Healthy Patients Research Articles

The role of sacro-iliac joint magnetic resonance imaging in the diagnosis of axial spondyloarthritis: focus on differential diagnosis in women.

To review the role of sacro-iliac magnetic resonance imaging (MRI) in the diagnosis of axial spondyloarthritis (AxSpA), with a focus on gender differences. The experience of the authors and the results of an informal literature review are reported. Inflammatory changes of the sacro-iliac joint are the hallmark of AxSpA. Early, non-radiographic sacroiliitis may be diagnosed with MRI through the assessment of bone marrow edema (BMO) as well as concomitant structural damage. The MRI protocol should include three necessary sequences, i.e., fat-saturated T2-weighted sequences on two orthogonal planes, T1-weighted semi-coronal sequence, and fat-suppressed T1-weighted semi-coronal sequence. Inflammatory changes comprise required signs (BMO and/or osteitis) and additional signs, including synovitis (better defined as joint space enhancement), enthesitis, and capsulitis. Structural changes consist of erosions, sclerosis, fat metaplasia, and ankylosis. Due to mechanical axial strain, inflammatory changes in the sacro-iliac joint can be found in healthy individuals, runners, and patients with nonspecific low back pain. The prevalence of BMO is higher in women during pregnancy and postpartum, even 12 months after childbirth, but the extent and distribution of MRI findings may help in the differential diagnosis. Other challenges in the MRI diagnosis of sacroiliitis are subchondral T2 hyperintensity during developmental age, periarticular sclerosis in healthy subjects, or osteitis condensans ilii, and several pathological conditions that may mimic AxSpA, some of which are more frequently found in women. The described diagnostic challenges impose a multidisciplinary approach combining imaging findings with clinical and laboratory data.

“Partner” cellulose gel with “dialysis” function: Achieve the integration of filtration-enrichment-SERS detection

Hydrogel and aerogel materials have garnered significant attention in constructing effective surface-enhanced Raman spectroscopy (SERS) substrates due to their excellent adsorption capabilities, high specific surface area, and abundant chemical groups. However, in liquids with complex compositions, non-specific adsorption of macromolecules can lead to surface scaling and pore clogging of the substrate material, limiting the selective enrichment and SERS detection of target molecules. To address this, an innovative aerogel-chimeric hydrogel material (CH@S-CNF/SA/Ag NPs) was developed. The aerogel component, with its high specific surface area and electronegative properties, functions as a SERS “chip” for adsorption and detection of target molecules. Simultaneously, the mesoporous structure of the hydrogel “shell” effectively filters macromolecules from the solution. These CH@S-CNF/SA/Ag NPs were utilized as SERS substrate materials for detecting urine from healthy individuals and patients with chronic kidney disease stage 5 (CKD5). When combined with machine learning algorithms, the detection accuracy reached 99.50%. This work represents a significant advancement in the specific adsorption and SERS detection of small molecules in complex biological samples such as urine and blood.

Drawing promotes memory retention in a patient with sleep-related anterograde amnesia.

Drawing is a powerful tool to enhance memory in healthy participants and patients with probable dementia. Here, we investigated whether the drawing effect could extend to patient CT, a young woman with severe anterograde amnesia. Following surgery for a midline tumor involving her septum pellucidium and extending down into her fornices bilaterally, CT experienced a severe case of sleep-related amnesia. She can remember information encountered throughout the day, but when waking up in the morning or following a nap she forgets information learned prior to sleep. Here, we tested CT and 21 age-matched controls in a 3-day within-subjects design, during which participants encoded words by either drawing or writing them down. Memory for encoded words was tested in two conditions that each followed a 12-h delay, once after a night of sleep, and once after 12 h of wake. Despite her severe memory impairment, CT showed a drawing effect that was comparable to controls in both sleep and wake conditions. Whereas CT's memory for written words was consistently impaired relative to controls, her memory for drawn words was at the lower control range following a waking delay and above chance following a sleep delay. We suggest that amnesic patients may benefit from the drawing effect due to the recruitment of brain regions outside of the hippocampal system for encoding and consolidation. Furthermore, in control participants, sleep benefited memory for written words, but not for drawn words, suggesting that sleep preferentially consolidates memories that are more dependent on the hippocampal system.

Plantar Fascia Thickness and Stiffness in Healthy Individuals vs Patients With Plantar Fasciitis.

Plantar fasciitis is a major cause of heel pain, resulting from repetitive trauma to the plantar fascia and leading to structural changes within the fascia. It has been observed that plantar fascia thickness in plantar fasciitis patients exceeds that of normal individuals. However, the biomechanical properties of the plantar fascia in patients with plantar fasciitis remain unclear. Therefore, this study aimed to compare plantar fascia stiffness between healthy individuals and patients with plantar fasciitis across different areas. Fifty-eight participants were divided into 2 groups: 29 healthy individuals and 29 individuals with plantar fasciitis. B-mode ultrasonography was used to assess plantar fascia thickness, whereas shear wave elastography was employed to measure plantar fascia stiffness. The study focused on 3 distinct areas: calcaneal insertion, 1-cm distal area, and 2-cm distal area. Additionally, the most painful area reported by patients was marked in the plantar fasciitis group. The findings showed that the plantar fasciitis group exhibited significantly greater plantar fascia stiffness in almost all areas compared to the healthy group (P < .05). Moreover, the stiffness of the plantar fascia in the most painful area demonstrated the highest value compared with other areas within the plantar fasciitis group (P < .05). This study suggests structural and mechanical changes in the plantar fascia in patients with plantar fasciitis.

Whole-brain turbulent dynamics predict responsiveness to pharmacological treatment in major depressive disorder.

Depression is a multifactorial clinical syndrome with a low pharmacological treatment response rate. Therefore, identifying predictors of treatment response capable of providing the basis for future developments of individualized therapies is crucial. Here, we applied model-free and model-based measures of whole-brain turbulent dynamics in resting-state functional magnetic resonance imaging (fMRI) in healthy controls and unmedicated depressed patients. After eight weeks of treatment with selective serotonin reuptake inhibitors (SSRIs), patients were classified as responders and non-responders according to the Hamilton Depression Rating Scale 6 (HAMD6). Using the model-free approach, we found that compared to healthy controls and responder patients, non-responder patients presented disruption of the information transmission across spacetime scales. Furthermore, our results revealed that baseline turbulence level is positively correlated with beneficial pharmacological treatment outcomes. Importantly, our model-free approach enabled prediction of which patients would turn out to be non-responders. Finally, our model-based approach provides mechanistic evidence that non-responder patients are less sensitive to stimulation and, consequently, less prone to respond to treatment. Overall, we demonstrated that different levels of turbulent dynamics are suitable for predicting response to SSRIs treatment in depression.

Urinary tract infections: pathogenesis, host susceptibility and emerging therapeutics.

Urinary tract infections (UTIs), which include any infection of the urethra, bladder or kidneys, account for an estimated 400 million infections and billions of dollars in health-care spending per year. The most common bacterium implicated in UTI is uropathogenic Escherichia coli, but diverse pathogens including Klebsiella, Enterococcus, Pseudomonas, Staphylococcus and even yeast such as Candida species can also cause UTIs. UTIs occur in both women and men and in both healthy and immunocompromised patients. However, certain patient factors predispose to disease: for example, female sex, history of prior UTI, or the presence of a urinary catheter or other urinary tract abnormality. The current clinical paradigm for the treatment of UTIs involves the use of antibiotics. Unfortunately, the efficacy of this approach is dwindling as the prevalence of antimicrobial resistance rises among UTI isolates, and the immense quantity of antibiotics prescribed annually for these infections contributes to the emergence of resistant pathogens. Therefore, there is an urgent need for new antibiotics and non-antibiotic treatment and prevention strategies. In this Review, we discuss how recent studies of bacterial pathogenesis, recurrence, persistence, host-pathogen interactions and host susceptibility factors have elucidated new and promising targets for the treatment and prevention of UTIs.

Automated Idiopathic Normal-Pressure Hydrocephalus Diagnosis via Artificial Intelligence-Based 3D T1 MRI Volumetric Analysis.

Idiopathic normal pressure hydrocephalus (iNPH) is reversible dementia, that is underdiagnosed. The purpose of this study was to develop an automated diagnostic method for iNPH using artificial intelligence techniques with a T1-weighted MRI scan. We quantified iNPH, Parkinson's disease, Alzheimer's disease, and healthy control patients on T1-weighted 3D brain MRI scans using 452 scans for training and 110 scans for testing. Automatic component measurement algorithms were developed for Evans' index, Sylvian fissure enlargement, high-convexity tightness, callosal angle, and normalized lateral ventricle volume. XGBoost models were trained for both automated measurements and manual labels for iNPH prediction. A total of 452 patients (200 men; mean age ± standard deviation, 73.2 ± 6.5 years) were included in the training set. Of the 452 patients, 111 (24.6%) had iNPH. We obtained AUC values of 0.956 for automatically measured high-convexity tightness and 0.830 for Sylvian fissure enlargement. Intra-class correlation values of 0.824 for the callosal angle and 0.924 for Evans' index were measured. Using the decision tree of the XGBoost model, the model trained on manual labels obtained an average cross-validation AUC of 0.988 on the training set and 0.938 on the unseen test set, while the fully automated model obtained a cross-validation AUC of 0.983 and an unseen test AUC of 0.936. We demonstrated a machine-learning algorithm capable of diagnosing iNPH from a 3D T1-weighted MRI scan that is robust to the failure. We propose a method to scan large numbers of 3D T1-weighted MRI scans with minimal human intervention, making possible large-scale iNPH screening. iNPH = idiopathic normal-pressure hydrocephalus; PD = Parkinson's disease; AD = Alzheimer's disease; HC = healthy control; CSF = cerebrospinal fluid; DESH = disproportionately enlarged subarachnoid space hydrocephalus; 3D = three-dimensional.

The relationship between severity of periapical periodontitis and next-generation systemic inflammatory biomarkers in children with early childhood caries

IntroductionEarly childhood caries (ECC) is closely associated with poor oral hygiene and cariogenic diet. Untreated ECC results in recurrent odontogenic infections and local and systemic consequences. In this study, our goal is to assess the relationship between the intensity of odontogenic infection-associated periapical periodontitis and new generation of systemic inflammatory markers (SII, NLR, PLR) in ECC-affected children.Material and method95 healthy patients in early childhood and demonstrating periapical periodontitis who underwent dental treatment under general anesthesia (GA) in the last two years were included in the present study. Their periapical statuses were dichotomized as mild and severe. Periapical Index (PAI) scores of 2 and 3 were regarded as “mild” whereas 4 and 5 as “severe”. Of the complete blood test (CBC) parameters, systemic inflammatory index (SII), neutrophil-to-lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), neutrophilic granulocyte (NEUT), lymphocyte (LYMPH) and platelet (PLT) were recorded. The relationship between the degree of periapical pathology and the evaluated markers was assessed using Receiver Operating Characteristic (ROC) analysis.ResultsResults of the present study revealed that mean NLR, SII and NEUT index scores of the patients having severe periapical periodontitis were statistically higher than those of the ones with mild pathology (p < 0.05). A positive, statistically significant interrelationship was found between the number of teeth demonstrating a PAI score of severe periapical periodontitis with the signs of exacerbation (PAI 5) and NLR and SII values (p < 0.05). Area under the ROC curve (AUC) values for NLR and SII were determined as 66.8% and 66.6% respectively, indicating that classification performance was sufficient and statistically significant (p < 0.05).ConclusionPostponing the management of odontogenic infections will induce some complications such as, infective endocarditis and cause the systemic inflammatory process to continue by aggravating the systemic effects of local lesions. Thus, underlying mechanism should be eliminated and oral hygiene should be maintained, also novel biomarkers may be recommended to be used for the decision-making process for the teeth with persistent periapical lesions unresponsive to treatment.

Analysis of risk indicators for implant failure in patients with chronic periodontitis

Dental implant restoration shows an effective method for the rehabilitation of missing teeth. The failure rate of periodontal implants in patients with chronic periodontitis is associated with periodontal flora, inflammation, and long-term periodontal bone resorption caused by chronic periodontitis. However, the therapeutic effects of dental implant restoration on inflammation in patients with chronic periodontitis have not addressed. The purpose of this study is to evaluate the risk indicators for inflammation, bone loss and implant failure in patients with chronic periodontitis. A total of 284 patients with dental implant restoration were recruited and divided into periodontally healthy patients (n = 128) and chronic periodontitis patients (n = 156). Periodontal indices including probing depth (PD), sulcus bleeding index (SBI), plaque index (PLI), gingival bleeding (GIL) and bleeding on probing (BOP) were compared in two groups. Inflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1 (IL-1), matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) levels at baseline, 6 and 12 months after surgery, and the implant survival rate at 12 months after surgery, as well as the risk factors associated with failure of dental implant were also assessed. Outcomes demonstrated that patients in the chronic periodontitis group had higher values of periodontal indices than those in the periodontally healthy group. All inflammatory parameters in the chronic periodontitis group were higher than those in the periodontally healthy group and negatively associated with the chronic periodontal index (CPI) in chronic periodontitis patients. Chronic periodontitis patients had higher the prevalence of mucositis and peri-implantitis than patients with healthy periodontium. Implant diameter, length and design was associated with the risk of implant failure for chronic periodontitis patients receiving dental implant. The cumulative implant failure rate and incidence of implant fractures for chronic periodontitis patients at 12 months after surgery were 12.10% and 7.23% (p < 0.05), respectively, while were lower in the heathy periodontitis patients. Location, diameter, implant design, immediate loading and bone defect were risk indicators for bone loss for dental implant patients. The risk factors associated with failure of dental implant was higher in chronic periodontitis patients than patients in the periodontally healthy group (14.25% vs. 4.92%, p < 0.05). In conclusion, data in the current study indicate that inflammation is a risk indicator bone loss, implant fracture and implant failure in patients with chronic periodontitis.

Assessing Fetal Circulatory Changes in Gestational Diabetes via Aortic Isthmus Doppler

Background: Gestational diabetes mellitus (GDM) is a common complication during pregnancy that can negatively impact fetal heart function and structure. This study aimed to investigate the hemodynamic characteristics of the fetal aortic isthmus in patients with GDM using Doppler ultrasound parameters. Methods:This was a cross-sectional observational study including 47 pregnant patients with GDM and 47 healthy pregnant patients as controls. Fetal biometric measurements and umbilical artery Doppler values were obtained. Aortic isthmus Doppler was used to measure systolic and diastolic flow velocity time integrals (S and D), peak systolic velocity (PSV), and systolic nadir (Ns) to calculate the isthmus flow index (IFI) = (S + D)/S and isthmus systolic index (ISI) = Ns/PSV. A generalized additive model was used to analyze the relationship between IFI, ISI and gestational age. Results: Compared to controls, the GDM group had significantly lower D (2.39 cm vs. 2.76 cm), Ns (11.48 cm/s vs. 14.06 cm/s), IFI (1.24 vs. 1.27) and ISI (0.14 vs. 0.16). Curve fitting showed IFI was lower in the GDM group for most gestational weeks and decreased with advancing weeks, while ISI remained constantly lower and decreased linearly. Conclusions: Fetal aortic isthmus Doppler parameters IFI and ISI were altered in GDM pregnancies, suggesting earlier changes in aortic arch hemodynamics compared to the umbilical artery. Combining IFI and ISI may provide more comprehensive assessment of fetal circulatory changes in GDM. These findings could enhance our understanding of the pathophysiologic impacts of maternal diabetes.

Inflammatory Intracellular Signaling in Neurons Is Influenced by Glial Soluble Factors in iPSC-Based Cell Model of PARK2-Associated Parkinson's Disease.

Neuroinflammation is considered to be one of the driving factors in Parkinson's disease (PD). This study was conducted using neuronal and glial cell cultures differentiated from induced pluripotent stem cells (iPSC) of healthy donors (HD) and PD patients with different PARK2 mutations (PD). Based on the results of RNA sequencing, qPCR and ELISA, we revealed transcriptional and post-transcriptional changes in HD and PD neurons cultivated in HD and PD glial-conditioned medium. We demonstrated that if one or both of the components of the system, neurons or glia, is Parkin-deficient, the interaction resulted in the down-regulation of a number of key genes related to inflammatory intracellular pathways and negative regulation of apoptosis in neurons, which might be neuroprotective. In PD neurons, the stress-induced up-regulation of APLNR was significantly stronger compared to HD neurons and was diminished by glial soluble factors, both HD and PD. PD neurons in PD glial conditioned medium increased APLN expression and also up-regulated apelin synthesis and release into intracellular fluid, which represented another compensatory action. Overall, the reported results indicate that neuronal self-defense mechanisms contribute to cell survival, which might be characteristic of PD patients with Parkin-deficiency.

Blood based metabolic markers of glioma from pre-diagnosis to surgery

Gliomas are highly complex and metabolically active brain tumors associated with poor prognosis. Recent reports have found altered levels of blood metabolites during early tumor development, suggesting that tumor development could be detected several years before clinical manifestation. In this study, we performed metabolite analyses of blood samples collected from healthy controls and future glioma patients, up to eight years before glioma diagnosis, and on the day of glioma surgery. We discovered that metabolites related to early glioma development were associated with an increased energy turnover, as highlighted by elevated levels of TCA-related metabolites such as fumarate, malate, lactate and pyruvate in pre-diagnostic cases. We also found that metabolites related to glioma progression at surgery were primarily high levels of amino acids and metabolites of amino acid catabolism, with elevated levels of 11 amino acids and two branched-chain alpha-ketoacids, ketoleucine and ketoisoleucine. High amino acid turnover in glioma tumor tissue is currently utilized for PET imaging, diagnosis and delineation of tumor margins. By examining blood-based metabolic progression patterns towards disease onset, we demonstrate that this high amino acid turnover is also detectable in a simple blood sample. These findings provide additional insight of metabolic alterations during glioma development and progression.

Orally Ingested Micro- and Nano-Plastics: A Hidden Driver of Inflammatory Bowel Disease and Colorectal Cancer.

Micro- and nano-plastics (MNPLs) can move along the food chain to higher-level organisms including humans. Three significant routes for MNPLs have been reported: ingestion, inhalation, and dermal contact. Accumulating evidence supports the intestinal toxicity of ingested MNPLs and their role as drivers for increased incidence of colorectal cancer (CRC) in high-risk populations such as inflammatory bowel disease (IBD) patients. However, the mechanisms are largely unknown. In this review, by using the leading scientific publication databases (Web of Science, Google Scholar, Scopus, PubMed, and ScienceDirect), we explored the possible effects and related mechanisms of MNPL exposure on the gut epithelium in healthy conditions and IBD patients. The summarized evidence supports the idea that oral MNPL exposure may contribute to intestinal epithelial damage, thus promoting and sustaining the chronic development of intestinal inflammation, mainly in high-risk populations such as IBD patients. Colonic mucus layer disruption may further facilitate MNPL passage into the bloodstream, thus contributing to the toxic effects of MNPLs on different organ systems and platelet activation, which may, in turn, contribute to the chronic development of inflammation and CRC development. Further exploration of this threat to human health is warranted to reduce potential adverse effects and CRC risk.

A novel super-resolution microscopy platform for cutaneous alpha-synuclein detection in Parkinson's disease.

Alpha-synuclein (aSyn) aggregates in the central nervous system are the main pathological hallmark of Parkinson's disease (PD). ASyn aggregates have also been detected in many peripheral tissues, including the skin, thus providing a novel and accessible target tissue for the detection of PD pathology. Still, a well-established validated quantitative biomarker for early diagnosis of PD that also allows for tracking of disease progression remains lacking. The main goal of this research was to characterize aSyn aggregates in skin biopsies as a comparative and quantitative measure for PD pathology. Using direct stochastic optical reconstruction microscopy (dSTORM) and computational tools, we imaged total and phosphorylated-aSyn at the single molecule level in sweat glands and nerve bundles of skin biopsies from healthy controls (HCs) and PD patients. We developed a user-friendly analysis platform that offers a comprehensive toolkit for researchers that combines analysis algorithms and applies a series of cluster analysis algorithms (i.e., DBSCAN and FOCAL) onto dSTORM images. Using this platform, we found a significant decrease in the ratio of the numbers of neuronal marker molecules to phosphorylated-aSyn molecules, suggesting the existence of damaged nerve cells in fibers highly enriched with phosphorylated-aSyn molecules. Furthermore, our analysis found a higher number of aSyn aggregates in PD subjects than in HC subjects, with differences in aggregate size, density, and number of molecules per aggregate. On average, aSyn aggregate radii ranged between 40 and 200 nm and presented an average density of 0.001-0.1 molecules/nm2. Our dSTORM analysis thus highlights the potential of our platform for identifying quantitative characteristics of aSyn distribution in skin biopsies not previously described for PD patients while offering valuable insight into PD pathology by elucidating patient aSyn aggregation status.

Comparing efficacies of various papain-based enzyme agents and 2.4% sodium hypochlorite gel in chemomechanical caries removal: a randomized controlled trial

ObjectiveThis study aimed to evaluate and compare the efficacies of Papacarie Duo gel, Brix 3000, Selecti-Solve gel, 2.4% sodium hypochlorite gel, and conventional rotary-mechanical method in caries removal and to evaluate the patient comfort.MethodsIt was a single-blinded, randomized, parallel-group, active-controlled trial with five arms. It was conducted at the Department of Restorative Dentistry and Endodontics, Damascus University. Seventy-five specimens were randomly allocated into five groups: chemomechanical caries removal (CMCR) using Selecti-Solve gel (G1), BRIX3000 (G2), Papacarie DUO gel (G3), or 2.4% sodium hypochlorite gel (G4), and caries excavation using conventional rotary-mechanical method (G5) (control group). The trial considered healthy patients aged 18–40. Permanent molars with class I carious lesions extending to the middle third of dentin with no pulpal and/or periodontal pathology were included. The efficacy of caries removal was considered the primary outcome measure, and the secondary outcome measures were treatment time, volumetric measurement of the cavity, and pain assessment.ResultsThe majority (73.30%) of cases from BRIX3000 and conventional rotary-mechanical method groups showed complete caries removal (p = 0.982). The mean time of caries removal was the highest (17.45 ± 4.42) in the 2.4% sodium hypochlorite gel group (p < 0.05), and the lowest (6.33 ± 1.69) was in the conventional rotary-mechanical method group (p < 0.05). The mean cavity volume was the highest (18.97 ± 9.76) in the Papacarie DUO gel group, and the lowest (14.87 ± 4.76) was in the 2.4% sodium hypochlorite gel group (p = 0.506). The conventional rotary-mechanical group exhibited the highest mean score (5.40 ± 1.72) of pain (p < 0.05). However, the mean score (2.67 ± 1.11) of pain reported reduced in the BRIX3000 group.ConclusionsCMCR agents could be a potential substitute for conventional rotary instrumentation methods, taking into account the long working time.

Assessment of oral hygiene habits and periodontal status of patients during and after orthodontic treatment

OBJECTIVE: This study evaluated the relationship between orthodontic treatment, oral hygiene practices, and periodontal health in individuals undergoing or completed orthodontic treatment. MATERIALS AND METHOD: Systemically healthy patients undergoing or completed stable orthodontic treatment were included in the study. The periodontal status of 142 participants was determined using a comprehensive oral hygiene questionnaire and clinical oral examinations to assess various periodontal indices. Chi-square and t-tests were used for statistical analyses to compare periodontal status metrics between groups. RESULTS: Statistical analyses revealed no significant differences between oral hygiene habits, periodontal indices, or periodontal status between the ongoing treatment (OT) and post-orthodontic treatment (PT) groups (p&amp;gt;0.05). However, significant differences were noted in attachment level, dental visit frequency, and reasons for visits between the OT and PT groups (p&amp;lt;0.05). While participants generally showed similar oral hygiene awareness and practices, differences arose in toothbrushing times during orthodontic treatment and adherence to orthodontist recommendations. CONCLUSION: This study investigated the effect of OT on oral health and concluded that OT did not change oral hygiene habits but affected attachment levels. Orthodontists should consistently guide patients on oral hygiene and managing clinical attachment loss. In these cases, the patient should be referred to a periodontist when necessary.

Cognitive Effects of Three β-Adrenoceptor Acting Drugs in Healthy Volunteers and Patients with Parkinson's Disease.

Noradrenergic signaling declines in Parkinson's disease (PD) following locus coeruleus neurodegeneration. Epidemiologic studies demonstrate that β-acting drugs slow PD progression. The primary objective was to compare the safety and effects of 3 β-adrenoceptor (β-AR) acting drugs on central nervous system (CNS) function after a single dose in healthy volunteers (HVs) and evaluate the effects of multiple doses of β-AR acting drugs in HVs and PD-patients. In Part A, HVs received single doses of 32 mg salbutamol, 160μg clenbuterol, 60 mg pindolol and placebo administered in a randomized, 4-way cross-over study. In Part B (randomized cross-over) and Part C (parallel, 2:1 randomized), placebo and/or clenbuterol (20μg on Day 1, 40μg on Day 2, 80μg on Days 3-7) were administered. CNS functions were assessed using the NeuroCart test battery, including pupillometry, adaptive tracking and recall tests. Twenty-seven HVs and 12 PD-patients completed the study. Clenbuterol improved and pindolol reduced the adaptive tracking and immediate verbal recall performance. Clenbuterol and salbutamol increased and pindolol decreased pupil-to-iris ratios. Clenbuterol was selected for Parts B and C. In Part B, clenbuterol significantly increased performance in adaptive tracking with a tendency toward improved performance in immediate and delayed verbal recall. In Part C trends toward improved performance in immediate and delayed verbal recall were observed in PD-patients. Typical cardiovascular peripheral β2-AR effects were observed with clenbuterol. This study demonstrates the pro-cognitive effects of clenbuterol in HVs with similar trends in PD-patients. The mechanism of action is likely activation of β2-ARs in the CNS.

Simultaneous Detection of Collagen I Alpha II and Cytokeratin 19 mRNA by Multiplex qPCR in Liquid Biopsy in Diagnosis of Patients with Resectable Solid Tumors.

The early detection of tumors is one of the key factors in increasing overall survival in cancer patients. A wide range of cancers still do not have a system of early diagnosis; therefore, the development of new non-invasive tools in this line is essential. Accordingly, the objective of our work was to develop a non-invasive screening method for the early detection of various carcinomas in plasma using a panel that combines two markers using RT-qPCR. A retrospective case-control study was conducted to develop a cancer screening test based on the detection of stromal and epithelial biomarkers (COL1A2 and KRT19) in plasma. The expression of biomarkers was evaluated using multiplex quantitative PCR applied to 47 cases with non-metastatic tumors and 13 control participants. For both biomarkers, a cut-off value was stablished using Youden's J index through ROC curve analysis and areas under the curve (AUC) were calculated. The plasma mRNA expression level of both biomarkers was significantly higher in diseased versus healthy patients. Moreover, ROC curve analysis showed an AUC value of 0.897 for the combined model. This model also resulted in a cutoff value of 0.664, as well as a sensitivity of 83% and a specificity of 84.6%. These results suggest that the plasma expression levels of COL1A2 and KRT19 could a have potential role in detecting various types of cancer at the early stages. The combined analysis of both stromal and epithelial biomarkers would provide a non-invasive screening method that would allow us to differentiate patients with an active neoplastic process.

Fuchs’ Endothelial Corneal Dystrophy evaluation using a high-resolution wavefront sensor

This study aims to evaluate the applicability of the high-resolution WaveFront Phase Imaging Sensor (WFPI) in eyes with Fuchs’ Endothelial Corneal Dystrophy (FECD) through qualitative and quantitative analysis using a custom-designed Automatic Guttae Detection Method (AGDM). The ocular phase was measured using the t·\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\cdot$$\\end{document}eyede aberrometer and then was processed to obtain its High-Pass Filter Map (HPFM). The subjects were pathological and healthy patients from the Fundación Jiménez-Díaz Hospital (Madrid, Spain). The AGDM was developed and applied in pupils with 3 and 5 mm of diameter. A set of metrics were extracted and evaluated like the Root-Mean-Square error (RMS), Number of guttae, Guttae Area, and Area of Delaunay Triangulation (DT). Finally, a Support Vector Machine (SVM) model was trained to classify between pathological and healthy eyes. Quantitatively, the HPFM reveals a dark spots pattern according to the ophthalmologist’s description of the slit-lamp examination of guttae distribution. There were significant statistical differences in all the metrics when FECD and Healthy groups were compared using the same pupil size; but comparing both pupil sizes for the same group there were significant differences in most of the variables. This sensor is a value tool to objectively diagnose and monitor this pathology through wavefront phase changes.

Multi-Biomarker Profiling for Precision Diagnosis of Lung Cancer.

Multi-biomarker analysis can enhance the accuracy of the single-biomarker analysis by reducing the errors caused by genetic and environmental differences. For this reason, multi-biomarker analysis shows higher accuracy in early and precision diagnosis. However, conventional analysis methods have limitations for multi-biomarker analysis because of their long pre-processing times, inconsistent results, and large sample requirements. To solve these, a fast and accurate precision diagnostic method is introduced for lung cancer by multi-biomarker profiling using a single drop of blood. For this, surface-enhanced Raman spectroscopic immunoassay (SERSIA) is employed for the accurate, quick, and reliable quantification of biomarkers. Then, it is checked the statistical relation of the multi-biomarkers to differentiate between healthy controls and lung cancer patients. This approach has proven effective; with 20µL of blood serum, lung cancer is diagnosed with 92% accuracy. It also accurately identifies the type and stage of cancer with 87% and 85%, respectively. These results show the importance of multi-biomarker analysis in overcoming the challenges posed by single-biomarker diagnostics. Furthermore, it markedly improves multi-biomarker-based analysis methods, illustrating its important impact on clinical diagnostics.