Mapping of catecholaminergic denervation, neurodegeneration, and inflammation in 6-OHDA-treated Parkinson's disease mice.

Efforts to develop disease-modifying treatments for Parkinson's disease (PD) have been hindered by the lack of animal models replicating all hallmarks of PD and the insufficient attention to extra-nigrostriatal regions pathologically critical for the prodromal appearance of non-motor symptoms. Among PD models, 6-hydroxydopamine (6-OHDA) infusion in mice has gained prominence since 2012, primarily focusing on the nigrostriatal region. This study characterized widespread tyrosine hydroxylase-positive neuron and fiber loss across the brain following a unilateral 6-OHDA (20 µg) infusion into the dorsal striatum. Our analysis integrates immunolabeling, brain clearing (iDISCO+), light sheet microscopy, and computational methods, including fMRI and machine learning tools. We also examined sex differences, disease progression, neuroinflammatory responses, and pro-apoptotic signaling in nigrostriatal regions of C57BL/6 mice exposed to varying 6-OHDA dosages (5, 10, or 20 µg). This comprehensive, spatiotemporal analysis of 6-OHDA-induced pathology may guide the future design of experimental PD studies and neurotherapeutic development.

Symptoms of Anxiety and Depression in Patients Undergoing Transcatheter Aortic Valve Implantation - The SAD-TAVI Study.

Symptoms of anxiety and/or depression (SAD) commonly co-exist in severe aortic stenosis (AS). In patients undergoing transcatheter aortic valve implantation (TAVI), these symptoms are associated with increased morbidity and mortality. Despite this, mental health remains under-researched in the TAVI literature. Drawing from the largest registry in Australia, we aimed to characterise the prevalence of SAD in TAVI patients. We also aimed to identify patient phenotypes at highest risk of these symptoms, examine how they evolve following TAVI and establish factors predictive of improvement and regression in mental health. 1279 patients undergoing TAVI between 2018 and 2023 included in a multi-centre Australian registry were analysed. Median age was 82 (IQR 77, 87), 41% female and median STS score 3.9 (2.3, 5.9). 353 (28%) patients reported moderate or worse SAD at baseline. Of this group, 260 (74%) had complete resolution in symptoms within 30-days. Body Mass Index<25 (adjusted odds ratio [aOR] 3.4, p<0.001), vascular site complications (aOR 3.4, p=0.029) and non-home discharge (aOR 2.4, p=0.036) independently predicted persistence of SAD. Only 72 (8%) patients developed new-onset SAD at 30-days following TAVI. Non-home discharge (aOR 2.12, p=0.025) and a composite cardiovascular endpoint including stroke, acute myocardial infarction, and heart-failure readmission (aOR 2.55, p=0.028) were independent predictors of new-onset SAD. In conclusion, symptoms of anxiety and depression are common but under recognised in aortic stenosis. TAVI is highly effective at improving these symptoms and regular screening for mental health should be considered in the management of all TAVI patients.

Convergence on CaMK4: a key modulator of autism-associated signaling pathways in neurons.

Although the precise underlying cause(s) of autism spectrum disorder remain unclear, more than 1000 rare genetic variations are associated with the condition. For a large number of people living with profound autism, this genetic heterogeneity has impeded the identification of common biological targets for therapy development for core and comorbid traits that include significant impairments in social communication, and repetitive and restricted behaviors. A substantial number of genes associated with autism encode proteins involved in signal transduction and synaptic transmission that are critical for brain development and function. CAMK4 is an emerging risk gene for autism spectrum disorder that encodes the Ca2+-calmodulin-dependent protein kinase-4 (CaMK4) enzyme. CaMK4 is a key component of a Ca2+-activated signaling pathway that regulates neurodevelopment and synaptic plasticity. In this review, we discuss three genetic variants of CAMK4 found in individuals with hyperkinetic movement disorder and comorbid neurological symptoms including autism spectrum disorder that are likely pathogenic with monogenic effect. We also comment on four other genetic variations in CAMK4 that display associations with autism spectrum disorder, as well as twelve examples of autism-associated variations in other genes that impact CaMK4 signaling pathways. Finally, we highlight three environmental risk factors that impact CaMK4 signaling based on studies in preclinical models of autism and/or clinical cohorts. Overall, we review molecular, genetic, physiological, and environmental evidence that suggest defects in the CaMK4 signaling pathway may play an important role in a common autism pathogenesis network across numerous patient groups, and propose CaMK4 as a potential therapeutic target.

The impact of a whole foods dietary intervention on gastrointestinal symptoms, inflammation, and fecal microbiota in pediatric patients with cystic fibrosis: A pilot study.

BACKGROUND: Gastrointestinal (GI) complications are a significant source of morbidity for people with cystic fibrosis (PwCF). Historically, dietary recommendations in CF have focused on calories, typically emphasizing a high fat diet. The changing landscape of CF highlights the need to update this nutritional strategy. There is little research into how the quality of calories consumed by PwCF influences nutritional outcomes, GI symptoms, or likely contributors: intestinal inflammation and GI microbiology. We assessed the feasibility of a whole foods-based diet (WFD) and avoidance of ultra-processed foods, measuring safety/tolerability, adherence, and GI symptoms, as well as fecal measures of inflammation and microbiota among children with CF (CwCF) with GI symptoms. METHODS: Single center, 4-week dietary intervention involving CwCF aged 5-14 years who screened positive on GI symptom questionnaire. Assessments included weight, symptom questionnaires and adverse events (AEs). Stool was analyzed for microbiota (16S rRNA) and calprotectin. RESULTS: 108 children were pre-screened, 9 enrolled and 8 initiated and completed the study. There were no significant changes in weight and no AEs. PEDS-QL GI identified overall improvement in symptoms. Certain symptom domains (constipation, diarrhea, gas/bloating, stomach pain and hurt) demonstrated significant improvement on the WFD. Of two participants with abnormal fecal calprotectin at enrollment, both exhibited decreased values on WFD. There was no significant change in microbiota diversity. CONCLUSION: A WFD diet was feasible and safe in CwCF. There was improvement in GI symptom scores based on both parent and child assessments. Larger studies are needed to further investigate effects on intestinal inflammation and microbiota.

Efficient Regeneration of Transgenic Rice from Embryogenic Callus via Agrobacterium-Mediated Transformation: A Case Study Using GFP and Apple MdFT1 Genes.

Genetic transformation is a critical tool for gene manipulation and functional analyses in plants, enabling the exploration of key phenotypes and agronomic traits at the genetic level. While dicotyledonous plants offer various tissues for in vitro culture and transformation, monocotyledonous plants, such as rice, have limited options. This study presents an efficient method for genetically transforming rice (Oryza sativa L.) using seed-derived embryogenic calli as explants. Two target genes were utilized to assess regeneration efficiency: green fluorescent protein (eGFP) and the apple FLOWERING LOCUS T (FT)-like gene (MdFT1). Antisense MdFT1 was cloned into a vector controlled by the rice α-amylase 3D (Ramy3D) promoter, while eGFP was fused to Cas9 under the Ubi promoter. These vectors were introduced separately into rice embryogenic calli from two Korean cultivars using Agrobacterium-mediated transformation. Transgenic seedlings were successfully regenerated via hygromycin selection using an in vitro cultivation system. PCR confirmed stable transgene integration in the transgenic calli and their progeny. Fluorescence microscopy revealed eGFP expression, and antisense MdFT1-expressing lines exhibited notable phenotypic changes, including variations in plant height and grain quality. High transformation efficiency and regeneration frequency were achieved for both tested cultivars. This study demonstrated the effective use of seed-derived embryogenic calli for rice transformation, offering a promising approach for developing transgenic plants in monocot species.

COVID-19 pandemic, pregnancy care, perinatal outcomes in Eastern Myanmar and North-Western Thailand: a retrospective marginalised population cohort.

BACKGROUND: The COVID-19 pandemic disrupted routine health care and antenatal and birth services globally. The Shoklo Malaria Research Unit (SMRU) based at the Thailand-Myanmar border provides cross border antenatal care (ANC) and birth services to marginalised pregnant women. The border between the countries entered lockdown in March 2020 preventing cross-border access for women from Myanmar to Thailand. SMRU adapted by opening a new clinic during the COVID-19 pandemic in Myanmar. This study explored the impact of the COVID-19 pandemic and response on access to ANC and pregnancy outcomes for marginalised pregnant women in the border regions between Thailand and Myanmar. METHODS: A retrospective review of medical records of all pregnancies delivered or followed at antenatal clinics of the SMRU from 2017 to the end of 2022. Logistic regression was done to compare the odds of maternal and neonatal outcomes between women who delivered pre-COVID (2017-2019) and women who delivered in the COVID-19 pandemic (2020-2022), grouped by reported country of residence: Thailand or Myanmar. RESULTS: Between 2017 and the end of 2022, there were 13,865 (5,576 resident in Thailand and 8,276 in Myanmar) marginalised pregnant women who followed ANC or gave birth at SMRU clinics. Outcomes of pregnancy were known for 9,748 women with an EGA ≥ 28 weeks. Unknown outcome of pregnancy among women living in Thailand did not increase during the pandemic. However, there was a high (60%) but transient increase in unknown outcome of pregnancy for women with Myanmar residence in March 2020 following border closure and decreasing back to the baseline of 20-30% after establishment of a new clinic. Non-literate women were more likely to have an unknown outcome during the pandemic. There was no statistically significant increase in known stillbirths or maternal deaths during the COVID pandemic in this population but homebirth was over represented in maternal and perinatal mortality. CONCLUSION: Decreasing barriers to healthcare for marginalised pregnant women on the Thailand-Myanmar border by establishment of a new clinic was possible in response to sudden border closure during the COVID-19 pandemic and most likely preventing an increase in maternal and perinatal mortality.

Oxygen therapy and noninvasive respiratory supports in acute hypoxemic respiratory failure: a narrative review.

BACKGROUND: This narrative review was written by an expert panel to the members of the jury to help in the development of clinical practice guidelines on oxygen therapy. RESULTS: According to the expert panel, acute hypoxemic respiratory failure was defined as PaO2 < 60 mm Hg or SpO2 < 90% on room air, or PaO2/FiO2 ≤ 300 mm Hg. Supplemental oxygen should be administered according to the monitoring of SpO2, with the aim at maintaining SpO2 above 92% and below 98%. Noninvasive respiratory supports are generally reserved for the most hypoxemic patients with the aim of relieving dyspnea. High-flow nasal cannula oxygen (HFNC) seems superior to conventional oxygen therapy (COT) as a means of avoiding intubation and may therefore be should probably be used as a first-line noninvasive respiratory support in patients requiring more than 6 L/min of oxygen or PaO2/FiO2 ≤ 200 mm Hg and a respiratory rate above 25 breaths/minute or clinical signs of respiratory distress, but with no benefits on mortality. Continuous positive airway pressure (CPAP) cannot currently be recommended as a first-line noninvasive respiratory support, since its beneficial effects on intubation remain uncertain. Despite older studies favoring noninvasive ventilation (NIV) over COT, recent clinical trials fail to show beneficial effects with NIV compared to HFNC. Therefore, there is no evidence to support the use of NIV or CPAP as first-line treatment if HFNC is available. Clinical trials do not support the hypothesis that noninvasive respiratory supports may lead to late intubation. The potential benefits of awake prone positioning on the risk of intubation in patients with COVID-19 cannot be extrapolated to patients with another etiology. CONCLUSIONS: Whereas oxygen supplementation should be initiated for patients with acute hypoxemic respiratory failure defined as PaO2 below 60 mm Hg or SpO2 < 90% on room air, HFNC should be the first-line noninvasive respiratory support in patients with PaO2/FiO2 ≤ 200 mm Hg with increased respiratory rate. Further studies are needed to assess the potential benefits of CPAP, NIV through a helmet and awake prone position in patients with acute hypoxemic respiratory failure not related to COVID-19.

Shear-Sensing by C-Reactive Protein: Linking Aortic Stenosis and Inflammation.

BACKGROUND: CRP (C-reactive protein) is a prototypical acute phase reactant. Upon dissociation of the pentameric isoform (pCRP [pentameric CRP]) into its monomeric subunits (mCRP [monomeric CRP]), it exhibits prothrombotic and proinflammatory activity. Pathophysiological shear rates as observed in aortic valve stenosis (AS) can influence protein conformation and function as observed with vWF (von Willebrand factor). Given the proinflammatory function of dissociated CRP and the important role of inflammation in the pathogenesis of AS, we investigated whether shear stress can modify CRP conformation and induce inflammatory effects relevant to AS. METHODS: To determine the effects of pathological shear rates on the function of human CRP, pCRP was subjected to pathophysiologically relevant shear rates and analyzed using biophysical and biochemical methods. To investigate the effect of shear on CRP conformation in vivo, we used a mouse model of arterial stenosis. Levels of mCRP and pCRP were measured in patients with severe AS pre- and post-transcatheter aortic valve implantation, and the presence of CRP was investigated on excised valves from patients undergoing aortic valve replacement surgery for severe AS. Microfluidic models of AS were then used to recapitulate the shear rates of patients with AS and to investigate this shear-dependent dissociation of pCRP and its inflammatory function. RESULTS: Exposed to high shear rates, pCRP dissociates into its proinflammatory monomers (mCRP) and aggregates into large particles. Our in vitro findings were further confirmed in a mouse carotid artery stenosis model, where the administration of human pCRP led to the deposition of mCRP poststenosis. Patients undergoing transcatheter aortic valve implantation demonstrated significantly higher mCRP bound to circulating microvesicles pre-transcatheter aortic valve implantation compared with post-transcatheter aortic valve implantation. Excised human stenotic aortic valves display mCRP deposition. pCRP dissociated in a microfluidic model of AS and induces endothelial cell activation as measured by increased ICAM-1 and P-selectin expression. mCRP also induces platelet activation and TGF-ß (transforming growth factor beta) expression on platelets. CONCLUSIONS: We identify a novel mechanism of shear-induced pCRP dissociation, which results in the activation of cells central to the development of AS. This novel mechanosensing mechanism of pCRP dissociation to mCRP is likely also relevant to other pathologies involving increased shear rates, such as in atherosclerotic and injured arteries.

Quality control of cardiac magnetic resonance imaging segmentation, feature tracking, aortic flow, and native T1 analysis using automated batch processing in the UK Biobank study.

Aims: Automated algorithms are regularly used to analyse cardiac magnetic resonance (CMR) images. Validating data output reliability from this method is crucial for enabling widespread adoption. We outline a visual quality control (VQC) process for image analysis using automated batch processing. We assess the performance of automated analysis and the reliability of replacing visual checks with statistical outlier (SO) removal approach in UK Biobank CMR scans. Methods and results: We included 1987 CMR scans from the UK Biobank COVID-19 imaging study. We used batch processing software (Circle Cardiovascular Imaging Inc.-CVI42) to automatically extract chamber volumetric data, strain, native T1, and aortic flow data. The automated analysis outputs (∼62 000 videos and 2000 images) were visually checked by six experienced clinicians using a standardized approach and a custom-built R Shiny app. Inter-observer variability was assessed. Data from scans passing VQC were compared with a SO removal QC method in a subset of healthy individuals (n = 1069). Automated segmentation was highly rated, with over 95% of scans passing VQC. Overall inter-observer agreement was very good (Gwet's AC2 0.91; 95% confidence interval 0.84, 0.94). No difference in overall data derived from VQC or SO removal in healthy individuals was observed. Conclusion: Automated image analysis using CVI42 prototypes for UK Biobank CMR scans demonstrated high quality. Larger UK Biobank data sets analysed using these automated algorithms do not require in-depth VQC. SO removal is sufficient as a QC measure, with operator discretion for visual checks based on population or research objectives.

Health data science course for clinicians: Time to bridge the skills gap?

BACKGROUND: Data science skills are highly relevant for clinicians working in an era of big data in healthcare. However, these skills are not routinely taught, representing a growing unmet educational need. This education report presents a structured short course that was run to teach clinicians data science and the lessons learnt. METHODS: A 1-day introductory course was conducted within a tertiary hospital in London. It consisted of lectures followed by facilitated pair programming exercises in R, an object-oriented programming language. Feedback was collated and participant responses were graded using a Likert scale. RESULTS: The course was attended by 20 participants. The majority of participants (69%) were in higher speciality cardiology training. While more than half of the participants (56%) received prior training in statistics either through formal taught programmes (e.g., a Master's degree) or online courses, the participants reported several barriers to expanding their skills in data science due to limited programming skills, lack of dedicated time, training opportunities and awareness. After the short course, there was a significant increase in participants' self-rated confidence in using R for data analysis (mean response; before the course: 1.69 ± 1.0, after the course: 3.2 ± 0.9, p = .0005) and awareness of the capabilities of R (mean response; before the course: 2.1 ± 0.9, after the course: 3.6 ± 0.7, p = .0001, on a 5-point Likert scale). CONCLUSION: This proof-of-concept study demonstrates that a structured short course can effectively introduce data science skills to clinicians and supports future educational initiatives to integrate data science teaching into medical education.

Effect of monsoonal rainfall and tides on salinity intrusion and mixing dynamics in a macrotidal estuary.

Studies on the temporal and spatial variations of estuarine hydrodynamics, particularly those focusing on the combination of extreme and transition periods in the estuary with seasonal fluctuation of discharge, are rarely reported. Due to its importance, this study investigates the effect of rainfall and tide on the salinity intrusion and mixing conditions in the monsoon-affected macrotidal Tanintharyi River estuary (TRE), Myanmar, during the period of 2017-2019. The maximum salinity intrusion and partially mixed to well-mixed conditions were found during the neap-spring tidal cycles of dry seasons. The minimum salinity intrusion, along with partially mixed to stratified conditions, was found during spring to neap tidal cycles of wet seasons. Further, the transitional periods before and after the wet season have different salinity intrusion and mixing conditions based on the different discharge fluctuations in the past months. The salinity intrusion and mixing conditions in the TRE were largely influenced by the lack of rainfall during the dry season, whereas the combined effect of rainfall and the tidal range dominated during the wet season. Finally, the salinity interface gradient (SIG10) index was found to be the convenient index to examine the mixing condition of a large area compared to the traditional indices because of the minimum data requirement with easiness of calculation by using the reference figures from the published articles.

Directly Isolated Allogeneic Virus-Specific T Cells in Progressive Multifocal Leukoencephalopathy.

Importance: Progressive multifocal leukoencephalopathy (PML) is a life-threatening viral infection with no approved antiviral treatment. Objective: To determine whether restoring the compromised immune system of patients with PML with directly isolated allogeneic virus-specific (DIAVIS) T cells is a promising therapeutic strategy, especially if other curative options are absent. Design, Setting, and Participants: A retrospective case series of patients with PML who were treated with DIAVIS T cells was conducted between March 2020 and February 2022. T cells were isolated from healthy donors within 24 hours and targeted against the BK polyomavirus. Patients with PML were treated monocentrically. Eligibility for treatment with DIAVIS T cells was assessed for patients with confirmed PML, and exclusion criteria included stable PML disease and previous treatment with natalizumab. Exposure: Fresh DIAVIS T cells were administered with a maximum dose of 2 × 104 CD3+ cells/kg body weight. Remaining T cells were cryopreserved in divided doses and administered in additional treatments approximately 2 and 6 weeks later. Main Outcomes and Measures: Primary outcome measures were clinical response and survival of patients, compared with the outcomes of a historical reference group of PML cases receiving best supportive treatment (BST) and with recently published real-world data of patients with PML who were treated with immune checkpoint inhibition. Results: The study cohort consisted of 28 patients (median [IQR] age, 60 [51-72] years; 20 male [71.4%]). Twenty-two patients (79%) treated with DIAVIS T cells showed response, resulting in significant clinical stabilization or improvement and a reduction in viral load. Six individuals (21%) were classified as nonresponders, deteriorated rapidly, and died, as did 2 other patients during a 12-month follow-up. Older age was the only predictor of a poor treatment response. Survival analysis revealed better 12-month survival rates (hazard ratio, 0.42; 95% CI, 0.24-0.73; P =.02) from diagnosis for patients treated with DIAVIS T cells (18 of 26 [69%]; 12-mo survival rate, 69%) compared with historical controls with BST (57 of 113 [50%]; 12-mo survival rate, including censored data, 45%). Conclusion and Relevance: This case series of DIAVIS T-cell therapy in PML provides first class IV evidence suggesting efficacy to reduce mortality and improve functional outcome. Further prospective studies are required to confirm these results.

Imaging for the diagnosis of acute myocarditis: can artificial intelligence improve diagnostic performance?

Myocarditis is a cardiovascular disease characterised by inflammation of the heart muscle which can lead to heart failure. There is heterogeneity in the mode of presentation, underlying aetiologies, and clinical outcome with impact on a wide range of age groups which lead to diagnostic challenges. Cardiovascular magnetic resonance (CMR) is the preferred imaging modality in the diagnostic work-up of those with acute myocarditis. There is a need for systematic analytical approaches to improve diagnosis. Artificial intelligence (AI) and machine learning (ML) are increasingly used in CMR and has been shown to match human diagnostic performance in multiple disease categories. In this review article, we will describe the role of CMR in the diagnosis of acute myocarditis followed by a literature review on the applications of AI and ML to diagnose acute myocarditis. Only a few papers were identified with limitations in cases and control size and a lack of detail regarding cohort characteristics in addition to the absence of relevant cardiovascular disease controls. Furthermore, often CMR datasets did not include contemporary tissue characterisation parameters such as T1 and T2 mapping techniques, which are central to the diagnosis of acute myocarditis. Future work may include the use of explainability tools to enhance our confidence and understanding of the machine learning models with large, better characterised cohorts and clinical context improving the diagnosis of acute myocarditis.

Mapping threatened Thai bovids provides opportunities for improved conservation outcomes in Asia.

Wild bovids provide important ecosystem functions as seed dispersers and vegetation modifiers. Five wild bovids remain in Thailand: gaur (Bos gaurus), banteng (Bos javanicus), wild water buffalo (Bubalus arnee), mainland serow (Capricornis sumatraensis) and Chinese goral (Naemorhedus griseus). Their populations and habitats have declined substantially and become fragmented by land-use change. We use ecological niche models to quantify how much potential suitable habitat for these species remains within protected areas in Asia and then specifically Thailand. We combined species occurrence data from several sources (e.g. mainly camera traps and direct observation) with environmental variables and species-specific and single, large accessible areas in ensemble models to generate suitability maps, using out-of-sample predictions to validate model performance against new independent data. Gaur, banteng and buffalo models showed reasonable model accuracy throughout the entire distribution (greater than or equal to 62%) and in Thailand (greater than or equal to 80%), whereas serow and goral models performed poorly for the entire distribution and in Thailand, though 5 km movement buffers markedly improved the performance for serow. Large suitable areas were identified in Thailand and India for gaur, Cambodia and Thailand for banteng and India for buffalo. Over 50% of suitable habitat is located outside protected areas, highlighting the need for habitat management and conflict mitigation outside protected areas.

The Influence of Obesity on Cholecystectomy Outcomes: A Systematic Review of Laparoscopic and Open Approaches.

This systematic review evaluates the impact of obesity on the outcomes of laparoscopic versus open cholecystectomy, analyzing data from five key studies. The review explores differences in operative times, complication rates, conversion rates, and recovery times among obese patients undergoing these surgical procedures. The findings indicate that while laparoscopic cholecystectomy in obese patients tends to require longer operative times, it does not significantly increase complication rates compared to open cholecystectomy. However, the risk of conversion to open surgery is modestly elevated. The review highlights the necessity for surgical guidelines to adapt to the challenges posed by obesity, recommending advanced training and innovative technologies to improve surgical outcomes. Limitations such as study design heterogeneity and variability in defining obesity underscore the need for further research. This review contributes to optimizing surgical care strategies and improving patient outcomes in the growing demographic of obese surgical patients.

The Association Between Periodontal Disease and Cardiovascular Disease: Insights From Imaging, Observational, and Genetic Data.

Background: Periodontal disease is the sixth most common disease worldwide and may be a contributory risk factor for cardiovascular disease (CVD). Objectives: This study utilizes noninvasive cardiac imaging and longitudinal and genetic data to characterize the association between periodontal disease and both cardiovascular magnetic resonance (CMR) imaging biomarkers of remodeling and incident coronary artery disease (CAD). Methods: From the UK Biobank, 481,915 individuals were included, 91,022 (18.9%) of whom had self-reported periodontal disease. For imaging analysis, 59,019 had paired CMR data. Multivariable linear regression models were constructed to examine the association of periodontal disease on CMR outcomes. The endpoints for the CMR analyses were left ventricle (LV) end-diastolic volume, LV ejection fraction, LV mass, LV mass:volume ratio, LV global longitudinal strain, and native T1 values. The relationship between periodontal disease and CVD was assessed using Cox proportional hazards regression models, with incident CAD as the endpoint. To examine the relationship of genetically determined periodontal disease on CAD, a genome-wide polygenic risk score was constructed. Results: Periodontal disease was associated with a significantly higher LV mass:volume ratio (effect size: 0.00233; 95% CI: 0.0006-0.004) and significantly lower T1 values (effect size: -0.86 ms; 95% CI: -1.63 to -0.09). Periodontal disease was independently associated with an increased hazard of incident CAD (HR: 1.09; 95% CI: 1.07-1.13) at a median follow-up time of 13.8 years. Each SD increase in the periodontal disease polygenic risk score was associated with increased odds of CAD (OR: 1.03; 95% CI: 1.02-1.05). Conclusions: Using an integrated approach across imaging, observational, and genomic data, periodontal disease is associated with biomarkers of subclinical remodeling as well as incident CAD. These findings highlight the potential importance of periodontal disease in the broader context of CVD prevention.

Metabolomic profile of cerebrospinal fluid from patients with diffuse gliomas.

BACKGROUND: Diffuse gliomas are among the most common brain tumors in adults and are associated with a dismal prognosis, especially in patients with glioblastoma. To date, tumor tissue acquisition is mandatory for conclusive diagnosis and therapeutic decision-making. In this study, we aimed to identify possible diagnostic and prognostic biomarkers in cerebrospinal fluid (CSF) and blood. METHODS: During glioma surgery at our institution, CSF and blood samples were collected from patients. Subsequently, targeted metabolomics analysis was used to detect and quantify circulating metabolites. The metabolome profiles of glioma patients were compared with those of patients in a control group who had undergone neurosurgery for other entities, such as nonglial tumors or hydrocephalus, and were correlated with established glioma diagnostic molecular markers. RESULTS: In this study, a total of 30 glioma patients were included, along with a control group of 21 patients without glioma. Serum metabolomic analysis did not detect any significant differences between the groups, whereas CSF-metabolome analysis revealed increased levels of six metabolites in glioma patients. Among these, the most pronounced differences were found for the biogenic amine putrescine (p = 0.00005). p-Cresol sulfate was identified as a potential CSF marker for determining isocitrate dehydrogenase (IDH) status in glioma patients (p = 0.0037). CONCLUSION: CSF-metabolome profiling, unlike blood profiling, shows promise as a diagnostic tool for glioma patients with the potential to assign molecular subtypes. The next step will involve a larger multicenter study to validate these findings, with the ultimate objective of integrating CSF metabolomics analysis into clinical practice.

Body appreciation is associated with optimism/pessimism in patients with chronic kidney disease: Results from a cross-sectional study and validation of the Arabic version of the Optimism-Pessimism Short Scale-2.

BACKGROUND: Chronic Kidney Disease (CKD) patients encounter many obstacles that affect their physical and psychological well-being. The primary objective of the present study was to investigate potential correlates of optimism/pessimism in a sample of patients with CKD, including socio-demographics, body appreciation and disordered eating symptoms. As a secondary objective, we proposed to examine the psychometric properties of an Arabic translation of the Optimism-Pessimism Short Scale-2 (SOP2) before its use in our sample. METHODS: A cross-sectional study was carried out between April and May 2023, enrolling 108 participants from three hospitals in Lebanon providing insights into their sociodemographic characteristics, physical activity levels, body appreciation, optimism, pessimism, and eating attitudes. RESULTS: Results indicated that the Arabic-language adaptation of the SOP2 has good reliability coefficients. The two facets of the scale displayed a strong correlation to each other, and highly similar correlations with external study variables (i.e., household crowding index, physical activity, body appreciation, disordered eating), suggesting that the SOP2 can be interpreted as a unidimensional measure for the psychological dispositional optimism as proposed by the developers. Furthermore, findings revealed a strong positive correlation between body appreciation and optimism, suggesting that CKD patients who appreciate their bodies tend to exhibit a more optimistic outlook on life. Conversely, higher body appreciation is associated with lower pessimism, indicating that a positive body image may mitigate feelings of hopelessness and despair in CKD patients. CONCLUSION: This study contributes to the literature in two ways. First, it offers the Arabic SOP2 as an brief tool to administer, and psychometrically sound instrument that can be useful for clinical and research purposes. Second, it unveils a clear correlation between higher body appreciation and a more optimistic, less pessimistic mindset in patients with CKD.

Hematopoietic Stem Cell Fates and the Cellular Hierarchy of Mammalian Hematopoiesis: from Transplantation Models to New Insights from in Situ Analyses.

Hematopoiesis is the process that generates the cells of the blood and immune system from hematopoietic stem and progenitor cells (HSPCs) and represents the system with the most rapid cell turnover in a mammalian organism. HSPC differentiation trajectories, their underlying molecular mechanisms, and their dysfunctions in hematologic disorders are the focal research questions of experimental hematology. While HSPC transplantations in murine models are the traditional tool in this research field, recent advances in genome editing and next generation sequencing resulted in the development of many fundamentally new approaches for the analyses of mammalian hematopoiesis in situ and at single cell resolution. The current review will cover many recent developments in this field in murine models, from the bulk lineage tracing studies of HSPC differentiation to the barcoding of individual HSPCs with Cre-recombinase, Sleeping Beauty transposase, or CRISPR/Cas9 tools, to map hematopoietic cell fates, together with their transcriptional and epigenetic states. We also address studies of the clonal dynamics of human hematopoiesis, from the tracing of HSPC clonal behaviours based on viral integration sites in gene therapy patients to the recent analyses of unperturbed human hematopoiesis based on naturally accrued mutations in either nuclear or mitochondrial genomes. Such studies are revolutionizing our understanding of HSPC biology and hematopoiesis both under homeostatic conditions and in the response to various forms of physiological stress, reveal the mechanisms responsible for the decline of hematopoietic function with age, and in the future may advance the understanding and management of the diverse disorders of hematopoiesis.