Podoplanin Positive Cell-derived Extracellular Vesicles Contribute to Cardiac Amyloidosis After Myocardial Infarction.

Background: Amyloidosis is a major long-term complication of chronic disease; however, whether it represents one of the complications of post-myocardial infarction (MI) is yet to be fully understood. Methods: Using wild-type and knocked-out MI mouse models and characterizing in vitro the exosomal communication between bone marrow-derived macrophages and activated mesenchymal stromal cells (MSC) isolated after MI, we investigated the mechanism behind Serum Amyloid A 3 (SAA3) protein overproduction in injured hearts. Results: Here, we show that amyloidosis occurs after MI and that amyloid fibers are composed of macrophage-derived SAA3 monomers. SAA3 overproduction in macrophages is triggered by exosomal communication from a subset of activated MSC, which, in response to MI, acquire the expression of a platelet aggregation-inducing type I transmembrane glycoprotein named Podoplanin (PDPN). Cardiac MSC PDPN+ communicate with and activate macrophages through their extracellular vesicles or exosomes. Specifically, MSC PDPN+ derived exosomes (MSC PDPN+ Exosomes) are enriched in SAA3 and exosomal SAA3 protein engages with Toll-like receptor 2 (TRL2) on macrophages, triggering an overproduction and impaired clearance of SAA3 proteins, resulting in aggregation of SAA3 monomers as rigid amyloid deposits in the extracellular space. The onset of amyloid fibers deposition alongside extra-cellular-matrix (ECM) proteins in the ischemic heart exacerbates the rigidity and stiffness of the scar, hindering the contractility of viable myocardium and overall impairing organ function. Using SAA3 and TLR2 deficient mouse models, we show that SAA3 delivered by MSC PDPN+ exosomes promotes post-MI amyloidosis. Inhibition of SAA3 aggregation via administration of a retro-inverso D-peptide, specifically designed to bind SAA3 monomers, prevents the deposition of SAA3 amyloid fibrils, positively modulates the scar formation, and improves heart function post-MI. Conclusion: Overall, our findings provide mechanistic insights into post-MI amyloidosis and suggest that SAA3 may be an attractive target for effective scar reversal after ischemic injury and a potential target in multiple diseases characterized by a similar pattern of inflammation and amyloid deposition. NOVELTY AND SIGNIFICANCE: What is known? Accumulation of rigid amyloid structures in the left ventricular wall impairs ventricle contractility.After myocardial infarction cardiac Mesenchymal Stromal Cells (MSC) acquire Podoplanin (PDPN) to better interact with immune cells.Amyloid structures can accumulate in the heart after chronic inflammatory conditions. What information does this article contribute? Whether accumulation of cumbersome amyloid structures in the ischemic scar impairs left ventricle contractility, and scar reversal after myocardial infarction (MI) has never been investigated.The pathophysiological relevance of PDPN acquirement by MSC and the functional role of their secreted exosomes in the context of post-MI cardiac remodeling has not been investigated.Amyloid structures are present in the scar after ischemia and are composed of macrophage-derived Serum Amyloid A (SAA) 3 monomers, although mechanisms of SAA3 overproduction is not established. SUMMARY OF NOVELTY AND SIGNIFICANCE: Here, we report that amyloidosis, a secondary phenomenon of an already preexisting and prolonged chronic inflammatory condition, occurs after MI and that amyloid structures are composed of macrophage-derived SAA3 monomers. Frequently studied cardiac amyloidosis are caused by aggregation of immunoglobulin light chains, transthyretin, fibrinogen, and apolipoprotein in a healthy heart as a consequence of systemic chronic inflammation leading to congestive heart failure with various types of arrhythmias and tissue stiffness. Although chronic MI is considered a systemic inflammatory condition, studies regarding the possible accumulation of amyloidogenic proteins after MI and the mechanisms involved in that process are yet to be reported. Here, we show that SAA3 overproduction in macrophages is triggered in a Toll-like Receptor 2 (TLR2)-p38MAP Kinase-dependent manner by exosomal communication from a subset of activated MSC, which, in response to MI, express a platelet aggregation-inducing type I transmembrane glycoprotein named Podoplanin. We provide the full mechanism of this phenomenon in murine models and confirm SAA3 amyloidosis in failing human heart samples. Moreover, we developed a retro-inverso D-peptide therapeutic approach, "DRI-R5S," specifically designed to bind SAA3 monomers and prevent post-MI aggregation and deposition of SAA3 amyloid fibrils without interfering with the innate immune response.

A comparison of differing organizational formats for teaching requesting skills to children with autism.

The selection of high-tech AAC for children diagnosed with autism spectrum disorder can be a challenging process due to the vast array of options available. One of the decisions that clinicians need to make involves how vocabulary will be organized on the display. This study aimed to compare a visual scene display (VSD) with a grid display using a multiple-probe design across participants with an embedded adapted alternating treatment design. Four young children with autism spectrum disorder who were beginning communicators were recruited and taught to request preferred items using two display formats: VSD and grid layout on a mainstream tablet with an AAC app. Two of the participants achieved criterion with both displays, the other two participants failed to achieve criterion in either display. For all participants, progress was similar in both displays. The results are discussed through the lens of each participant's characteristics with suggestions for clinical decision-making.

Impact of vitamin D deficiency on iron status in children with type I diabetes.

Vitamin D deficiency (VDD) and anemia are both public health nutrition concerns. An association between VDD and anemia has been suggested in various healthy and diseased populations. The current study aimed to elucidate the effect of VDD on iron status in children with type I diabetes mellitus (T1DM). The study recruited two groups of children with T1DM: control group comprised of 38 T1DM children with sufficient vitamin D (> 30 ng/ml) and a case group, consisted of 52 T1DM children with VDD (< 20 ng/ml). Both groups had comparable gender, age, BMI, and disease duration. The laboratory measurements included analysis of blood indices, markers of iron metabolism, hepcidin and inflammatory markers included interleukin 6 (IL-6) and C-reactive protein (CRP). Compared to control group, T1DM children with VDD differs specifically in terms of some markers of blood indices, such as decreased hemoglobin and increased red blood cell distribution width. Moreover, decreased serum iron, ferritin, total iron-binding capacity and transferrin along with elevated inflammatory markers were observed in case group. Results of the study indicated that VDD had increased the risk of iron deficiency anemia in children with T1DM as well as inflammatory related anemia. Furthermore, in T1DM children, VDD had raised the incidence of both absolute and functional iron deficiency, with greater incidence of the former. This study may indicate that VDD may be a risk factor that may worsen iron deficiency anemia in T1DM.

Europinidin Attenuates Methamphetamine-induced Learning and Memory Impairments and Hippocampal Alterations in Rodents: Based on Molecular Docking through a Mechanism of Neuromodulatory Cytokines/ Caspases-3/ CREB/BDNF Pathway.

BACKGROUND: Methamphetamine (MA) is well recognized as a psychostimulant that can cause neurotoxicity and neurodegeneration, which is associated with cognitive decline, has been confirmed experimentally. OBJECTIVE: The research aimed to investigate the neuroprotective properties of europinidin (Eu) in rodents affected by methamphetamine (MA)-induced cognitive impairments and hippocampal alterations. This was achieved by inhibiting lipid peroxidation and pro-inflammatory markers. METHODS: Rats were exposed to cognitive impairment produced by MA. The Morris water maze (MWM) is utilized for evaluating behavioral parameters. Tests were conducted on malondialdehyde (MDA), catalase (CAT), interleukins-1ß (IL-1ß), reduced glutathione (GSH), tumor necrosis factor-α (TNF-α), superoxide dismutase (SOD), and the expression of neurotransmitters (Norepinephrine [NE], dopamine [DA], glutamate, and gamma-aminobutyric acid [GABA]) as well as cAMP response element-binding protein (CREB), IL-6, brain-derived neurotrophic factor (BDNF), and caspase 3 proteins. An investigation was carried out using docking methodology to ascertain whether Eu interacts with relevant molecular targets. RESULTS: Significant decline in the transfer latency and there were significant changes in the amount of SOD, GSH, CAT, and MDA and alterations in levels of IL-6, IL-1ß, CREB, TNF-α, BDNF, and Caspase 3 proteins expression, as well as considerably alterations in level of neurotransmitters (NE, DA, Glutamate, and GABA) were observed in the Eu-treated rats compared to the MA-induced rats. Eu had a favorable affinity towards BDNF with docking scores of -9.486 kcal/mol. CONCLUSION: The experiment found that administering Eu to rats improved cognitive abilities by changing antioxidant enzymes, reducing cytokines, and modifying neurotransmitter levels, compared to rats in the control group treated with MA.

Prevalence of smoking and its associated factors among students of the University of Dongola, Northern State, Sudan: a cross-sectional study.

Background: Smoking is one of the leading causes of morbidity and mortality worldwide, and its prevalence has increased globally, particularly among university students. Objective: The study aimed to assess the smoking prevalence and its associated factors among students at University of Dongola, Northern State, Sudan. Methods: A multi-centred cross-sectional study was conducted among students of University of Dongola. Data was collected via an online Google form questionnaire. Descriptive and comparative analyses were performed using SPSS, version 26. Statistical significance was considered at p less than or equal to 0.05. Results: A total of 642 students participated in the study, of which 51.9% were females. Most of the students (73.6%) were aged 20-25 years and came from health & medical faculties (60.7%). The overall prevalence of smoking was 11.7%. The determined risk factors for smoking included male gender (P≤0.001), older age (P≤0.001), non-health and non-medical faculties (P≤0.001), uneducated fathers (P=0.032), and low socio-economic status (P=0.001). The most common reason for smoking was stress (36%), with cigarettes being the most commonly used type (88%). Personal savings were the main source of smoking expenses (73.3%). Most smokers (88%) were aware of the harmful effects of smoking. Conclusion: The overall smoking prevalence was relatively low among students at University of Dongola. Male gender, older age, non-health and non-medical faculties, uneducated fathers, and low socio-economic status were significant risk factors for smoking. The majority of smokers were aware of the harmful effects of smoking.

Sulforaphane protects against LPS-induced liver injury in mice by antagonizing oxidative stress and apoptosis through AMPK activation.

Objectives: Given the adverse effect of liver injury on a multitude of body functions, it is vital to understand its underlying mechanism and how to overcome it. In this study, lipopolysaccharide (LPS) was used to induce liver injury, while sulforaphane (SFN), a natural phytochemical, was used as the antagonist to overcome the deleterious effect. Methods: Twenty-four mice were divided into three groups: Control group (0.9% saline), LPS induction group (0.75 mg/kg), and SFN treatment (25 mg/kg) followed by LPS induction group (0.75 mg/kg), all with access to food and water ad libitum. Blood samples from retro-orbital sinus were used to measure liver function through two aminotransferases (i.e., alanine transaminase [ALT] and aspartate transaminase [AST]) whereas liver homogenate was used to measure glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD) (antioxidant activity markers); caspase-3 (apoptosis marker); malondialdehyde (MDA) (lipid peroxidation marker); and NO. AMP-activated protein kinase (AMPK), a cellular energy homeostasis and lipid metabolism sensor, was also measured. Statistical analysis including normalization, analysis of variance, Kruskal-Wallis test, and significance of P < 0.05 were applied to all collected data. Results: SFN treatment significantly attenuated all tests compared to the induced liver injury by LPS where significant reduction was observed in the levels of hepatic function markers (AST and ALT), lipid peroxidation marker (MDA) as well as apoptosis marker (caspase-3) whereas a marked increase was observed for antioxidant activity markers (SOD, CAT, and GSH) and AMPK. Conclusion: These results indicate the protective effect of SFN as it re-instated the levels of antioxidation while decreasing the level of the biomarkers, which were significantly increased during liver injury induction by LPS.

Growth arrest-specific protein 6 as a marker of nephritis in systemic sclerosis and juvenile systemic lupus erythematosus patients.

Background: Renal impairments commonly occur as a complication of autoimmune connective tissue diseases (CTDs). Therefore, early nephritis prediction is vital for patient outcomes. Growth Arrest-Specific Protein 6 (GAS6) was found to be upregulated in many types of inflammatory renal disease, including diabetic nephropathy.Aim: To evaluate GAS6 as a predictor of renal impairment in adults with systemic sclerosis (SSc) and children with systemic lupus Erythematosus (SLE).Methods: The study included 60 patients with SSc and 40 children with SLE. The serum level of GAS6 was measured using the ELISA technique. In adults with SSc, total proteins in 24-h urine concentration of >300 mg/24 h indicated renal inflammation, while in children with SLE, nephritis was diagnosed by abnormal renal pathology.Results: In SSc patients, GAS6 significantly increased in patients with proteinuria. GAS6 is an independent predictor of nephritis with an odds ratio (OR) of 1.06 and a 95% confidence interval (CI) of 1.0-1.1. at cutoff 12.2 ng/mL GAS6 predicted proteinuria with sensitivity 86.7% (95% CI: 59.5% to 98.3%), specificity 57.8% (95% CI: 42.1% to 72.3%), positive predictive value 40.6% (95% CI: 31.5% to 50.4%), negative predictive value 92.9% (95% CI: 77.7% to 97.73%), and accuracy 65.0% (95% CI: 51.6% to 76.9%). In SLE patients, Serum GAS6 did not differ significantly between children with and without lupus nephritis.Conclusion: GAS6 is an independent predictor of nephritis in patients with SSc. However, there is no association between GAS6 and nephritis in juvenile patients with SLE.

Beyond the Individual: A Multidisciplinary Model for Critical Thinking in the Intensive Care Unit.

Health profession educators readily identify with the goal of fostering healthcare providers who are critical thinkers focused on quality patient care. In the following paper, we aim to delve into critical thinking at the team level and help educators begin the process of creating a shared mental model focusing on cognition to identify gaps and opportunities for growth in their trainees. We will distinguish between microcognition (an individual's own critical thinking process in a controlled environment), macrocognition (critical thinking process in a real-world environment), and team cognition (the interaction and relationship among team members to augment macrocognition). A common case example will be used to guide the discussion as well as provide a model framework to be used for clinician educators in the future.

The Prevalence of Anxiety Among University Students in the United Arab Emirates Following the COVID-19 Lockdown.

INTRODUCTION: The COVID-19 pandemic, with its consequential lifestyle changes, is anticipated to contribute to increased anxiety levels, particularly among university students who already contend with significant academic stress. We aim to assess the prevalence of anxiety among university students in the United Arab Emirates (UAE) following the COVID-19 lockdown period. METHODS: We conducted a descriptive cross-sectional study among students enrolled in UAE universities. A self-administered questionnaire was utilized to gather demographic data, assess anxiety levels using the generalized anxiety disorder-7 scale, explore potential factors associated with heightened anxiety, investigate the impact of increased anxiety on academic performance, and identify coping mechanisms employed post-lockdown. RESULTS: Of the 369 participating students, anxiety levels were minimal in 87 (23.6%), mild in 163 (44.2%), and moderate to severe in 119 (32.2%) subjects. Moreover, increased anxiety levels were significantly correlated with poor/fair sleep quality (p=0.002). Importantly, students with moderate to severe anxiety levels exhibited poorer performance in exams and assignments (p=0.001) and encountered difficulties in maintaining focus on studies (p<0.001). The predominant coping mechanisms employed by students included self-distraction, prayer, and maintaining a positive attitude. CONCLUSION: The majority of students in our study experienced mild to severe levels of anxiety following the COVID-19 lockdown period. We hope that our findings will prompt university and government officials to implement effective screening and preventive strategies to adequately support university students in future public health crises.

Epigenetic mechanisms regulate sex differences in cardiac reparative functions of bone marrow progenitor cells.

Historically, a lower incidence of cardiovascular diseases (CVD) and related deaths in women as compared with men of the same age has been attributed to female sex hormones, particularly estrogen and its receptors. Autologous bone marrow stem cell (BMSC) clinical trials for cardiac cell therapy overwhelmingly included male patients. However, meta-analysis data from these trials suggest a better functional outcome in postmenopausal women as compared with aged-matched men. Mechanisms governing sex-specific cardiac reparative activity in BMSCs, with and without the influence of sex hormones, remain unexplored. To discover these mechanisms, Male (M), female (F), and ovariectomized female (OVX) mice-derived EPCs were subjected to a series of molecular and epigenetic analyses followed by in vivo functional assessments of cardiac repair. F-EPCs and OVX EPCs show a lower inflammatory profile and promote enhanced cardiac reparative activity after intra-cardiac injections in a male mouse model of myocardial infarction (MI). Epigenetic sequencing revealed a marked difference in the occupancy of the gene repressive H3K9me3 mark, particularly at transcription start sites of key angiogenic and proinflammatory genes in M-EPCs compared with F-EPCs and OVX-EPCs. Our study unveiled that functional sex differences in EPCs are, in part, mediated by differential epigenetic regulation of the proinflammatory and anti-angiogenic gene CCL3, orchestrated by the control of H3K9me3 by histone methyltransferase, G9a/Ehmt2. Our research highlights the importance of considering the sex of donor cells for progenitor-based tissue repair.

Understanding the determinants of sweet taste liking in the African and East Asian ancestry groups in the U.S.-A study protocol.

BACKGROUND: The liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation. METHODS: We will determine the differences in allele frequencies in sweet-related genetic variants and their effects on sweet liking in 426 adults of either African or East Asian ancestry, who have the highest and lowest average added sugars intake, respectively, among ancestry groups in the U.S. We will collect information on participants' sweet-liking phenotype, added sugars intake (sweetness exposure), anthropometric measures, place-of-birth, and for immigrants, duration of time living in the U.S. and age when immigrated. Ancestry-specific polygenic scores of sweet liking will be computed based on the effect sizes of the sweet-related genetic variants on the sweet-liking phenotype for each ancestry group. The predictive validity of the polygenic scores will be tested using individuals of African and East Asian ancestry from the UK Biobank. We will also compare sweet liking between U.S.-born individuals and immigrants within each ancestry group to test whether differences in environmental sweetness exposure during childhood affect sweet liking in adulthood. DISCUSSION: Expanding genetic research on taste to individuals from ancestry groups traditionally underrepresented in such research is consistent with equity goals in sensory and nutrition science. Findings from this study will help in the development of a more personalized nutrition approach for diverse populations. TRIAL REGISTRATION: This protocol has been preregistered with the Center for Open Science (https://doi.org/10.17605/OSF.IO/WPR9E).

Outcome assessment methods of bioactive and biodegradable materials as pulpotomy agents in primary and permanent teeth: a scoping review.

BACKGROUND: Pulpotomy procedures aiming to preserve and regenerate the dentin-pulp complex have recently increased exponentially due to developments in the field of biomaterials and tissue engineering in primary and permanent teeth. Although the number of studies in this domain has increased, there is still scarcity of evidence in the current literature. OBJECTIVES: (1) Report the methods of outcome assessment of pulpotomy clinical trials in both primary and permanent teeth; (2) Identify the various bioactive agents and biodegradable scaffolds used in pulpotomy clinical trials in both primary and permanent teeth. MATERIALS AND METHODS: A scoping review of the literature was performed, including a search of primary studies on PubMed, Scopus, Web of Science, ProQuest and Clinicaltrials.gov. A search for controlled trials or randomized controlled trials published between 2012 and 2023 involving primary or permanent teeth receiving partial or full pulpotomy procedures using bioactive/regenerative capping materials was performed. RESULTS: 127 studies out of 1038 articles fulfilled all the inclusion criteria and were included in the current scoping review. More than 90% of the studies assessed clinical and radiographic outcomes. Histological, microbiological, or inflammatory outcomes were measured in only 9.4% of all included studies. Majority of the studies (67.7%) involved primary teeth. 119 studies used non-degradable bioactive cements, while biodegradable scaffolds were used by 32 studies, natural derivates and plant extracts studies were used in only 7 studies. Between 2012 (4 studies) and 2023 (11 studies), there was a general increase in the number of articles published. India, Egypt, Turkey, and Iran were found to have the highest total number of articles published (28, 28,16 and 10 respectively). CONCLUSIONS: Pulpotomy studies in both primary and permanent teeth relied mainly on subjective clinical and radiographic outcome assessment methods and seldom analyzed pulpal inflammatory status objectively. The use of biodegradable scaffolds for pulpotomy treatments has been increasing with an apparent global distribution of most of these studies in low- to middle-income countries. However, the development of a set of predictable outcome measures as well as long-term evidence from well conducted clinical trials for novel pulpotomy dressing materials are still required.

Over-the-Counter Bronchodilators Use Among Asthmatic Patients in Al-Medina Al-Monawwara.

Asthma is a prevalent chronic disease that affects a significant number of individuals worldwide. Proper diagnosis and assessment of asthma patients are crucial before determining the appropriate inhaler for them. Many asthmatic patients self-medicate with over-the-counter (OTC) inhaled and orally taken bronchodilators, leading to overuse and serious adverse effects. This study aims to identify the extent of OTC bronchodilator usage in the Al-Medina Al-Monawwara region. and urge health authorities to address the issue and prevent potential side effects arising from the overuse of bronchodilators. This cross-sectional observational study was conducted among individuals with asthma residing in the Al-Medina Al-Monawwara region of Saudi Arabia. The study encompassed multiple hospitals. It was carried out between September 2021 and February 2023, utilizing a convenience sampling method. A total of 419 participants were included in the study; the majority of them, 362 (86.4%), reported being prescribed asthma inhalers at least once in their lives, while 57 (13.6%) always used asthma inhalers without a prescription. However, most of our participants reported having a prescription for their short-acting bronchodilators, with 46.3% always obtaining them with a prescription and the remaining obtaining them over the counter. The current study indicates that the use of OTC Bronchodilators increases the risk of significant ER visits; this observation is quite concerning as the increasing use of short-acting beta-agonists (SABA) might indicate less asthma control and more SABA overuse; further research is needed to address the issue of short-acting bronchodilators overuse.

Development of a highly sensitive fluorescent probe using Delonix regia (Gulmohar) tree pod shell for precise sarcosine detection in human urine samples: advancing prostate cancer diagnosis.

We designed a highly sensitive fluorescent sensor for the early detection of sarcosine, a potential biomarker for prostate cancer. This sensor was based on surface-cobalt-doped fluorescent carbon quantum dots (Co-CD) using a FRET-based photoluminescent sensing platform. Blue luminescent carbon quantum dots (CQD) were synthesised through a hydrothermal approach, utilizing Delonix regia tree pod shells. Cobalt was employed to functionalize the CQD, enhancing the quantum-entrapped effects and minimizing surface flaws. To optimize Co-CD preparation, we employed a Box-Behnken design (BBD), and response surface methodology (RSM) based on single-factor experiments. The Co-CD was then used as a fluorescent probe for selective Cu2+ detection, with Cu2+ quenching Co-CD fluorescence through an energy transfer process, referred to as 'turn-off'. When sarcosine was introduced, the fluorescence intensity of Co-CD was restored, creating a 'turn-on' response. The sensor exhibited a Cu2+ detection limit (LOD) of 2.4 µM with a linear range of 0 µM to 10 µM. The sarcosine detection in phosphate buffer saline (PBS, pH 7.4) resulted in an LOD of 1.54 µM and a linear range of 0 to 10 µM. Importantly, the sensor demonstrated its suitability for clinical analysis by detecting sarcosine in human urine. In summary, our rapid and highly sensitive sensor offers a novel approach for the detection of sarcosine in real samples, facilitating early prostate cancer diagnosis.Communicated by Ramaswamy H. Sarma.

Understanding the Determinants of Sweet Liking in the African and East Asian Ancestry Groups in the U.S. - A Study Protocol.

Background: The liking for sweet taste is a powerful driver for consuming added sugars, and therefore, understanding how sweet liking is formed is a critical step in devising strategies to lower added sugars consumption. However, current research on the influence of genetic and environmental factors on sweet liking is mostly based on research conducted with individuals of European ancestry. Whether these results can be generalized to people of other ancestry groups warrants investigation. Methods: We will determine the differences in allele frequencies in sweet-related genetic variants and their effects on sweet liking in 426 adults of either African or East Asian ancestry, who have the highest and lowest average added sugars intake, respectively, among ancestry groups in the U.S. We will collect information on participants' sweet-liking phenotype, added sugars intake (sweetness exposure), anthropometric measures, place-of-birth, and for immigrants, duration of time living in the U.S. and age when immigrated. Ancestry-specific polygenic scores of sweet liking will be computed based on the effect sizes of the sweet-related genetic variants on the sweet-liking phenotype for each ancestry group. The predictive validity of the polygenic scores will be tested using individuals of African and East Asian ancestry from the UK Biobank. We will also compare sweet liking between U.S.-born individuals and immigrants within each ancestry group to test whether differences in environmental sweetness exposure during childhood affect sweet liking in adulthood. Discussion: Expanding genetic research on taste to individuals from ancestry groups traditionally underrepresented in such research is consistent with equity goals in sensory and nutrition science. Findings from this study will help in the development of a more personalized nutrition approach for diverse populations. Trial registration: This protocol has been preregistered with the Center for Open Science (https://doi.org/10.17605/OSF.IO/WPR9E) and is approved by the City University of New York Human Research Protection Program (IRB#: 2023-0064-Brooklyn).

Trends in Simple and Complex Appendicitis in Children and the Potential Correlation to Common Viral Pathogens-A Retrospective Cohort Study between 2010 and 2019 in The Netherlands.

The aim of this study was to evaluate the annual, seasonal and monthly trends in children with simple and complex appendicitis and their correlation to common viral pathogens in the Netherlands. A consecutive multicenter retrospective cohort study was performed between 2010 and 2019 including children (<18 years) surgically treated for appendicitis. The primary outcome was the distribution of children with simple and complex appendicitis per year, season and month. Relevant seasonal variation was defined as ≥5%. The secondary outcome was a positive correlation of the number of patients with simple and complex appendicitis to common viral pathogens (data anonymously provided by the Dutch Working Group on Clinical Virology from the Dutch Society for Clinical Microbiology (NVMM)). In total, 896 patients were included: N = 524 (58%) patients with simple and N = 372 (42%) with complex appendicitis. Of the children aged 0-5 years, 81% had complex appendicitis, versus 38% in 6-18 years (p < 0.001). An overall decline was demonstrated for both simple and complex appendicitis between 2010 and 2019. No seasonal variation was found for simple appendicitis. For complex appendicitis, the highest number of patients was found in spring, and lowest in summer (N = 372, spring 28.2 ± 5.1% versus summer 21.0 ± 5.8%, p = 0.011), but the variance was regarded as not relevant (<5% from baseline). A positive correlation was found between complex appendicitis with Adenovirus 40.41 (R = 0.356, 95%CI 0.045-0.604, p = 0.026) and simple appendicitis with Adenovirus NON 40.41 (R = 0.332, 95%CI 0.019-0.586, p = 0.039), but these correlations did not remain significant after a Bonferroni correction (p < 0.003). In conclusion, we found no relevant seasonal variation for simple or complex appendicitis, nor positive correlation with common viral pathogens.