Early Indicator Research Articles

Oral Manifestations of Human Immunodeficiency Virus Infection: Early Diagnostic Indicators

Oral Manifestations of Human Immunodeficiency Virus Infection: Early Diagnostic Indicators

Association Between Acute Ischemic Stroke and Raised Serum Gamma Glutamyl Transferase

The serum gamma-glutamyl transferase level predicts the development of cardiovascular illnesses. Serum gamma-glutamyl transferase levels have been linked to atherosclerosis in several investigations, indicating that gamma-glutamyl transferase may be utilized as an early indicator of atherosclerosis. Objective: To determine the association between acute ischemic stroke and raised serum gamma-glutamyl transferase. Methods: After obtaining ethical approval, in this case-control study, 310 patients fulfilling the selection criteria were included from the Medical Emergency Department of, KEMU/ Affiliated hospital, Lahore from August 2022 to February 2023. Informed consent was obtained. After matching for age (40-80 years) and gender (both male and female), 155 controls enrolled preferably the accompanying healthy attendants of the patients and 155 cases i.e. ischemic stroke patients. Venous blood samples were obtained from cases at the time of presentation in the Emergency Department for serum gamma-glutamyl transferase (GGT). Data was collected in structured proforma. Data scrutiny was done using SPSS version 26.0. Mean and standard deviation were used for quantitative variables and frequency for qualitative data. Data were stratified for effect modifiers, and p≤0.05 was taken as significant. Results: In the current study, the frequency of raised GGT was found more among cases as compared to controls i.e. 74% vs 20%, p<0.00001 and OR calculated was 11.5. Conclusions: It was concluded that a considerable percentage of patients had raised gamma-glutamyl transferase at the time of presentation with acute ischemic stroke. These results emphasize the need to keep an eye on GGT levels in ischemic stroke patients as a possible stroke marker.

Prevalence of peripheral artery disease in young coronary artery disease patients

Background and objectives. Peripheral artery disease (PAD) and coronary artery disease (CAD) are progressive inflammatory conditions caused by arteriosclerosis, typically presenting after the age of 50. However, assessing peripheral vascular disease (PVD) in younger populations may offer early indications of coronary heart disease (CHD) risk. This study investigates the prevalence of abnormal ankle brachial index (ABI) values among young myocardial infarction (MI) patients and examines the correlation of ABI with other cardiovascular risk factors. Material and methods. This cross-sectional study was conducted at Saveetha Medical College and Hospital, involving 147 patients aged 40 years or younger who were admitted with MI symptoms. The study focused on the incidence and severity of MI in relation to age, sex, and the presence of risk factors such as smoking, alcohol use, dyslipidemia, hypertension (HTN), and diabetes mellitus (DM). Results. The study analyzed the incidence of myocardial infarction (MI) in a population under 40 years old. It was found that the incidence rate increased with age within this group. Specifically, males were more frequently affected than females, with 70% of cases occurring in males. Among female participants, all were over 30 years old. In terms of ankle-brachial index (ABI) values, 40% of females exhibited abnormal ABI, compared to 25% of males. Significant risk factors identified included smoking, with 60% of participants reporting tobacco use, alcohol consumption at 50%, and dyslipidemia present in 45% of cases. Hypertension (HTN) and diabetes mellitus (DM) were less prevalent, affecting 20% and 15% of participants, respectively. There was a significant correlation between low ABI values and the use of tobacco (p<0.01) and alcohol (p<0.05). However, the analysis showed no significant relationship between the number of vascular involvements indicated by ABI and the length of hospital stay. The length of hospital stay did increase with patient age, with an average increase of 2 days for every decade of age, but this was not significantly associated with ABI values. Conclusion. ABI is a valuable diagnostic tool in young populations for detecting early signs of CHD, offering advantages over routine blood pressure measurements. This study supports the broader use of ABI in both young and older populations to improve early detection and management of cardiovascular risks. Further research is needed to explore the implications of ABI in routine clinical practice and its correlation with other cardiovascular risk factors.

AI-Driven Realtime Monitoring of Early Indicators for Ichthyophthirius multifiliis Infection of Rainbow Trout.

A novel video-based real-time system based on AI (artificial intelligence) was developed to detect clinical signs in fish exposed to pathogens. We selected a White Spot Disease model involving rainbow trout as the experimental animal and the parasitic ciliate Ichthyophthirius multifiliis as a pathogen. We compared two identical fish tank systems: one tank was infected by co-habitation, whereas the other tank was kept non-infected (sham infection). The two fish tanks were separately video monitored (full top and side view) during the course of infection, during which fish were removed whenever they developed clinical signs (direct visual inspection by the observer). Image analysis (object detection, classification and tracking) was used to track behavioural changes in fish (in every recorded video frame), focusing on movement patterns and spatial localisation. Initially, the two fish groups (infected and non-infected) exhibited similar behaviour and non-infected fish did not change behaviour during the 15 d observation period (from 5 d before infection until 10 dpi). At 4, 7, 8, 9 and 10 dpi some infected fish showed clinical signs (equilibrium disturbance, gasping and lethargy) and were removed from the experiment. Anorexia occurred from 5 dpi and a gradual progression of gasping behaviour was noted, whereas the frequency of fish flashing (rubbing/scratching against objects) was low. Equilibrium disturbances and the development of white spots in the skin appeared to be a much later (8-10 dpi at this temperature) indicator of infection. The video analysis showed a general distribution of non-infected fish in all parts of the fish tank during the entire experiment, whereas infected fish already at 4-5 dpi moved towards higher water currents in the top and bottom positions. This change of fish positioning within the tank appeared as a promising early indicator of infection. The study suggests that continuous monitoring of fish behaviour using AI can potentially optimise the timing of humane endpoints, indicate disease signs earlier and thereby improve animal welfare in both animal experimentation and in aquaculture settings.

Preliminary Investigation of Potential Early Biomarkers for Gestational Diabetes Mellitus: Insights from PTRPG and IGKV2D-28 Expression Analysis

Gestational diabetes mellitus (GDM) poses significant health risks to both mothers and infants, emphasizing the need for early detection strategies to mitigate its impact. However, the existing diagnostic methods, particularly the oral glucose tolerance test (OGTT) administered in the second or third trimester, show limitations in the detection of GDM during its early stages. This study aimed to explore the potential of the genes Protein Tyrosine Phosphatase Receptor-type Gamma (PTPRG) and Immunoglobulin Kappa Variable 2D-28 (IGKV2D-28) as early indicators for GDM among Filipino pregnant women. Utilizing reverse transcription–quantitative polymerase chain reaction (RT-qPCR), the gene expressions were analyzed in first-trimester blood samples obtained from 24 GDM and 36 non-GDM patients. The diagnostic performance of PTPRG and IGKV2D-28 was analyzed and evaluated using receiver operating characteristic (ROC) curves. The findings revealed elevated expression levels of PTPRG and IGKV2D-28 within the GDM cohort. Remarkably, PTPRG exhibited a sensitivity of 83%, while IGKV2D-28 demonstrated a specificity of 94% at determined cut-off values. Combining both genes yielded an improved but limited diagnostic accuracy with an area under the curve (AUC) of 0.63. This preliminary investigation of PTPRG and IGKV2D-28 sheds light on novel avenues for early GDM detection. While these findings are promising, further validation studies in larger cohorts are necessary to confirm these results and explore additional biomarkers to enhance diagnostic precision in GDM pregnancies and, ultimately, to improve maternal and fetal outcomes.

A Biomarker Signature Associated With Future Functional Decline And Outcomes On The Frailty-Disability Cascade

Abstract Background Biological ageing is a dynamic and heterogeneous process that occurs due to dysregulation at the molecular, cellular, physiological and functional level, manifesting in functional decline. We investigated whether biomarker data across a range of biological systems predicted incident functional decline and frailty-disability cascade outcomes. Methods Secondary data analyses were performed on n=4,961 participants aged 50+ years from waves 1-5 of The Irish Longitudinal Study on Ageing (TILDA). We examined 18 blood biomarkers representing key systems that become dysregulated with ageing (inflammatory, cardiovascular, metabolic, renal, cognitive, musculoskeletal and senescence). Model-based clustering classified participants as belonging to one of three biomarker signatures - low, medium and high risk. These biomarker signatures were utilized to predict 4-year functional decline (grip strength, timed up and go test (TUG) and gait speed) using mixed effect models; 8-year frailty and disability using logistic regression models; and 12-year mortality using Cox-Proportional Hazard models. All models were adjusted for age, sex, education, smoking history, lipid lowering and anti-hypertensive medications. Results The prevalence of the low, medium and high-risk groups was 58.5%, 9.2% and 32.3%. Medium and high-risk biomarker signatures had progressively increased hazard of 12-year mortality (HR:1.54, 95%CI:1.13-2.10) and (HR:1.89, 95%CI:1.53-2.34) respectively. Participants with the high-risk signature also had significantly higher odds of 8-year incident frailty (OR:2.1, 95%CI:1.60-2.74) and disability (OR:1.72, 95%CI:1.30-2.29), with the medium-risk group showing attenuated associations. The biomarker signatures had a dose response relationship with functional decline; with the high-risk group having lower grip strength, slower walking speed and higher time to complete the TUG over 4-year follow-up (p<0.01). Findings were replicated in a US cohort. Conclusion We report a unique biomarker signature that was consistently associated with mortality, incident frailty and disability, and functional decline. This signature may be a useful early indicator and risk stratification tool to predict future functional decline and frailty-disability cascade outcomes.

Retinal microcirculation changes in prediabetic patients with short-term increased blood glucose using optical coherence tomography angiography.

Retinal microcirculation alterations are early indicators of diabetic microvascular complications. Optical coherence tomography angiography (OCTA) is a noninvasive method to assess these changes. This study analyzes changes in retinal microcirculation in prediabetic patients during short-term increases in blood glucose using OCTA. To investigate the changes in retinal microcirculation in prediabetic patients experiencing short-term increases in blood glucose levels using OCTA. Fifty volunteers were divided into three groups: Group 1 [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)], Group 2 (both IFG and IGT), and a control group. Retinal microcirculation parameters, including vessel density (VD), perfusion density (PD), and foveal avascular zone (FAZ) metrics, were measured using OCTA. Correlations between these parameters and blood glucose levels were analyzed in both the fasting and postprandial states. One hour after glucose intake, the central VD (P = 0.023), central PD (P = 0.026), and parafoveal PD (P < 0.001) were significantly greater in the control group than in the fasting group. In Group 1, parafoveal PD (P < 0.001) and FAZ circularity (P = 0.023) also increased one hour after glucose intake. However, no significant changes were observed in the retinal microcirculation parameters of Group 2 before or after glucose intake (P > 0.05). Compared with the control group, Group 1 had a larger FAZ area (P = 0.032) and perimeter (P = 0.018), whereas Group 2 had no significant differences in retinal microcirculation parameters compared with the control group (P > 0.05). Compared with Group 1, Group 2 had greater central VD (P = 0.013) and PD (P = 0.008) and a smaller FAZ area (P = 0.012) and perimeter (P = 0.010). One hour after glucose intake, Group 1 had a larger FAZ area (P = 0.044) and perimeter (P = 0.038) than did the control group, whereas Group 2 showed no significant differences in retinal microcirculation parameters compared with the control group (P > 0.05). Group 2 had greater central VD (P = 0.042) and PD (P = 0.022) and a smaller FAZ area (P = 0.015) and perimeter (P = 0.016) than Group 1. At fasting, central PD was significantly positively correlated with blood glucose levels (P = 0.044), whereas no significant correlations were found between blood glucose levels and OCTA parameters one hour after glucose intake. A short-term increase in blood glucose has a more pronounced effect on retinal microcirculation in prediabetic patients with either IFG or IGT.

Association between hydroxychloroquine intake and damage to the outer nuclear layer in eyes without manifest retinal toxicity

BackgroundHydroxychloroquine (HCQ) is widely used to treat various autoimmune diseases but carries a risk of retinal toxicity, particularly with prolonged use. Despite advancements, uncertainty persists regarding optimal screening methods. Recent advances in OCT have enabled early detection of retinal damage, with studies suggesting that thinning of specific retinal layers may be an early indicator of toxicity. However, there is a gap in research on outer nuclear layer (ONL) thinning in HCQ users without apparent retinal toxicity. This information is crucial for improving screening and identifying the ONL as a reliable biomarker for screening. Therefore, this study aimed to investigate the association between HCQ intake and ONL damage in eyes without manifest retinal toxicity.MethodsA case‒control study was conducted at the ophthalmology department of Eye and Ear Hospital International from July 2022 to June 2023. The study included 20 individuals on HCQ and 20 age-matched controls. The data were obtained through chart reviews, and participants underwent comprehensive ophthalmic assessments.ResultsA total of 80 eyes were analyzed. Patients on HCQ exhibited significantly thinner perifoveal, parafoveal, and overall ONL compared to controls (P < .001, P < .012, and P < .004, respectively). Similarly, this association was found in the nasal, inferior, and temporal quadrants of both the inner (region 3: P < .01, region 4: P < .001, and region 5: P < .03) and outer zones (region 7: P < .04, region 8: P < .001, region 9: P < .02), most pronounced in the inferior regions. The cumulative dose was weakly associated with decreased ONL thickness only in the nasal quadrant of the inner zone (region 3: P < .047). Correlation analysis of the initial and most recent OCT scans in the same individuals revealed a weak association with ONL thinning in the central zone (region 1: P < .0048).ConclusionThe thickness of the ONL can significantly decrease in patients taking HCQ, even in the absence of of manifest retinal toxicity. This study is the first to evaluate this association in eyes with negative screening and diagnostic tests for HCQ retinopathy. The findings suggest that ONL thickness could serve as an early diagnostic indicator for HCQ retinal toxicity.

Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia.

Hydroxyurea (HU) constitutes the first-line treatment in most patients with essential thrombocythemia (ET), but criteria for changing therapy are not clearly established. The prognostic value of complete hematological response (CHR) and resistance/intolerance to HU was assessed in 1080 patients from the Spanish Registry of ET, classified according to revised IPSET-Thrombosis stratification (Very low- n = 61, Low- n = 83, Intermediate- n = 261, and High-risk n = 675). With a median therapy duration of 5 years, CHR was registered in 720 (67%) patients (1-year probability 51%) and resistance/intolerance in 219 (20%) patients (5-years probability 13%). After correction by other risk factors, High-risk patients achieving CHR showed a reduced risk of arterial thrombosis (HR: 0.35, 95%CI: 0.2-0.6, p = 0.001) and a trend towards lower risk of venous thrombosis (HR: 0.45, 95%CI: 0.2-1.02, p = 0.06) whereas no association was observed for intermediate- or low-risk patients. In comparison with non-responders, intermediate- and high-risk patients achieving CHR had longer survival and lower myelofibrosis incidence. Development of resistance/intolerance to HU, mainly cytopenia, was associated with higher probability of myelofibrosis but no effect on survival or thrombotic risk was demonstrated. In conclusion, CHR with HU is associated with better outcomes and might be an early indicator for selecting candidates to second-line clinical trials.

Clinical utility of ctDNA by amplicon based next generation sequencing in first line non small cell lung cancer patients.

The assessment of ctDNA has emerged as a minimally invasive avenue for molecular diagnosis and real-time tracking of tumor progression in NSCLC. However, the evaluation of ctDNA by amplicon-based NGS has been not endorsed by all the healthcare systems and remains to be fully integrated into clinical routine practice. To compare tissue single-gene with plasma multiplexed testing, we retrospectively evaluated 120 plasma samples from 12 consecutive patients with advanced non-squamous NSCLC who were part of a prospective study enrolling treatment-naïve patients and in which tissue samples were evaluated using a single-gene testing approach. While the plasma ctDNA detection of EGFR and BRAF mutations had an acceptable level of concordance with the archival tissue (85%), discordance was seen in all the patients in whom ALK alterations were only detected in tissue samples. Among six responders and six non-responders, early ctDNA mutant allelic frequency (MAF) reduction seemed to predict radiologic responses and longer survival, whereas increasing MAF values with the emergence of co-mutations like BRAFV600E, KRASG12V or TP53M237I seemed to be an early indicator of molecular and radiologic progression. This report using an amplicon-based NGS assay on ctDNA underscores the real-life need for plasma and tissue genotyping as complementary tools in the diagnostic and therapeutic decision-making process.

Portable Electrochemical System and Platform with Point-of-Care Determination of Urine Albumin-to-Creatinine Ratio to Evaluate Chronic Kidney Disease and Cardiorenal Syndrome.

The urine albumin (Alb)-to-creatinine (Crn) ratio (UACR) is a sensitive and early indicator of chronic kidney disease (CKD) and cardiorenal syndrome. This study developed a portable and wireless electrochemical-sensing platform for the sensitive and accurate determination of UACR. The developed platform consists of a carbon nanotube (CNT)-2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)(ABTS)-based modified UACR sensor, a miniaturised potentiostat, a cup holder embedded with a magnetic stirrer and a smartphone app. The UACR sensing electrode is composed of two screen-printed carbon working electrodes, one screen-printed carbon counter electrode and a screen-printed AgCl reference electrode. The miniaturised potentiostat, which is controlled by the developed app, performs cyclic voltammetry and amperometry to detect Alb and Crn, respectively. Clinical trials of the proposed system by using spot urine samples from 30 diabetic patients indicate that it can accurately classify all three CKD risk statuses within 30 min. The high accuracy of our proposed sensing system exhibits satisfactory agreement with the commercial biochemical analyser TBA-25FR (Y = 0.999X, R2 = 0.995). The proposed UACR sensing system offers a convenient, reliable and affordable solution for personal mobile health monitoring and point-of-care urinalysis.

An early Transcriptomic Investigation in Adult Patients with Spinal Muscular Atrophy Under Treatment with Nusinersen

Spinal muscular atrophy (SMA) is a rare degenerative disorder with loss of motor neurons caused by mutations in the SMN1 gene. Nusinersen, an antisense oligonucleotide, was approved for SMA treatment to compensate the deficit of the encoded protein SMN by modulating the pre–mRNA splicing of SMN2, the centromeric homologous of SMN1, thus inducing the production of a greater amount of biologically active protein. Here, we reported a 10-month transcriptomics investigation in 10 adult SMA who received nusinersen to search for early genetic markers for clinical monitoring. By comparing their profiles with age-matched healthy controls (HC), we also analyzed the changes in miRNA/mRNAs expression and miRNA-target gene interactions possibly associated with SMA. A multidisciplinary approach of HT-NGS followed by bioinformatics/biostatistics analysis was applied. Within the study interval, those SMA patients who showed some clinical improvements were characterized by having the SMN2/SMN1 ratio slightly increased over the time, while in the stable ones the ratio decreased, suggesting that the estimation of SMN2/SMN1 expression may be an early indicator of nusinersen efficacy. On the other hand, the expression of 38/147 genes/genetic regions DE at T0 between SMA and HC like TRADD and JUND resulted “restored” at T10. We also confirmed the dysregulation of miR-146a(-5p), miR-324-5p and miR-423-5p in SMA subjects. Of interest, miR-146a-5p targeted SMN1, in line with experimental evidence showing the key role of astrocyte-produced miR-146a in SMA motor neuron loss. Molecular pathways such as NOTCH, NF-kappa B, and Toll-like receptor signalings seem to be involved in the SMA pathogenesis.

How effective are ecological metrics in supporting conservation and management in degraded streams?

AbstractBiodiversity loss is increasing worldwide, necessitating effective approaches to counteract negative trends. Here, we assessed aquatic macroinvertebrate biodiversity in two river catchments in Switzerland; one significantly degraded and associated with urbanisation and instream barriers, and one in a near-natural condition. Contrary to our expectations, environmental heterogeneity was lower in the near-natural stream, with enhanced productivity in the degraded system resulting in a greater range of environmental conditions. At face value, commonly employed alpha, beta and gamma biodiversity metrics suggested both catchments constituted healthy systems, with greater richness or comparable values recorded in the degraded system relative to the near-natural one. Further, functional metrics considered to be early indicators for anthropogenic disturbance, demonstrated no anticipated differences between degraded and near-natural catchments. However, investigating the identity of the taxa unique to each river system showed that anthropogenic degradation led to replacement of specialist, sensitive species indicative of pristine rivers, by generalist, pollution tolerant species. These replacements reflect a major alteration in community composition in the degraded system compared with the near-natural system. Total nitrogen and fine sediment were important in distinguishing the respective communities. We urge caution in biodiversity studies that employ numerical biodiversity metrics alone. Assessing just one aspect of diversity, such as richness, is not sufficient to track biodiversity changes associated with environmental stress. We advocate that biodiversity monitoring for conservation and management purposes must go beyond traditional richness biodiversity metrics, to include indices that incorporate detailed nuances of biotic communities that relates to taxon identity.

Disulfiram-Copper Potentiates Anticancer Efficacy of Standard Chemo-therapy Drugs in Bladder Cancer Animal Model through ROS-Autophagy-Ferroptosis Signalling Cascade.

Cost-effective management of Urinary Bladder Cancer (UBC) is an unmet need. Our study aims to demonstrate the efficacy of a drug repurposing strategy by using disulfiram (DSF) and copper gluconate (Cu) as an add-on treatment combination to traditional GC-based chemother-apy against N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced UBC mice (C57J) model. Male C57BL/6J mice were given 0.05% BBN in drinking water ad libitum, and tumour for-mation was verified by histological and physical evaluation. Animals were subsequently divided into eight groups and received treatment with different drug combinations. Control animals received only ve-hicle (DMSO). At the end of the treatment schedule, the bladder tumour was excised and further used to check the expression (mRNA and protein) of ALDH1 isoenzymes using qRT-PCR, western blot, and IHC methods. Autophagy induction was assessed by quantifying the expression of LC3B and SQSTM1/p62 proteins through IHC. Biochemical analysis of superoxide dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation levels in the freshly isolated tumours was performed to check the alterations in the antioxidant system caused by combination treatment. We observed significant induction of an invasive form of bladder cancer in the mice after nine-teen weeks of BBN exposure. The animals began exhibiting early indications of inflammatory alterations as early as the sixth week following BBN treatment. Furthermore, the wet bladder weight and overall tu-mour burden were significantly decreased (p&#60; 0.0001) by DSF-Cu co-treatment in addition to the GC-based chemotherapy. Real-time PCR analysis revealed that treatment with disulfiram and copper glu-conate significantly decreased (p&#60;0.0001) the mRNA expression of ALDH1 isoenzymes. Comparing the triple drug combination group (GC+DSF-Cu) to the untreated mice, a significant rise in LC3B puncta (p&#60;0.0001) and a decrease in P62/SQSTM1 (p=0.0002) were noted, indicating the induction of autophagy flux in the add-on group. When GC+DSF-Cu treated mice were compared to the untreated tumour group, a substantial decrease in ALDH1/2 protein expression was observed (p= 0.0029 in IHC and p&#60;0.0001 in western blot). Lipid peroxidation was significantly higher (p&#60;0.0001) in the triple drug combination group than in untreated mice. There was a simultaneous decrease in reduced glutathione (GSH) and en-zyme superoxide dismutase (SOD) levels (p&#60;0.0001), which strongly suggests the generation of reactive oxygen species and induction of ferroptotic cell death in the add-on therapy group. Additionally, in both IHC and western blot assays, ALDH1A3 expression was found to be significantly increased (p=0.0033, &#60;0.0001 respectively) in GC+DSF-Cu treated mice relative to the untreated group, suggesting a potential connection between the ferroptosis pathway and ALDH1A3 overexpression. It was found that disulfiram with copper treatment inhibits bladder tumour growth through ferroptosis-mediated ROS induction, which further activates the process of autophagy. Our results prove that DSF-Cu can be an effective add-on therapy along with the standard chemotherapy drugs for the treatment of UBC.

Unlocking the Secrets: Predictive Risk Factors for Long-term Olfactory Dysfunction in COVID-19 Patients

&lt;b&gt;Introduction:&lt;/b&gt; COVID-19 is a multisystem disease that can severely impact overall health. It causes non-lethal complications that may significantly affect the quality of life, such as smell dysfunction, which has been identified as an essential and early indicator of infection. A substantial proportion suffer from prolonged or even permanent loss of smell.&lt;b&gt;Aim:&lt;/b&gt; The study aims to identify key clinical and demographic risk factors that significantly predict the prognosis of such an olfactory loss in patients with COVID-19.&lt;b&gt;Materials and method:&lt;/b&gt; A prospective, cross-sectional, descriptive study. Qualified patients were aged ≥ 18 years with a past COVID-19 infection confirmed by PCR. They all underwent thorough clinical assessments and nasoendoscopy to exclude other nasal pathologies. The Alcohol Threshold Test (ATT) was used to assess olfactory function and only patients with severe hyposmia and anosmia were included in the study. The Arabic version of the Kessler Psychological Distress Scale (K10) was used to assess the emotional impact on the patient.&lt;b&gt;Results:&lt;/b&gt; The study included 100 patients suffering from severe smell loss. Sixty-two patients (62%) were ≥39 years and 38 (38%) were ≤ 40 years old. The mean age of the patients was 37.5 10.8 years. There were 62 females (62%). The mean duration of olfactory loss was 4.4 2.8 months. Sudden onset was reported in 98 patients. Only 2 patients (2%) had rhinorrhea. Eighty-one patients (81%) suffered from mild symptoms of COVID infection. There were 21 smokers (21%). Eighteen patients (18%) had comorbidities. Twenty-seven patients (27%) belonged to the low socioeconomic status. Severe hyposmia (TS of ATT = 4–5) was reported in 96 patients (96%) and anosmia (TS of ATT = 6) in 4 patients (4%). Kessler’s test indicated that 63 patients (63%) experienced moderate to severe distress.&lt;b&gt;Conclusions:&lt;/b&gt; The following risk factors showed significant differences in the prognosis of olfactory loss: older age, long duration of loss, smoking, presence of comorbidities, low socioeconomic status, and increased severity of COVID-19. These factors may be important predictors of the persistence of olfactory loss. Factors like sex, onset type, nasal symptoms, severity of olfactory loss, and Kessler’s test score did not show significant differences.

The Clinical Significance of Pancreatic Steatosis in Pancreatic Cancer: A Hospital-Based Study.

Background/Objectives: Pancreatic cancer remains one of the deadliest malignancies worldwide with a pressing need for early detection and intervention strategies. Emerging evidence has suggested a potential link between pancreas steatosis, characterized by excessive pancreatic fat accumulation, and an increased risk of pancreatic cancer development. This retrospective imaging study aims to elucidate the association between pancreatic steatosis and the subsequent development of pancreatic cancer. In the study, we aimed to determine the characteristics of pancreatic cancer with pancreatic steatosis. Methods: During the period of January 2022 to December 2022, we conducted a retrospective study, collecting 101 newly diagnosed pancreas cancer cases from the available image datasets. A comprehensive database of retrospective abdominal imaging studies, comprising computed tomography (CT) and magnetic resonance imaging (MRI), was established from a diverse patient population and subsequently analyzed. Inclusion criteria encompassed patients having available baseline imaging data, allowing for the assessment of pancreatic fat content. Pancreatic fat content was quantified using validated radiological techniques, while demographic, clinical, and histopathological data were all collected. The clinical data and patient characteristics were collected from medical records and analyzed. Results: Preliminary analysis revealed a significant correlation between elevated pancreatic fat content and an increased incidence of subsequent pancreatic cancer. Moreover, subgroup analysis based on age, gender, and comorbidities provided valuable insight into potential risk factors associated with this progression. Additionally, the study identified novel radiological markers that may serve as early indicators of pancreatic cancer development in individuals with pancreatic steatosis. Conclusions: In the imaging study, approximately 30% (30/101) of pancreatic cancer patients presented with pancreatic steatosis. Chronic pancreatitis emerged as the primary factor contributing to pancreatic steatosis in these patients. Importantly, pancreatic steatosis did not significantly impact the prognosis of pancreatic cancer. Follow-up data revealed no significant differences in survival duration between patients with or without pancreatic steatosis. Additionally, no association was found between pancreatic steatosis and hepatic steatosis.

Exploring the Nicotine-Parkinson's disease link – Insights from the UK Biobank

IntroductionEvidence suggests an inverse correlation between smoking and Parkinson's disease (PD), yet the mechanisms remain unclear. This study examines the changing risk relationship between smoking and PD diagnosis using alcohol consumption, another reward-driven behavior, as a comparative measure. MethodsA nested case-control study was conducted using the UK Biobank (UKBB) database. Participants in the prediagnostic phase of PD were identified, and self-reported data on tobacco and alcohol use were analyzed employing conditional binary logistic regression. Polynomial and piece-wise regression models were employed to discern shifting associations with PD over time. ResultsOf 502,304 participants (63 ± 5.3 years, 63 % male), 3049 prediagnostic PD cases were identified. Non-smokers had a heightened PD risk, and this association strengthened closer to diagnosis. The odds ratio (OR [95 % CI]) associated with PD in non-smokers was 2.02 [1.07–3.81] 1–4 years before diagnosis, compared to 1.36 [1.02–1.83] at >10-year intervals (linear trend, p = 0.012). The time trajectory of ORs was best depicted by a quadratic function, identifying a shift in risk 7.5 years before diagnosis documentation. Similar patterns emerged among alcohol non-consumers, with an 8.5-year interval inflection point. ConclusionThis study identified two disparate risk trajectories among non-smokers: an initial low-amplitude increased risk at prolonged prediagnostic intervals possibly related to genetic/personality factors, followed by a sharp escalation in risk association commencing 7–8 years before diagnosis, possibly propelled by reverse causality. Similar trends in alcohol consumption reinforce these conclusions. These findings could suggest that smoking cessation may serve as an early indicator of PD.

What Impact Does the Diagnosis of Mild Cognitive Impairment Have on the Wellbeing, Everyday Behavior, and Healthcare Utilization of People and Their Carers? A Systematic Review.

Dementia is a major cause of disability and dependency globally. Mild cognitive impairment (MCI) is considered an early indicator of developing dementia. There are growing efforts to detect and diagnose MCI earlier; consequently, we need to understand the perspectives of individuals and carers regarding the implications of an MCI diagnosis. To systematically review qualitative literature to understand the impact of a MCI diagnosis on both the individual and their carers, focusing on wellbeing, everyday behaviors, and healthcare utilization. Key search terms were input into five databases. Studies were included if they were peer-reviewed qualitative research published in English that obtained perspectives of community-dwellers with MCI or carers and focused on either their wellbeing, everyday behaviors and/or healthcare utilization. The protocol was pre-registered on PROSPERO (CRD42021291995). Data was synthesized narratively. Key findings from 15 eligible articles highlighted the negative impact of an MCI diagnosis on the wellbeing of both individuals and carers, due to stigma and limited understanding regarding diagnosis/prognosis. Changes in everyday behavior varied, particularly regarding motivation to engage with physical activity, hobbies and social opportunities. Both individuals and carers were sometimes dissatisfied with healthcare services; ineffective communication during clinical consolations highlighted as a reason for lack of trust in clinicians. Results indicate that an MCI diagnosis impacts both people with MCI and their carers across key facets of life. There is a critical need to effectively communicate the diagnosis and prognosis of MCI to support wellbeing and everyday activities and ensure trust in healthcare services.

Blood immune profiles reveal a CXCR3/CCR5 axis of dysregulation in early sepsis

Abstract We report on a pilot study exploring whether blood immune signatures can reveal early specific indicator profiles for patients meeting sepsis criteria upon hospital admission. We analysed samples of sepsis-suspected patients (N=20) and age-spanning healthy controls (N=12), using flow cytometry-based assays. We measured inflammatory markers from plasma fractions, and immunophenotyped freshly isolated unfixed PBMCs for leukocytes subsets representation and expression of activation markers, including chemokine receptors. We found that beside IL-6 and sCD14, CXCR3 ligands (CXCL9 and CXCL10) separated sepsis-suspected patients from healthy controls. The abundance of CD4+ T cells was significantly reduced in patients, while they displayed substantial losses of CCR5-expressing monocytes and CXCR3/CCR5 double positive T cells. Post-hoc subgrouping of patients according to their sepsis diagnosis on discharge, identified CXCR3/CCR5 double expression on T cells as a separating characteristic for confirmed cases. This work suggests a potential novel axis of dysregulation affecting CXCR3 and CCR5 in early sepsis.

Assembly and evaluation of a confocal microscopy image analysis pipeline useful in revealing the secrets of plant-fungal interactions

The ability of laser scanning confocal microscopy to generate high-contrast 2D and 3D images has become essential in studying plant-fungal interactions. Techniques such as visualization of native fluorescence, fluorescent protein tagging of microbes, GFP/RFP-fusion proteins, and fluorescent labelling of plant and fungal proteins have been widely used to aid in these investigations. Use of fluorescent proteins has several pitfalls including variability of expression in planta and the requirement of gene transformation. Here we used the unlabeled pathogens Parastagonospora nodorum, Pyrenophora teres f. teres, and Cercospora beticola infecting wheat, barley, and sugar beet respectively, to show the utility of a staining and imaging pipeline that uses propidium iodide (PI), which stains RNA and DNA, and wheat germ agglutinin labeled with fluorescein isothiocyanate (WGA-FITC), which stains chitin, to visualize fungal colonization of plants. This pipeline relies on the use of KOH to remove the cutin layer of the leaf, increasing its permeability, allowing the different stains to penetrate and effectively bind to their targets, resulting in a consistent visualization of cellular structures. To expand the utility of this pipeline, we used the staining techniques in conjunction with machine learning to analyze fungal biomass through volume analysis, as well as quantifying nuclear breakdown, an early indicator of programmed cell death (PCD). This pipeline is simple to use, robust, consistent across host and fungal species and can be applied to most plant-fungal interactions. Therefore, this pipeline can be used to characterize model systems as well as non-model interactions where transformation is not routine.