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.

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.

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.

Idiopathic pulmonary fibrosis, a chronic and fatal condition with no effective cure, is a challenging disease within the group of interstitial lung diseases. The pathogenic mechanisms of this disease are still not fully understood. In this context, the research on miRNAs, which are small non-coding RNAs that regulate messenger RNAs, is of utmost importance. These miRNAs, released into the circulation outside the cell through exosomes, play a crucial role in the pathogenic pathways and mechanisms involved in IPF development. The analysis of miRNAs in the serum/plasma of IPF patients has opened up new possibilities in the search for biomarkers. This review focuses on circulating miRNAs validated by real-time PCR in IPF and the evidence reported about the pulmonary fibrotic process.

Medication non-adherence remains a substantial obstacle in asthma care, prompting the exploration of novel therapeutic modalities that prioritize rapid symptom relief, anti-inflammatory activity and facilitate patients’ compliance. This task is well served by a new form of therapy - inhaled triple-combination medications ICS/LABA/LAMA (inhaled glucocorticosteroid/long-acting beta2-agonist/long-acting muscarinic antagonist). The integration of three medications within a singular inhalation device culminates in the reduction of the effective dose of the principal therapeutic agent for asthma management, namely, ICS. This consolidation yields a dual benefit of minimizing the likelihood of adverse effects typically linked with ICS while concurrently optimizing bronchodilator efficacy. The accumulated evidence suggests that adding LAMA to a medium- or high-dose ICS/LABA results in a decrease of asthma exacerbations compared to medium- or high-dose ICS/LABA alone, accompanied by sustained enhancements in lung function parameters. We propose in adult patients experiencing suboptimal asthma control despite medium/high-dose ICS/LABA treatment - regardless of adherence to GINA-recommended strategies, such as MART therapy as a first-line approach or alternative second-line strategies - the preferred course for intensifying asthma therapy involves the addition of a LAMA, ideally in the form of SITT.

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.

Proteomics in respiratory allergic diseases has such a battery of techniques and programs that one would almost think that there is nothing impossible to find, invent or mold. All these resources that we document here, are involved in solving problems in allergic diseases, both diagnostic, prognostic, treatment and immunotherapy development. The main perspectives, according to this version, are in three strands and / or lockout immunological system: 1) In blocking the diapedesis of cells involved, 2) modifications and blocking of paratopes and epitopes being understood by modifications to antibodies, antagonism or blocking them and 3) blocking FcεR1 receptors to prevent specific IgEs from sticking to mast cells and basophils. These tools and targets in the allergic landscape are, in our view, the prospects in the field.

Eosinophils are key therapeutic targets in severe asthma as they accumulate in tissues, resulting in local damage through the release of toxic mediators. Benralizumab is a monoclonal antibody with a direct anti-eosinophilic activity that has proved significant clinical efficacy in patients with severe eosinophilic asthma, and its use in real-life went well beyond what we had expected from the pivotal trials, especially in the reduction of asthma exacerbations and oral steroids usage. Benralizumab induces eosinophil apoptosis due to a mechanism of antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells. Within this review, we will discuss benralizumab pharmacological and pharmacokinetic aspects in the treatment of severe asthma, with an emphasis on the novel immunological effects of benralizumab on NK cells. Overall, these findings account for the clinical efficacy and safety profile of benralizuamb, previously described in patients with an eosinophilic phenotype of the disease.

A case-crossover study examined how PM_2.5 from Asian Dust Storms (ADS) affects the number of emergency room (ER) admissions for cardiovascular diseases (CVDs) and respiratory diseases (RDs). Our data indicated that PM_2.5 concentration from ADS was highly correlated with ER visits for CVDs and RDs. The odds ratios (OR) increased by 2.92 (95% CI: 1.22-5.08) and 1.86 (95% CI: 1.30-2.91) per increase 10 µg/m³ in PM_2.5 levels, for CVDs and RDs, respectively. A 10 µg/m³ increase in PM_2.5 from ADSs was significantly associated with increase in ER visits for CVDs among those 65 years of age and older (an increase of 2.77 in OR) and for females (an increase of 3.09 in OR). In contrast, PM_2.5 levels had a significant impact on RD ER visits among those under 65 years of age (OR=1.77). The risk of ER visits for CVDs increased on the day when the ADS occurred in Taiwan and the day after (lag 0 and lag 1); the corresponding risk increase for RDs only increased on the fifth day after the ADS (lag 5). In Taiwan’s late winter and spring, the severity of ER visits for CVDs and RDs increases. Environmental protection agencies should employ an early warning system for ADS to reduce high-risk groups’ exposure to PM_2.5.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

Monkeypox (mpox) caused by the monkeypox virus (MPXV) is currently the most common orthopoxvirus (OPXV) zoonotic disease. Since 2022, a multi-country outbreak of mpox has been reported with atypically rapid human-to-human transmission. The present work aimed to investigate the frequency of MPXV and OPXV DNA detection in different clinical materials taken at acute and convalescent phases of the infection in Bulgarian patients. A total of 181 clinical samples from 42 Bulgarian patients with possible mpox infections were tested. Screening for MPXV DNA (F3L gene) and OPXV DNA (rpo18 gene) were performed by real-time PCR assays. Of all tested patients six (14%) were confirmed with mpox infection. MPXV DNA was detected in 23/181 (12,71%) and OPXV DNA in 20/181 (11,05%) clinical samples. All confirmed patients were men who have sex with men, aged 23 to 44 (at an average age of 35,17±7,91 years) and two of them were HIV positive. The commonest clinical features of patients were fever (5/6), vesicular-pustular rash: perianal (6/6), penile (4/6), and limbs (4/6). MPXV DNA was found with the greatest frequency in specimens of vesicle contents and nasal/oropharyngeal swabs in 6/6 and 5/6. OPXV DNA mainly was detected in vesicle contents (6/6), nasal/oropharyngeal swabs (4/6), and urine (4/6). In the collected follow-up samples, MPXV DNA was detected in the highest percentage in the specimen's vesicle contents (6/6) and urine (6/6) and not demonstrated in samples of feces and saliva. The laboratory surveillance of MPXV is critical to contain the outbreak and to elucidate the new fast transmission of the virus.

This review examines the effects of lingonberry (Vaccinium vitis-idaea L.) on general and oral health. The effects of lingonberry are based on the vitamins, minerals, fibers and polyphenolic compounds it contains. Lingonberry's bioactive substances have a diverse range of antimicrobial, anti-inflammatory, antiproteolytic, anticarcinogenic and antioxidant properties. Research results suggest that lingonberries can have a positive effect on human health. Berries, lingonberry juice/lingonberry nectar/fermented lingonberry juice and polyphenol fractions have been used in clinical studies. Lingonberries balance post-meal blood sugar, free fatty acids and insulin levels. Fermented lingonberry juice reduces Streptococcus mutans, Candida and periodontal pathogen counts, but is probiotic because it favors growth of Lactobacilli. In addition, it increases saliva secretion and thus lowers the risk of oral infections. It lowers the clinical parameters of periodontitis and the active matrix metalloprotease-8, reducing the low-grade inflammation associated with periodontal diseases. More studies on humans are needed.

Darier disease (DD) is an autosomal dominant disorder due to mutation of ATP2A2 gene causing an isolated skin manifestation based on keratinocyte disconnection and apoptosis. Systemic manifestations of DD have not been demonstrated so far although a high incidence of neuropsychiatric syndromes suggest an involvement of central nervous system. A Novel ATP2A2 Gene Mutation c.118G>A, causing keratinocyte and cardiomyocyte disconnection in Darier disease, is reported. Their common pathologic pathway, still unreported, was documented by both skin and left ventricular endomyocardial biopsy because of cardiac dilatation and dysfunction appeared several decades after skin manifestations.Keratinocyte disconnection was paralleled by cardiomyocyte separation at lateral junction. Cardiomyocyte separation was associated to cell disarray, sarcoplasmic reticulum dilatation and increased myocyte apoptosis. Clinically, hyperkeratotic skin papules were associated to chest pain, severe muscle exhaustion and ventricular arrhythmias that improved following administration of aminophylline, a phosphodiesterase inhibitor enhancing SERCA2 protein phosphorylation.Specific mutations of ATP2A2 gene may cause cardiac involvement in patients with DD. Cardiac pathologic changes are similar to those documented in the skin including cardiomyocyte disconnection that promotes precordial pain and cardiac arrhythmias. Phosphodiesterase inhibitors, enhancing SERCA2 protein phosphorylation may substantially attenuate the symptoms.

Mammarenavirus Wenzhouense (WENV) is broadly distributed in Asia, while the he dynamics process of WENV infection remains unclear. A field derived strain of WENV was used to inoculate Sprague-Dawley (SD) rats by intramuscular injection, the process of virus infection was de-tected by controlling time for 28 days. Viral RNA became detectable in the blood at 3 d pi, and remained detectable for about 12 d. In most organ tissues, viral RNA peaked at 7 d pi, then began to decline by 14 d, however remained detectable in intestine and brain tissues at 21 and 28 d pi. Virus shedding had been detected from fecal samples for 5 days from 6 to 11 d pi using qRT-PCR, and was recovered from feces collected at 8 d pi. Horizontal contact infection occurred among cage-mates at 14 and 21 d pi. Antibodies against the nucleocapsid were detected at 5 dpi, next increased and persisted until the end of experiment. The results enabled to discriminate the kinetic of viremic response, virus shedding in feces and horizontal transmission, as well as the potential sites for WENV replication or maintenance of the virus in nature.

Aim: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been in the past associated with adverse effects on human health among which belong also respiratory diseases. Our study is focused on the evaluation of PAH exposure by measuring the concentrations of their monohydroxylated metabolites (OH-PAHs) in urine and comparing their concentrations with the incidence of respiratory diseases in 2-year-old children from two locations of the Czech Republic – a control locality Ceske Budejovice and a previously highly contaminated mining district Most. Methods: The total number of 248 participants were sampled for urine samples that were analysed for the presence of 11 OH-PAHs using liquid-liquid extraction with ethyl acetate and clean-up employing dispersive solid phase extraction with a sorbent Z-Sep. Separation, identification and quantification of the target compounds was achieved by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The incidence of respiratory diseases was evaluated according to the questionnaires provided by the paediatricians. Results and discussion: The concentrations of measured OH-PAHs were higher in the urine samples collected from 2-year-old children living in Most compared to 2-year-old children from Ceske Budejovice. The same trend was observed also when the urine samples were analysed when these children were studied as newborns in our previous study. From all of the monitored respiratory diseases, only influenza due to unidentified influenza virus showed a difference between tested locations where the 2-year-old children living in Most were more frequently diagnosed with this disease. Conclusion: Even though the air pollution and lifestyle in both cities is very similar, we have observed higher incidence of respiratory diseases as well as higher concentration of OH-PAHs in urine of the 2-year-old children from Most. Therefore, we hypothesize that the population living in this previously highly contaminated location (in 1970s and 1980s) can carry some long-term health burden.

Respiratory Syncytial Virus is a common respiratory pathogen known for causing respiratory illnesses, ranging from mild symptoms to severe lower respiratory tract infections in infants and the elderly. This virus is responsible for one-third of pneumonia deaths in the pediatric population, but there are currently only a few effective vaccines and pharmacological treatments. The frac-talkine (CX3CL1) receptor (CX3CR1) is a co-receptor for RSV expressed by airway epithelial cells and a diversity of immune cells. Recent research has highlighted the role of CX3CR1 in the host immune response to RSV infection, and its potential role in the development of an efficient vaccine and novel treatments.

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.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes owing to COVID-19 include QT prolongation and ST-T changes; however, there have been no studies on ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24-h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 a 76-year-old man with hypertension and diabetes, and Case 3 a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. LP, TWA, HRV, and HRT were all positive in three cases with no significant structural cardiac disease at the initial phase of admission. There is a possibility that LP, TWA, HRV, and HRT have the potential to be risk stratifiers of COVID-19 pneumonia in the early phase of admission. Further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed.

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 < 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.

Idiopathic pulmonary fibrosis (IPF) is a difficult to treat condition to treat with a high mortality rate. While preclinical models such as Bleomycin (Bleo)-induced fibrosis recapitulate some aspects of IPF, new models that more closely mimic the disease are warranted. We have developed and characterized a novel model in BALB/c mice using a transient overexpression of IL-6 combined with Bleo. This model’s transcriptomic signature was compared to published human IPF datasets. BALB/c females were treated with AdIL-6 in combination with Bleo (AdIL-6+Bleo) or control comparators, and underwent assessments of histopathology (ECM, α-SMA accumulation), collagen content and lung physiology (Elastance, EST). Flow cytometry was used to characterize T cell and Macrophage subsets, and T cell depletion studies (anti-CD4/CD8) were completed to assess T cells role in fibrosis. Bulk RNA sequencing generated gene signatures were compared to that of other rodent fibrosis models and published human datasets of IPF datasets. The AdIL-6+Bleo treatment resulted in robust fibrosis measures (day21), sustained fibrosis until at least day 50, a unique cytokine profile at day 7, and increased activated CD4+Tcells, CD8+Tcells, and CD16+MHChi/Clec7a/iNOS-/Arg1-/CD206- macrophages. T cell depletion markedly decreased fi-brotic responses and this population of macrophages. The Day 21 AdIL-6+Bleo transcriptome shared more genes with each of two human IPF datasets than Bleo alone in C57Bl/6 mice or other rodent models. We conclude that AdIL-6+Bleo in BALB/c mice offers a superior preclinical model for studying IPF mechanisms and potential therapeutic intervention.

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.

Chronic obstructive pulmonary disease (COPD) patients are particularly susceptible to respiratory infections like influenza, which exacerbate symptoms and increase healthcare utilization. While smoking cessation and influenza vaccination are recommended preventive measures, their combined impact on healthcare resource utilization is underexplored. The Charlson Comorbidity Index (CCI) assesses comorbidity burden in COPD patients and may influence healthcare outcomes. We conducted a retrospective analysis of 357 COPD patients, evaluating smoking cessation success over one year and influenza vaccination receipt, stratifying patients by CCI scores. Healthcare utilization outcomes included emergency room visits, hospitalizations, and medical expenses. Results showed that 51.82% of patients quit smoking and 59.66% received influenza vaccination, with higher comorbidity prevalence in advanced COPD stages (p=0.002). Both smoking cessation and influenza vaccination independently correlated with decreased emergency room visits, hospital admissions, days, and costs. Patients who both quit smoking and received influenza vaccination exhibited the lowest healthcare utilization rates. In conclusion, smoking cessation and influenza vaccination significantly reduce healthcare resource utilization in COPD patients, with the combination yielding synergistic benefits, particularly in those with lower CCI scores. Integrating these interventions and comorbidity management in COPD strategies is essential for optimizing patient outcomes and healthcare efficiency.

Background: The secretion of alarmin cytokines by epithelial cells, including thymic stromal lymphopoietin (TSLP), interleukin (IL)-25, and IL-33, heralds the onset of the inflammatory cascade and immune effector infiltration in asthma. However, alarmin cytokine expression in the upper airways in asthma remains largely unknown. Methods: We recruited 40 participants with asthma who were categorized into four severity groups as per the Global Initiative for Asthma (GINA) classifications (10 in each group of GINA-1/2, -3, -4, and -5). Cells were derived from buccal, nasal and throat brushings, and intracellular alarmin cytokine expression (TSLP, IL-25, and IL-33) was assessed in cytokeratin 8+ (Ck8+) epithelial cells immediately after collection using flow cytometry with fluorescence minus one (FMO) controls. We assessed differences in alarmin cytokine expressions across asthma severity using quantile regression adjusted for age and sex. Results: Of all patients, 24 (60%) were females with a mean (standard deviation [SD]) age of 41 (16) years. TSLP levels in Ck8+ epithelial cells in nasal samples of GINA-5 patients were significantly (p=0.03) higher than other GINA groups after adjusting for age and sex but did not differ between patients with and without nasal comorbidities. However, we did not find any significant changes in TSLP levels in Ck8+ epithelial cells in buccal and throat samples across GINA groups. IL-25 or IL-33 (obtained from nasal, buccal, and throat epithelial cell samples) were not significantly different across GINA groups. Conclusions: Our study demonstrates for the first time that Ck8+ nasal epithelial cells from GINA-5 asthmatics express elevated levels of TSLP.

Background: Features of post-traumatic stress disorder and anxiety may be present in Pulmonary Embolism (PE) patients along with impaired Quality of Life (QoL). We aim to evaluate health related QoL, anxiety and satisfaction with life, during the pandemic, in patients with a PE. Methods: Patients with PE were enrolled during their follow-up. All participants completed the Short Form 36 (SF-36) questionnaire, the State Trait Anxiety Inventory (STAI) X1 and X2 form, and the Satisfaction with Life Scale (SWLS). Results: 92 PE patients were included (mean age±SD=62.50±15.33 years, 56.5% males). Most of the mean values of the SF36 subscales were above the normative value except for “physical role functioning”) (45.92±42.41). “Emotional role functioning” (51.26±43.31) and “general health perceptions” (GH) (54.02±18.79) were slightly above the normative value of 50. Mean STAIX1 levels were 37.05±11.17 and mean STAIX2 levels were 39.80±10.47. Mean SWLS levels were 23.31±6.58. According to multiple linear regression analysis, mental healthscore (MH) and GH were predictive of SWLS(F (10,76) = 10.576, p

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.

Several recent studies have indicated that miR-30a plays critical roles in various biological processes and diseases. However, the mechanism of miR-30a participation in the regulation of idiopathic pulmonary fibrosis (IPF) is ambiguous. Our previous study demonstrated that miR-30a may function as a novel therapeutic target for lung fibrosis by blocking mitochondrial fission, which is dependent on dynamin-related protein-1 (Drp-1). However, the regulatory mechanism between miR-30a and Drp-1 has yet to be investigated. In addition, whether miR-30a can act as a potential therapeutic has not been verified in vivo. In this study, the miR-30a expression in IPF patients was evaluated. Computational analysis and a dual luciferase reporter system assay were used to identify the target gene of miR-30a, and cell transfection was used to confirm this relationship. Ten-eleven translocation 1 (TET1) was validated as a direct target of miR-30a, and the transfection of miR-30a mimic/inhibitor significantly reduced/increased the expression of TET1 protein. Further experiment verified that the interference on TET1(siRNA) could inhibit the hydroxymethlation of the Drp-1 promoter. Finally, miR-30a agomir was designed and applied to identify and validate the therapeutic effect of miR-30a in vivo. Our study demonstrated that miR-30a could inhibit the TET1 expression by base pairing with complementary sites in the 3′ untranslated region to regulate the hydroxymethlation of the Drp-1 promoter. Furthermore, miR-30a could act as a potential therapeutic target for IPF.

In February 2004, the Food and Drug Administration (FDA) was the first to approve the combination of cisplatin (CDDP) and pemetrexed (PEM) as standard first-line chemotherapy for untreated, unresectable malignant pleural mesothelioma (MPM). However, after that approval, no progress was made in the standard first-line treatment of MPM for almost 15 years. Positive results from a phase 3 study (Mesothelioma Avastin Cisplatin Pemetrexed Study: MAPS) verifying the effect of bevacizumab, an anti-angiogenesis agent added to CDDP/PEM for unresectable MPM, were published in The Lancet in December 2015; however, this did not lead to approval by national drug regulatory agencies. Furthermore, no second-line treatment was established for cases refractory to CDDP/PEM. In August 2018, the Pharmaceuticals and Medical Devices Agency of Japan was the first in the world to approve monotherapy with nivolumab, an immune checkpoint inhibitor (ICI), for previously unresectable, advanced, or recurrent MPM. Following Japan, in October 2020, the FDA approved the combination of nivolumab and ipilimumab for the treatment of previously untreated, unresectable MPM. In this article, we review the transition of drug treatment for MPM, in light of the historical background, focusing on the benefits of ICIs.

Hemophagocytic lymphohistiocytosis (HLH) is a serious haematologic condition that can be re-lated to various diseases, including tuberculosis (TB). The patient is a previously healthy 26-years-old man, originally from Western Africa, admitted to hospital for fever and weight loss. Given the results of computed tomography (CT) scan, ocular examination and microbiologic tests, a miliary TB with pulmonary, lymph nodal and ocular involvement was diagnosed. Following introduction of antitubercular treatment (ATT) an increase in inflammation indexes and severe pancytopenia were observed; at this point the patient presented six of eight diagnostic criteria for HLH and the diagnosis of HLH secondary to TB was raised. Therefore, HLH treatment with high dose of dexamethasone was started with a good clinical response. We performed a literature re-view of TB-related HLH, which shows a high mortality rate; ATT is necessary to ensure patient survival to remove the antigenic driver. Our patients developed HLH after initiation of ATT as a paradoxical reaction, that may be linked to the release of antigens due to the bactericidal effect of ATT.

Introduction: Although aging is a natural phenomenon, in recent years it has accelerated. One key factor implicated in the aging process is oxidative stress. Oxidative stress play also role in frailty (frail) and metabolic syndrome (MetS). Methods: 66 elderly persons (65 years old and older) with no acute or severe chronic disorders were assessed: waist circumference (WC), arterial blood pressure, glycemia, glycated hemoglobin (HbA1c), plasma lipids and activity of erythrocyte superoxide dismutase (SOD-1). Patients were classified as NonMetS-Nonfrail (n=19), NonMetS-frail (n=20), MetS-Nonfrail (n=17), and MetS-frail (n=10). Results: There were no significant differences in superoxide dismutase activity among investigated elderly groups. However, the data suggests that MetS individuals, both frail and nonfrail, have higher risk factors for cardiovascular disease compared to NonMetS individuals. The correlations analyses of SOD-1 and other metabolic indices suggest that SOD-1 levels may be influenced by age, total cholesterol, HDL cholesterol, and fasting glucose levels in certain groups of seniors. Conclusions: Aging is associated with decreased antioxidant enzyme SOD-1 activity with glucose alteration in frailty syndrome as well as with lipids disturbances in metabolic syndrome.

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.

Many ailments can be diagnosed while they are asymptomatic, meaning that the patient has no signs or symptoms of a progressing disease. If caught in their initial stage of formation, these maladies can be effectively treated, leading to successful outcomes; curative therapies can halt illnesses from advancing, thus improving the quality of life, and long-term survival of the patient. Still cutting-edge upgrades in precision technologies are necessary for early, reliable, affordable, and rapid disease detection, but also are vital for the well-being of people and the future of global public health. The emerging role and utility of non-invasive and repeatable diagnostic test approaches for detection of health conditions has been liquid biopsies based on genomic biomarkers. As such, biological fluids permit any measurable molecular indicator or signature (e.g., proteins), to provide valuable information on individual’s wellness and/or disease. Among the bodily secretions used for non-invasive diagnostics is sputum, a complex viscous gel-like biopolymeric network, that has gained growing recognition as a rich source of biomarkers of airway infections, pulmonary diseases, and serves as a determinant to reveal other illnesses. As per the World Health Organization, the burden of respiratory conditions is exacerbated by factors, ranging from considerable subjection to air pollution and occupational contaminants, to tobacco smoking and second-hand smoke, in addition to poor socio-economic status. Due to the likely increase of these determinants, respiratory tract ailments are on the rise, affecting the health of many individuals, in addition to putting stress on healthcare facilities and services worldwide. We therefore highlight the need to use expectorated or induced sputum specimens as a routine sample source for testing valuable protein biomarkers to diagnose these chronic maladies, to predict inflammation and disease progression, as well as monitor the effectiveness of treatments. Further, we discuss the urgency for fast and reliable point-of-care methods to detect and quantify crucial protein biomarkers in sputum specimens, and limitations faced when dealing with their complex matrices.

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.

The short study implicates few basic similarities of COVID-19 such as diseases origination, symptoms, diagnosis with other relatable viral diseases viz SARS-CoV, common Flu, pneumonia etc. In the present situation, other viral diseases are frequently chaotic and misled with COVID-19 disease because of few clinical features similarities in signs and symptoms and also due to lack of specific diagnostic test. To avoid unnecessary suspects, quarantines of false positive results and to prevent the spread of COVID-19 diseases, the scientific technical research field are highly encourage to implement an efficient, rapid and sophisticated superior test for early stages of infection detection. It will be significantly convenient for physician, laboratory technicians and most importantly the common population facing a psychological disturbance.

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 < 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.

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.

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.

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.

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).

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.

In July 2017, a family of three members; a 46-year-old male, a 45-year-old female and their 8-year-old daughter, returned to South Africa from Thailand. They presented symptoms consistent with mosquito-borne diseases, including fever, headaches, severe body aches and nausea. Mosquito bites in all family members suggested recent exposure to arthropod-borne viruses. Dengue virus 1 (Genus Orthoflavivirus) was isolated (isolate no. SA397) from the serum of the 45-year-old female via intracerebral injection in neonatal mice and subsequent passage in VeroE6 cells. Phylogenetic analysis of this strain indicated close genetic identity with cosmopolitan genotype 1 DENV1 strains from Southeast Asia, assigned to major lineage K, minor lineage 1 (DENV1I_K.1), such as GZ8H (99.92%) collected in November 2018 from China and DV1I-TM19-74 isolate (99.72%) identified in Bangkok, Thailand, in 2019. Serum samples from the 46-year-old male yielded a virus isolate that could not be confirmed as DENV1, prompting unbiased metagenomic sequencing for virus identification and characterization. Illumina sequencing identified multiple segments of a Mammalian orthoreovirus (MRV), designated Human/SA395/SA/2017. Genomic and phylogenetic analysis classified Human/SA395/SA/2017 as MRV-3 and assigned a tentative genotype MRV-3d based on the S1 segment. Genomic analyses suggested Human/SA395/SA/2017 may have originated from reassortments of segments among swine, bat, and human MRVs. The closest identity of the viral attachment protein σ1 (S1) was related to a human isolate identified from Tahiti, French Polynesia, in 1960. This indicates ongoing circulation and cocirculation of Southeast Asian and Polynesian strains, but detailed knowledge is hampered by limited availability of genomic surveillance. This case represents a rare concurrent importation of two distinct viruses with different transmission routes in the same family with similar clinical presentations. It highlights the complexities of diagnosing diseases with similar sequelae in travellers returning from tropical areas.

Immunity against respiratory pathogens is often short-term, and consequently there is an unmet need for effective prevention of such infections. One such infectious disease is COVID-19, which is caused by the novel Beta coronavirus SARS-CoV-2 that emerged around the end of 2019. The World Health Organization declared the illness a pandemic on March 11, 2020, and since then it has killed or sickened millions of people globally. The development of COVID-19 systemic vaccines, which impressively led to a significant reduction in disease severity, hospitalization, and mortality, con-tained the pandemic's expansion. However, these vaccines have not been able to stop the virus from spreading because of the restricted development of mucosal immunity. As a result, breakthrough infections have frequently occurred and new strains of the virus have been emerging. Furthermore, SARS-CoV-2 will likely continue to circulate and, like the influenza virus, co-exist with humans. The upper respiratory tract and nasal cavity are the primary sites of SARS-CoV-2 infection and thus, a mucosal/nasal vaccination to induce a mucosal response and stop the virus transmission is warrant-ed. In this review, we present the status of the systemic vaccines, of the approved mucosal vaccines and those under evaluation in clinical trials. Furthermore, we present our approach of a B-cell pep-tide-based vaccination applied by prime-boost schedule for eliciting both systemic and mucosal immunity.

Objective: Several authors have analyzed the impact of the pandemic on the incidence rates of different conditions. Our aim was to analyze the impact of the COVID-19 pandemic on primary care new diagnoses of respiratory diseases. Methods: This was an observational retrospective study performed to describe the impact of COVID-19 pandemic on primary care new diagnosis of respiratory diseases other than lung cancer. Incidence rate ratio between pre-pandemic and pandemic period was calculated. Results: We found an decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications. Instead, we found increases in new diagnoses of flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). Conclusion: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic. The real clinical impact of this situation is still unknown. Large-scale real-life studies will make it possible to evaluate the long-term true impact of COVID-19 pandemic on the respiratory diseases management.

The 2019 novel coronavirus (2019-nCoV) causes novel coronavirus pneumonia (NCP). Given that approved drug repurposing becomes a common strategy to quickly find antiviral treatments, a collection of FDA-approved drugs can be powerful resources for new anti-NCP indication discoveries. In addition to synthetic compounds, Chinese Patent Drugs (CPD), also play a key role in the treatment of virus related infections diseases in China. Here we compiled major components from 38 CPDs that are commonly used in the respiratory diseases and docked them against two drug targets, ACE2 receptor and viral main protease. According to our docking screening, 10 antiviral components, including hesperidin, saikosaponin A, rutin, corosolic acid, verbascoside, baicalin, glycyrrhizin, mulberroside A, cynaroside, and bilirubin, can directly bind to both host cell target ACE2 receptor and viral target main protease. In combination of the docking results, the natural abundance of the substances, and botanical knowledge, we proposed that artemisinin, rutin, glycyrrhizin, cholic acid, hyodeoxycholic acid, puerarin, oleanic acid, andrographolide, matrine, codeine, morphine, chlorogenic acid, and baicalin (or Yinhuang Injection containing chlorogenic acid and baicalin) might be of value for clinical trials during a 2019-nCov outbreak.

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.

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.

The objective of this study was to investigate the impact of athletes' respiratory muscle strength, as assessed through maximal inspiratory (MIP) and expiratory pressure (MEP), on aerobic endurance, as indicated by maximal oxygen consump-tion (Max VO2) kinetics. Respiratory muscle strength was assessed using a digital spirometer (Pony FX Cosmed, Italy), while maximal oxygen utilization capacity was measured using a breath-by-breath automatic portable gas analysis system (Cosmed K5, Italy). Statistical analysis was conducted utilizing SPSS 22.0. Based on the standardized regression coefficients (β), it was found that MEP (mean ± SD: 130.95 ± 42.82) and inspiratory diaphragmatic circumference values significantly influenced ventilatory equivalent (VE), oxygen consumption (VO2), and carbon dioxide pro-duction (VCO2). Conversely, the remaining predictor variables did not exhibit a sig-nificant effect on VE (mean ± SD: 134.80 ± 36.69), VO2 (mean ± SD: 3877.52 ± 868.47 ml), and VCO2 (mean ± SD: 4301.27 ± 1001.07 ml). In contrast, measurements of chest circumference (mean ± SD: 91.40 ± 10.72 cm), MEP, and diaphragmatic cir-cumference during inspiration (mean ± SD: 95.20 ± 10.21 cm) were found to signifi-cantly impact Max VO2 (mean ± SD: 58.52 ± 10.74 ml/kg/min), while the other pre-dictor variables did not demonstrate a significant effect on Max VO2. Conclusively, the study revealed that measured values of diaphragmatic circumference during inspiration and MEP exerted a notable influence on Max VO2, VE, VO2, and VCO2. Our findings underscore the importance of considering respiratory muscle strength in assessing and enhancing athletes' aerobic performance. These insights contribute to a deeper understanding of the interplay between respiratory function and exercise capacity, offering potential avenues for optimizing training regimens and perfor-mance outcomes in athletic contexts.

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.

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.

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.

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.

Aortic stenosis (AS) is a prevalent valvular disorder that often requires surgical aortic valve replacement (SAVR) to alleviate symptoms and improve survival. However, the selection of an appropriate prosthetic valve size is crucial to avoid patient-prosthesis mismatch (PPM), which can lead to suboptimal hemodynamic outcomes. Von Willebrand factor (VWF), a key component of hemostasis, has been shown to be altered in AS patients and may contribute to the hemostatic imbalance observed following valve replacement. This prospective study aimed to investigate the impact of PPM on postprocedural VWF levels in patients undergoing SAVR for severe AS. The study included 31 consecutive patients diagnosed with severe AS who underwent SAVR. By focusing on the relationship between PPM and VWF dynamics, this study sought to provide valuable insights into the potential role of VWF as a marker for hemostatic changes associated with PPM, ultimately informing strategies for optimal valve selection and perioperative management to minimize complications.

The persistence of symptoms following COVID-19 infection represents a significant challenge in healthcare management. During the outbreak, tele-rehabilitation emerged as a new tool to support healthcare structures in providing rehabilitation services. This study assessed the effectiveness and the feasibility of a 3-week home-based motor and respiratory rehabilitation program for long COVID-19 individuals after traditional rehabilitation. Twenty-three patients completed the program and underwent functional tests at different time points (i.e. baseline, after hospital discharge, and after tele-rehabilitation). Motor function was evaluated using the instrumented Six-Minutes Walking Test (i6MWT), with monitored heart rate and oxygen saturation. Conversely, respiratory function was measured via forced vital capacity (FVC) and maximal voluntary ventilation (MVV) tests. Significant improvements (p &lt; 0.05) in motor and respiratory function were observed throughout the intervention, including an 18.3% increase in walked distance from the baseline. The findings suggest that a home-based tele-rehabilitation can enhance motor and respiratory function in post-COVID patients. Despite limitations such as sample size and lack of control group, the positive outcomes seem to support the feasibility of the proposed tele-rehabilitation program in managing long COVID symptoms and promoting functional recovery. Further research is needed to validate these findings and explore tele-rehabilitation’s potential in broader patient populations.

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

The output of non-ferrous metal smelters is 450,000 tons (3.1% of world output), and copper ranks 10th in the world for health impact evaluation. According to the latest information from smelters, the overall average concentration in 2020 was 8.2 ppb each of SO2, NO2, O3, PM10, and PM2.5. 7.5 ppb, 30.8 ppb, 21.3 μg/m3, and 13.2 μg/m3, and the maximum concentrations were 390 ppb, 50 ppb, 167 ppb, 148 μg/m3, and 107 μg/m3. Art Corporation, A2C (Atmosphere to CFD) model was used to investigate the resident health follow-up management (cohort study) study (SAS Enterprise Guide) as the basis for the source of diffuse pollution in the area. The average concentration of PAHs (polynuclear aromatic hydrocarbons) among carcinogens in the air by survey site was the highest in Seokpo 4-ri (60.7 ng/m3), followed by Seokpo 1-ri (48.6 ng/m3) and Seokpo. Among the respiratory diseases, the disease (Acute upper respiratory tract disease(J00-J06), Other upper respiratory tract diseases (J32-J39), Acute lower respiratory tract infection (excluding pneumonia) (J20-J22), Chronic lower respiratory disease (persons) (excluding J40-J47, J45-J46), Asthma (J45-J46), Rhinitis (J30-J31), Respiratory disease (J00-J99), Cough (R05)) that has a correlation between the exposed area and the control area is as follows.

Introduction: The association between epilepsy and myasthenia gravis has rarely been reported, and only in small case series. Objective: To report the frequency of epilepsy and myasthenia gravis and to describe a case series of patients with myasthenia gravis and epilepsy, focusing on their clinical characteristics and searching for a possible physiopathological mechanism. Methods: A retrospective, observational, adult center study was conducted in 2022. Patients were recruited from the database of the outpatient clinic of the Myasthenia Gravis unit and Epilepsy unit. Results: Five patients were included. Frequency of epilepsy in the myasthenia gravis cohort was 5/469 (1.1%), and of myasthenia gravis in the epilepsy cohort was 5/1432 (0.35%). All patients suffered focal epilepsy, mainly fronto-central, and drug-resistant in half of them. Myasthenia gravis was generalized and with exacerbations in half of them. Three patients were thymectomized. Other autoimmune diseases were found in 2 (40%). Epilepsy onset preceded myasthenia gravis onset in all patients. Both diseases were considered autoimmune-related in 3/5 (60%). Conclusion: Epilepsy and myasthenia gravis are only infrequently associated. In adult patients, epilepsy onset precedes myasthenia onset in most cases. In some cases, epilepsy has an autoimmune aetiology and coexists with other autoimmune conditions.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

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.

Background: RSV, or respiratory syncytial virus, is a deadly condition that is present all over the world today. The infection is initially contained in the lower respiratory tract without systemic transmission. The objective of the study: Bioinformatics was used in Egypt to create an mRNA vaccine against the Respiratory syncytial virus (RSV). Methodology: In the present screening experimental study, a lipid nanoparticles vaccine of mRNA of the surface fusion protein of Respiratory syncytial virus was manufactured. The present vaccine delivery system was lipid nanoparticles with a particle size of approximately 90 nanometres, manufactured by the hot micro-emulsion method. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current vaccination lacked antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies exacerbate infection by activating cytokines and complement cascade through the formation of immune complexes or enhancement of the virus entry and replication in the host cells. On the other hand, the current RSV mRNA vaccine of the surface fusion protein consequent on the production of powerful neutralizing antibodies with prolonged immunity especially to infants and elderly candidates who received the optimal dosage regimen.

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.

(1) Background: Heart rate variability (HRV) has emerged as a potential prognostic tool in cardiovascular diseases, offering individualized insights into autonomic nervous system activity. However, real-time HRV data during the acute phase of STEMI, particularly during percutaneous coronary intervention (PCI), was not previously explored. (2) Methods: This single-center, observational cohort study included 104 STEMI patients undergoing primary percutaneous coronary intervention (PCI). HRV parameters were measured using a wearable device (CE marked) during PCI, capturing dynamic responses. The association between HRV parameters and adverse outcomes, including in-hospital mortality and major adverse cardiovascular events (MACE), were assessed. (3) Results: HRV parameters significantly decreased after myocardial revascularization, particularly SDNN, RMSSD, pNN50, HF, SD1, and SD2/SD1 ratio. Significant associations were found between reduced SD2/SD1 ratio, approximate entropy, and adverse outcomes, including increased in-hospital mortality and MACE. The SD2/SD1 ratio was significantly lower in patients who died during the hospital stay (p = 0.008) compared to survivors. Approximate entropy was also significantly lower in deceased patients (p = 0.019). (4) Conclusions: Real-time HRV monitoring using wearable technology offers valuable data regarding dynamic physiological changes during primary PCI. The integration of HRV into routine clinical practice, facilitated by wearable devices, could improve the risk stratification and event prediction in STEMI patients.

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.

The mechanistic Target of Rapamycin Complex 1 (mTORC1) regulates ribosome biogenesis and the transcription of ribosomal genes. Its inactivation impacts protein synthesis necessary for transport of cell adhesion molecule. In Dictyostelium discoideum, the activity of mechanistic Target of Rapamycin Complex 2 (mTORC2) is crucial for cAMP synthesis and relay, processes that depend on heterotrimeric G-proteins and Ras GTPases. Mutants lacking rip3 or lst-8 genes exhibit impaired adenyl cyclase activation and cAMP signaling, resulting in deficient expression of the cell adhesion protein CsaA. Despite this, rip3^- cells, which have impaired mTORC2, upregulate Cad-1 expression, a cell adhesion protein regulated by Ras-GTPases, to compensate for the loss of CsaA. lst-8^- cells, which have both mTORC1 and mTORC2 inactivated, show reduced nutrient sensing, premature CsaA expression and solitary cell behavior. These cells also show defective transport of adhesion proteins to the cell surface, impeding aggregation. Similar defects are observed with caffeine treatment, suggesting both mTORC1 and mTORC2 inhibition. This study highlights the interplay between mTORC1 and mTORC2 in regulating cell adhesion and aggregation through cAMP signaling and protein synthesis pathways in Dictyostelium.

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.

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.

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.

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.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

Background: Respiratory syncytial virus[ RSV] is a lethal overwhelming defectiveness that influences people all over the world. The infection gets down in the lower respiratory tract and does not disperse to the remainder of the body. The objective of the study: Bioinformatics was used to create an mRNA vaccine against the Respiratory syncytial virus( RSV). Methodology: Lipid nanoparticle vaccines containing the Respiratory syncytial virus's surface fusion protein's mRNA were created for the current screening experimental investigation. Lipid nanoparticles[ LNP] with a particle size of around 90 nanometres that were created using the hot micro-emulsion process comprise the current vaccine delivery system. In stages 1 and 2 of clinical trials, the immunogenicity of the current mRNA RSV vaccine was evaluated. Results: The current vaccine demonstrated 81% immunogenicity in animal testing, but only 69% in stages 1 and 2 of clinical trials. Its side effects were manageable. The results persisted for a while. In the current trial, the vaccination proved effective as a preventative measure against RSV infection. The current immunization lacks antibody-dependent enhancement, which causes non-protective antibodies to develop. These non-neutralizing antibodies worsen infection by enhancing viral entrance and replication in the host cells, activating cytokines and the complement cascade through the production of immunological complexes, or both. However, the current LPN-RSV mRNA vaccine of the surface fusion protein resulted in the formation of potent neutralizing antibodies with persistent protection, especially for newborns and elderly individuals who get the ideal dose regimen. Conclusion: The invention of the LNP-mRNA RSV vaccine, which might prevent RSV-caused bronchiolitis and fatal pneumonia, made the current study promising

According to many research groups, high glucose induces over production of superoxide anions, and reactive oxygen species (ROS) in general is the link between high glucose levels and the toxicities seen at cellular levels. Respiratory complex anomalies could lead to the production of ROS. Calcium [Ca2+], at physiological levels serves as a second messenger in many physiological functions. Accordingly, mitochondrial calcium [Ca2+]m overload leads to ROS production which could be lethal to the mitochondria through various mechanisms. The F1F0-ATPase (ATP syn-thase or complex V) is the enzyme that is responsible for catalyzing the final step of oxidative phosphorylation. It does so by coupling the translocation of protons in the mitochondrial in-termembrane space and shuttling them to the mitochondrial matrix for ATP synthesis to take place. Mitochondrial complex V T8993G mutation specifically blocks the translocation of protons across the intermembrane space thereby blocking ATP synthesis leading to Neuropathy, Ataxia and Retinitis Pigmentosa Syndromes (NARP). This study seeks to explore the possibility of [Ca2+]m overload mediating the pathological roles of high glucose in defective respiratory chain mediated mitochondrial stress. The NARP cybrids are the in vitro experimental models for the cells with F1FO-ATPase defects, these cells harbor 98% of mtDNA T8993G mutation. Their coun-terparts 143B osteosarcoma cell lines are the parental cell lines used for comparisons. We uncov-ered that, NARP cells mediated and enhanced the death of the cells (apoptosis) when incubated with hydrogen peroxide (H2O2) and high glucose respectively as depicted by the MTT assay of cell viability. Furthermore, using the fluorescence probe-coupled laser scanning confocal imag-ing microscopy, NARP cells significantly enabled mitochondrial reactive oxygen species (mROS) formation and enhanced the depolarization of the mitochondrial membrane potential (ΔΨm). Elucidating the mechanisms of sugar enhanced toxicity on mitochondria would help in the fu-ture to alleviate the symptoms of patients associated with (NARP) syndromes.

Global public health systems have continuously faced challenges from the advent of novel infectious illnesses, necessitating quick and efficient actions to stop their spread.First discovered in Saudi Arabia in 2012, Middle East respiratory syndrome (MERS) is a viral respiratory disorder caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). Since then, the nation has reported most cases and fatalities related to this sickness, with occasional outbreaks happening in other nations and regions. Severe sickness and high mortality are caused by MERS-CoV, especially in older persons and those with underlying chronic conditions. Through intimate contact, the virus can spread from people to dromedary camels and vice versa. It has sparked multiple epidemics both domestically and abroad in the Middle East, raising the possibility of fatalities and widespread transmission, especially in susceptible groups. The Riyadh region was the main target of the most current MERS-CoV outbreak in Saudi Arabia, which began in 2023 and ended on September 1, 2023, with 312 confirmed cases and ninety-seven fatalities. With the use of published studies and their contributions to the field, we hope to present a thorough overview of the MERS-CoV outbreak in Saudi Arabia in this review of the literature, including its epidemiological investigation, public health response, impact, and lessons learned. In addition to highlighting the importance and continued relevance of this problem, our work suggests ways to lower the risk of MERS-CoV transmission and avert further outbreaks.

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.

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. The rise in airways epithelial barrier permeability alters the tissue homeostasis and allows the allergen and other external agents penetration. Different factors contribute to barrier impairment, such as eosinophilic infiltrate and allergens proteases action: the eosinophilic cationic proteins and the allergens' proteolytic activity have a central role in contributing to epithelial damage. In the airways, the allergens proteases degrade the epithelial junctional proteins allowing the allergen penetration and the uptake by dendritic cells. The increase in allergen-immune system interactions induce the release of the alarmins and the activation of type 2 inflammatory pathways causing, or worsening, the main symptoms at skin, bowel and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic proteases-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance and progression. We further will explore clinical and radiological potential biomarkers of airways remodeling in allergic asthma patients.

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.

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.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study TM9 was effective against three murine coronavirus strains, demonstrating the therapeutic window is large enough to allow use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

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.

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

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.

Background: Permanent tracheostomy because of total laryngectomy surgery entails great conse-quences for the patient regarding respiratory physiopathology such as the filtering, humidifying, and heating function of the air by the nose is lost. The use of special stomal filters can determine adequate protection of the trachea-broncho-pulmonary system with a reduction in respiratory pathologies. In fact, in most cases laryngectomee patients are first cigarette smokers who for this reason already have also respiratory diseases such as chronic obstructive pulmonary disease (COPD). Despite the availability of tracheal filters, multiple times, as reported in the literature, the patient tends to limit their use due to reported breathing difficulties, especially in conditions of intense breathing. Methods: The objective of this clinical study was to evaluate the most suitable stomal filter for the laryngectomee patient during physical activity. The filters studied were an INHEALTH device (Blom-Singer SpeakFree HME); two ATOS devices (Provox® Life™ Energy HME and Provox® Life™ Home HME); and an FAHL device (Laryvox HME Sport). Results: For this purpose, the performances of 31 laryngectomee patients, subjected to medi-um-high physical effort, were analyzed through a standardized pneumological test, the Six Minute Walking Test (6MWT) which involves a sustained walk lasting six minutes, with evaluation , every 60 seconds, heart rate, oxygen saturation and meters travelled; furthermore, it examines two sub-jective indices, namely, the basal and final dyspnea index and the initial and final muscular fatigue index.

Background: The aim of this study was to investigate a series of complete blood cell count – based biomarkers of systemic inflammation as predictors of clinical outcomes in patients who underwent first-line chemoimmunotherapy for advanced NSCLC. Methods: Consecutive patients with pathologically diagnosed stage III/IV NSCLC who underwent first-line chemoimmunotherapy were retrospectively enrolled. The clinical outcomes used for biomarker evaluation were Objective Response Rate (ORR) and Overall Survival (OS). Results: Non-responders had significantly higher values of neutrophil to lymphocyte ratio (NLR, median: 5.36; IQR: 2.78–10.82 vs. 3.31; IQR: 2.15–4.12, p = 0.019), neutrophil to monocyte ratio (NMR, median: 14.00; IQR: 8.82–21.20 vs. 9.20; IQR: 7.45–11.20, p = 0.013), and systemic inflammation index (SII, median: 1,395; IQR: 929–3,334 vs. 945; IQR: 552–1,373, p = 0.025), but only NLR and NMR remained independently related with clinical response in multivariate logistic regression. In univariate analysis white blood cells (OR:1.2202; 95% CI: 1.0339 - 1.4400, p=0.019), neutrophils (OR:1.2916; 95% CI: 1.0692 - 1.5604, p=0.008), NLR (OR:1.3601: 95% CI: 1.0949 - 1.6896, p=0.005) and NMR (OR:1.2159; 95% CI: 1.00396 - 1.4221, p=0.015) were significantly associated with survival; Cox regression models confirmed that neutrophils, NLR and MLR were independently associated with survival; NLR at a cut-off value of 4.0 showed the better AUC (0.749) in predicting survival. Conclusions: Baseline complete blood cell count biomarkers, especially the NLR, can predict clinical outcomes in patients with advanced NSCLC treated with first-line chemoimmunotherapy.

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.

In recent years, the prevalence of tobacco and electronic cigarette (e-cigarette) use among adolescents has raised significant public health concerns worldwide. This study aims to investigate respiratory symptoms among Polish adolescents. We conducted an online survey among Polish school students from all provinces, collecting data over two months in Spring 2021. Students voluntarily complete the anonymous survey, answering questions about respiratory symptoms, smoking habits (both traditional and electronic cigarettes), and demographic information. Analysis focused on four subgroups: non-tobacco users, traditional cigarette smokers, e-cigarette users, and dual users, totaling 10,388 pupils aged 12-18 years, predominantly attending secondary technical and comprehensive schools. A total of 10388 pupils participated in the study, 55.6 % (5778) of whom were girls and 44.4 % (4610) boys. Adolescents, who admitted using both e-cigarettes and traditional cigarettes experienced more frequent episodes of cough during the day (39.70%) and at night (18.40%) compared to their peers in other groups. Chest discomfort, including pain and pressure, was also reported more often by adolescents, who used e-cigarettes and traditional cigarettes concurrently (27.60%) compared to their peers in other groups. Chest pressure was experienced less commonly by non-smoking adolescents (14.40%) than by smokers (18.90%). Higher severity of cough during the day and at night was observed in the group of adolescents using traditional cigarettes and e-cigarettes concurrently compared to the other groups. The adolescents in the dual user group experienced more severe dyspnoea and wheezing compared to the other groups included in the comparison. The results of this study confirm the correlation between the occurrence of respiratory symptoms in adolescents who smoke cigarettes, use e-cigarettes and in dual users. The respiratory symptoms occur most frequently and are the most severe in the group of adolescents who use e-cigarettes and traditional cigarettes

Abstract: Chronic Obstructive Pulmonary Disease (COPD) is a continually advancing respiratory disorder, characterized by enduring airflow limitation along with long-lasting inflammation in the airways. An expanding pool of evidence is emphasizing how mitochondrial dysfunction directly impacts the development and progression of COPD. This comprehensive review delves deeper into the intricate cellular and molecular biology of mitochondria within the framework of COPD, spotlighting significant alterations in structure and function that accompany mitochondrial dysfunction. In this narrative, we delve into the observed changes in mitochondrial shape, behavior, and respiratory chain complex alterations seen in individuals afflicted with COPD. The discussion includes implications on cellular signaling pathways and how this affects the natural process of programmed cellular death (apoptosis) and cellular aging, particularly in reference to COPD. Additionally, we consolidate ongoing therapeutic strategies, honing in on the management of COPD through a focus on mitochondrial dysfunction. Prominent among these strategies is the potential role of antioxidants and mitochondrial biogenesis inducers, which are emerging as promising fields of intervention. Furthermore, we embark on an overview of the possible use of mitochondrial biomarkers as innovative tools in diagnosing COPD, evaluating disease progression, and monitoring the efficacy of COPD treatments. As we unravel the rather complex interplay between mitochondrial biology and COPD, this review highlights the critical importance of formulating treatments that target mitochondrial dysfunction. The ultimate goal of these strategic interventions is to slow down the rate of COPD progression and significantly improve patient outcomes. Lastly, though our understanding of the nexus between COPD and mitochondrial dysfunction has significantly enhanced, ample scope remains for further investigation. Improved insights into the mechanisms of mitochondrial dysfunction, discovered biomarkers, and targeted therapies could encompass a revolutionary step towards comprehensive disease management. The future of COPD treatment seems to lean towards a combination of strategies, prioritizing not only the management of symptoms but also focused on preserving and restoring lung function, improving physical capacity, and enhancing quality of life for COPD patients.

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.