Healthy Counterparts Research Articles

The impact of yoga in pregnancy on placental growth factor levels and mean arterial pressure in pre-eclampsia: A randomized controlled trial

Context: Pre-eclampsia is a pregnancy-related condition characterized by hypertension, proteinuria, and edema occurring after 20 weeks of pregnancy or during the postpartum period. Several markers are often assessed to determine the suitable option for confirming pre-eclampsia diagnosis, one of which is the examination of placental growth factor (PlGF) as a placental ischemia indicator. Aims: To evaluate the impact of prenatal yoga on PlGF and mean arterial pressure (MAP) levels in pre-eclampsia within the Madura region. Methods: A randomized controlled trial was conducted on fifty subjects that were randomly allocated to the experimental group with pre-post control groups consisting of 50 participants, namely 25 pregnant women with pre-eclampsia and 25 healthy individuals. The selection was conducted based on the following inclusion criteria: belonging to Madura ethnicity spanning three generations, exhibiting pregnancy duration >20 weeks, maternal ages ranging from 20–35 years, pre-pregnancy body mass index (BMI) >25, a history of hypertension, diabetes mellitus (DM), kidney disorders, pre-eclampsia, chronic hypertension, or family history of chronic high blood pressure and pre-eclampsia among those at risk. PlGF levels were estimated using an ELISA kit, while blood pressure was measured with an Omron brand sphygmomanometer. Results: Statistical analysis performed with the Wilcoxon sign test and T-test indicated significant differences (p<0.005) in systolic blood pressure, diastolic blood pressure, and MAP between the groups. Furthermore, a significant difference was observed in PlGF levels before and after engaging in prenatal yoga practice (p<0.05). Conclusions: The results showed that prenatal yoga contributed to the elevation of PlGF levels in women with pre-eclampsia, compared to their healthy counterparts.

Is cerebral blood flow altered by anxiety and depression in a sex-dependent manner?

Background: It is well-known that premenopausal females have greater cerebral blood flow (CBF) than age-matched males. People with anxiety and/or depression (A/D) have altered CBF compared to those without A/D. For example, males with depression may have greater CBF, and females with depression may have lower CBF, than their healthy counterparts. In contrast, anxiety may be correlated with higher CBF in certain brain regions such as the amygdala and hippocampus in both sexes. However prior studies assessing the effect of sex and A/D on CBF did not control for the menstrual cycle, something which is known to influence CBF in females. Objective: To determine if A/D is linked to CBF alterations in young healthy adults, in a sex-specific pattern, while controlling for menstrual cycle and hormonal contraception (HC). Hypothesis: As most of our subjects had depression, we hypothesized that CBF would be higher in control (CON) females than CON males and this difference will be abolished in A/D subjects, due to a greater CBF in A/D males compared to CON males and a lower CBF in A/D females compared to CON females. Methods: Twenty females (4 A/D) and 21 males (8 A/D) had their CBF (ml/100gm/min) measured using magnetic resonance imaging (MRI, 3T) with arterial spin labelling (ASL). A/D was diagnosed by a physician. Subjects in all 4 groups were matched for age (mean ± SD; 21 ± 2 y). Females were studied during days 1-5 of the menstrual cycle and were not taking HC. CBF data were tested using 2-way mixed effects analyses (sex*group (i.e., CON vs. A/D)) in: grey matter (GM), white matter (WM), and 8 emotional/memory regions of the brain, including the accumbens, amygdala, caudate, anterior cingulate, hippocampus, entorhinal, parahippocampus, and precuneus. Results: A trend for significant sex*group interaction (all p ≥ 0.052) but not group main effects (all p ≥ 0.100) was observed. CBF in GM and WM as well as in the 8 emotional/memory regions was higher in females compared to males (main effect of sex, p ≤ 0.004). This sex effect appeared to be driven by the CON groups ( p < 0.0001 for all areas), as there were no CBF differences in any area between males and females in the A/D group (all p ≥ 0.089).Exploratory analyses showed significantly greater CBF in A/D males compared to CON males in GM as well as the accumbens, caudate, hippocampus, precuneus, and anterior cingulate gyrus (all p ≤ 0.049). No differences were observed for any outcome. Conclusion: These data suggest that while CON females have greater CBF than CON males at rest, this sex difference may be abolished in those with A/D. Albeit preliminary, these data are in line with previous findings whereby CBF appears to decrease more in females with depression and either remain unchanged or increase in males with depression. The higher CBF in certain regions in A/D males is interesting and in line with previous research showing increased CBF in the hippocampus with anxiety. As our sample size was small and included a mix of people with either anxiety or depression, future research should be conducted to assess the differential effects of these conditions in young adults. Support by NIH (HL150361). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Vibrational microspectroscopy as a tool to unveil new chemotherapeutic strategies against osteosarcoma

Over the years, osteosarcoma therapy has had a significative improvement with the use of a multidrug regime strategy, increasing the survival rates from less than 20 % to circa 70 %. Different types of development of new antineoplastic agents are critical to achieve irreversible damage to cancer cells, while preserving the integrity of their healthy counterparts. In the present study, complexes with two and three Pd(II) centres linked by the biogenic polyamines: spermine (Pd2SpmCl4) and spermidine (Pd3Spd2Cl6) were tested against non-malignant (osteoblasts, HOb) and cancer (osteosarcoma, MG-63) human cell lines. Either alone or in combination according to the EURAMOS-1 protocol, they were used versus cisplatin as a drug reference. By evaluating the cytotoxic effects of both therapeutic approaches (single and drug combination) in HOb and MG–63 cell lines, the selective anti-tumoral potential is assessed. To understand the different treatments at a molecular level, Synchrotron Radiation Fourier Transform Infrared and Raman microspectroscopies were applied. Principal component analysis and hierarchical cluster analysis are applied to the vibrational data, revealing the major metabolic changes caused by each drug, which were found to rely on DNA, lipids, and proteins, acting as biomarkers of drug-to-cell impact. The main changes were observed for the B-DNA native conformation to either Z-DNA (higher in the presence of polynuclear complexes) or A-DNA (preferably after cisplatin exposure). Additionally, a higher effect upon variation in proteins content was detected in drug combination when compared to single drug administration proving the efficacy of the EURAMOS-1 protocol with the new drugs tested.

Towards an understanding of the mechanisms of therapeutic ultrasound on biomimetic models of cancer

Therapeutic ultrasound is transforming the treatment of a range of malignancies in a non-invasive and non-systemic manner. Low-intensity ultrasound (LIUS) has been proposed to selectively eradicate cancer cells but the underlying biological mechanisms remains unknown. To gain an understanding of this phenomenon, 2D breast cancer monocultures were sonicated at varying acoustic intensities (0.1–0.5 W·cm−2) and excitation times (1–10 minutes). Additionally, 2D monocultures consisting of healthy cell lines were sonicated at varying acoustic intensities (0.1–0.5 W·cm−2) to determine any distinguishing biological responses. To begin recapitulating in vivo conditions, breast cancer cells were also seeded into 3D collagen hydrogels. At a 1 MHz frequency, 20% duty cycle, 100 Hz pulse repetition frequency, a significant drop in cancer cell viability is observed at a sonication intensity of 0.5 W·cm−2 and over 10 minute excitation time. Healthy counterparts subjected to the same parameters revealed no distinguishing effects. Sonication of breast cancer cells seeded in 3D collagen hydrogels revealed no effect in cell viability compared to non-sonicated controls. The acoustic wave propagation software OptimUS was used to determine the influence culturing plates have on ultrasound propagation, revealing these materials can significantly vary the acoustic field at frequencies relevant to LIUS.

Diagnostic Potential Role of CXCL3 and Leptin Levels in Breast Cancer

The risk of breast cancer development is believed to be attributed to the alterations of a number of key biological components. Within this context, elevated levels of some chemokines that act as growth factors and can promote cancer development. The current study was designed to evaluate CXCL3 (a chemokine C-X-C Motif Ligand 3) and leptin (a peptide hormone synthesized by adipose tissue with cytokine activity) serum of Iraqi breast cancer patients in comparison to healthy controls. A total of 90 participants consisted of 60 patients diagnosed with breast cancer and 30 healthy women as control group were enrolled into this case-control study. Venous blood samples were collected from all participants to evaluate CXCL3 and leptin serum levels using ELISA. The results demonstrated significantly (P≤0.001) higher mean levels of CXCL3 and leptin in breast cancer patients (1.19±0.10 ng/mL and 130.44± 3.72pg/mL) compared to those of their healthy counterparts (0.430± 0.02\ng/mL and 57.1± 3.2pg/mL respectively). Interestingly, vast majority of the assessed breast cancer cases (up to 95-98%) showed to have elevated serum levels of both of the assessed potential biomarkers (CXCL3 and leptin). The present study results suggest an association of both CXCL3 and leptin in breast cancer pathogenicity. This supports the possibility of utilizing these potential biomarkers for breast cancer early detection and diagnosis.

Cardiopulmonary functional capacity in Taiwanese children with atrial septal defects.

Most existing studies measure atrial septal defect (ASD) outcomes based on morbidity rates such as atrial arrhythmias and heart failure rather than the functional assessment of physical capacity postprocedure. Few studies have evaluated cardiopulmonary function in ASD children. This study represents the largest sample population in the current research, encompassing a total of 122 Taiwanese children with ASD who had undergone treatment, to evaluate cardiopulmonary functional capacity through the implementation of cardiopulmonary exercise testing (CPET), and to investigate whether variations in treatment may impact their cardiopulmonary function. This is a retrospective cohort study with the data collected from January 2010 to December 2021. All patients and controls (age-, sex-, and body mass index-matched) underwent CPET and pulmonary function testing. In total, 122 ASD patients (surgically closed ASDs 27, transcatheter-closed ASDs 48, and follow-up unrepaired ASD 47) and 244 healthy controls were recruited. The ASD group exhibited lower peak metabolic equivalent (MET), peak oxygen consumption (VO 2 , p < 0.001), and peak minute ventilation ( p = 0.028) along with MET and VO 2 at the anaerobic threshold (AT) ( p = 0.012) compared to the control group. No statistically significant differences were observed in the pulmonary function test. Among surgically closed, transcatheter closed and unrepaired ASD subgroups, no significant variances were seen in CPET and pulmonary function tests. Taiwanese ASD children exhibited diminished exercise capacity and cardiopulmonary performance compared to their healthy counterparts. Differences among specific ASD treatments in cardiopulmonary tests were non-significant.

Genome-wide association studies reveal differences in genetic susceptibility between single events vs. recurrent events of atrial fibrillation and myocardial infarction: the HUNT study.

Genetic research into atrial fibrillation (AF) and myocardial infarction (MI) has predominantly focused on comparing afflicted individuals with their healthy counterparts. However, this approach lacks granularity, thus overlooking subtleties within patient populations. In this study, we explore the distinction between AF and MI patients who experience only a single disease event and those experiencing recurrent events. Integrating hospital records, questionnaire data, clinical measurements, and genetic data from more than 500,000 HUNT and United Kingdom Biobank participants, we compare both clinical and genetic characteristics between the two groups using genome-wide association studies (GWAS) meta-analyses, phenome-wide association studies (PheWAS) analyses, and gene co-expression networks. We found that the two groups of patients differ in both clinical characteristics and genetic risks. More specifically, recurrent AF patients are significantly younger and have better baseline health, in terms of reduced cholesterol and blood pressure, than single AF patients. Also, the results of the GWAS meta-analysis indicate that recurrent AF patients seem to be at greater genetic risk for recurrent events. The PheWAS and gene co-expression network analyses highlight differences in the functions associated with the sets of single nucleotide polymorphisms (SNPs) and genes for the two groups. However, for MI patients, we found that those experiencing single events are significantly younger and have better baseline health than those with recurrent MI, yet they exhibit higher genetic risk. The GWAS meta-analysis mostly identifies genetic regions uniquely associated with single MI, and the PheWAS analysis and gene co-expression networks support the genetic differences between the single MI and recurrent MI groups. In conclusion, this work has identified novel genetic regions uniquely associated with single MI and related PheWAS analyses, as well as gene co-expression networks that support the genetic differences between the patient subgroups of single and recurrent occurrence for both MI and AF.

TFEB regulates dendritic cell antigen presentation to modulate immune balance in asthma

ObjectiveAsthma stands as one of the most prevalent chronic respiratory conditions in children, with its pathogenesis tied to the actived antigen presentation by dendritic cells (DCs) and the imbalance within T cell subgroups. This study seeks to investigate the role of the transcription factor EB (TFEB) in modulating the antigen presentation process of DCs and its impact on the differentiation of T cell subgroups.MethodsBone marrow dendritic cells (BMDCs) were activated using house dust mites (HDM) and underwent RNA sequencing (RNA-seq) to pinpoint differentially expressed genes. TFEB mRNA expression levels were assessed in the peripheral blood mononuclear cells (PBMCs) of both healthy children and those diagnosed with asthma. In an asthma mouse model induced by HDM, the TFEB expression in lung tissue DCs was evaluated. Further experiments involved LV-shTFEB BMDCs co-cultured with T cells to explore the influence of TFEB on DCs’ antigen presentation, T cell subset differentiation, and cytokine production.ResultsTranscriptomic sequencing identified TFEB as a significantly differentially expressed gene associated with immune system pathways and antigen presentation. Notably, TFEB expression showed a significant increase in the PBMCs of children diagnosed with asthma compared to healthy counterparts. Moreover, TFEB exhibited heightened expression in lung tissue DCs of HDM-induced asthmatic mice and HDM-stimulated BMDCs. Silencing TFEB resulted in the downregulation of MHC II, CD80, CD86, and CD40 on DCs. This action reinstated the equilibrium among Th1/Th2 and Th17/Treg cell subgroups, suppressed the expression of pro-inflammatory cytokines like IL-4, IL-5, IL-13, and IL-17, while augmenting the expression of the anti-inflammatory cytokine IL-10.ConclusionTFEB might have a vital role in asthma’s development by impacting the antigen presentation of DCs, regulating T cell subgroup differentiation, and influencing cytokine secretion. Its involvement could be pivotal in rebalancing the immune system in asthma. These research findings could potentially unveil novel therapeutic avenues for treating asthma.

P071 Exploring experiences and preferences of people with rheumatoid arthritis for digital interventions to promote physical activity (PA)

Abstract Background/Aims Physical activity (PA) is effective for managing symptoms of rheumatoid arthritis (RA) but people with RA are less active than their healthy counterparts. A digital intervention (DI) to promote PA, is a potential solution. There is a paucity of literature available exploring the requirements of people with RA for a digital intervention. It is important to explore experiences and preferences before developing such an intervention. Aims: 1. Identify digital technology currently used by people with RA to support PA. 2. Understand the preferences and acceptability of people with RA for potential DI delivery. Methods A survey was developed to address these aims. A patient research partner (CS) and ‘think aloud’ pilots contributed to development. The survey was circulated once to members of the National Rheumatoid Arthritis Society in November 2022. This study was approved by the National Health Service Research Ethics Committee (reference 22/NE/0158). Results 1178 people consented to take part (86% female, 64% aged 55-74). The majority used digital technology every day (97%). 84% anticipated using a potential DI to support PA, most preferably every day (48%) or 2-3 times a week (14%). 16% never anticipated using DI to support PA. 34% reported currently using technology to support PA; mostly an app without healthcare professional (HCP) interaction (42%) or internet videos (40%). A further 27% had tried technology to support PA but discontinued, and 39% had never tried. An app was the most preferable delivery platform (56%), followed by a website (43%) or internet videos (28%). 51% would prefer to be offered or signposted to digital technology to support PA by an exercise professional with specific rheumatology training or a healthcare professional (22%). Potential DI delivery methods were rated on a Likert scale of 1-5 for general acceptability, a score of five indicating highest acceptability: automated response mean[SD] 3.6[0.9], ad-hoc HCP interaction 3.5[0.8] pre-arranged HCP interaction 3.4[1] and no interaction 3.1[1]. Conclusion People with RA are using digital technology regularly and many anticipated using a DI to support PA. Despite this, only a third are currently using digital technology to support PA. An app or website platform was the preferred delivery method suggesting that an internet delivered intervention is acceptable. Acceptability ratings of DI delivery methods were similar. Further sub-group analysis and exploration of free text responses is planned to inform tailoring of DI delivery. Disclosure C. Gerlis: None. A. Berry: None. S. Halls: None. M. Loizou: None. C. Swales: None. F. Cramp: None.

Effect of tyrosine kinase inhibitors on male fertility in patients with chronic phase chronic myeloid leukemia

Advancements in the management of patients with chronic myeloid leukemia (CML) allowed them to achieve survival comparable with their healthy counterparts. Consequently, their care has widened with growing focus on quality of life, including parenting children. Although tyrosine kinase inhibitors (TKI) are contraindicated in pregnancy given their teratogenic effect, their effect on male fertility is less clear with contradictory results from animal studies and case reports/series. We compared the sperm analysis parameters, as the gold-standard assessment for male fertility, of 11 patients with CP- CML before and after TKI therapy. Median therapy duration was 5.1 years (range: 2.5–16.5). The sperm concentration, % progressive, and total motility before and after therapy were not significantly different (p = 0.376, 0.569, and 0.595, respectively). Our results suggest no impairment in fertility potential in male patients after TKI therapy. A larger sample size is crucial to support/refute our findings.

Cellular Determinants of Visual Outcomes in Eyes with Epiretinal Membrane: Insights from Adaptive Optics OCT

Objective or PurposeIn this study, we aimed to evaluate cellular alterations in the foveal neuroglia of eyes with idiopathic epiretinal membrane (ERM) and examine their correlation with visual function. We also aimed to identify prognostic markers for visual outcomes post-vitrectomy. DesignA prospective longitudinal study. Subjects, Participants, and/or ControlsThe study comprised 84 subjects, including 50 eyes diagnosed with idiopathic ERM and 34 healthy eyes serving as controls. MethodsThe foveal neuroglial changes in eyes with idiopathic ERM were determined using adaptive optics optical coherence tomography (AO-OCT) by comparing them with healthy eyes. For patients with ERM, the ERM and inner limiting membrane were removed during vitrectomy in all eyes. Main Outcome MeasuresFoveal microstructures on AO-OCT images, best-corrected visual acuity (BCVA) and M-CHARTS scores, evaluated preoperatively and at 1, 3, and 6 months postoperatively, and associations between foveal neuroglial changes and these parameters. ResultsAO-OCT revealed discernible differences in the foveal cones of the eyes with ERM and their healthy counterparts. The thickness of the ellipsoid zone (EZ) band was augmented in eyes with ERM. The alignment of the Müller cells was more vertical, and the density of the foveal cone cell nuclei was higher in eyes with ERM than in healthy eyes. Within the AO-OCT parameters, the higher cone nuclei count correlated with worse M-CHARTS scores, both preoperatively and 6 months postoperatively (P = 0.004, 0.010, respectively). Greater EZ thickness was significantly associated with poorer 6-month postoperative BCVA (P = 0.005). ConclusionsAO-OCT can be used to precisely identify cellular alterations in eyes with ERM that are closely related to visual function impairments. These cellular insights enhance our understanding of ERM pathology and offer promising prognostic indicators of visual outcome after vitrectomy.

Twenty-four hour physical activity, sedentary behaviour and sleep profiles in adults living with rheumatoid arthritis: a cross-sectional latent class analysis

BackgroundRheumatoid Arthritis (RA), an autoimmune systemic inflammatory disease, affects more than 17 million people globally. People with RA have higher risk of premature mortality; often experience chronic fatigue, pain and disrupted sleep; and are less physically active and more sedentary than healthy counterparts. It remains unclear how people with RA may balance sleep and awake movement activities over 24-hours, or how differences in 24-hour behaviours may be associated with determinants of health, or alignment with published activity guidelines.MethodsCross-sectional exploration of objective measures of 24-hour sleep-wake activities in 203 people with RA. Latent Class Analysis (LCA) derived classes from time, by tertile, in six sleep-awake activities over 24 h. Comparisons of model fit statistics, class separation and interpretability defined best fit for number of classes. Variations in sleep-awake behaviour across classes and association of profile allocation with determinants of health, quality metrics for sleep, sitting and walking and alignment with published guidelines were explored. Multinomial logistic regression identified factors associated with likelihood of profile allocation.ResultsLCA identified 2 to 6 classes and a 4-class model was determined as best fit for 24-hour sleep-awake behaviour profiles. One profile (26%) presented with more balanced 24-hour sleep, sitting and walking behaviours. The other three profiles demonstrated progressively less balanced 24-hour behaviours including: having low (< 7 h), high (> 8 h), or recommended (7–8 h) sleep duration in respective combination with high sitting (> 10 h), limited walking (< 3 h) or both when awake. Age, existing sitting and walking habit strength and fatigue were associated with likelihood of belonging to different profiles. More balanced 24-hour behaviour was aligned with better quality metrics for sleep, sitting and walking and published guidelines.DiscussionFor people living with RA it is important to understand the ‘whole person’ and their ‘whole day’ to define who may benefit from support to modify 24-hour sleep-awake behaviours and which behaviours to modify. Supports should be informed by an understanding of personal or health-related factors that could act as barriers or facilitators for behavioural change, including exploring existing habitual sitting and walking behaviours.Trial registrationsClinicalTrials.gov ID: NCT02554474 (2015-09-16) and ClinicalTrials.gov ID: NCT03404245 (2018-01-11)

The Application of Intraoral Scanners in Orthodontic Care for Adolescents with Disabilities

Access to dental services for young disabled patients is challenging and expensive, often necessitating treatment under general anesthesia. Additionally, ensuring accuracy during impression-taking procedures can be very difficult or outright impossible using traditional methods. Newly developed systems for capturing three-dimensional images of the oral cavity can facilitate the treatment of patients with disabilities. The research aimed to assess the timing of intraoral scanning using a scanner in orthodontic treatment, comparing disabled patients undergoing clear aligner therapy with their healthy counterparts. Scanning times were compared in two patient groups. Group I comprised patients with a certificate of disability, while Group II (control) consisted of patients without a certificate of disability. Maxillary and mandibular scans, as well as bite registration, were performed with the intraoral scanner. The mean scanning time in study Group I was 8.59 min, while in control Group II, it was 5.71 min. The results demonstrated statistical significance, reaching a significance level of p &lt; 0.001. The scanning of disabled patients proved to be more challenging and time-consuming compared to patients in the control group. Consequently, doctors must consider the need to allocate more time to a disabled person during a visit. Despite the difficulties, disabled patients accepted this method of bite scanning. There was no need to carry out such a procedure under general anesthesia. This confirms that scanning should be the preferred method in orthodontic treatment for disabled patients.

Molecular functions of microRNAs in colorectal cancer: recent roles in proliferation, angiogenesis, apoptosis, and chemoresistance.

MiRNAs (microRNAs) constitute a group of diminutive molecules of non-coding RNA intricately involved in regulating gene expression. This regulation is primarily accomplished through the binding of miRNAs to complementary sequences situated in the 3'-UTR of the messenger RNA (mRNA) target; as a result, they are degraded or repressed. The multifaceted biogenesis of miRNAs is characterized by a meticulously orchestrated sequence of events encompassing transcription, processing, transportation, and decay. Colorectal cancer stands as a pervasive and formidable ailment, afflicting millions across the globe. Colorectal cancer is not well diagnosed early, and metastasis rates are high, which results in low survival rates in advanced stages. The genesis and progression of colorectal cancer are subject to the influence of genetic and epigenetic factors, among which miRNAs play a pivotal role. When it comes to colorectal cancer, miRNAs have a dual character, depending on the genes they target, functioning as either tumor suppressors or oncogenes and the prevailing cellular milieu. Their impact extends to modulating critical facets of colorectal cancer pathogenesis, including proliferation, angiogenesis, apoptosis, chemoresistance, and radiotherapy response. The discernible potential of miRNAs which are used as biomarkers to diagnose colorectal cancer, prognosis, and treatment response has come to the forefront. Notably, miRNAs are easily found and detected readily in a variety of biological fluids, including saliva, blood, urine, and feces. This prominence is attributed to the inherent advantages of miRNAs over conventional biomarkers, including heightened stability, specificity, sensitivity, and accessibility. Various investigations have pinpointed miRNA signatures or panels capable of differentiating colorectal cancer patients from their healthy counterparts, predicting colorectal cancer stage and survival, and monitoring colorectal cancer recurrence and therapy response. Although there has been research on miRNAs in various diseases, there has been less research on miRNAs in cancer. Moreover, updated results of preclinical and clinical studies on miRNA biomarkers and drugs are required. Nevertheless, the integration of miRNAs as biomarkers for colorectal cancer is not devoid of challenges and limitations. These encompass the heterogeneity prevalent among colorectal cancer subtypes and stages, the variability in miRNA expression across different tissues and individuals, the absence of standardized methodologies for miRNA detection and quantification, and the imperative for validation through extensive clinical trials. Consequently, further research is imperative to conclusively establish the clinical utility and reliability of miRNAs as colorectal cancer biomarkers. MiR-21 demonstrates carcinogenic characteristics by targeting several tumor suppressor genes, which encourages cell division, invasion, and metastasis. On the other hand, by controlling the Wnt/β-catenin pathway, the tumor suppressor miRNA miR-34a prevents CRC cell proliferation, migration, and invasion. Furthermore, in colorectal cancer, the miR-200 family increases chemotherapy sensitivity while suppressing epithelial-mesenchymal transition (EMT). As an oncogene, the miR-17-92 cluster targets elements of the TGF-β signaling pathway to encourage the growth of CRC cells. Finally, miR-143/145, which is downregulated in CRC, influences apoptosis and the progression of the cell cycle. These miRNAs affect pathways like Wnt, TGF-β, PI3K-AKT, MAPK, and EMT, making them potential clinical biomarkers and therapeutic targets. This review summarizes recent research related to miRNAs, their role in tumor progression and metastasis, and their potential as biomarkers and therapeutic targets in colorectal cancer. In addition, we combined miRNAs' roles in tumorigenesis and development with the therapy of CRC patients, leading to novel perspectives on colorectal cancer diagnosis and treatment.

Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer.

Colorectal cancer (CRC) ranks among the most prevalent malignant tumors globally. Recent reports suggest that Fusobacterium nucleatum (F. nucleatum) contributes to the initiation, progression, and prognosis of CRC. Butyrate, a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber, is known to inhibit various cancers. This study is designed to explore whether F. nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid. To investigate the mechanism by which F. nucleatum affects CRC occurrence and development. Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F. nucleatum. Additionally, DLD-1 and HCT116 cell lines were exposed to sodium butyrate (NaB) and F. nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function. Our research indicates that the prevalence of F. nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts, while the prevalence of butyrate-producing bacteria is notably lower. In mice colonized with F. nucleatum, the population of butyrate-producing bacteria decreased, resulting in altered levels of butyric acid, a key intestinal metabolite of butyrate. Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells. Consequently, this leads to modulated production of adenosine triphosphate and reactive oxygen species, thereby inhibiting cancer cell proliferation. Additionally, NaB triggers the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, blocks the cell cycle in HCT116 and DLD-1 cells, and curtails the proliferation of CRC cells. The combined presence of F. nucleatum and NaB attenuated the effects of the latter. By employing small interfering RNA to suppress AMPK, it was demonstrated that AMPK is essential for NaB's inhibition of CRC cell proliferation. F. nucleatum can promote cancer progression through its inhibitory effect on butyric acid, via the AMPK signaling pathway.

Enhancing Parkinson’s Disease Prediction Using Deep Learning-Based Convolutional Neural Networks

Recently significant advances in the field of medical diagnostics can be seen. Nonetheless, diagnosing Parkinson's disease (PD) remains difficult, especially in terms of timeliness and precision. The inability of present technological methods to identify this complicated neurodegenerative disease emphasizes the urgent need for more research. PD is a complicated neurological condition that is becoming more commonplace worldwide. A timely and precise PD diagnosis is critical because it directly determines the quality of patient care and the success of treatment. However, our current diagnostic approaches, which primarily rely on clinical assessments, have substantial limits in terms of sensitivity and specificity. Thus, the need for a more reliable and objective diagnosing procedure is essential. Convolutional neural networks (CNNs) are employed in this study to investigate complex spiral and wave patterns and to overcome this significant challenge. Drawings from both PD patients and their healthy counterparts were included in the large dataset that was used to train the robust CNN model, which is a key component of the research technique. The training and intensive testing of the model on this dataset confirms its capacity to distinguish between PD instances and non-PD cases. The results of this investigation demonstrate how well the CNN model can predict Parkinson's disease (PD) based on spiral and wave patterns, with a 93% classification accuracy. The high sensitivity and specificity of the model are especially impressive because they significantly lower the chances of false positives and false negatives. The discussion that follows offers a considered evaluation of these findings, emphasising the model's potential for early diagnosis, its capacity to support professional judgments, and its crucial role in enhancing patient outcomes. This study highlights the great potential of deep learning methods for disease diagnosis, especially for PD. The effective integration of the CNN model into a React application for real-time prediction and continuous monitoring of patient performance has important implications for telemedicine and remote healthcare management. This breakthrough makes Parkinson's disease treatment more approachable and proactive.

Association between proinflammatory cytokines and arterial stiffness in type 1 diabetic adolescents.

Type 1 diabetes mellitus is considered a state of chronic low-grade inflammation and activation of the innate immune system, which is regulated by several proinflammatory cytokines and other acute-phase reactants. Arterial stiffness, a dynamic property of the vessels evaluated by the determination of pulse wave velocity (PWV), is increased in diabetic patients and is associated with microvascular and macrovascular complications of diabetes and higher cardiovascular risk. In the present study, we aimed to compare the proinflammatory state and arterial stiffness in diabetic and non-diabetic adolescents, and to characterize the association between these two parameters. Twenty-three type 1 diabetic patients, aged 12-16 years, followed at a tertiary center, and 23 adolescents nonoverweighted healthy controls, from a Portuguese birth-cohort, were included in the present analysis. Anthropometry, blood pressure, glycemic control data, and lipid parameters were collected. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity. Proinflammatory cytokines' concentrations (TNF-α, IL-1β, IL-6, IL-10, IFN-γ, and GM-CSF) were quantified by multiplex immunoassays using a Luminex 200 analyzer. There were no statistically significant differences between the proinflammatory cytokines' concentrations in the two groups. PWV [6.63 (6.23-7.07) vs. 6.07 (5.15-6.65) m/s, p=0.015] was significantly higher in the diabetic group. PWV was negatively correlated with GM-CSF (ρ=-0.437, p=0.037) in the diabetic group. A linear association was found between diabetes duration and PWV (with PWV increasing by 0.094 m/s (95 % confidence interval, 0.019 to 0.169) per month of disease duration). In the diabetic group, HbA1c was negatively correlated with IL-10 (ρ=-0.473, p=0.026). Negative correlations were also found between IL-10 and total, HDL, and LDL cholesterol only in the diabetic group. Diabetic adolescent patients present higher PWV, when compared to their healthy counterparts, even though we could not find differences in the levels of several proinflammatory cytokines between the two groups. The negative correlation found between IL-10 and HbA1c might translate a protective counterbalance effect of this anti-inflammatory cytokine, which might also explain the negative correlations found with blood lipids. Further studies are needed to better clarify the association between arterial stiffness and the proinflammatory milieu of diabetes.

Spiritual Health and COVID-Related Anxiety Among Adolescents with and Without Chronic Disease

Background: Spiritual health has been linked to the mental health of adolescents. Yet, the impact of the coronavirus pandemic on the spiritual health of adolescents with chronic diseases, as opposed to the mental health of their healthy counterparts in Iran, has not been explored. Objectives: The aim of this study was to examine the association between spiritual health and COVID-19-induced anxiety among adolescents, both with and without chronic diseases. Methods: This descriptive cross-sectional study involved 85 adolescents with chronic diseases (selected through convenience sampling) and 80 adolescents without chronic diseases (selected through cluster random sampling) in Tehran, Iran. The Spiritual Well-Being Scale (SWBS) and the Corona Disease Anxiety Scale (CDAS) were utilized for data collection. Results: The findings indicated that anxiety levels related to COVID-19 were significantly higher among adolescents with chronic diseases compared to their healthy peers (P = 0.001). Additionally, spiritual well-being was significantly lower in adolescents with chronic diseases than in healthy adolescents (P = 0.001). Conclusions: The COVID-19 pandemic appears to be linked to psychological and spiritual vulnerabilities in adolescents with chronic diseases, suggesting a need for psychological support and special consideration for these individuals.

Unearthing Subtle Cognitive Variations: A Digital Screening Tool for Detecting and Monitoring Mild Cognitive Impairment

Early diagnosis of mild cognitive impairment (MCI) is pivotal in mitigating the risk of cognitive impairment and the onset of dementia. However, prevailing clinical cognitive screening tests and biomarker assessment approaches often suffer from drawbacks such as high cost, invasiveness, time consumption, or subjectivity. In China, existing digital cognitive assessment tools face multiple challenges due to their distinctive cultural, language, and healthcare landscape. Therefore, we embarked on a study to develop a digital cognitive assessment tool, evaluate its efficacy in distinguishing between healthy individuals and MCI patients, and examine its acceptability among Chinese older adults. Through a series of symposiums, programming, and interviews with stakeholders, we iteratively designed the "BrainNursing" mobile application. The system consists of eleven single tasks and three dual tasks, each taking only 1–3 minutes. Subsequently, we conducted statistical comparisons of movement kinetics and physiological signals recorded during cognitive testing in 181 older adults to investigate which parameters could serve as effective digital biomarkers for MCI screening. Leveraging machine learning classifiers and a majority voting principle, we evaluated the classification performance of the BrainNursing system in detecting MCI, yielding an accuracy rate of 90.3%. Furthermore, our analysis of movement kinetics revealed that time, score, and sequence features are crucial in cognitive assessment. Contrasting with their healthy counterparts, MCI patients exhibited decreased heart rate variability, increased sympathetic nervous system activity, and weakened autonomic nervous system regulation in response to stimuli during cognitive testing. Finally, user experience feedback indicated that participants universally perceived BrainNursing as a convenient and user-friendly cognitive screening tool and provided valuable insights for further improvement.

Age at natural menopause and development of chronic diseases in the female population of Kharameh, Iran: A historical cohort study.

Declines in estradiol levels after menopause have been reported to be associated with several health outcomes. This study aimed to determine the effect of age at natural menopause (ANM) on some of the most common chronic diseases. This historical cohort study was performed on 2636 postmenopausal women aged 40-70 years participating in phase one of the PERSIAN cohort study in Kharameh, Iran, during 2015-2017. The effect of early (<45 years), intermediate (45-53 years), and late menopause (>53 years) on chronic diseases such as hypertension, diabetes, ischemic heart diseases, stroke, thyroid diseases, and depression was assessed using classic logistic regression for diseases with an incidence rate of more than 10% and Firth's logistic regression for diseases with an incidence of less than this amount. The mean age of women was 53.48 ± 8.59. Respectively, early and intermediate menopause was associated with ischemic heart disease (odds ratio [OR = 1.61, 95% confidence interval [CI]: 1.08-2.42; p = 0.020), (OR = 1.57, 95% CI: 1.13-2.21; p = 0.008) and thyroid diseases (OR = 3.10, 95% CI: 1.64-6.24; p < 0.001), (OR = 1.83, 95% CI: 1.02-3.57; p = 0.042). furthermore, early menopause was a risk factor for diabetes (OR = 1.46, 95% CI: 1.07-2.00; p = 0.018), depression (OR = 4.79, 95% CI: 2.20-11.79; p = <0.001) and stroke (OR = 3.00, 95% CI: 1.08-9.32; p = 0.034). In this study, women with diabetes, ischemic heart diseases, stroke, thyroid disorders, and depression had a younger ANM compared to their healthy counterparts. Therefore, applying appropriate strategies to postpone the age of menopause, can reduce the incidence of these types of chronic diseases.