informs the cognitive science of belief revision and has practical implications for social media platform designers.

Hinokitiol Inhibits Breast Cancer Cells In Vitro Stemness-Progression and Self-Renewal with Apoptosis and Autophagy Modulation via the CD44/Nanog/SOX2/Oct4 Pathway.

Breast cancer (BC) represents one of the most prevalent malignant threats to women globally. Tumor relapse or metastasis is facilitated by BC stemness progression, contributing to tumorigenicity. Therefore, comprehending the characteristics of stemness progression and the underlying molecular mechanisms is pivotal for BC advancement. Hinokitiol (ß-thujaplicin), a tropolone-related compound abundant in the heartwood of cupressaceous plants, exhibits antimicrobial activity. In our study, we employed three BC cell lines (MDA-MB-231, MCF-7, and T47D) to assess the expression of stemness-, apoptosis-, and autophagy-related proteins. Hinokitiol significantly reduced the viability of cancer cells in a dose-dependent manner. Furthermore, we observed that hinokitiol enhances apoptosis by increasing the levels of cleaved poly-ADP-ribose polymerase (PARP) and phospho-p53. It also induces dysfunction in autophagy through the upregulation of LC3B and p62 protein expression. Additionally, hinokitiol significantly suppressed the number and diameter of cancer cell line spheres by reducing the expression of cluster of differentiation44 (CD44) and key transcription factors. These findings underscore hinokitiol's potential as a therapeutic agent for breast cancer, particularly as a stemness-progression inhibitor. Further research and clinical studies are warranted to explore the full therapeutic potential of hinokitiol in the treatment of breast cancer.

Assessment of the unwanted tooth movement associated with an extended maxillary fixed retainer (3D analysis).

BACKGROUND: Posttreatment changes after orthodontic treatment are challenging. One of the main reasons for such a phenomenon is the lack of patient compliance with removable retainers especially in the maxillary arch, due to palatal coverage, deterioration of speech, decreased masticatory efficiency, and loss of retainers. Fixed retainers have been introduced to overcome patient compliance and provide longer stable results. However, teeth still show movements when a six-unit fixed retainer is in place. Thus, in this study, an eight-unit fixed retainer was evaluated in an attempt to eliminate unwanted movements. THE AIM OF THIS RESEARCH: was to assess short-term positional changes associated with an eight-unit extended maxillary fixed retainer. MATERIALS AND METHODS: A single-arm clinical trial was conducted to address the aim of the study. This research was approved by the institutional review board of the Faculty of Dentistry, Alexandria University (IORG:0008839, No-0479-8/2022). The registration date of this study was 5/06/2023. Twenty-eight patients (19.8 ± 4.5 years) who had finished the active orthodontic phase and started retention had an eight-unit extended maxillary fixed retainer that was bonded to the palatal surface of the maxillary incisors, canines, and the first premolars or the second premolars. Pre-retention and one-year post-retention intra-oral scans were made to produce STL files that were superimposed to determine the amount of tooth change. Additionally, analysis of digital casts and lateral cephalometric radiographs was performed. RESULTS: Statistically significant changes in all planes and the rotation of teeth after one year of retention were found. The upper right lateral incisor exhibited the most evident change in the vertical plane, while the upper right central incisor exhibited the greatest change overall. Minimal changes in the cast measurements were observed. Lateral cephalometric measurements showed minimal changes after one year of retention, and these changes were not statistically significant except in the interincisal angle and the angle between the upper incisor and the line connecting the A-point to the pogonion. CONCLUSION: Increasing the extension of maxillary fixed retainers did not eliminate unwanted tooth movement in the first year of retention.

Tip, torque and rotation of maxillary molars during distalization using Invisalign: a CBCT study.

BACKGROUND: Desirable molar distalization by bodily movement is challenging and can be difficult to achieve. This study investigated changes in molar angulation (mesiodistal tipping), molar inclination (buccolingual torque) and rotation during distalization using clear aligner therapy (CAT). MATERIALS AND METHODS: This retrospective study included 38 cone beam computed tomographic images (CBCTs) taken for patients treated with molar distalization using CAT. The study evaluated pre- (T0) and post-treatment (T1) CBCTs of 19 adult patients (36.68 ± 13.50 years) who underwent maxillary molar distalization using Invisalign® aligners (Align Technology, Inc., San José, CA, USA) with a minimum of 2 mm distalization. Changes in maxillary molar tip, torque and rotation were measured for 61 molars (183 roots). Paired t-test was used to evaluate the differences between pre- and post-treatment readings. The level of significance was set at p ≤ 0.05. The reproducibility of measurements was assessed by the intraclass correlation coefficient (ICC). RESULTS: Molar angulation did not show significant change after distalization (p = 0.158) however, there was significant increase in buccal molar inclination (p = 0.034) and mesiobuccal molar rotation (p < 0.001). CONCLUSION: Molar distalization of 2 mm did not cause significant molar tipping. Maxillary molars showed significant buccal inclination (increased torque) and mesiobuccal rotation after distalization.

Assessment of Ecological and Health Risks of Potentially Toxic Elements in Soil and Plant Under Long-Term Sewage Wastewater Irrigation.

This paper aimed to evaluate the ecological and health risks for some potentially toxic trace elements (PTEs) in agricultural soils irrigated with sewage wastewater for more than 50 years. Therefore, soil and plant samples were collected from 21 sites at sewage wastewater irrigated area and these samples were analyzed for their contents of PTEs i.e. Cd, Cr, Cu, Ni, and Pb. The risks of PTEs pollution in the study area were analyzed using indices such as the individual and comprehensive potential ecological risk indices (Eri and RI, respectively), hazard quotient (HQ), hazard index (HI), and carcinogenic risk (CR) model. The results showed that the PTEs in soil samples ranged from 1.70 to 9.90 mg/kg for Cd, from 39.9 to 183.4 mg/kg for Cr, from 31.5 to 655.1 mg/kg for Cu, from 18.8 to 113.1 mg/kg for Ni and from 5.4 to 65.4 mg/kg for Pb. The results also demonstrated that the soil samples were characterized by high to very high ecological risk for Cd. According to the health risk assessment, the mean HQ and HI of the PTEs in soil for adults and children were below the risk threshold of 1, indicating no risk for non-carcinogenic health effects. However, the HI of PTEs via plant consumption was > 1, suggesting a non-carcinogenic health risk. The CR for most plant samples was above the acceptable range. These findings may offer helpful information regarding the ecological and human risks related to PTEs exposure in soil and plants irrigated with wastewater under arid conditions.

Decoding hepatocarcinogenesis from a noncoding RNAs perspective.

Being a leading lethal malignancy worldwide, the pathophysiology of hepatocellular carcinoma (HCC) has gained a lot of interest. Yet, underlying mechanistic basis of the liver tumorigenesis is poorly understood. The role of some coding genes and their respective translated proteins, then later on, some noncoding RNAs (ncRNAs) such as microRNAs have been extensively studied in context of HCC pathophysiology; however, the implication of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in HCC is indeed less investigated. As a subclass of the ncRNAs which has been elusive for long time ago, lncRNAs was found to be involved in plentiful cellular functions such as DNA, RNA, and proteins regulation. Hence, it is undisputed that lncRNAs dysregulation profoundly contributes to HCC via diverse etiologies. Accordingly, lncRNAs represent a hot research topic that requires prime focus in HCC. In this review, the authors discuss breakthrough discoveries involving lncRNAs and circRNAs dysregulation that have contributed to the contemporary concepts of HCC pathophysiology and how these concepts could be leveraged as potential novel diagnostic and prognostic HCC biomarkers. Further, this review article sheds light on future trends, thereby discussing the pathological roles of lncRNAs and circRNAs in HCC proliferation, migration, and epithelial-to-mesenchymal transition. Along this line of reasoning, future recommendations of how these targets could be exploited to achieve effective HCC-related drug development is highlighted.

Human yolk sac-like haematopoiesis generates RUNX1-, GFI1- and/or GFI1B-dependent blood and SOX17-positive endothelium.

The genetic regulatory network controlling early fate choices during human blood cell development are not well understood. We used human pluripotent stem cell reporter lines to track the development of endothelial and haematopoietic populations in an in vitro model of human yolk-sac development. We identified SOX17-CD34+CD43- endothelial cells at day 2 of blast colony development, as a haemangioblast-like branch point from which SOX17-CD34+CD43+ blood cells and SOX17+CD34+CD43- endothelium subsequently arose. Most human blood cell development was dependent on RUNX1. Deletion of RUNX1 only permitted a single wave of yolk sac-like primitive erythropoiesis, but no yolk sac myelopoiesis or aorta-gonad-mesonephros (AGM)-like haematopoiesis. Blocking GFI1 and/or GFI1B activity with a small molecule inhibitor abrogated all blood cell development, even in cell lines with an intact RUNX1 gene. Together, our data define the hierarchical requirements for RUNX1, GFI1 and/or GFI1B during early human haematopoiesis arising from a yolk sac-like SOX17-negative haemogenic endothelial intermediate.

Sleep duration and cognitive function among older adults with chronic kidney disease: results from the National Health and Nutrition Examination Survey (2011-2014).

BACKGROUND: Short and long sleep durations are associated with cognitive dysfunction. Given the increased prevalence of sleep abnormalities in the chronic kidney disease (CKD) population, we tested whether the association between sleep duration and cognitive function differed between older adults with and without CKD. METHODS: This was a study of 3215 older adults (age ≥60 years) enrolled in the National Health and Nutrition Examination Survey (2011-14) evaluating sleep duration, cognitive function (immediate recall, delayed recall, verbal fluency, executive function and processing speed and global cognition) and kidney function. We quantified the association between sleep duration and cognitive function using linear regression and tested whether the associations differed among those with CKD and without using a Wald test for interaction. RESULTS: Among 3215 participants, 13.3% reported 2-5 hours of sleep/day, 75.2% reported 6-8 hours, and 11.5% reported ≥9 hours. Persons with CKD were more likely to sleep ≥9 hours [odds ratio 1.73 (95% confidence interval 1.22-2.46)]. Among participants with CKD, those with a sleep duration ≥9 hours demonstrated worse global cognitive function (P for interaction = .01), immediate recall (P for interaction = .01) and verbal fluency (P for interaction = .004) than those with a sleep duration of 6-8 h; no differences were observed for participants with CKD who slept 2-5 hours. Among participants without CKD, sleep was not associated with any measures of cognitive function. CONCLUSIONS: Longer sleep duration is associated with worse cognitive function only among persons with CKD, and global cognition, delayed recall and verbal fluency are particularly affected. Studies should identify interventions to improve sleep patterns and quality in this population.

Facilitators and barriers to seasonal malaria chemoprevention (SMC) uptake in Nigeria: a qualitative approach.

BACKGROUND: SMC was adopted in Nigeria in 2014 and by 2021 was being implemented in 18 states, over four months between June and October by 143000 community drug distributors (CDDs) to a target population of 23million children. Further expansion of SMC is planned, extending to 21 states with four or five monthly cycles. In view of this massive scale-up, the National Malaria Elimination Programme undertook qualitative research in five states shortly after the 2021 campaign to understand community attitudes to SMC so that these perspectives inform future planning of SMC delivery in Nigeria. METHODS: In 20 wards representing urban and rural areas with low and high SMC coverage in five states, focus group discussions were held with caregivers, and in-depth interviews conducted with community leaders and community drug distributors. Interviews were also held with local government area and State malaria focal persons and at national level with the NMEP coordinator, and representatives of partners working on SMC in Nigeria. Interviews were recorded and transcribed, those in local languages translated into English, and transcripts analysed using NVivo software. RESULTS: In total, 84 focus groups and 106 interviews were completed. Malaria was seen as a major health concern, SMC was widely accepted as a key preventive measure, and community drug distributors (CDDs) were generally trusted. Caregivers preferred SMC delivered door-to-door to the fixed-point approach, because it allowed them to continue daily tasks, and allowed time for the CDD to answer questions. Barriers to SMC uptake included perceived side-effects of SMC drugs, a lack of understanding of the purpose of SMC, mistrust and suspicions that medicines provided free may be unsafe or ineffective, and local shortages of drugs. CONCLUSIONS: Recommendations from this study were shared with all community drug distributors and others involved in SMC campaigns during cascade training in 2022, including the need to strengthen communication about the safety and effectiveness of SMC, recruiting distributors from the local community, greater involvement of state and national level pharmacovigilance coordinators, and stricter adherence to the planned medicine allocations to avoid local shortages. The findings reinforce the importance of retaining door-to-door delivery of SMC.

Salivary E-cadherin as a biomarker for diagnosis and predicting grade of periodontitis.

OBJECTIVES: To determine the abilities of salivary E-cadherin to differentiate between periodontal health and periodontitis and to discriminate grades of periodontitis. BACKGROUND: E-cadherin is the main protein responsible for maintaining the integrity of epithelial-barrier function. Disintegration of this protein is one of the events associated with the destructive forms of periodontal disease leading to increase concentration of E-cadherin in the oral biofluids. MATERIALS AND METHODS: A total of 63 patients with periodontitis (case) and 35 periodontally healthy subjects (control) were included. For each patient, periodontal parameters including bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) were recorded. Concentration of salivary E-cadherin was determined by ELISA. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to determine the diagnostic potentials of E-cadherin. RESULTS: Level of salivary E-cadherin was significantly higher in periodontitis cases than controls. The ROC analysis showed that salivary E-cadherin exhibits excellent sensitivity and specificity (AUC 1.000) to differentiate periodontal health from periodontitis with a cutoff concentration equal to 1.325 ng/mL. The AUCs of E-cadherin to differentiate grade A from grade B and C periodontitis were 0.731 (cutoff point = 1.754 ng/mL) and 0.746 (cutoff point = 1.722 ng/mL), respectively. However, the AUC of salivary E-cadherin to differentiate grade B from grade C periodontitis was lower (0.541). Additionally, BOP and PPD were significantly and positively correlated with the concentration of salivary E-cadherin. CONCLUSION: Salivary E-cadherin exhibited excellent sensitivity and specificity to differentiate periodontitis from a healthy periodontium. The level of accuracy of E-cadherin was also sufficient to recognize grade A periodontitis from grade B and C periodontitis.