Hereditary Hemorrhagic Telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is a rare and inherited vascular disorder, characterized by the development of arteriovenous malformations (AVMs) in various organs and telangiectasia (small AVM) in the mucocutaneous. The majority of HHT patients have haploinsufficiency of genes involved in the transforming growth factor-beta (TGFβ) signaling pathway, including endoglin (ENG), activin receptor-like kinase 1 (ALK1, also known as ACVRL1), or SMAD4. Active angiogenesis is also required for telangiectasia and AVM development. Anti-angiogenic strategies have been tested in patients and animal models extensively. However, the exact mechanisms for telangiectasia and AVM development remain unclear. In this review, we discuss recent advances in identifying disease mechanisms, and potential therapeutic targets.

The 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, also known as statins, are administered as first-line therapy for hypercholesterolemia, both as primary and secondary prevention. Besides the lipid-lowering effect, statins have been suggested to inhibit the development of cardiovascular disease through anti-inflammatory, antioxidant, vascular endothelial function-improving, plaque-stabilizing, and platelet aggregation-inhibiting effects. The preventive effect of statins on atherothrombotic stroke has been well established, but statins can influence other cerebrovascular diseases. This suggests that statins have many neuroprotective effects in addition to lowering cholesterol. Furthermore, research suggests that statins cause pro-apoptotic, growth-inhibitory, and pro-differentiation effects in various malignancies. Preclinical and clinical evidence suggests that statins inhibit tumor growth and induce apoptosis in specific cancer cell types. The pleiotropic effects of statins on cardiovascular and cerebrovascular diseases have been well established; however, the effects of statins on cancer patients have not been fully elucidated and are still controversial. This review discusses the recent evidence on the effects of statins on cardiovascular and cerebrovascular diseases and cancer. Additionally, this study describes the pharmacological action of statins, focusing on the aspect of ‘beyond lipid-lowering.’

Abstract: Endoglin (ENG) is a causative gene of type 1 hereditary hemorrhagic telangiectasia (HHT1). HHT1 patients have arteriovenous malformations (AVMs) in multiple organs, including the brain. In mice, Eng deletion induced by R26RCreER or SM22aCre leads to AVM development in the brain and other organs. We have reported that the severity of brain AVM in mice with activin receptor-like kinase 1 (Alk1, an HHT2 causative gene) mutation is correlated with the number of Alk1 negative endothelial cells (ECs). We hypothesized that increase of Eng negative ECs will enhance AVM severity. To increase EC Eng deletion, we used a codon improved cre (icre), which is more potent in recombination of floxed alleles than the wild type (WT) cre. R26RCreER;Eng^f/f mice that have Rosa promoter driving and tamoxifen (TM) inducible WT cre expression globally and PdgfbiCreER;Eng^f/f that have Pdgfb promoter driving and TM inducible icre expression in ECs were treated with 3 intra-peritoneal injections of TM (2.5 mg/25g of body weight) to delete Eng globally or in the ECs. AAV-VEGF was stereotactically injected into the brain to induce brain focal angiogenesis and brain AVM. We found that iCre caused more Eng deletion in the brain indicated by lower level of Eng proteins (p<0.001) and fewer Eng positive ECs (p=0.01) than mice with WT cre. Mice with iCre mediated Eng deletion have more abnormal vessels (p=0.02), CD68⁺ macrophages (p=0.002), and hemorrhage (p=0.04), and less vascular pericyte and smooth muscle coverage than mice with WT cre. In addition, arteriovenous shunts were detected in the intestines of icre mice, a phenotype that have not been detected in WT cre mice before. RNAseq analysis showed that 8 out of the 10 top upregulated pathways identified by Gene Ontology (GO) analysis are related to the inflammation. Therefore, increase of Eng deletion in ECs exacerbates AVM severity, which is associated with enhanced inflammation. Strategies that can reduce Eng negative ECs could be used to develop new therapies to reduce AVM severity for HHT1 patients.

Wall Shear Stress (WSS) abnormalities in carotid artery blood flow are key hemodynamic factors leading to arterial endothelial damage, atherosclerotic plaque formation, and carotid artery stenosis. Precise simulation of carotid artery blood flow WSS in vitro play an important role in understanding the underlying hemodynamic mechanism of carotid artery stenosis. This study presents a design for a microfluidic cell culture chamber with a variable cross-section and a step structure, leveraging microfluidic technology and principles of fluid dynamics. We propose an optimization strategy for microchannel dimensions based on Computational Fluid Dynamics (CFD) simulations. This strategy aims to replicate the distinct WSS waveform features found at various locations within the carotid bifurcation as observed in vivo. Our simulations indicate that with a step height of 0.09 mm, a width of 4 mm for the initial segment, and 5 mm for the subsequent wider channel, the device can effectively model the characteristics of low oscillatory WSS seen at sites of carotid sinus stenosis. Furthermore, it accurately represents the high-magnitude pulsatile WSS waveforms in the more uniform arterial sections downstream of the carotid sinus. The study also reveals that vortex formation and variations in low oscillatory WSS within the stepped section of the microchannel correlate with the step's height and width, as well as with the dimensions of the wider channel section. An increase in step width leads to a decrease in both the vortex area and the magnitude of negative WSS oscillations. When the step height is less than 0.03 mm, vortex formation is inhibited, challenging the simulation of low oscillatory WSS patterns. The variable cross-section microfluidic channel developed in this study provides a platform for simulating carotid artery WSS waveforms and facilitates research into the interplay between low oscillatory WSS at sites of carotid sinus stenosis and arterial endothelial dysfunction.

Background: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. Methods: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from Surveillance Epidemiology and End Results database with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general US population. Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. Results: A total of 563298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during study period. While age and surgery positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, more recent year (2001-2015) of diagnosis as well as multiple primary or distant tumors experienced a lower risk of CVSM. Interpretation: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM, which may be helpful for risk stratification and therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Not in the history of transmissible illnesses has there been an infection as strongly associated with acute cerebrovascular disease as the novel human coronavirus, SARS-CoV-2. While the risk of stroke has known associations with other viral infections, such as influenza and human immunodeficiency virus, the risk of ischemic and hemorrhagic stroke related to SARS-CoV-2 is unprecedented. Furthermore, the coronavirus disease 2019 (COVID-19) pandemic has so profoundly impacted psychosocial behaviors and modern medical care that we have witnessed shifts in epidemiology and have adapted our treatment practices to reduce transmission, address delayed diagnoses, and mitigate gaps in health care. In this narrative review, we summarize the history and impact of the COVID-19 pandemic on cerebrovascular disease, and lessons learned regarding the management of patients as we endure this period of human history.

Background: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 to 2019. The in-hospital mortality rates, length of stay (LoS) and healthcare costs were determined. Results: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p&lt;0.001). The estimated total care cost for all patients with T1DM with CCD was approximately US $326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77) and stroke (OR 1.47, 95%CI 1.04-2.09). Conclusions: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

Alzheimer’s disease (AD) is an age-associated neurodegenerative disorder. A wealth of evidence indicates that the amyloid β (Aβ) aggregates result from dyshomeostasis between Aβ production and clearance, which plays a pivotal role in the pathogenesis of AD. Consequently, therapies targeting Aβ reduction represent a promising strategy of AD intervention. Tetramethylpyrazine nitrone (TBN) is a novel tetramethylpyrazine derivative with the potential for the treatment of AD. Previously, we demonstrated that TBN markedly improved cognitive functions and reduced Aβ, APP, BACE 1 and hyperphosphorylated tau levels in 3 × Tg-AD mice. However, the mechanism by which TBN inhibits Aβ deposition still unclear. In this study, we employed the APP/PS1 mice treated with TBN (60 mg/kg, ig, bid) for six months and N2a/APP695swe cells treated with TBN (300 μM) to explore the mechanism of TBN on the Aβ reduction. Our results indicated that TBN significantly alleviated cognitive impairment and reduced Aβ depositions in APP/PS1 mice. Further investigation of the underlying mechanisms revealed that TBN decreased the expression of APP and BACE1, activated the AMPK/mTOR/ULK1 autophagy pathway and inhibited the PI3K/AKT/mTOR/ULK1 autophagy pathway, as well as decreased the phosphorylation levels of JNK and ERK in APP/PS1 mice. Moreover, TBN was found to significantly reduce the mRNA levels of APP and BACE1, as well as those of SP1, CTCF, TGF-β, and NF-κB, transcription factors involved in regulating gene expression. Additionally, TBN was observed to decrease the level of miR-346 and increase the levels of miR-147 and miR-106a in the N2a/APP695swe cells. These findings indicate that TBN may reduce Aβ levels likely via reducing APP expression by regulating APP gene transcriptional factors and miRNAs, reducing BACE1 expression, and promoting autophagy activities.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

Background: We evaluate the genetic and phenotypic features of a cohort of 12 Italian patients affected by Retinitis Pigmentosa (RP) associated with RP1 sequence variants.; Methods: Retrospective, single center study (Careggi Hospital, Florence), including a cohort of twelve Italian patients (Five male and seven female) affected by RP carrying pathogenic variants of the RP1 gene. A complete ophthalmic assessment and pedigree analysis was conducted with focus on the onset of disease symptoms, the patient’s age at the first diagnosis, the follow up duration and the possible presence of comorbidities; Results: The mean age at onset of symptoms was 31,0 ± 24,1 years old, with a mean follow-up period of 9,1± 2,4 years. The main symptoms at presentation were hemeralopia and visual field constriction. Fundus evaluation revealed a classic type of RP. Fundus autofluorescence (FAF), Optical Coherence Tomography (OCT), Electroretinogram (ERG), and visual field confirmed in most of the cases the typical features of classic retinitis pigmentosa.; (4) Conclusions: This single-center cohort of Italian patients provided information on the clinical and genetic features of RP1-associated RP. By comprehensively clarifying the genetic variations and their associated clinical manifestations, we can better tailor therapeutic interventions aimed at targeting specific genetic abnormalities. This ultimately promises to improve the prognosis and quality of life for individuals with RP-associated RP1.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (Pi*M, Pi*S, Pi*Z) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. Methods: We performed a prospective study in 5 referral centers for HIV care in Italy. PLHIV who consented to participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI that started chemoprophylaxis were followed until the ending of therapy. Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, 6 were lost to follow-up before discriminating between latent and active TB. Among PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

Conventional cancer clinical trials can be time-consuming and expensive, often yielding results with limited applicability to real-world scenarios and presenting challenges for patient participation. Real-world data (RWD) studies offer a promising solution to address evidence gaps and provide essential information about the effects of cancer treatments in real-world settings. Defining RWD based on its original intent, which is the collection of data at the point of care for clinical purposes, can distinguish it from conventional clinical trial data. RWD can be generated using experimental designs that resemble those used in conventional clinical trials, but with several advantages, such as improved efficiency and a better balance between internal and external validity. RWD can support pharmacovigilance, insights into disease progression, and the development of external control groups. Prospective RWD collection enables evidence generation based on pragmatic clinical trials (PCTs) that support randomized study designs and expand clinical research to the point of care. To ensure the quality of real-world studies, it is crucial to implement auditable data abstraction methods and develop new incentives to capture clinically relevant data electronically at the point of care. The treatment landscape is constantly evolving, with the integration of front-line immune checkpoint inhibitors (ICIs), either alone or in combination with chemotherapy, affecting subsequent treatment lines. Real-world effectiveness and safety in underrepresented populations, such as the elderly, patients with poor performance status (PS), hepatitis, or human immunodeficiency virus-infected patients, are still largely unexplored. Similarly, the cost-effectiveness and sustainability of these innovative agents are important considerations in the real world.

This study delves into the dynamic field of medical education research, emphasizing the integration of research training within medical curricula. It seeks to understand the impact of such integration on the competencies of future medical professionals. The primary aim is to systematically categorize and analyze the current trends and future directions in medical education research. This involves assessing the influence of research training on medical students' skills and the methodologies used in such research. Methods: The research employs an extensive bibliographic literature review across multiple databases. It classifies studies into categories like experiential or case studies, editorials, and original research articles. This classification is based on criteria such as geographical location, research objectives, theoretical frameworks, and methodologies. Results: Findings reveal a diverse landscape in medical education research, with a significant emphasis on research training. The research showcases varying methodologies and approaches used globally, highlighting the thematic focus and geographical distribution of these studies. Conclusion: Medical education research is a globally expansive and evolving field. It underscores the importance of continuous investigation, particularly focusing on integrating research elements at curricular levels and exploring innovative educational strategies. The study also points out potential gaps in research, especially in underrepresented regions, indicating directions for future research efforts.

Pulmonary hypertension (PH) is a progressive and potentially fatal complication of sickle cell disease (SCD) affecting 6-10% of adult SCD patients. Various mechanisms and theories have been evaluated to explain the pathophysiology of the disease. However, questions remain, particularly regarding the clinical heterogeneity of the disease in terms of symptoms, complications, and survival. Beyond the classical mechanisms that have been thoroughly investigated and include hemolysis, nitric oxide availability, endothelial disorders, thrombosis, and left heart failure, attention is focused nowadays on the potential role of the genes involved in such processes. Potential candidate genes are investigated through next-generation sequencing, with the TGF-β pathway being the initial target. This field of research may also provide novel targets for pharmacologic agents in the future as is already the case with idiopathic PH. The collection and processing of data and samples from multiple centers can yield safe results that will allow a better understanding of SCD-related PH as a part of the disease’s clinical spectrum. The following review attempts to capture the most recent findings of studies on gene polymorphisms that have been associated with PH in SCD patients.

Interferon-gamma (IFN-γ) is an important cytokine in host defense against tuberculosis infection. In some cases, administration of IFN-γ during tuberculosis infection can promote faster cure. In the present work, we have shown that in a mouse model, human interferon-gamma, exhibits some anti-tuberculosis activity, especially in combination with isoniazid.

This study is aimed to assess the prevalence of Coxiella burnetii infection among veterinary medicine students from two Bulgarian Universities, located in Sofia and Stara Zagora. A total of 185 veterinary students blood samples were collected and tested for the detection of C. burnetii phase II antibodies and presence of DNA using an enzyme-linked immunosorbent assay (ELISA) and end-point PCR test, respectively. Out of all samples, 29.7% were positive for at least one C. burnetii phase II antibody marker or by PCR test. Veterinary students from Stara Zagora showed significantly seropositive status of Q fever (33.6%), then those who studied in Sofia (23%). The evidence for recent exposition with detection of anti-C. burnetii IgM (+) antibodies had 14.6%. Seroprevalence among students in Stara Zagora was higher (15.3%). Anti-C. burnetii phase II IgG antibodies were detected in 21.6% examined samples. Our study revealed a higher seropositivity among male students (32.8%) as compared to the female ones (16.0%). End-point PCR assay detected as positive 5.9% blood samples. The relative risk (RR) of Q fever exposure for male students was 40.7%, whereas for female (24.6%). Findings from this study indicated that the C. burnetii infection is widely distributed amongst veterinary students from Bulgaria. The study emphasizes the need for improved safety protocols and infection control measures in veterinary training programs.

Extracellular vesicles (EVs) hold enormous potential in the diagnosis and treatment of diseases, benefit from their roles in intercellular signaling, as well as their plentiful presence and stability in body fluids. However, conventional EV isolation methods are labor-intensive, and harvest EVs with low purity and compromised recovery. In addition, the drawbacks, such as limited sensitivity and specificity of traditional EV analysis methods hinder the application of EVs in clinical use. Therefore, it is urgent to develop effective and standardized methods for isolating and detecting EVs. Microfluidics technology is a powerful and rapidly developing technology that has been introduced as a potential solution for the above bottlenecks. It holds the advantages of high integration, short analysis time, low consumption of samples and reagents. In this review, we summarize the traditional techniques alongside microfluidic-based methodologies for the isolation and detection of EVs. We emphasize the separation advantages of microfluidic technology in enhancing EV capture efficiency and precise targeting, while summarizing its analytical role in targeted detection and discussing the significance of EV detection in the tumor microenvironment, providing a direction for achieving automated and high-throughput EV detection in clinical samples.

M184V is a single-base mutation in the YMDD domain of reverse transcriptase (RT). The M184V resistance-associated mutation is related to virological unresponsiveness to lamivudine (3TC) and emtricitabine (FTC) and induces high-level resistance to these two antiretroviral agents. M184V is rapidly selected in the setting of non-suppressive antiretroviral therapy (ART) and accumulates in the HIV reservoir. There were continuous efforts to evaluate the impact of M184V mutation on the treatment outcomes in people with HIV (PWH). Since lamivudine remains an extensively used part of recommended antiretroviral combinations, M184V is commonly detected in patients with virological failure. ART guidelines do not recommend the use of drugs impacted by resistance-associated mutations as they have been confirmed to comprise a risk factor for virological failure. However, previous authors suggest that 3TC/FTC can remain active even in the presence of M184V. Obtaining the viral resistance profile for each individual both treated or ART-naïve is a key challenge for lifelong treatment management.Given the potential benefits of lamivudine in the ART combinations, the investigation of M184V remains of high interest for clinicians and researchers. This is a review of literature for the challenges in treating both naïve and experienced individuals carrying the M184V resistance mutation, including virological failure, virological suppression, and resistance to ART.

Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

This study aimed to evaluate the impact of Candida albicans on subgingival biofilm formation on dental implant surfaces. Scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) were used to compare biofilm structure and microbial biomass in the presence and absence of the fungus after periods of 24, 48, and 72 h. Quantitative polymerase chain reaction (qPCR) was used to quantify the number of viable and total micro-organisms for each of the biofilm-forming strains. A general linear model was applied to compare CLSM and qPCR results between control and test conditions. The biofilm developed with C. albicans at 72 h had a higher bacterial biomass, with a significantly higher cell viability (p &lt; 0.05). After both 48 and 72 h of incubation, in the presence of C. albicans, there was a significant increase in counts of Fusobacterium nucleatum and Porphyromonas gingivalis and in the cell viability of Streptococcus oralis, Aggregatibacter actinomycetemcomitans, F. nucleatum, and P. gingivalis. Using a dynamic in vitro multispecies biofilm model, C. albicans exacerbated the development of the biofilm grown on dental implant surfaces, significantly increasing the number and cell viability of periodontal bacteria.

Dried blood spot (DBS) testing on confetti is one of the most common methods used to collect and extract DNA from field samples for molecular epidemiology of malaria studies. Here, we investigated whether ethanol or other solutions used to clean scissors are a source of sample contamination. DBS were prepared from 3 drops of blood from two Plasmodium falciparum cultures spotted on confetti, and 3 solutions (water, ethanol and DNase) were used to clean scissors between spots during DNA extraction. For each cleaning solution, two blank confetti were used as negative controls. Samples were analyzed by PCR-based genotyping of merozoite surface proteins 1 & 2 (msp-1 and msp-2), and P. falciparum chloroquine resistance transporter (Pfcrt). A total of 15 samples were analyzed. Based on msp-1 and msp-2 amplification, P. falciparum was detected on blank confetti when scissors were washed with ethanol. Based on Pfcrt amplification, DNA of P. falciparum was detected on blank confetti when scissors were cleaned with ethanol or water. No P. falciparum genes were detected on blank confetti when scissors were cleaned with DNase. Scissors cleaned with DNase prevented cross-contamination between samples during processing of dried blood spots, whereas ethanol (which is commonly used) fails to avert cross-contamination.

Background: Large-cell neuroendocrine carcinoma presents significant treatment challenges owing to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were treated with ei-ther standard chemotherapy plus atezolizumab or standard chemotherapy alone. The primary outcomes measured were progression-free survival (PFS) and overall survival (OS), with an ex-ploratory analysis of miR375 in plasma as a potential biomarker. Results: Of the 22 screened patients, 17 met the inclusion criteria and were stratified into the atezolizumab and chemotherapy (n=10) or chemotherapy alone(n=7) groups. After a median follow-up of 23.3 months, the 12-month survival rate for the atezolizumab group was 57.1% (95% CI: 32.6%-100%) and 45.7% at 24 months (95% CI: 22.4%-93.2%). In contrast, the chemotherapy group had a 14.3% survival rate at both 12 and 24 months (95% CI: 2.33%-87.7%). The log-rank test for survival showed a statistically significant difference in the atezolizumab-treated group (chi-squared = 4, df = 1, p = 0.04). A non-significant correlation was found between disease pro-gression and elevated levels of miR375. Conclusions: This pilot study suggests that atezolizumab combined with chemotherapy may be effective in treating metastatic LCNEC. The non-significant correlation between plasma miR375 levels and disease progression suggests its biomarker potential, warranting further validation research.

In the majority of children with growth hormone (GH) deficiency (GHD), normal GH secretion may occur before the attainment of final height. The aim of the study was to assess the incidence of persistent and transient GHD and the effectiveness of recombined human GH (rhGH) therapy in children with isolated idiopathic GHD, with respect to the moment of therapy withdrawal and according to different diagnostic criteria of GHD. Analysis included 260 patients (173 boys, 87 girls) with isolated idiopathic GHD who completed rhGH therapy and have reassessed GH and IGF-1 secretion. The incidence of transient GHD with respect to different pre- and post-treatment criteria was compared together with assessment of GH therapy effectiveness. Incidence of transient GHD, even with respect to pediatric criteria was very high. Normal GH secretion occurred before the attainment of near-final height. Application of more restricted criteria decreased the number of children diagnosed with GHD but not the incidence of transient GHD among them. Poor response to GH therapy was observed mainly in patients with normal IGF-1 before treatment, suggesting that diagnosis of GHD may be false positive. Further efforts should be made to avoid overdiagnosis GHD and overtreatment of the patients.

Background Sarcopenia is a state with progressive and generalized loss of skeletal muscle mass and strength. It is a serious complication occurring in chronic kidney disease (CKD) patients which increases morbidity and mortality rate. Sarcopenia is diagnosed when loss of both compartments - muscle strength and skeletal muscle quality or quantity are present. However, there are still numerous patients, also with CKD, diagnosed as pre-sarcopenic individuals with low muscle strength and normal skeletal muscle quality or quantity and conversely, with correct muscle strength and decreased skeletal muscle mass, who are prone to develop sarcopenia in future life. It is crucial to examine numerous variables possibly associated with changes of skeletal muscle mass and muscle strength in terms of preventing the development of sarcopenia. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in advanced stages of CKD. Methods The study sample consisted of 84 non-dialysis dependent patients of both sexes (including 45.2% of women) with eGFR < 45 ml/min/1.73m²: 26.2% with eGFR 30-44 mL/min/1.73 m², 65.5% with eGFR 15-29 mL/min/1.73 m² and 8.3% with eGFR < 15 mL/min/1.73 m². Muscle strength was estimated by measuring hand grip strength (HGS) with the use of handheld hydraulic dynamometer. Muscle quantity was measured by bioimpedance spectroscopy using Body Composition Monitor. Appendicular skeletal muscle mass (ASM) was calculated according to Lin’s formula. Serum creatinine, urea, uric acid and albumin were measured. Results In bivariate analysis we found that ASM significantly and positively correlated with anthropometric variables such as body mass (r=0.903, p<0.001), NH weight (r=0.882, p<0.001), height (r=0.694, p<0.001), body mass index (BMI) (r=0.701, p<0.001), lean tissue mass (LTM) (r=0.664, p<0.001), lean tissue index (LTI) (r=0.433, p<0.001), fat mass (r=0.614, p<0.001) and fat tissue index (FTI) (r=0.449, p<0.001), and was negatively associated with clinical variable such as hydration status (p<0.001). HGS significantly and positively correlated with anthropometric parameters such as body mass (r=0.319, p=0.003), NH weight (r=0.315, p=0.004), height (r=0.666, p<0.001), LTM (r=0.490, p<0.001), LTI (r=0.238, p=0.029), and ASM (r=0.501, p<0.001), and was negatively associated with clinical variables like uric acid (p=0.039) and urea (p<0.001). After adjustment for age, sex and height, HGS remained significantly and negatively related with uric acid (β=-1.078, p=0.041) and hydration status (β=-0.805, p=0.042). Conclusions In CKD patients, ASM is determined mainly by anthropometric parameters but HGS - both by anthropometric and clinical variables specific for CKD.

The global antibiotic resistance crisis, driven by antibiotic overuse and misuse, is multifaceted. This study aimed to assess the microbiological and genetic characteristics of raw retail pork meat, including the isolation, antibiotic susceptibility testing (AST), whole genome sequencing (WGS) of selected indicator bacteria, antibiotic residue testing, and metagenomic sequencing. Samples were purchased from 10 randomly selected retail stores in Gauteng, South Africa. Samples were aseptically separated, with a portion sent to an external laboratory for isolating indicator bacteria and antibiotic residue testing. Identification of the isolated bacteria was reconfirmed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). AST was performed using the Microscan Walkaway system. WGS and metagenomic sequencing were performed using the Illumina NextSeq 550 instrument. The isolated E. coli and enterococci exhibited little phenotypic resistance, with WGS revealing tetracycline resistance genes. Isolated bacteria and meat samples all harboured tetracycline resistance genes, and the antibiotic residue concentrations were within acceptable limits for human consumption. In the metagenomic context, most identified bacteria were of food/meat spoilage and environmental origin, with the resistome analysis primarily indicating beta-lactam, tetracycline and multidrug resistance genes. Further research is needed to understand the broader implications of these findings on environmental health and antibiotic resistance.

Carbapenemase-producing Enterobacter spp. Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (CP-ESCPM) are increasingly identified as causative agents of nosocomial infections but are still not under systematic genomic surveillance. In this study, using a combination of whole genome sequencing and conjugation experiments, we sought to elucidate the genomic characteristics and transferability of resistance genes in clinical CP-ESCPM isolates from Bulgaria. Among the 36 sequenced isolates, NDM-1 (12/36), VIM-4 (11/36), VIM-86 (8/36) and OXA-48 (7/36) carbapenemases were identified; two isolates carried both NDM-1 and VIM-86. The majority of carbapenemase genes were found on self-conjugative plasmids. IncL plasmids were responsible for the spread of OXA-48 among E. hormaechei, C. freundii and S. marcescens. IncM2 plasmids were generally associated with the spread of NDM-1 in C. freundii and S. marcescens, and also of VIM-4 in C. freundii. IncC plasmids were involved in the spread of the recently described VIM-86 in P. stuartii isolates. IncC plasmids carrying blaNDM-1 and blaVIM-86 have been observed too. blaNDM-1 was also detected on IncX3 in S. marcescens and on IncT plasmid in M. morganii. The significant resistance transfer rates highlight the role of the ESCPM group as a reservoir of resistance determinants and stress the need for strengthening the infection control measures.

The article presents the case of a 27-year-old female patient with idiopathic congenital complete heart block who was referred by her primary care physician for cardiological evaluation. The conduction disturbance was recognized at the age of 6 years and was asymptomatic. The disqualification from pacemaker implantation included detailed history of a patient’s symptoms, echocardiographic assessment of the heart, exercise testing and ECG Holter monitoring. The aid of salbutamol administered orally was also useful.

Neurological disorders are the leading cause of cognitive and physical disability worldwide, affecting 15% of the global population. Due to the demographics of aging, the prevalence of neurological disorders, including neurodegenerative diseases, will double over the next two decades. Unfortunately, while available therapies provide symptomatic relief for cognitive and motor impairment, there is an urgent unmet need to develop disease-modifying therapies that slow the rate of pathological progression. In that context, biomarkers could identify at-risk and prodromal patients, monitor disease progression, track response to therapy, and parse causality of molecular events to identify novel targets for further clinical investigation. Thus, identifying biomarkers that discriminate between diseases and reflect specific stages of pathology would catalyze the discovery and development of therapeutic targets. This review will describe the prevalence, known mechanisms, ongoing or recently concluded therapeutic clinical trials, and biomarkers of three of the most prevalent neurodegenerative diseases, including Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), and Parkinson’s disease (PD).

Determining the genetic contribution of susceptibility to severe SARS-CoV-2 infection outcomes is important for public health measures and individualized treatment. Through intense research on this topic, several hundred genes have been implicated as possibly contributing to the severe infection phenotype(s); however, the findings are complex and appear to be population-dependent. We aimed to determine the contribution of human rare genetic variants associated with a severe outcome of SARS-CoV-2 infections and their burden in the Slovenian population. A panel of 517 genes associated with severe SARS-CoV-2 infection were obtained through an extensive review of the literature, and additionally included target genes identified by the COVID-19 Host Genetic Initiative, as well as the curated Research COVID-19 associated genes from PanelApp, England Genomics. Whole genome sequencing was performed using PCR-free WGS on DNA from 60 patients hospitalized due to severe COVID-19 disease, and the identified rare genomic variants were analyzed and classified according to the ACMG criteria. Background prevalence in the general Slovenian population was determined by comparison with sequencing data from 8025 individuals included in the Slovenian genomic database (SGDB). Results show that several rare pathogenic/likely pathogenic genomic variants in genes CFTR, MASP2, MEFV, TNFRSF13B, and RNASEL likely contribute to the severe infection outcomes in our patient cohort. These results represent an insight into the Slovenian genomic diversity associated with severe COVID-19 outcome.

Immune checkpoint inhibitors (ICI’s) are in the forefront of advanced Non Small Cell Lung Cancer (NSCLC) treatment. Still, only 27- 46% of patients respond to initial therapy with ICI’s and of those, up to 65% develop resistance within four years. After disease progression (PD), treatment options are limited, with 10% Objective Response Rate (ORR) to second or third-line chemotherapy. In this context, ICI rechallenge is an appealing option for NSCLC. Most data on the efficacy of ICI rechallenge are based on retrospective real-world studies of small, heavily pretreated, and heterogeneous patient groups. Despite these limitations, these studies suggest that ICI monotherapy rechallenge in unselected NSCLC patient populations who discontinued initial ICI due to PD is generally ineffective, with a median Progression-Free Survival (PFS) of 1.6-3.1 months and a Disease Control Rate (DCR) of 21.4%-41.6%. However, there is a subpopulation that benefits from this strategy, and further characterization of this subgroup is essential. Furthermore, immunotherapy rechallenge in patients who discontinued initial immunotherapy following treatment protocol completion and progressed after an immunotherapy-free interval showed promising efficacy, with a DCR of 75-81%, according to post-hoc analyses of several clinical trials. Future research of ICI rechallenge for NSCLC should focus on better patient stratification, to reflect the underlying biology of immunotherapy resistance more accurately.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

Epithelial ovarian cancer (EOC) has not significantly benefited from advances in immunotherapy, mainly because of the lack of well-defined actionable antigen targets. Using proteogenomic analyses of primary EOC tumors, we previously identified 91 aberrantly expressed tumor-specific antigens (TSAs) originating from unmutated genomic sequences. Most of these TSAs derive from non-exonic regions, and their expression results from cancer-specific epigenetic changes. The present study aimed to evaluate the immunogenicity of 48 TSAs selected according to two criteria: presentation by highly prevalent HLA allotypes and expression in a significant fraction of EOC tumors. Using targeted mass spectrometry analyses, we found that pulsing with synthetic TSA peptides leads to a high-level presentation on dendritic cells. TSA abundance correlated with the predicted binding affinity to the HLA allotype. We stimulated naïve CD8 T cells from healthy blood donors with TSA-pulsed dendritic cells and assessed their expansion with two assays: MHC-peptide tetramer staining and TCR Vβ CDR3 sequencing. We report that these TSAs can expand sizeable populations of CD8 T cells and, therefore, represent attractive targets for EOC immunotherapy.

Compared to the general population, patients with inflammatory bowel disease (IBD) are less likely to be vaccinated, putting them at an increased risk of vaccine-preventable illnesses. This risk is further compounded by the immunosuppressive therapies commonly used in IBD management. Therefore, developing new treatments for IBD that maintain immune function is crucial, as successful management can lead to better vaccination outcomes and overall health for these patients. Here, we investigate the potential of recombinant banana lectin (rBanLec) as a supporting therapeutic measure to improve IBD control and possibly increase vaccination rates among IBD patients. By examining the therapeutic efficacy of rBanLec in a murine model of experimental colitis, we aim to lay the foundation for its application in improving vaccination outcomes. After inducing experimental colitis in C57BL/6 and BALB/c mice with 2,4,6-trinitrobenzene sulfonic acid, we treated animals orally with varying doses of rBanLec 0.1-10 µg/ml (0.01 – 1 µg/dose) during the course of the disease. We assessed the severity of colitis and rBanLec’s modulation of the immune response compared to control groups. rBanLec administration resulted in a dose-dependent reduction in colitis severity (less pronounced weight loss, less shortening of the colon) and an improved recovery profile, highlighting its therapeutic potential. Notably, rBanLec-treated mice exhibited significant modulation of the immune response, favoring anti-inflammatory pathways (primarily reduction in a local [TNFα]/[IL-10]) crucial for effective vaccination. Our findings suggest that rBanLec could mitigate the adverse effects of immunosuppressive therapy on vaccine responsiveness in IBD patients. By improving the underlying immune response, rBanLec may increase the efficacy of vaccinations, offering a dual benefit of disease management and prevention of vaccine-preventable illnesses. Further studies are required to translate these findings into clinical practice.

This review article focuses on the role of Artificial Intelligence (AI) in transforming healthcare in Africa, specifically in combatting infectious diseases, neglected tropical diseases (NTDs), and antimicrobial resistance. We provide a comprehensive overview of the significance of AI in the healthcare industry, highlighting its urgency and importance in addressing these specific health challenges in Africa. We begin by discussing the role of AI in infectious disease surveillance and outbreak detection. We explore how AI technology can be employed for real-time tracking and prediction of outbreaks, providing examples of successful AI applications in infectious disease surveillance within the African context.Next, we examine the potential of AI-enabled diagnosis and treatment for faster and more accurate diagnoses of infectious diseases and NTDs. We highlight specific examples of AI applications in diagnosing and treating these diseases in Africa, showcasing the potential of AI to improve clinical outcomes and save lives.Furthermore, we focus on how AI-driven drug discovery and development can expedite the search for new treatments for infectious diseases and combat antimicrobial resistance. We present examples of AI applications in drug discovery within the African context, illustrating the potential for AI to revolutionize the development of effective therapeutics.In addition, we delve into how AI-powered public health interventions can enhance the design and implementation of targeted interventions. We explore how AI can optimize resource allocation and facilitate data-driven decision-making processes, providing examples of AI applications in public health in Africa.Finally, we address the challenges and limitations of implementing AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. We discuss potential barriers and ethical concerns surrounding AI applications in healthcare, aiming to encourage informed and responsible utilization of AI technologies.Overall, this review emphasizes the importance and potential of AI in combatting infectious diseases, NTDs, and antimicrobial resistance in Africa. It positions AI as a catalyst for revolutionizing healthcare in the region, leading to more effective disease surveillance, diagnosis, treatment, drug discovery, and public health interventions.

In Brazil, Brazilian borreliosis (BB), characterized molecularly, exhibits symptoms akin to Lyme disease (LD) but presents unique epidemiological, clinical, and morphological features. This study explores the incidence, diagnostic challenges, and awareness initiatives regarding this disease in Brazil. Employing a narrative review methodology, data were sourced from Pubmed, Ebsco, Google Scholar, and Web of Science without temporal constraints. Results reveal diagnostic complexities in Brazil due to the low sensitivity of conventional tests and the use of North American B. burgdorferi antigens. Despite challenges, epidemiological studies indicate an upswing in cases in humans and animals. Therefore, there is an urgent need to define new biomarkers, molecular strategies, or new antigenic targets to advance the development of vaccines and diagnostics. Early and accurate pathogen identification is crucial for active surveillance to comprehend and manage this zoonosis.

The domestic ducks (Anas platyrhynchos domesticus) are resistant to most of the highly pathogenic avian influenza virus (HPAIV) infections. In this study, we characterized the lung proteome and phosphoproteome of ducks infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala) at 12 hr, 48 hr and 5 days post infection condition. Total 2082 proteins were differentially expressed and 320 phosphorylation sites mapping to 199 phosphopeptides corresponding to 129 proteins were identified. Functional annotation of proteome data analysis reveals activation of RIG-I-like receptor and Jak-STAT signaling pathways, that lead to induction of interferon stimulated genes (ISGs) expression. The pathway analysis of phosphoproteome datasets also confirms the activation of RIG I, Jak-STAT signaling, NF-kappa B signaling and MAPK signaling pathways in the lung tissues. The induction of ISGs proteins (STAT1, STAT3, STAT5B, STAT6, IFIT5 and PKR) establishes protective antiviral immune response in duck lung tissue. Further, the protein-protein interaction network analysis identified proteins like AKT1, STAT3, JAK2, RAC1, STAT1, PTPN11, RPS27A, NFKB1 and MAPK1 as main hub proteins that might play important roles in disease progression in ducks. Together, functional annotation of proteome and phosphoproteome datasets reveals the molecular basis of the disease progression and disease resistance mechanism in ducks infected with HPAI H5N1 virus.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

Dementia, characterized by cognitive decline beyond age-related expectations, poses a formidable global health challenge. With an estimated 55 million individuals affected worldwide and 10 million new cases annually, dementia profoundly impacts memory, comprehension, language, and behavior. Then, the global diabetes population increased from 108 million in 1980 to 422 million in 2014, with a more rapid rise in prevalence observed in low- and middle-income countries compared to high-income countries. Individuals with diabetes have an increased risk of cognitive problems, including a higher likelihood of developing dementia, Alzheimer's disease, and vascular dementia, especially in older age. Managing diabetes through diet, physical activity, medication, and consistent screening and treatment for complications can prevent or delay its consequences.Globally ranking as the seventh leading cause of death, dementia's societal implications are substantial. The chapter delves into Mild Cognitive Impairment (MCI), a precursor to dementia, emphasizing its global epidemiological trends. Neuroimaging, particularly Functional Near-Infrared Spectroscopy (fNIRS), emerges as a non-invasive diagnostic tool, surpassing traditional imaging methods' portability. The chapter investigates the effects of non-invasive electrical stimulation on neurovascular tissues, shedding light on its impact including potential to address metaboreflex related reduced exercise tolerance. Furthermore, the chapter presents a clinical trial (ClinicalTrials.gov NCT04626453 and NCT04812288) examining the effects of a 2-month exercise program on cognitive function and muscular oxidative capacity in older adults with type 2 diabetes. The study's design, individualized exercise regimens to address muscle mechanoreflex and metaboreflex responses, and their physiological changes during exercise are discussed, offering insights into the interplay between exercise tolerance, cognition, and vascular health. The findings contribute to tailored and effective interventions for cognitive well-being. Here, our exploration extends to the application of transcranial electrical stimulation (tES) in optimizing exercise performance, with a focus on its various forms, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS). A physiological modeling approach based on the neurovascular unit (NVU) is employed, revealing potential avenues for also treating vascular dementia (often noted to have a strong association with type 2 diabetes) through tACS, guided by human-in-the-loop approaches. Here, modal analysis for control is applied to assess the NVU model's characteristic dynamics under tACS, providing a comprehensive understanding of neurovascular coupling modes.In summary, this chapter synthesizes diverse facets in type 2 diabetes comorbidity and cognitive decline, ranging from global impact and diagnostic criteria to innovative interventions like exercise and transcranial electrical stimulation. The multidisciplinary approach integrates epidemiology, clinical trials, and physiological modeling, contributing valuable insights into the holistic management of cognitive health and neurovascular function.

Since the discovery of transposable elements (TEs) in Maize in the 1940s by Barbara McClintock [1] transposable elements have been described as junk, as selfish elements with no benefit to the host, and more recently as major determinants of genome structure and genome evolution. TEs are DNA sequences that are capable of moving to new sites in the genome and make additional copies while doing so. To limit the propagation of TEs, host silencing mechanisms are directed at transposon-encoded genes that are required for mobilization. The mutagenic properties of TEs, the potential of TEs to form new genes and affect gene expression, together with the host silencing mechanisms shape eukaryotic genomes and drive genome evolution. While TEs constitute more than half of the genome in many higher eukaryotes, transposable elements in the nematode C. ele-gans form a relatively small proportion of genome, about 15% [2]. Genetic studies of transposon silencing and the discovery of RNAi in C. elegans, propelled C. elegans to the forefront of studies of RNA-based mechanisms that silence TEs. Here, I will review the transposable elements that are present and active in the C. elegans genome, and the host defense mechanisms that silence these elements.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

Background. During the COVID-19 pandemic, there was an increased number of the hospitalized COVID-19 positive patients suffering from type 2 diabetes mellitus (T2DM). The objective of this research was to explore factors associated with the length of hospitalization of patients with T2DM and mild form of COVID-19. Material and Methods. This retrospective cohort study involved all patients who tested positive for COVID-19 and were treated in the dedicated COVID department of the University Clinical Center (UCC) in Nis between September 10, 2021, and December 31, 2021. Upon admission, patients underwent blood tests for biochemical analysis, including blood count, kidney and liver function parameters (C-reactive protein-CRP, creatinine kinase, D-dimer), as well as glycemia and HbA1c assessments. Additionally, all patients underwent lung radiography. Univariate and multivariate regression analyses were employed to assess the impact of specific factors on the length of hospitalization among patients with T2DM. Results. Out of the total 549 COVID-19 positive patients treated, 124 (21.0%) had T2DM, while 470 (79.0%) did not have diabetes. Among patients with T2DM, men were significantly younger than women (60.6±16.8 vs. 64.2±15.3, p

Immunosuppressed individuals, such as people living with HIV (PLWH), remain vulnerable to severe COVID-19. We analyzed the persistence of specific SARS-CoV-2 humoral and cellular immune responses in a retrospective, cross-sectional study in PLWH on antiretroviral therapy. Among 104 participants, 70.2% had anti-S IgG antibodies and 55.8% had significant neutralizing activity against the Omicron variant in a surrogate virus neutralization test. Only 38.5% were vaccinated (8.76 ± 4.1 months prior), all displaying anti-S IgG, 75% with neutralizing antibodies and anti-S IgA. 29.8% had no SARS-CoV-2 serologic markers and displayed significantly lower CD4 counts and HIV viral load. Severe immunosuppression (present in 12.5% of participants) was linked to lower levels of detectable anti-S IgG (0.0003), anti-S IgA (p &lt; 0.0001) and lack of neutralizing activity against Omicron variant (p &lt; 0.0001). T-cell responses were present in 86.7% of tested participants, even in those lacking serological markers. In PLWH without severe immunosuppression, neutralizing antibodies and T-cell responses persisted for up to 9 months post-infection or vaccination. Advanced immunosuppression led to diminished humoral immunity, but retained cellular immune.

Mpox, formerly known as Monkeypox, is a rare viral disease initially discovered in Africa in 1958. Since its first identification, several outbreaks have occurred in various African nations. Recently, the global community has witnessed a resurgence in the number of Mpox cases reported worldwide, prompting the World Health Organization (WHO) to declare the ongoing multi-country outbreak a public health emergency in July 2022. This study reports on the first cases of Mpox detected in Khartoum State, Sudan, outlining the epidemiology, preparedness, and public health response to this new challenge. A total of 55 suspected cases were identified, with two confirmed cases. The clinical manifestations observed in these cases align with the classic skin rash typical of Mpox, presenting alongside symptoms like fever, headache, and joint pain. The findings underscore the need for heightened surveillance, early detection, and timely intervention to prevent the domestic spread of Mpox and its potential impact on public health. Continued global efforts are needed to support effective screening, diagnostic, and control measures, ultimately enhancing preparedness and response in the face of this emerging disease.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

Despite available global efforts and funding, Tuberculosis (TB) continues to affect a considerable number of patients worldwide. Policy makers and stakeholders set clear goals to reduce TB incidence and mortality, but the emergence of multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) complicate the reach of these goals. Drug-resistance TB needs to be diagnosed rapidly and accurately to effectively treat patients, prevent the transmission of MDR-TB, minimise mortality, reduce treatment costs and avoid unnecessary hospitalisations. In this narrative review, we provide a comprehensive overview of laboratory methods for detecting drug resistance in MTB, focusing on phenotypic, molecular and other drug susceptibility testing (DST) techniques. We found a large variety of methods used, with the BACTEC MGIT 960 being the most common phenotypic DST and the Xpert MTB/RIF being the most common molecular DST. We emphasise the importance of integrating phenotypic and molecular DST to address issues like resistance to new drugs, heteroresistance, mixed infections and low-level resistance mutations. Notably, most of the analysed studies adhered to the outdated definition of XDR-TB and did not consider the pre-XDR definition, thus posing challenges in aligning diagnostic methods with the current landscape of TB resistance.

ABSTRACTCaffeine is known to impair both growth and development in the model social amoeba Dictyostelium discoideum. However, little is known about the transcriptional regulation in response to caffeine treatment in Dictyostelium. In yeast cells, caffeine mimics the effect of rapamycin in inhibiting mTORC1 activity. Here, we investigated whether changes in growth and development of Dictyostelium in the presence of caffeine or rapamycin are mediated by mTORC1 and/or mTORC2. Results: Treatment of wild type cells with caffeine or rapamycin resulted in severely impaired growth and in the formation of small aggregates in comparison to untreated cells. rip3‾ cells (lacking a mTORC2 component) and lst8‾cells (lacking a component of both mTOR complexes) showed higher and slower growth rates, respectively, in comparison to parental AX3 cells. Parental AX3 and rip3‾ cells displayed similar sensitivity to rapamycin and caffeine, while lst8‾ cells were more sensitive to these compounds. When developed in the presence of caffeine or rapamycin, AX3 cells formed aggregates after a long delay. Caffeine did not alter the morphology of small rip3‾ mounds and lst8‾ cells continued to remain solitary. However, in the presence of 1µM rapamycin rip3‾cells failed to form mounds while AX3 cells streamed and formed aggregates. Complementation of lst8‾ cells with the wild type lst8 gene rescued the aggregation phenotype. cDNA microarray analysis to uncover the spectrum of differentially regulated genes in response to caffeine treatment revealed 104 and 193 differentially expressed genes at 3-and 6-hours of development, respectively, in comparison to control cells. After 6 hours of starvation in the presence of caffeine, 25 genes encoding ribosomal proteins and 4 encoding elongation factors were up regulated. Furthermore, we identified that upon caffeine treatment at the 3- and 6-hours’ time points, 12 (10 up and 2 down) and 21 (13 up and 8 down) genes, respectively, encoding proteins involved in early development. Conclusion: We conclude that caffeine and rapamycin have similar effects in decreasing the growth rate and in reducing the aggregate size of D. discoideum. Studies with lst8‾ and rip3‾ cells suggest that these compounds affect cell growth and aggregation by acting on both mTOR complexes, mTORC1 and mTORC2. Analysis of the differentially expressed genes after caffeine treatment suggests a key role of these genes in growth and aggregation.

The detection of Fasciola eggs in ruminant fecal samples typically occurs around 15 weeks post-infection during patent infections. The recent introduction of coproantigen ELISA (cELISA) diagnostics, which capture antigenic enzymes in fecal material, holds promise for monitoring Fasciola fecal egg count (FFEC) to implement control programs, particularly targeted treatments. This study compared two study groups, those with positive FFEC (FFEC+ve) and negative FFEC (FFEC-ve), to assess the sensitivity of Flukefinder sedimentation and a cELISA kit. This study reports that the coproantigen ELISA detection limit was 4.5 eggs per gram (epg) for a 100% positivity rate. Additionally, a moderate, statistically significant positive correlation (r²=0.716, p-value < 0.01) and an odds ratio of 1.96 (p-value < 0.01) were observed between FFEC and Fasciola coproantigen from cELISA. This implies that for every single unit increase in FFEC, there is a 96% likelihood of obtaining a higher optical density (OD) reading from the cELISA test. The results suggest that cELISA can complement fecal sedimentation tests, serving as a valuable tool for detecting cattle with high FFEC. This capability facilitates targeted treatment strategies, thereby aiding in the control and prevention of the spread of fasciolosis within the studied area.

Cardiovascular and cerebrovascular disease incidence has risen mainly due to poor control of preventable risk factors and still constitutes a significant financial and health burden worldwide. ChatGPT is an artificial intelligence language-based model developed by OpenAI. Due to the model’s unique cognitive capabilities beyond data processing and the production of high-quality text, there has been a surge of research interest concerning its role in the scientific community and contemporary clinical practice. To fully exploit ChatGPT's potential benefits and reduce its possi-ble misuse, extreme caution must be taken to ensure its implications ethically and equitably. In this article, we explore the language model's possible applications and limitations while empha-sizing its potential value for diagnosing, managing, and prognosis cardiovascular and cerebro-vascular disease.

Background: Substance use continues to be on the rise in the United States and has been linked to new onset cardiovascular (CVDs) and cerebrovascular disorders (CeVDs) leading to hospitalizations. We aimed to study the association of different subtypes of substance use disorders (SUDs) among hospitalized patients, with the different subtypes of CVDs and CeVDs, using the National Inpatient Sample (NIS) Database. Additionally, we aimed to assess the odds of hospitalizations with new onset CVDs and CeVDs among patients with different types of SUDs. Methods: A retrospective study of the NIS database (2016-2017) using the ICD-10-CM codes was performed. The hospitalizations with a secondary diagnosis of SUDs were identified. Weighted univariate analysis using the chi-square test and multivariate survey logistic regression analysis was performed to evaluate for the incidence, prevalence, and odds of association between vascular events and SUDs. Results: There were a total of 58,259,589 hospitalizations, out of which 21.42% had SUDs. Out of all the hospitalized patients between the age 18-50, more patients had SUDs than not (31.83%, p< 0.0001). This difference existed for all the different subtypes of SUDs including alcohol related disorder (42.61%), amphetamine dependence (76.17% vs 31.83%), cannabis related disorder (75.17%), cocaine related disorders (57.87%), hallucinogen related disorder (82.91%), inhalant related disorders (67.25%), opioid related disorders (52.86%), and nicotine dependence (35.72%). We found a significant association of acute ischemic stroke with amphetamine dependence (OR 1.23, 95%CI 1.14-1.33), cocaine related disorders (1.17, 1.12-1.23) and nicotine dependence (1.42, 1.40-1.43). Similarly, the association of intracerebral hemorrhage was higher with amphetamine dependence (2.58, 2.26-2.93), and cocaine related disorders (1.62, 1.46-1.79). The association of subarachnoid hemorrhage was noted to be higher with amphetamine dependence (1.82, 1.48-2.24) and nicotine dependence (1.47, 1.39-1.55). In terms of association of cardiovascular disorders with SUDs,the patients with myocardial infarction had higher odds of nicotine dependence (1.85, 1.83-1.87) than not, Similarly, the patients with angina pectoris were noted to have a higher association with cocaine related disorders (2.21, 1.86-2.62), and those with atrial fibrillation had a higher association alcohol related disorders (1.14, 1.11-1.17). Conclusion: Our study demonstrates the variability of CVD and CeVD in patients hospitalized for SUD. Findings from our study may help promote increased awareness and early management of these events. Further studies are needed to evaluate specific effects of frequency and dose on the incidence and prevalence of CVD and CeVD in patients with SUD.

This study describes KPC-204, a novel variant of Klebsiella Pneumoniae carbapenemase, characterized by a KDD amino acid insertion at Ambler position 269 deviates from KPC-2. This variant was identified in an ST11-type clinical isolate of carbapenem-resistant Klebsiella Pneumoniae from China. Notably, KPC-204 exhibits resistance to both ceftazidime-avibactam and carbapenems. Genetic analysis revealed that blaKPC-204 was located on a highly mobile IncFII/IncR plasmid within a complex genetic structure that facilitates its spread. Functional analysis, achieved through cloning into E. coli DH5α, validates KPC-204's contribution to increased resistance to ceftazidime-avibactam. The kinetic parameters showed that KPC-204 exhibited similar affinity to KPC-2 toward ceftazidime and reduced sensitivity to avibactam. Mating experiments demonstrated the resistance's transmissibility. This investigation underscores the evolving diversity of KPC variants affecting ceftazidime-avibactam resistance, highlighting the necessity for continuous monitoring.

Mulberry leaves, when infected by pathogens, can suffer significant yield loss or even death if early disease detection and timely spraying are not performed. To enhance the detection performance of mulberry leaf diseases in natural environments and to precisely locate early small lesions, we propose a high-precision, high-efficiency disease detection algorithm named YOLOv8-RFMD. Based on improvements to You Only Look Once version 8 (YOLOv8), we first proposed the Multi Dimension Feature Attention (MDFA) module, which integrates important features at the pixel-level, spatial and channel dimensions. Building on this, we designed the RFMD Module, which consists of the Conv-BatchNomalization-SiLU (CBS) module, Receptive-Field Coordinated Attention (RFCA) Conv, and MDFA, replacing the Bottleneck in the model’s Residual block. We then employed Adown down sampling structure to reduce the model size and computational complexity. Finally, to improve the detection precision of small lesion features, we replaced the complete intersection over union (CIOU) loss function with the Normalized Wasserstein Distance (NWD) loss function. Results show that the YOLOv8-RFMD model achieves an mAP50 of 94.3% and an mAP50:95 of 67.8% on experimental data, representing increases of 2.9% and 4.3% respectively compared to the original model. The model size is reduced by 0.53 MB to just 5.45 MB, and the number of floating-point operations is reduced by 0.3 G to only 7.8 G. The improved model meets the deployment requirements of mobile embedded devices and can provide a theoretical reference for the automated spraying operations of mulberry leaves.

Background: Resistant hypertension (HTN) is associated with high risk of cardiovascular complications. Our study aimed to assess prevalence, characteristics and treatment of patients with resistant HTN; Methods: We screened 4340 consecutive cardiovascular patients and identified 3762 with HTN. Of them 128 fulfilled criteria for resistant HTN and were included in our study. We matched these patients to 128 hypertensive patients with controlled HTN; Results: Resistant HTN patients were 3.4% of all hypertensives. Most of these patients (67.2%) were at high or very high cardiovascular risk compared to controlled HTN patients (40.6%), p&lt;0001. Resistant HTN patients had more frequently concomitant chronic kidney disease (CKD) (60.9%), overweight/obesity (52.3%), dyslipidemias (35.2%), smoking (27.3%) and diabetes (21.9%) compared to controlled HTN patients (37.5%, 29.7%, 28.1%, 14.1% and 7.8% respectively), p&lt;0.001. Regression analysis showed strongest association of resistant HTN with CKD (OR 6.64), stage III HTN (OR 3.07) and obesity/overweight (OR 2.60). In contrast, single-pill combinations (SPCs) were associated with lower likelihood of uncontrolled HTN (OR 0.58); Conclusions: Resistant HTN represented a small proportion of all hypertensives in our study, but it was characterized by high/very high cardiovascular risk. Optimized therapy including increased usage of SPCs could improve blood pressure control and long-term prognosis of these patients.

Enterococcus faecalis is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04 (ФKEN04), isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR Enterococcus faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between -80ᵒC and 37ᵒC. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G+C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that ФKEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.

Air pollution, climate change and global warming show direct linkage. Introduction - Background: Research in the field has proposed and demonstrated their link to increased allergenicity in plants, leading to increased allergic diseases. Allergen patterns are changing in response to climate change. Across Europe, up to 12% of the population suffers from allergic diseases (bronchial asthma and allergic rhinitis) caused by the pollen grains. The medical costs of these types of allergies are enormous and are increasing with the spread of common ragweed - Ambrosia artemisiifolia* in Europe. In practice, more and more patients are turning to allergists. Methods: Based on these data, the research aims to identify safety measures and specific legislation to control and eradicate common ragweed in the countries most affected by the spread of this plant in Europe, increase in population exposure in countries affected by the presence of common ragweed and the socio-economic impact of allergic rhinitis and bronchial asthma at European level.[1][2] Our database search did not reveal any other research that has addressed this topic to date. Results: This research identifies specific legislation to the countries most affected by the spread of this plant pollen grains at European level, changes in allergen patterns and monitoring/safety eradication measures decided by local authorities, and data on the spread of common ragweed over the last two decades, costs per treatment, increased allergic rhinitis and bronchial asthma morbidity in the most affected areas. Conclusions: At European level, there are no universally valid models for eradicating this weed. Various methods can be used to limit the spread of common ragweed and its pollen production (e.g. mowing once or twice a year of overgrown land, ploughing, chemical control, public information, etc.). Local and regional cooperation should be considered essential to promote phytosanitary &amp; safety measures and exchange of information on methods to identify and manage the spread of common ragweed. Unified legislation at European level would help all affected countries; reduce morbidity from respiratory allergic diseases and the costs of treating these diseases.

Oilseed plants of the Brassicaceae plant family are cultivated for food, feed and industrial purposes on large-scale in Europe. This review gives an overview of current market-oriented applications of new genomic techniques (NGTs) in relevant Brassicaceae oilseed crops based on a literature survey. In this respect, changes in oil quality, yield, growth and resistance to biotic and abiotic stress are goals in oilseed rape (B. napus) and camelina (C. sativa). Environmental risk assessment scenarios are developed for specific NGT applications in Brassicaceae oilseed crops with either a changed oil composition or with fitness related traits. In case of a changed oil composition an increase or decrease of polyunsaturated fatty acids (PUFA) demonstrates risks for health and survival of pollinators. In case of fitness related traits other risks were identified, i. e. an increased risk of spread and persistence of NGT plants. Furthermore, there are indications for potential disturbance of interactions with the environment, involving signalling pathways and reaction to stress conditions. It is shown that for a comprehensive risk assessment the technological potential of NGTs, the plants’ biology and the scale of releases have to be considered in combination. Therefore, the release of NGT plants into the environment for agricultural purposes will require risk assessment and monitoring of single traits as well as of combinatorial and long-term cumulative effects. In addition, risk management should develop concepts and measures to control and potentially restrict the scale of releases. This is especially relevant for NGT Brassicaceae in Europe which is a centre of diversity of this plant family.

Lipoprotein (a) is a highly atherogenic, lipid particle whose concentration is genetically determined, and represents an independent risk factor for cardiovascular disease. On the other hand, metabolic syndrome represents a cluster of interconnected cardiovascular risk factors (obesity, insulin resistance, arterial hypertension, dyslipidemia) that are a direct consequence of an unhealthy lifestyle. Some evidence suggests a connection between each component of metabolic syndrome and high levels of lipoprotein (a). Still, the exact mechanisms are not fully understood and may involve complex interactions between various metabolic pathways. High levels of lp(a) are associated with insulin resistance, a key feature of type 2 diabetes mellitus and obesity. Although there is no significant association between lp(a) and other lipid levels (LDL-C, HDL-C, triglycerides), studies have shown a strong synergistic effect of genetically elevated LDL-C and Lp (a) on the development of cardiovascular events. Also, there is supporting evidence that hypertensive patients with high levels of lp(a) have higher cardiovascular risk, there is no direct association between hypertension and lp (a). Treatment of metabolic syndrome is often long-term and challenging but very important to reduce the overall cardiovascular risk, especially in individuals with higher levels of Lp (a), in whom the risk of developing cardiovascular disease is much higher.

Porcine parvovirus 8 (PPV8), a novel virus in the Parvoviridae family, was first identified in 2022 in lung samples of domestic pigs from China. Retrospective analyses showed that it had been circulating in China since 1998, but no other countries had reported its presence so far. A recent study conducted in South America did not detect any PPV8-positive samples in that region. Here we report the detection of PPV8 in Hungarian and Slovakian pig farms and the estimated prevalence of the virus in Hungary. Altogether 2230 serum, 233 oral fluid, and 115 processing fluid samples were systematically collected from 23 Hungarian and 2 Slovakian pig farms between 2020 and 2023. A real-time quantitative PCR method was developed to detect the viral genome. Our results revealed the presence of PPV8 on 65% of the Hungarian farms and on both Slovakian farms included in our study, marking its first detection in Europe. Oral fluid samples showed the highest positivity rates, reaching up to 100% in some herds. The viral genome was successfully detected in serum and processing fluid samples too, but with significantly lower prevalence rates of 4% and 5%, respectively. Genetic analysis of 11 partial VP2 sequences demonstrated high similarity to the original Chinese strain but with unique amino acid mutations, suggesting possible local evolution of the virus. Our study presents the first scientific evidence of PPV8 infection outside of China and offers a comprehensive assessment of its prevalence in the Hungarian pig population. Further research is required to understand its potential impact on swine health.

Clostridial infections in cattle are a significant concern for Brazilian livestock. These diseases are caused by various species of Clostridium, which are known for their ability to produce potent toxins. Botulism in cattle is a serious and often fatal condition caused by the ingestion of neurotoxins produced by C. botulinum. This bacterium thrives in decomposing organic matter, such as spoiled feed, carcasses, and contaminated water. Tetanus while less common, tetanus is a serious disease following contamination of wounds with Clostridium tetani spores. It results in muscle stiffness, spasms, and often death due to respiratory failure. Blackleg (C. chauvoei) is this disease primarily affects young cattle, leading to acute lameness, swelling, and high fever. Malignant edema (C. septicum and others) is characterized by rapid onset of swelling at wound sites, malignant edema can occur after injuries or surgical procedures. Enterotoxemia is triggered by the rapid growth of C. perfringens in the gut following excessive carbohydrate intake. This leads to toxin production that causing sudden death. In conclusion, clostridial bovine infections remain a persistent challenge for Brazilian cattle farmers. With continued focus on vaccination, good management practices, and research, the impact of these diseases can be minimized, safeguarding the livestock industry's economic viability.

The emergence of drug-resistant mycobacteria has rendered many clinical drugs and regimens ineffective, imposing significant economic and healthcare burden on individuals and society. Repurposing drugs intended for treating other diseases is a time-saving, cost-effective, and efficient approach for identifying excellent anti-mycobacterial candidates or lead compounds. This study is the first to demonstrate that rupatadine (RTD), a drug used to treat allergic rhinitis, possesses excellent activity against mycobacteria without detectable resistance, particularly Mycobacterium tuberculosis and Mycobacterium marinum, with a minimal inhibitory concentration as low as 3.13 µg/mL. Furthermore, RTD exhibited moderate activity against nonreplicating M. tuberculosis with the minimal inhibitory concentrations lower than drugs targeting the cell wall, suggesting that RTD has the great potential to be modified and used for the treatment of nonreplicating M. tuberculosis. Additionally, RTD exhibits partial synergistic effects when combined with clofazimine, pretomanid, and TB47 against M. tuberculosis, providing the theoretical foundation for the development of treatment regimens. Transcriptomic profiling leads us to speculate that eight essential genes may be the targets of RTD or may be closely associated with the mycobacterial resistance to RTD. In summary, RTD may be a promising hit for further anti-mycobacterial drug or regimen optimization, especially in case of nonreplicating mycobacteria.

Chronic granulomatous disease (CGD) is a group of rare primary inborn errors of immunity characterised by a defect in the phagocyte respiratory burst, which leads to severe and life-threatening infective and inflammatory complications. Despite recent advances in our understanding of the genetic and molecular pathophysiology of X-linked and autosomal recessive CGD, and growth in the availability of functional and genetic testing, there remain significant barriers to early and accurate diagnosis. In the current review, we provide an up-to-date summary of CGD pathophysiology, which underpins methods of diagnostic testing for CGD and closely related disorders. We present an overview of the benefits of early diagnosis and when to suspect and test for CGD. We discuss current and historical methods for functional testing of NADPH oxidase activity, as well as assays for measuring protein expression of NADPH oxidase subunits. Lastly, we focus on genetic and genomic methods employed to diagnose CGD, including gene-targeted panels, comprehensive genomic testing and ancillary methods. Throughout, we highlight general limitations of testing, and caveats specific to interpretation of results in the context of CGD and related disorders, and provide an outlook for newborn screening and the future.

Background and Objectives: To analyze survival in peritoneal and hemodialysis patients using chest radiography and biochemical parameters, determine dialysis etiologies and common mortality causes, reveal prognostic factors, and contribute to clinical practice. Materials and Methods: This retrospective cohort study was based on the analysis of data from 33 peritoneal dialysis and 37 hemodialysis patients who were followed and treated in our hospital between October 2018 and February 2020. Chest X-ray measurements (cardiothoracic index, pulmonary vascular pedicle width, right pulmonary artery diameter, diaphragmatic height) and biochemical parameters (urea, albumin, creatinine, parathormone, ferritin, hemoglobin, arterial blood gas, potassium) were analyzed to assess their impact on survival. Statistical analyses were performed using the Shapiro-Wilk, Wilcoxon signed rank test, Mann-Whitney U test, McNemar test, Kaplan-Meier survival analysis, Cox regression analysis, Spearman correlation test, Phi test, and ROC analysis. Results: The most common etiologies of dialysis were hypertension, type 2 diabetes mellitus, and urogenital disorders. The most common cause of death in peritoneal dialysis patients was peritonitis (38.5%), while in hemodialysis patients, it was cardiovascular diseases (47.4%). In chest X-ray measurements, pulmonary vascular pedicle width (p=0.003) and pulmonary artery diameter increased significantly (p=0.002) in hemodialysis patients, while pulmonary vascular pedicle width (p=0.028) and diaphragmatic height (p=0.004) increased significantly in peritoneal dialysis patients. No significant difference was found between the two groups in terms of biochemical parameters. Kaplan-Meier survival analysis showed that there was no significant difference in survival between peritoneal dialysis and hemodialysis methods (P>0.05). Significant correlations were found between both radiologic status and clinical status and between intact parathormone levels and pulmonary vascular pedicle width (p=0.016, p=0.024). In Cox regression analysis, age, intact parathormone levels, iPTH/PVPW ratio, and clinical status were found to be factors affecting survival (p

Antisense oligonucleotides (ASOs) are short oligodeoxynucleotides designed to bind to specific regions of target mRNA. ASOs can modulate pre-mRNA splicing, increase levels of functional proteins and decrease levels of toxic proteins. ASOs are being developed for the treatment of several diseases, including motor neuron diseases (MNDs), a group of neurodegenerative disorders characterised by the loss of motor neurons, including spinal muscular atrophy (SMA), amyotrophic lateral sclerosis (ALS) and spinal and bulbar muscular atrophy (SBMA). The biggest success has been the ASO known as nusinersen, the first effective therapy for SMA, able to improve symptoms and slow disease progression. Another success is tofersen, an ASO designed to treat ALS patients with SOD1 gene mutations. Both ASOs have been approved by the FDA and EMA. On the other hand, ASO treatment in ALS patients with the C9orf72 gene mutation did not show any improvement in disease progression. The aim of this review is to provide an up-to-date overview of ASO research in MND, from preclinical studies to clinical trials and, where available, regulatory approval. We highlight the successes and failures, underline the strengths and limitations of the current ASO research, and suggest possible approaches that could lead to more effective treatments.

Pulmonary hypertension (PH) is a serious condition linked to immune-system dysfunction. Myositis-specific/associated antibodies (MSA/MAA) play a role in idiopathic inflammatory myopathy (IIM) and interstitial lung disease (ILD), but their significance in PH remains unclear. We believe the presence of these antibodies, may be underestimated. This study analyzed adult PH patients without pre-existing IIM for MSA/MAA prevalence using a line-blot assay. We compared PH patients with and without ILD signs to a cohort clinically suspected of IIM/ILD (n=558). Our PH cohort (n=121) showed a significantly higher prevalence of overall weak positive MSA/MAAs and positive overlap syndrome-associated MAAs than the suspected IIM/ILD group (p

Oral squamous cell carcinoma (OSCC) is a highly prevalent and aggressive malignancy, with mortality rates that reach 60%, mainly due to an excessive diagnostic delay. MiRNAs, a class of crucial epigenetic gene-expression regulators, have emerged as potential diagnostic biomarkers, with >200 molecules reported to be dysregulated in OSCC. We had previously established an in silico methodology for the identification of the most disease-specific molecules by bridging genetics and epigenetics. Here, we identified the stage-specific miRNAs that govern the asymptomatic early stages of oral tumorigenesis by exploiting the reverse interplay between miRNA-levels and their target-genes’ expression. Incorporating gene expression data from our group’s experimental hamster model of sequential oral oncogenesis, we bioinformatically detected the miRNAs that simultaneously target/regulate >75% of the genes that are characteristically upregulated or downregulated in the consecutive stages of hyperplasia, dysplasia and early-invasion OSCC, while exhibiting the opposite expressional dysregulation in OSCC-derived tissue and/or saliva specimens. We found that all stages share the downregulation of miR-34a-5p, miR124-3p, and miR-125b-5p, while miR-1-3p is underexpressed in dysplasia and early-invasion. Malignant early-invasion stage is distinguished by the downregulation of miR-147a and the overexpression of miR-155-5p, miR-423-3p and miR-34a-5p. The identification of stage-specific miRNA molecules may facilitate their utilization as biomarkers for presymptomatic OSCC diagnosis.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

In the last few years, the agricultural field has undergone a digital transformation, incorporating artificial intelligence systems to make good employment of the growing volume of data from various sources and derive value from it. Within artificial intelligence, machine learning is a powerful tool for confronting the numerous challenges of developing knowledge-based farming systems. This study aims to comprehensively review the current scientific literature from 2017 to 2023, emphasizing machine learning in agriculture, especially viticulture, to detect and predict grape infections. Most of these studies (88%) were conducted within the last five years. A variety of machine learning algorithms were used, with those belonging to the neural network (CNN) standing out having the best results most of the time. Out of the list of diseases, the ones most researched were Grapevine Yellow, Flavescence Dorée, Esca, Downy mildew, Leafroll, Pierce’s, and Root Rot. Also, some other fields were studied which are water management, plant deficiencies, and classification. Because of the difficulty of the topic, it was collected all datasets that were available about grapevines, and it is described each dataset with the type of data (e.g., statistical, images, type of images), along with the number of images where it was mentioned. This work provides a unique source of information for a general audience comprising AI researchers, agricultural scientists, wine grape growers, and policymakers. Among others, its outcomes could be effective at curbing diseases in viticulture, which in turn will drive sustainable gains and boost success. Additionally, it could help build resilience in related farming industries such as winemaking.

Weight-bearing computed tomography (WBCT) enables acquisition of three dimensional bony structure images in a physiological weight-bearing position, which is fundamental in under-standing the pathologic lesions and deformities of the ankle joint. Over the past decade, re-searchers focused on validating and developing WBCT measurements, which has significantly enhanced our knowledge of common foot and ankle disease. Consequently, understanding the application of WBCT in clinical practice is becoming more important to produce improved out-comes in the treatment of disease around the ankle joint. This review will describe an overview of what is currently being evaluated in the foot and ankle surgery using WBCT and where the course of research will be heading in the future.

Introduction Livestock abortigenic agents, which are microorganisms that lead to premature foetal death and expulsion before completion of the gestation period, are common in Africa and Asia. Abortion events cause economic losses by lowering reproduction (and hence herd/flock sizes) and effects on milk production. Despite the importance of livestock production for food security and livelihoods of millions of the world’s poorest communities, very little is known about the scale, magnitude or causes of livestock abortion in Africa. The aim of this review was to determine the current status of the burden of livestock abortion and surveillance measures adopted for livestock abortigenic pathogens in Africa and Asia, and to explore feasible surveillance technologies. Methodology A systematic literature search was conducted using Preferred Reporting of Systematic Reviews and Meta-analyses (PRISMA) guidelines in four databases for studies published between 1 Jan 1990 and 31 July 2021 that reported epidemiological surveys of livestock abortigenic pathogens in cattle, goats and sheep in Africa and Asia including; Brucella spp., Neospora caninum, Toxoplasma gondii, Rift valley fever virus, Coxiella burnetii, Chlamydia, Leptospira and Bovine viral Diarrhoea Virus. A meta-analysis was used to estimate the species-specific prevalence of the abortigenic diseases and the region where they were detected. Results In the systematic literature search, 48 full papers were included which in total included 50 species-specific surveillance reports from Africa and 19 from Asia. Adjusted median seroprevalence calculations estimated Brucella at 6.85% (range 1.2-11.6) of 9071 sheep, 3.35% (range 0.90-5.40) of 17,007 goats, 8.95% (range 0.50-63.60) of 171,733 cattle, Neospora at 6.80% (range 6.80 -6.80) of 555 sheep, 10.80 (range 10.80-10.80) of 185 goats, 12.65% (range 3.40- 25.60) of 3775 cattle, Toxoplasma at 27.50% (range 1.40 – 75.90) of 2284 sheep, 32.0% (range 20.00- 64.80) of 1226 goats, 7.50% (range 7.50 - 7.50) of 174 cattle, Coxiella at 9.20 (range 9.20 – 9.20) of 184 sheep, 24.20% (range 24.20-24.20) of 91 goats, 13.80% (range 13.80-13.80) of 217 cattle, Rift valley fever virus at 7.70 (2.40-40.00) of 874 sheep, 20.95 (range 2.50-40.00) of 547 goats, 7.45% (range 3.60-11.30) of 309 cattle, Bovine viral diarrhea virus at 78.90 (range 78.90 – 78.90) of 398 cattle, Leptospira at 70.50 (range 70.50 – 70.50) of 373 cattle and Chlamydia at 6.60 (6.60-6.60) of 803 sheep. We found that most studies, 45 (89%) used serological surveys, 1 (2%) used molecular and 1 (2%) reported to have used Mobile-phone based surveillance approach. Three studies (6.25%) of the 48 included were embedded in the national surveillance programs of the respective countries they were conducted, majority 89% were stand-alone cross-sectional studies. Conclusion In conclusion, livestock abortigenic pathogens are still a burden in many African and Asian countries.

Primary biliary cholangitis (PBC) is a cholestatic liver disease characterized by immune-mediated injury to small bile ducts. Although PBC is an autoimmune disease, the results of traditional immunosuppressive therapy are disappointing. Nearly 40% of PBC patients do not respond to the first-line drug UDCA. Without appropriate intervention, PBC patients would eventually progress to liver cirrhosis and even death. There is an urgent need to develop new therapies. The gut-liver axis emphasizes the interconnection between the gut and the liver, and there is increasing evidence that gut microbiota and bile acids play an important role in cholestatic diseases. Dysbiosis of gut microbiota, imbalance of bile acids, and immune-mediated bile duct injury constitute the triad of pathophysiology in PBC. Understanding the gut microbiota-bile acid network and corresponding immune functions in PBC provides a new perspective for its treatment strategies. Therefore, we summarize the latest advancements in research of gut microbiota and bile acids in PBC and, for the first time, explore the potential of immune factors related to them as novel immunotherapy targets. This article discusses potential therapeutic approaches focusing on regulating gut microbiota, maintaining bile acid homeostasis, their interactions, and related immune factors.

During choriogenesis in insects, chorion (eggshell) is formed by surrounding follicular epithelial cells in ovarioles. However, the regulatory endocrine factor(s) activating choriogenesis and the chemical components on eggshell deserve further exploration. In two representative Coleopterans, a Coccinellid Henosepilachna vigintioctopunctata and a Chrysomelid Leptinotarsa decemlineata, genes encoding the 20-hydroxyecdysone (20E) receptor heterodimer, ecdysone receptor (EcR) and ultraspiracle (USP), and two chitin biosynthesis enzymes UDP-N-acetylglucosamine pyrophosphorylase (UAP) and chitin synthase (ChS1), were highly expressed in ovaries of the young females. RNA interference (RNAi)-aided knockdown of either HvEcR or Hvusp in H. vigintioctopunctata inhibited oviposition, suppressed the expression of HvChS1, and lessened the positive signal of Calcofluor staining on the chorions, which suggests the reduction of a chitin-like substance (CLS) deposited on eggshells. Similarly, RNAi of LdEcR or Ldusp in L. decemlineata constrained oviposition, decreased the expression of LdUAP1 and LdChS1, and declined CLS contents in the resultant ovaries. Knockdown of LdUAP1 or LdChS1 caused similar defective phenotypes, i.e., reduced oviposition and CLS contents in the L. decemlineata ovaries. These results, for the first time, indicate that 20E signaling activates choriogenesis in two Coleopteran species. Moreover, our findings propose the deposition of a CLS on the chorions.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Previous high throughput screening studies indicated trans-eQTLs tend to be tissue specific. In this study, I probed if this feature can be used to identify tissue-specific gene regulatory networks. eQTL data (P<5e-8) for 16,259 genes were identified and their summary association statistics were obtained from the eQTLGene database. Next, eQTLs that display both cis and trans regulatory effects were selected and the association between their corresponding genes were examined using Mendelian randomization. A total of 169 genes that exerted trans-regulatory impacts on 692 genes were identified. 90% of the genes (N=749) aggregated into a gene regulatory network significantly enriched in hemo-immune processes. The robustness of finding was confirmed through simulation. The identified network displayed the scale-free topology. This provided the reason to examine the association of the network’s hub genes with the phenome. The outcome of analyses revealed GSDMB and ORMDL3 impact several disorders of immune origin and ALDH2 overexpression contributes to obesity. This study reports trans-eQTLs can be used to identify tissue-specific gene regulatory networks and describes a workflow to achieve this purpose. The network identified in this study showed scale-free topology indicating the hub genes of a GRN could be targeted to prevent disease outcomes.

Numerous investigations have consistently underscored the impact of societal stigma on the well-being of transgender individuals, encompassing both those experiencing gender dysphoria (transgender) and those who have undergone gender-affirming interventions (transsexual). The primary objective of the current research is to translate and adapt the Attitudes Toward Transgendered Individuals Scale into the Greek language. This scale specifically assesses stigma, excluding components such as discreteness and violence, and is tailored to evaluate individuals within the general populace. Employing confirmatory factor analysis (CFA) and assessing gender metric equivalence, the analyses yielded highly favourable outcomes, demonstrating excellent scale fit, reliability, and content validity, reflecting the robustness of the adapted tool for the Greek population.

Microglial cells are brain macrophages that support and protect the central nervous system enviroment. Aging induces alterations in microglial polarization, resulting in a shift towards a neurotoxic phenotype characterized by increased expression of pro-inflammatory markers. Dysregulation of microglial cells regulatory pathways and interactions with neurons contribute to chronic activation and neurodegeneration. A better understanding the involvement of microglia in neurodegenerative diseases like Alzheimer's and Parkinson's, is a critical topic to studying the role of inflammatory responses in disease progression. Furthermore, the metabolic changes in aged microglia, including downregulation of oxidative phosphorylation are discussed in this review. Understanding these mechanisms is crucial for developing better preventive and therapeutic strategies.

Despite saltmarshes being considered as nature-based solutions (NbS) towards climate change mitigation, India’s saltmarsh ecosystems are least studied. This study quantifies the seasonal variation in carbon stocks mono-specific saltmarsh species (Porteresia coarctata) and its potential to play an important role in India’s climate change mitigation plans. Seasonal (pre-and post-monsoon) sampling of P. coarctata surface water, biomass and 30 cm sediment core was collected across four locations on the east coast of India to quantify sediment dry bulk density (DBD), organic matter (OM%), organic carbon (Corg%), Corg stocks of sediment and biomass, total carbon (C%) and nitrogen (N%) and stable isotopes of δ13C and δ15N. In general, the sediment DBD, OM and Corg of P. coarctata meadows was higher in post-monsoon and was influenced by salinity and pH changes. Isotope (δ¹³C) modelling of various sediment C sources suggested, particulate organic matter (POM) contribution was highest (0.04-0.79%) followed by P. coarctata (0.01–052%) and other macrophytes across our study locations. The seasonal variation of δ¹³C showed increased contribution of marine derived particulate and dissolved organic matter into P. coarctata meadows in post-monsoon season. Heavier δ¹⁵N values were observed in post-monsoon season suggesting anthropogenic input, that was utilized by P. coarctata to increase its above and below-ground biomass and shoot density. The combined ecosystem (30 cm sediment + biomass) Corg stocks of P. coarctata was 1.7-fold higher in post-monsoon (4021.20± 917 Mg C) compared to pre-monsoon (2297.36 ±647 Mg C) season among the four locations with a sediment Corg contribution >70%. Based on the International Panel for Climate Change Tier II assessment the P. coarctata meadows (443 ha) can help in avoiding the pre and post-monsoon emissions of 8431.34 and 14757.84 Mg CO₂ respectively. The combined price of the total CO₂ equivalent stored in P. coarctata meadows in pre- and post-monsoon is US$ 14.50 and US$ 25.38 million respectively. Further studies quantifying the NbS potential of P. coarctata mono-specific and mixed meadows of India’s coast is needed along with integration of saltmarsh ecosystems into India’s National Action Plan on Climate Change.

The main purpose of the study was to study the effects of a specific rowing ergometer training program on the athletic performance of young adolescents (n=56; 11.73 ± 1.4 years old) com-pared to a workout based on general strength training. Eight-week training program was im-plemented, with four sessions per week and two-hours per session. Sample was divided in two groups: a control group (CG) that performed circuit training with exercises aimed at building general strength and an experimental group (EG) who focused on specifically training on a rowing ergometer (rowing machine). The data obtained in a rowing meter test over the compe-tition distance were analyzed to obtain the average power attained (W) at the beginning of the training, at the middle (4 weeks), at the end of the training (8 weeks) and one year after the ex-perimentation. The results show that, although both forms of training improve the average W obtained in both categories, the EG subjects (+29.94W) obtained better averages in all phases of the study compared to the CG (+5.88W). Furthermore, this increase was greater in male rowers (+ 34.06W) than in female rowers (+24.54W). These results reveal that a specific rower rowing ergometer training program has a significant effect than a general strength program and these effects can even be observed a year after the intervention.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

Background: As a relatively high number of ST-segment elevation myocardial infarction (STEMI) patients develop major adverse cardiovascular events (MACE) following percutaneous coronary intervention (PCI), our aim was to determine the significance, and possible predictive value of QRS complex width and ST-segment elevation. Methods: Our patient sample included 200 PCI-treated STEMI patients, which were divided into two groups, based on the duration of symptoms: (I) less than 6 hours, and (II) 6-12 hours. For every patient, ECG was performed at 6 different time points. Long-term follow-up lasted 6 years from the STEMI onset. Statistical analysis was performed. Results: The mean age was 60.6±11.39 years, and 142 were male. Wider QRS complex, more pronounced ST-segment elevation, and more frequently absent ST-segment resolution were more common in the second group. Presentation of MACE was more frequent in this group. An increase of pre-PCI QRS complex width by 1 msec increases the risk of 6-year MACE by 3%, and an increase in pre-PCI ST-segment elevation by 1mm increases the risk of 6-year MACE by 3.26 times. Conclusion: To the best of our understanding, this study represents a pioneer research that utilized these ECG elements in the context of predicting a 6-year MACE. A wider QRS complex and a more pronounced ST-segment elevation were associated with longer total ischemic time. More research is needed to confirm these findings.

Background: over the past 20 years, the treatment scenario of multiple sclerosis (MS) has radically changed and an ever-increasing number of disease-modifying treatments has emerged. Among high efficacy treatment agents, monoclonal antibodies (mAbs) have become a mainstay in the MS patient’s treatment due to their targeted mechanism, high efficacy and favorable risk profile. The latter varies from drug to drug and a skin cancer warning has emerged with sphingosine 1-phosphate receptors inhibitors. Several cases of skin malignancy in people with MS (pwMS) undergoing therapy with mAbs have also been described, but dermatological follow-up is not currently indicated. Objectives: the aim of this review is to investigate cases of cutaneous ma-lignancy during mAbs therapy and to explore possible pathophysiological mechanisms to evaluate the potential need for regular dermatological follow-up in pwMS treated with mAbs. Methods: literature search for original articles and review in PubMed. No date restrictions. Results: 1019 results were retrieved. Duplicates were removed using Endnote and manually. Only peer-reviewed studies published in English were considered for inclusion. At the end of these screening procedures, 54 studies published between 2001 and 2023 that met the objectives of this review were selected and reported. Conclusions: the available data do not show a clear link be-tween monoclonal antibody (mAb) treatment in pwMS and the risk of skin cancer. At present, these treatments remain contraindicated for people with cancer. Dermatological screening is ad-visable before starting mAb treatment in pwMS, and subsequent follow-up should be individual-ised according to each patient's risk profile.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Oral candidiasis is a common problem among immunocompetent patients. The frequent resistance of Candida strains to popular antimycotics makes it necessary to look for alternative methods of treatment. The authors conducted a systematic review following the PRISMA 2020 guidelines. The objective of this review was to determine whether curcumin-mediated aPDT and blue light could be considered as an alternative treatment for oral candidiasis. PubMed, Google Scholar and Cochrane Library databases were searched using a combination of the following keywords: (Candida OR candidiasis oral OR candidosis oral OR denture stomatitis) AND (curcumin OR photodynamic therapy OR aPDT OR photodynamic antimicrobial chemotherapy OR PACT OR photodynamic inactivation OR PDI). The review included in vitro laboratory studies with Candida spp., in vivo animal studies, and randomized control trials (RCTs) involving patients with oral candidiasis or prosthetic stomatitis, published only in English. The method of elimination of Candida species in the studies was curcumin-mediated aPDT. 757 studies were identified. Following the analysis of the titles and abstracts of the studies, only 42 studies were selected for in-depth screening, after which 26 were included in this study. All studies evaluated the antifungal efficacy of curcumin-mediated aPDT against C. albicans and non-albicans Candida. In studies conducted with planktonic cells solutions, seven studies demonstrated complete elimination of Candida spp. cells. The remaining studies demonstrated only partial elimination. In all cases, experiments on single-species yeast biofilms demonstrated partial, statistically significant inhibition of cell growth and reduction of biofilm mass. In vivo, curcumin-mediated aPDT has shown good antifungal activity against oral candidiasis also in an animal model. However, its clinical efficacy as a potent therapeutic strategy for oral candidiasis requires further RCTs.

Background: Over the past decades, efforts have been made to improve the nutritional well-being in people with cystic fibrosis (pwCF). Due to the correlation observed between nutritional indices and lung function, prevailing recommendations consistently advocate for BMI percentile goals at or above the 50th percentile in pwCF. Recent global trends show a notable increase in overweight and obese statuses among pwCF. This study aims to explore the nutritional status of Italian pwCF. Methods: Data from the Italian CF Patient’s Registry were analysed to assess the proportion of individuals categorized as underweight, target weight, overweight, and obese from 2010 to 2021. Patient-level comparison data from 2021 were also examined to identify potential determinants of overweight and obesity. Results: Analysis spanning 2010 to 2021 reveals a decrease of approximately 40% in underweight status among adults, while the proportion of malnourished patients 90, and lower prevalence of Pseudomonas aeruginosa colonization. Conclusions: Our study confirms the evolving nutritional status landscape among Italian adult pwCF, with a significant shift towards overweight and obesity over the past decade. These trends highlight the need for proactive measures within CF standards of care to adapt and address the changing needs of patients.

Patients who survived critical COVID-19 frequently reported post-acute sequelae of COVID-19 (PASC) such as psychosomatic and neurocognitive health problems. The goal of this study was to identify clinical risk factors and other predictors for such long-term consequences in severely ill COVID-19 patients. Adult COVID-19 intensive care unit (ICU) survivors from August 2020 to May 2021 were enrolled. A broad range of clinical, laboratory and chest computed tomography (CT) data was collected during ICU stay. The association between ICU predictors and psychosomatic, respiratory and neurocognitive assessments 12 months after ICU discharge was analyzed using univariate regression analysis. In 17 patients (mean age 58.9 ± 11.4 years), laboratory markers (CRP, lymphocytes, hemoglobin), ICU severity (SOFA, SAPS II, need for mechanical ventilation), complications (ARDS), and lung CT data (ground-glass opacity) were promising predictors of depressive and anxiety symptoms, fatigue, and sleep problems. Recovery of psychosomatic health such as fatigue, depression and anxiety correlated with lower levels of inflammation and high hemoglobin levels. ARDS, mechanical ventilation and worse SOFA and SAPS II scores were further risk factors for depressive and anxiety symptoms. Our study identified novel associations such as pulmonary ground-glass opacity being positively associated with depression, anxiety, fatigue, and insomnia levels.

Recycling information can be complex and often confusing which may subsequently reduce the participations in any waste recycling schemes. As a result, this research explored the roles as well as the importance of a holistic approach in designing recycling information using 15 expert-based in-depth interviews. The rationale was to offer a better understanding of what constitutes waste, recycling, and how recycling information should be designed and presented to make recycling more attractive/convenient. Based on the research participants’ perceptions with supports from the existing studies, this research sub-categorised recycling information into three different themes, termed the “WWW” of recycling information components. As a result, these components (or attributes) were extensively described (using findings of semi-structured interviews) to elicit pragmatic guidance for practitioners, policy-makers, and other stakeholders in designing structured communication or information strategies that may simplify and subsequently increase waste-recycling practices. The policy implications of holistic information in enhancing recycling are further discussed.

Acute lower respiratory tract infection is a major health problem that affects more than 15% of the total population of Saudi Arabia each year. Epidemiological studies conducted over the last three decades have indicated that viruses are responsible for the majority of these infections. The epidemiology of respiratory viruses in Saudi Arabia is believed to be affected mainly by the presence and mobility of large numbers of foreign workers and the gathering of millions of Muslims in Mecca during the Hajj and Umrah seasons. Knowledge concerning the epidemiology, circulation pattern, and evolutionary kinetics of respiratory viruses in Saudi Arabia are scant, with the available literature being inconsistent. After reviewing the available data on epidemiology and evolution of respiratory viruses, this study examines the effect of varying vaccination rates across different age groups during the 2019/2020 influenza season in Saudi Arabia. Utilizing an age-structured SEIR (Susceptible–Exposed–Infectious–Recovered) model, it develops customized vaccination policies by considering age-specific incidence rates. This pioneering research segments the population into five age groups—infants and school-aged children, junior and older youth, young adults and adults, middle-aged, and seniors—across five regional areas in Saudi Arabis: Eastern, Central, Northern, Western, and Southern. A contact matrix, compiled from multiple sources, is used to delineate the dynamics of influenza transmission. The study undertakes a thorough comparison of three distinct vaccination scenarios: no vaccination, national vaccination, and optimized vaccine allocation policy, under various potential pandemic situations. It examines their impact on vaccination campaigns in terms of the total number of infections, mortality, and morbidity rates. The results emphasize the crucial impact of population demographics on disease transmission and vaccine distribution. According to the findings, the optimized vaccination scenario proved to be the most effective strategy in all scenarios.

Renal cell carcinoma (RCC) accounts for approximately 90-95% of all kidney cancers in adults, with the clear cell RCC (ccRCC) the most frequently identified subtype. RCC is known for its responsiveness to immunotherapy, making it an area of significant research interest. Immune checkpoint (IC) molecules, which regulate immune surveillance, are established therapeutic targets in RCC. The aim of this study was to analyze the influence of polymorphisms in genes HVEM and CD160 on susceptibility to ccRCC and patient overall survival (OS) with over a ten-year period of observation. We genotyped three HVEM single nucleotide polymorphisms (SNPs): rs1886730, rs2234167, and rs8725, and two CD160 SNPs: rs744877 and rs2231375, in 238 ccRCC patients and 521 controls. Our findings indicated that heterozygosity within rs2231375 and/or rs2234167 increases ccRCC risk. Furthermore, in women, heterozygosity within additional HVEM SNPs, rs8725 and rs1886730, is associated with an increased ccRCC risk. The presence of a minor allele for rs1886730, rs2234167, rs8725, and rs2231375 was also correlated with certain clinical features of the disease. Moreover, the rs1886730 SNP was found to be associated with patients' OS. In conclusion, our study highlights an association between HVEM and CD160 polymorphisms and the risk of developing ccRCC as well as patient’s OS.

Natural host defensins, also sometimes termed antimicrobial peptides, are evolutionarily conserved. They have been studied as antimicrobials, but some pharmaceutical properties, undesirable for clinical use, led to the development of synthetic molecules with constructed peptide arrangements and/or peptides not found in nature. The leading development currently is synthetic small molecule nonpeptide mimetics, whose physical properties capture the characteristics of the natural molecules, and share their biological attributes. We studied brilacidin, an arylamide of this type, for its activity in vitro against fungi (40 clinical isolates, 20 species) that the World Health Organization has highlighted as problem human pathogens. We find antifungal activity at low concentrations for many pathogens, which indicates further screening for activity, particularly in vivo, is justified to evaluate this compound, and other mimetics, as attractive leads for development of effective antifungal agents.

The global increase in population has placed significant pressure on food security, leading to the emergence of aquaculture as a vital source of aquatic foods. However, rising costs and the limited availability of fishmeal in aquafeeds have spurred the search for alternative protein sources. While plant-based ingredients have been integrated into commercial aquafeeds, they come with challenges, including low protein content, palatability issues, and the presence of antinutritional factors. In this context, fish silage, derived from fish waste and discarded fish, stands out as a promising alternative technology due to its cost-effectiveness and sustainability attributes. The production of fish silage involves the addition of organic/inorganic acids or lactic acid bacteria to homogenized fish waste. This process yields a valuable mixture rich in peptides, free amino acids, and partially hydrolyzed proteins, offering significant nutritional benefits for animal diets. Beyond its nutritional advantages, fish silage contributes to environmental sustainability by reducing the impact of waste disposal and enhancing the value of fish waste. The objective of this review is to promote sustainable practices in the aquaculture industry in response to the increasing demand for high-quality feed nutrients. To achieve this, it includes an analysis of research results related to silage technology, an appraisal of the advantages and disadvantages of using fish silage as a feed additive, and a focus on emerging trends in this field.

Every individual at some point encounters the progressive biological process of aging which is considered one of the major risk factors for common diseases. The main drivers of aging are oxi-dative stress, senescence, and Reactive oxygen species (ROS). The renin-angiotensin-aldosterone system (RAAS) includes several systematic processes for the regulation of blood pressure which is caused by an imbalance of electrolytes. During activation of RAAS, binding of angiotensin II (ANG II) to angiotensin II type I receptor (AGTR1) activates intracellular NADPH oxidase to generate superoxide anions and promote uncoupling of endothelial NO synthase, which in turn decreases NO availability and increases ROS production. Promoting oxidative stress and DNA damage mediated by ANG II is tightly regulated. Individuals with sodium deficiency-associated diseases such as Gitelman syndrome (GS) and Bartter syndrome (BS) show down-regulation of inflammation-related processes and have reduced oxidative stress and ROS. Additionally, the histone deacetylase-Sirtuin-1(SIRT1) has a significant impact on the aging process with reduced activity with age. However, GS/BS patients generally sustain higher levels of SIRT1 activity than aged-matched healthy individuals. In this review, we highlight the importance of the hallmarks of aging, inflammation, and the RAAS system in GS/BS patients and how this might impact healthy aging. We further propose fu-ture research directions for studying the etiology of GS/BS at the molecular level using pa-tient-derived renal stem cells and induced pluripotent stem cells.

The process of developing therapies to treat rare diseases is fraught with financial, regulatory, and logistical challenges that have limited our ability to build effective treatments. Recently, a novel type of therapy called antisense therapy has shown immense potential for the treatment of rare diseases, particularly through single-patient N-of-1 trials. Several N-of-1 antisense therapies have been developed recently for rare diseases, including the landmark study of milasen. In response to the success of N-of-1 antisense therapy, the Food and Drug Administration (FDA) has developed unique guidelines specifically for the development of antisense therapy to treat N-of-1 rare diseases. This policy change establishes a strong foundation for future therapy development, and addresses some of the major limitations that previously hindered the development of therapies for rare diseases.

: Background: Brain-derived neurotrophic factor (BDNF) is a crucial mediator of neuronal plasticity. Here, we investigated the effects of controlled normobaric hypoxia (NH) combined with physical inactivity on BDNF blood levels and executive functions. Methods: Twenty-five healthy adults (25.8±3.3 years, 15 female) were analyzed in a randomized, controlled cross-over study. Each intervention began with a 30 min resting phase under normoxia (NOR), followed by a 90 min continuation of NOR or NH (peripheral oxygen saturation [SpO₂] 85-80%). Serum and plasma samples were collected every 15 min. Heart rate and SpO₂ were continuously measured. Before and after each exposure, cognitive tests were performed and after 24 h another follow-up blood sample was taken. Results: NH decreased SpO₂ (p<.001, η_p²=.747) and increased heart rate (p=.006, η_p²=.116) significantly. The 30-min resting phase under NOR led to a significant BDNF reduction in serum (p <.001, η_p²=.581) and plasma (p <.001, η_p²=.362). Continuation of NOR further significantly reduced BDNF after another 45 min (p=.018) in serum and after 30 min (p=.040) and 90 min (p=.005) in plasma. There was no significant BDNF decline under NH. 24 h Follow-up examination showed a significant decline of serum BDNF, both after NH and NOR. Conclusion: Our results show that NH has the potential to counteract physical inactivity-induced BDNF decline. Therefore, our study emphasizes the need for a physically active lifestyle and its positive effects on BDNF. This study also demonstrates the need for a standardized protocol for future studies to determine BDNF in serum and plasma.

Background Gingivitis can develop without mechanical cleaning within three weeks. The first clinical sign is bleeding on positive probing. The accumulation of dental biofilm generates an inflammatory gingival response. In the past decade, attention has focused mainly on the interproximal areas and the use of customsized interproximal toothbrushes.The aim of the study was to evaluate the effectiveness of individualized oral hygiene education and its role in dental prevention among patients with dental problems. Methods Before treatment, patients were clinically and radiologically examined, full mouth plaque score (FMPS), full mouth bleeding score (FMBS), and bleeding on brushing (BOB) were recorded, and matrix-metalloproteinase-8 (MMP-8) was measured by using a chair-side MMP-8 measuring system. Patients in group A had gingivitis, but no periodontal damage and patients in group B had periodontal damage. Patients in both groups A and B were identified in to four subgroups based on their toothbrushing habits and the oral health education they received. The three months after initial examination, each patient was examined three more times (2, 4 and 12 weeks later). Results It was concluded that subjects in groups A1 and B1 showed significant reduction in BOB, MMP-8, FMBS and FMPS levels after two weeks. Solo Prophylaxis (A1and B1) remained as a well-constructed protocol with hte complete resolution of interdental inflammation after two weeks. Other subgroups achieved significant reductions only after 12 weeks. Conclusions BOB and MMP-8 are valuable complements in preventive dentistry, and are able to detect potential pathological processes in interproximal spaces. The clinical relevance of BOB, in addition to FMBS, FMPS and gingival inflammation can be demonstrated to patients, which may increase compliance.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

Background: While the clinical factors of the post-COVID-19 condition (PCC) are becoming clearer, the economic implications remain uncertain, posing a challenge to healthcare professionals in terms of understanding and managing this emerging phenomenon. This article aims to investigate the demographic and clinical characteristics of PCC patients and quantify the economic impact of their healthcare resource utilisation. Methods: A retrospective and case-control observational study was conducted, comparing the case group of PCC population before and after diagnosis with a control group. Demographic and clinical variables were analysed with the objective of describing the population. Economic analysis was performed to evaluate the resource costs in procedures and primary, secondary (both outpatient and inpatient) and emergency care. Findings: PCC patients (N=341) exhibited older age and elevated cardiovascular risk factors compared to controls (N=49,078). There were differences in the socio-economic distribution between male and female patients in the PCC patients. Hypertension and diabetes mellitus type 2 were the most common chronic diseases observed among the case patients. Economic analysis revealed that PCC patients were approximately four times as costly as control patients, with increased utilisation of healthcare resources. However, post-diagnosis PCC patients showed a reduction in costs, primarily driven by decreased primary care visits and hospitalisations. Conclusion: Coordinated care management for PCC patients is associated with reduced costs and improved healthcare resource utilisation. Further research is warranted to investigate long-term health outcomes and establish causal relationships between COVID-19 sequelae and healthcare resource utilisation.

The picornavirus genome encodes a large single polyprotein that is processed by viral proteases to form an active replication complex. The replication complex is formed with the viral genome, host proteins, and viral proteins that are produced/translated directly from each of the viral genomes (cis-provided viral proteins). Efficient complementation in vivo of replication complex formation by trans-provided viral proteins, thus exogenous or ectopically expressed viral proteins, remains to be demonstrated. Here we report an efficient trans-complementation system for the replication of defective poliovirus (PV) mutants by a viral polyprotein precursor in HEK 293 cells. Viral 3AB in the polyprotein, but not 2BC, was processed exclusively in cis. Replication of a defective PV replicon mutant, with a disrupted cleavage site for viral 3Cpro protease between 3Cpro and 3Dpol (3C/D[A/G] mutant) could be rescued by a trans-provided viral polyprotein. Only a defect of 3Dpol activity, of the replicon could be rescued in trans; inactivating mutations in 2CATPase/hel, 3B, and 3Cpro of the replicon completely abrogated the trans-rescued replication. An intact N-terminus of the 3Cpro moiety, of the trans-provided 3CDpro, was essential for the trans-rescue activity. By using this trans-complementation system, a high-titer defective PV pseudovirus (> 107 infectious units per mL) could be produced with the defective mutants, whose replication was completely dependent on trans-complementation. This work reveals potential roles of exogenous viral proteins in PV replication and offers insights into protein/protein and protein/RNA interactions during picornavirus infection.

CO2 emission activity of xylotrophic fungi response to an increase in temperature in the range of 10-30 °C on the example of pure dikaryotic cultures of Fomes fomentarius s. str., F. inzengae, Fomitopsis betulina, F. pinicola, Phellinus igniarius was analyzed. Emission activity was assessed by the difference in CO2 concentration in 0.5-liter exposure chambers with Petri dishes with mycelium growing on agar at the beginning of exposure and an hour later using a Gasmet DX-4030 FTIR spectrometer (Gasmet Technologies Oy, Finland), error measurements ±50 ppm. Specific (μg CO2/cm2/h) and total (μg CO2/h) emission activity and its relationship with temperature and size (area) of the mycelium were assessed. It has been shown that in the range of 10-30 °C, the specific and total CO2 emission activity of the mycelium is closely and positively related to temperature. Specific emission, which is an indicator of the respiratory activity of the mycelium, does not depend on its size; its only driver is temperature, the relationship with which is linear: an increase in temperature by 10 °C causes an increase in the specific emission activity of the mycelium by 1.7 times. The total CO2 emission activity, which is an indicator of the total amount of CO2 emitted, is directly proportional to the specific emission activity and the size of the mycelium. In the range of 10-30 °C, an increase in temperature causes an almost equal increase in both the specific emission activity of the mycelium (Q10 1.7) and its growth (Q10 1.5) and causes an exponential increase in the total emission of CO2. This must be taken into account when predicting CO2 emissions from woody debris under climate change, as it could potentially contribute to accelerating climate change.