Life, Volume 14, Issue 5 (May 2024) – 50 articles

Obstructive sleep apnea/hypopnea syndrome (OSAHS) is a condition linked to severe cardiovascular and neuropsychological consequences, characterized by recurrent episodes of partial or complete upper airway obstruction during sleep, leading to compromised ventilation, hypoxemia, and micro-arousals. Polysomnography (PSG) serves as the gold standard for confirming OSAHS, yet its extended duration, high cost, and limited availability pose significant challenges. In this paper, we employ a range of machine learning techniques, including Neural Networks, Decision Trees, Random Forests, and Extra Trees, for OSAHS diagnosis. This approach aims to achieve a diagnostic process that is not only more accessible but also more efficient. The dataset utilized in this study consists of records from 601 adults assessed between 2014 and 2016 at a specialized sleep medical center in Colombia. This research underscores the efficacy of ensemble methods, specifically Random Forests and Extra Trees, achieving an area under the Receiver Operating Characteristic (ROC) curve of 89.2% and 89.6%, respectively. Additionally, a web application has been devised, integrating the optimal model, empowering qualified medical practitioners to make informed decisions through patient registration, an input of 18 variables, and the utilization of the Random Forests model for OSAHS screening. Full article

This study aims to describe the epidemiological and clinical characteristics and trends of these admissions in Spain. This retrospective study drew data from the Hospital Discharge Records Database of the Spanish National Health System. We used the diagnostic codes for leprosy from the International Classification of Diseases, ninth and tenth revisions, to retrieve leprosy admissions from 1997 to 2021. There were 1387 hospitalizations for leprosy The number of annual cases decreased gradually, from 341 cases in 1997–2001 to 232 in 2017–2021 (p < 0.001). Patients’ median age increased, from 65 years in 1997–2001 to 76 years in 2017–2021 (p < 0.001), as did the prevalence of some comorbidities, such as hypertension (15% in 1997–2001 to 27.6% in 2017–2021; p < 0.001). The mortality rate (6%) and the frequency of leprosy complications remained stable. After Spain (79.1%), the most common country of origin was Paraguay (4.4%). Admissions decreased significantly in Andalusia, from 42% in 1997–2001 to 10.8% in 2017–2021 (p < 0.001), and in the Canary Islands, from 7.9% in 1997–2001 to 2.6% in 2017–2021 (p = 0.001), whereas they increased in Madrid, from 5.9% in 1997–2001 to 12.1% in 2017–2021 (p = 0.005). Overall, leprosy admissions in Spain have declined, even in the regions with the highest prevalence. Patients admitted for leprosy have become older and sicker. Full article

Background: Recent studies have suggested a possible connection between rosacea and patients’ gut microbiota. Objective: To investigate the differences in fecal microbial profiles between patients with rosacea and healthy controls. Methods: Gut microbiota of 54 rosacea patients (RP) were analyzed using MiSeq 16S rRNA sequencing. Enterotypes, the Firmicutes/Bacteroides (F/B) ratio, the significance of alpha and beta diversity, and differential abundance analysis (DAA) were calculated and compared with age- and gender-matched controls (CP, n = 50). Results: Significant changes in the enterotypes and F/B ratio were observed between the RP and CP (p = 0.017 and p = 0.002, respectively). The RP showed a decreased microbial richness and diversity compared to the CP (Shannon p = 0.012, inverse Simpson p = 0.034). Beta diversity also differed between both groups (PERMANOVA, p = 0.006). Fourteen significantly different taxa were detected according to DAA. Faecalibacterium prausnitzii (coef. −0.0800, p = 0.008), Lachnoospiraceae ND 3007 group sp. (coef. −0.073, p < 0.001), and Ruminococcaceae (coef. −0.072, p = 0.015) were significantly decreased; Oscillobacter sp. (coef. 0.023, p = 0.031), Flavonifractor plautii (coef. 0.011, p = 0.037), and Ruminococccaceae UBA 1819 (coef. 0.010, p = 0.031) were significantly increased in the RP compared to the CP. Conclusion: Significant alterations in gut microbiota were present in the RP. Taxonomic shifts and reduced richness and diversity were observed when compared to the CP. Larger prospective studies are needed to investigate correlations with clinical features and to translate these findings into future therapeutic approaches. Full article

Smoking is a well-known cause of impairment in wound healing and postoperative outcomes; however, its effects on treating meniscus issues remain unclear. This study assesses the relationship between smoking and meniscus treatment outcomes. PubMed, Scopus, Cochrane, and CINAHL were searched from inception to 24 December 2023. Inclusion criteria encompassed studies examining smoking’s impact on patient outcomes regarding meniscus pathology. A secondary PubMed search targeted randomized controlled trials (RCTs) in the top ten orthopedic journals focusing on meniscus pathology and smoking as a demographic variable. Meta-analysis of six studies (n = 528) assessed meniscus failure rate based on smoking status. Eighteen observational studies (n = 8353 patients; 53.25% male; mean age: 51.35 ± 11.53 years; follow-up: 184.11 ± 117.34 months) were analyzed, covering meniscus repair, meniscectomy, allograft transplant, conservative care, and arthroscopy. Results showed four studies (36.36%) linked smoking with worse meniscus repair outcomes, while seven studies (63.64%) did not find significant associations. Meta-analysis from six studies showed no significant impact of smoking on repair failure (p = 0.118). Regarding meniscectomy, one study (33.33%) identified a significant association with smoking, but two did not. Only one (3.8%) of the RCTs in leading orthopedic journals included smoking as a factor. The evidence on smoking’s effect on meniscus treatment is mixed, necessitating further investigation. Full article

Olive oil (Olea europaea) is one of the major components of the Mediterranean diet and is composed of a greater percentage of monounsaturated fatty acids, such as oleic acid; polyunsaturated fatty acids, such as linoleic acid; and minor compounds, such as phenolic compounds, and particularly hydroxytyrosol. The latter, in fact, are of greater interest since they have found widespread use in popular medicine. In recent years, it has been documented that phenolic acids and in particular hydroxytyrosol have anti-inflammatory, antioxidant, and antiproliferative action and therefore interest in their possible use in clinical practice and in particular in neoplasms, both solid and hematological, has arisen. This work aims to summarize and analyze the studies present in the literature, both in vitro and in vivo, on the possible use of minor components of olive oil in some hematological neoplasms. In recent years, in fact, interest in nutraceutical science has expanded as a possible adjuvant in the treatment of neoplastic pathologies. Although it is worth underlining that, regarding the object of our study, there are still few preclinical and clinical studies, it is, however, possible to document a role of possible interest in clinical practice. Full article

Pregnane neuroactive steroids, notably allopregnanolone and pregnenolone, exhibit efficacy in mitigating inflammatory signals triggered by toll-like receptor (TLR) activation, thus attenuating the production of inflammatory factors. Clinical studies highlight their therapeutic potential, particularly in conditions like postpartum depression (PPD), where the FDA-approved compound brexanolone, an intravenous formulation of allopregnanolone, effectively suppresses TLR-mediated inflammatory pathways, predicting symptom improvement. Additionally, pregnane neurosteroids exhibit trophic and anti-inflammatory properties, stimulating the production of vital trophic proteins and anti-inflammatory factors. Androstane neuroactive steroids, including estrogens and androgens, along with dehydroepiandrosterone (DHEA), display diverse effects on TLR expression and activation. Notably, androstenediol (ADIOL), an androstane neurosteroid, emerges as a potent anti-inflammatory agent, promising for therapeutic interventions. The dysregulation of immune responses via TLR signaling alongside reduced levels of endogenous neurosteroids significantly contributes to symptom severity across various neuropsychiatric disorders. Neuroactive steroids, such as allopregnanolone, demonstrate efficacy in alleviating symptoms of various neuropsychiatric disorders and modulating neuroimmune responses, offering potential intervention avenues. This review emphasizes the significant therapeutic potential of neuroactive steroids in modulating TLR signaling pathways, particularly in addressing inflammatory processes associated with neuropsychiatric disorders. It advances our understanding of the complex interplay between neuroactive steroids and immune responses, paving the way for personalized treatment strategies tailored to individual needs and providing insights for future research aimed at unraveling the intricacies of neuropsychiatric disorders. Full article

Although the role of microbiota has been investigated in relation to different oral diseases, it is unknown if its composition has any effect on the course of recovery after third molar alveotomy. Our aim was to determine the influence of patient clinical characteristics as well as pericoronary microbiota composition on the course of recovery after a semi-impacted third molar alveotomy. Thirty-six patients were included and samples obtained with paper points, swabs, and tissue samples were analyzed using DNA hybridization and culture methods. Among the 295 organisms detected, the most frequent were Streptococcus spp. (22.4%; 66/295) followed by Fusobacterium spp. (11.9%; 35/295), and T. forsythia (9.1%; 27/295). A comparison of microbiota composition in patients with better and worse recovery did not show significant differences. Worse recovery outcomes were more frequent in patients with a grade 2 self-assessment of oral health (p = 0.040) and better recovery courses were observed in patients with a grade 4 self-assessment (p = 0.0200). A worse recovery course was statistically significant more frequently in patients with previous oral surgical procedures (p = 0.019). Although we demonstrate that worse recovery outcomes were more frequent when certain bacteria were detected, there was no statistically significant difference. Further research is needed to identify microbial profiles specific to the development of worse outcomes after a third molar alveotomy. Full article

Our research has developed a highly sensitive and simple assay to detect small amounts of animal and human biological material in less than 40 min. The handheld SaLux19 device developed at the Max Planck Institute of Experimental Medicine in Göttingen, Germany, was used to validate our concept. The proposed system uses isothermal amplification of DNA in a rapid assay format. Our results show that the assay can detect Sus scrofa nucleic acids with very high sensitivity and specificity. This detection system has potential for forensic scenarios. Full article

Investigating the biophysiological substrates of psychiatric illnesses is of great interest to our understanding of disorders’ etiology, the identification of reliable biomarkers, and potential new therapeutic avenues. Schizophrenia represents a consolidated model of γ alterations arising from the aberrant activity of parvalbumin-positive GABAergic interneurons, whose dysfunction is associated with perineuronal net impairment and neuroinflammation. This model of pathogenesis is supported by molecular, cellular, and functional evidence. Proof for alterations of γ oscillations and their underlying mechanisms has also been reported in bipolar disorder and represents an emerging topic for major depressive disorder. Although evidence from animal models needs to be further elucidated in humans, the pathophysiology of γ-band alteration represents a common denominator for different neuropsychiatric disorders. The purpose of this narrative review is to outline a framework of converging results in psychiatric conditions characterized by γ abnormality, from neurochemical dysfunction to alterations in brain rhythms. Full article

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017–2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28–7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18–4.96), lower arterial pH (aOR 0.02, CI 0.00–0.31), higher lactate (aOR 2.42, CI 1.00–1.19), and lower hemoglobin (aOR 0.83, CI 0.71–0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS. Full article

(1) Background: Oxygen has exerted a great effect in shaping the environment and driving biological diversity in Earth’s history. Green lineage has evolved primary and secondary carotenoid biosynthetic systems to adapt to Earth’s oxygenation, e.g., Haematococcus lacustris, which accumulates the highest amount of secondary astaxanthin under stresses. The two systems are controlled by lycopene ε-cyclase (LCYE) and β-cyclase (LCYB), which leave an important trace in Earth’s oxygenation. (2) Objectives: This work intends to disclose the underlying molecular evolutionary mechanism of Earth’s oxygenation in shaping green algal carotenogensis with a special focus on lycopene cyclases. (3) Methods: The two kinds of cyclases were analyzed by site-directed mutagenesis, phylogeny, divergence time and functional divergence. (4) Results: Green lineage LCYEs appeared at ~1.5 Ga after the first significant appearance and accumulation of atmospheric oxygen, the so-called Great Oxygenation Event (GOE), from which LCYBs diverged by gene duplication. Bacterial β-bicyclases evolved from β-monocyclase. Enhanced catalytic activity accompanied evolutionary transformation from ε-/β-monocyclase to β-bicyclase. Strong positive selection occurred in green lineage LCYEs after the GOE and in algal LCYBs during the second oxidation, the Neoproterozoic Oxygenation Event (NOE). Positively selected sites in the catalytic cavities of the enzymes controlled the mono-/bicyclase activity, respectively. Carotenoid profiling revealed that oxidative adaptation has been wildly preserved in evolution. (5) Conclusions: the functionalization of the two enzymes is a result of primary to secondary adaptations to Earth’s oxygenation. Full article

While the pathology of acute hemorrhagic fever with renal syndrome (HFRS) has been widely researched, details on the chronic HFRS sequelae remain mainly unexplored. In this study, we analyzed the clinical and laboratory characteristics of 30 convalescent HFRS patients 14 years after the disease contraction, mainly emphasizing several endothelial dysfunction parameters. Convalescent HFRS patients exhibited significantly higher serum levels of erythrocyte sedimentation rate, von Willebrand factor, uric acid, C-reactive protein and immunoglobulin A when compared to healthy individuals. Furthermore, 24 h urine analyses revealed significantly lower sodium and potassium urine levels, as well as significantly higher proteinuria, microalbumin levels and β2-microglobulin levels when compared to healthy individuals. First morning urine analysis revealed significantly higher levels of hematuria in convalescent HFRS patients. None of the additional analyzed endothelium dysfunction markers were significantly different in post-HFRS patients and healthy individuals, including serum and urine P-selectin, E-selectin, soluble intercellular adhesion molecule 1, vascular intercellular adhesion molecule 1 (sVCAM-1) and vascular endothelial growth factor (VEGF). However, binary logistic regression revealed a weak association of serum sVCAM-1 and urine VEGF levels with HFRS contraction. Generally, our findings suggest mild chronic inflammation and renal dysfunction levels in convalescent HFRS patients 14 years after the disease contraction. Full article

Desmoplastic melanoma accounts for 5% of all cases of melanoma, but its diagnosis can be difficult due to its frequent clinical presentation with amelanotic lesions. Histologically, spindled melanocytes surrounded by a collagenous stroma are observed. Compared with other types of melanoma, the desmoplastic types presents greater local aggression, and is more prone to local recurrence, but has a lower risk of lymph node metastasis. Early detection, accurate staging, and proper surgical management are the main factors associated with higher survival rates in melanoma patients. Reflectance confocal microscopy (RCM) has proven to be a valuable imaging tool in the diagnosis of skin neoplasms, being useful for orientating practitioners towards the diagnosis of melanoma and indicating the necessity of performing a diagnostic biopsy. We present the case of 52-year-old woman, who presented to the dermatology department with an irregular, dark-colored plaque in the right deltoid region. Dermoscopy showed asymmetry with an atypical network and some areas of regression. RCM revealed pagetoid cells in the upper epidermis, cell atypia, non-edged papillae, dermal inflammation, and nucleated cells in the dermis, which are highly suggestive of melanoma. A biopsy was also performed. A histopathology exam confirmed the diagnosis of superficially spreading melanoma with a desmoplastic component, and revealed a Breslow index of 0.9 mm, Clark level IV, an absence of mitoses, angiolymphatic invasion and regression, and complete excision. The CT and PET-CT scans were negative. A biopsy of the axillary sentinel lymph node was conducted, with a negative result obtained, establishing the IB stage of the disease. The patient will remain under follow-up to look for a recurrence or a new primary melanoma. Full article

Background: An imbalance between pro- and anti-inflammatory mechanisms is indicated in the pathophysiology of atherosclerotic plaque. The coronary artery and carotid disease, despite sharing similar risk factors, are developed separately. The aim of this study was to analyze possible mechanisms between trace element hair–scalp concentrations and whole blood counts that favor atherosclerotic plaque progression in certain locations. Methods: There were 65 (36 (55%) males and 29 (45%) females) patients with a median age of 68 (61–73) years enrolled in a prospective, preliminary, multicenter analysis. The study group was composed of 13 patients with stable coronary artery disease (CAD group) referred for surgical revascularization due to multivessel coronary disease, 34 patients with carotid artery disease (carotid group) admitted for vascular procedure, and 18 patients in a control group (control group). Results: There was a significant difference between the CAD and carotid groups regarding lymphocyte (p = 0.004) counts. The biochemical comparison between the coronary and carotid groups revealed significant differences regarding chromium (Cr) (p = 0.002), copper (Cu) (p < 0.001), and zinc (Zn) (p < 0.001) concentrations. Spearman Rank Order Correlations between lymphocyte counts and trace elements in the analyzed groups were performed, revealing a strong correlation with zinc (R = 0.733, p < 0.001) in the control group (non-CAD, non-carotid). Conclusion: Significant differences in hair–scalp concentrations related to atherosclerosis location were observed in our analysis. The interplay between zinc concentration and lymphocyte count may play a pivotal role in cardiovascular disease development. Full article

(1) Background: Children are the most vulnerable to pollution due to their decreased stature, heightened respiratory rate, and frequent outdoor engagement. PM_2.5, nitrogen dioxide (NO₂), ozone, and cold weather are associated with pediatric asthma. In this study, we investigated the nexus between air pollution, climate factors, and pediatric asthma emergency room visits (ERVs). (2) Method: Pediatric asthma ERV data for healthcare quality from the Taiwanese National Insurance in the Taipei area were obtained from 2015 to 2019. Air pollution and climate factor data were also collected. Poisson regression was employed to determine the relationships with relative risks (RRs). (3) Results: The incidence of pediatric asthma ERVs decreased, with a crude RR of 0.983 (95% CI: 0.98–0.986, p < 0.001). Fine particulate matter (PM_2.5) had an adjusted RR of 1.102 (95% CI: 1.037–1.172, p = 0.002) and a 7.7 µg/m³ increase, and air temperature had an adjusted RR of 0.813 (95% CI: 0.745–0.887, p < 0.001) comparing between the highest and lowest quarter air temperature associated with pediatric asthma ERVs. (4) Conclusions: This inquiry underscores the positive associations of PM_2.5 and cold weather with pediatric asthma ERVs. The findings could guide the government to establish policies to reduce air pollution and promote children’s health. Full article

Background: Sarculator and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms are freely available risk prediction scores for surgically treated patients with primary sarcomas. Due to the rarity of angiosarcomas, these scores have only been tested on small cohorts of angiosarcoma patients. In neither the original patient cohort upon which the Sarculator is based nor in subsequent studies was a distinction made between primary and secondary angiosarcomas, as the app is intended to be applied to primary sarcomas. Therefore, the objective of our investigation was to assess whether the Sarculator reveals a difference in prognosis and whether such differentiation aligns with actual clinical data. Patients and Methods: Thirty-one patients with primary or secondary soft tissue angiosarcoma, treated at our Sarcoma Center from 2001 to 2023, were included in the study. Actual survival rates were compared with nomogram-derived data for predicted 5-year survival (Sarculator), as well as 4-, 8- and 12-year sarcoma-specific death probabilities (MSKCC). Harrell’s c-index was utilized to assess predictive validity. Results: In total, 31 patients were analyzed. The actual overall 5-year survival was 22.57% with a predicted 5-year survival rate of 25.97%, and the concordance index was 0.726 for the entire cohort. The concordance index results from MSKCC for angiosarcoma patients were below 0.7 indicating limited predictive accuracy in this cohort, particularly when compared to Sarculator. Summary: Nomogram-based predictive models are valuable tools in clinical practice for rapidly assessing prognosis. They can streamline the decision-making process for adjuvant treatments and improve patient counselling especially in the treatment of rare and complicated tumor entities such as angiosarcomas. Full article

Background: Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. Methods: The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. Results: A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (−6.4 ± 19.7 vs. −3.4 ± 22.9 mmol/mol) and weight loss (−4.6 ± 7.1 vs. −2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). Conclusions: This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation. Full article

This narrative review comprehensively examines the impact of oxidative stress on military personnel, highlighting the crucial role of physical exercise and tailored diets, particularly the ketogenic diet, in minimizing this stress. Through a meticulous analysis of the recent literature, the study emphasizes how regular physical exercise not only enhances cardiovascular, cognitive, and musculoskeletal health but is also essential in neutralizing the effects of oxidative stress, thereby improving endurance and performance during long-term missions. Furthermore, the implementation of the ketogenic diet provides an efficient and consistent energy source through ketone bodies, tailored to the specific energy requirements of military activities, and significantly contributes to the reduction in reactive oxygen species production, thus protecting against cellular deterioration under extreme stress. The study also underlines the importance of integrating advanced technologies, such as wearable devices and smart sensors that allow for the precise and real-time monitoring of oxidative stress and physiological responses, thus facilitating the customization of training and nutritional regimes. Observations from this review emphasize significant variability among individuals in responses to oxidative stress, highlighting the need for a personalized approach in formulating intervention strategies. It is crucial to develop and implement well-monitored, personalized supplementation protocols to ensure that each member of the military personnel receives a regimen tailored to their specific needs, thereby maximizing the effectiveness of measures to combat oxidative stress. This analysis makes a valuable contribution to the specialized literature, proposing a detailed framework for addressing oxidative stress in the armed forces and opening new directions for future research with the aim of optimizing clinical practices and improving the health and performance of military personnel under stress and specific challenges of the military field. Full article

Reptiles are known to be asymptomatic carriers of various zoonotic pathogens. A number of Gram-negative opportunistic commensals are causative agents of bacterial infections in immunocompromised or stressed hosts and are disseminated by reptiles, whose epidemiological role should not be neglected. Since most studies have focused on exotic species, in captivity or as pet animals, the role of wild populations as a potential source of pathogens still remains understudied. In the present study, we isolated a variety of Gram-negative bacteria from the cloacal microbiota of free-living lizard and tortoise hosts (Reptilia: Sauria and Testudines) from the Bulgarian herpetofauna. We evaluated their pathogenic potential according to their antibiotic susceptibility patterns, biofilm-forming capacity, and extracellular production of some enzymes considered to play roles as virulence factors. To our knowledge, the phenotypic manifestation of virulence factors/enzymatic activity and biofilm formation in wild reptile microbiota has not yet been widely investigated. All isolates were found to be capable of forming biofilms to some extent and 29.6% of them could be categorized as strong producers. Two strains proved to be excellent producers. The majority of the isolated strains showed extracellular production of at least one exoenzyme. The most pronounced pathogenicity could be attributed to the newly isolated Pseudomonas aeruginosa strain due to its multiresistance, excellent biofilm formation, and expression of exoenzymes. Full article

Calcitonin gene-related peptide (CGRP) has long been implicated in both the physiology and pathophysiology of the respiratory tract. The objective of our study was to determine the serum concentration of alpha CGRP (αCGRP) in cystic fibrosis (CF) that arises from mutations in the gene responsible for encoding the cystic fibrosis transmembrane conductance regulator (CFTR) protein. Currently, there are not many data in the literature about the role of CGRP in CF. The serum level of αCGRP was estimated using the enzyme-linked immunosorbent assay among 64 patients with CF and 31 healthy controls. The αCGRP concentration in the CF group was 62.51 ± 15.45 pg/mL, while in the control group it was 47.43 ± 8.06 pg/mL (p < 0.001). We also compared the level of αCGRP in CF patients according to the type of CFTR mutation. Homozygotes for ΔF508 had higher αCGRP levels than heterozygotes (67.9 ± 10.2 vs. 54.5 ± 18.3 pg/mL, p < 0.01). The level of this neuropeptide was statistically higher in patients with severe disease than in those with mild CF (p = 0.003) when patients were divided into three groups by spirometry results. αCGRP concentration was not correlated with age, sex, clinical parameters, and pulmonary function test results in the study participants. The results of our study suggest a significant increase in the concentration of αCGRP in the serum of patients with CF compared to the control group. This observation opens interesting possibilities for understanding the role of αCGRP in the context of CF pathophysiology. Full article

The binary nature of life is deeply ingrained in daily experiences, evident in the stark distinctions between life and death and the living and the inert. While this binary perspective aligns with disciplines like medicine and much of biology, uncertainties emerge in fields such as microbiology, virology, synthetic biology, and systems chemistry, where intermediate entities challenge straightforward classification as living or non-living. This contribution explores the motivations behind both binary and non-binary conceptualizations of life. Despite the perceived necessity to unequivocally define life, especially in the context of origin of life research and astrobiology, mounting evidence indicates a gray area between what is intuitively clearly alive and what is distinctly not alive. This prompts consideration of a gradualist perspective, depicting life as a spectrum with varying degrees of “lifeness”. Given the current state of science, the existence or not of a definite threshold remains open. Nevertheless, shifts in epistemic granularity and epistemic perspective influence the framing of the question, and scientific advancements narrow down possible answers: if a threshold exists, it can only be at a finer level than what is intuitively taken as living or non-living. This underscores the need for a more refined distinction between the inanimate and the living. Full article

A novel aerotolerant anaerobic bacterium (strain M4Ah^T) was isolated from a terrestrial mud volcano (Taman Peninsula, Russia). Cells were small, cell-wall-less, non-motile cocci, 0.32–0.65 μm in diameter. The isolate was a mesophilic, neutrophilic chemoorganoheterotroph, growing on carbohydrates (D-glucose, D-trehalose, D-ribose, D-mannose, D-xylose, D-maltose, D-lactose, D-cellobiose, D-galactose, D-fructose, and D-sucrose), proteinaceous compounds (yeast extract, tryptone), and pyruvate. Strain M4Ah^T tolerated 2% oxygen in the gas phase, was catalase-positive, and showed sustainable growth under microaerobic conditions. The dominant cellular fatty acids of strain M4Ah^T were C_16:0 and C_18:0. The G+C content of the genomic DNA was 32.42%. The closest phylogenetic relative of strain M4Ah^T was Mariniplasma anaerobium from the family Acholeplasmataceae (order Acholeplasmatales, class Mollicutes). Based on the polyphasic characterization of the isolate, strain M4Ah^T is considered to represent a novel species of a new genus, for which the name Peloplasma aerotolerans gen. nov., sp. nov. is proposed. The type strain of Peloplasma aerotolerans is M4Ah^T (=DSM 112561^T = VKM B-3485^T = UQM 41475^T). This is the first representative of the order Acholeplasmatales, isolated from a mud volcano. Full article

Oxidative stress is one of the most important environmental exposures associated with psychiatric disorders, but the underlying molecular mechanisms remain to be elucidated. In a previous study, we observed a substantial alteration of the gene expression landscape in neuron-like cells that were differentiated from SH-SY5Y cells after or during exposure to oxidative stress, with a subset of dysregulated genes being enriched for neurodevelopmental processes. To further explore the regulatory mechanisms that might account for such profound perturbations, we have now applied small RNA-sequencing to investigate changes in the expression of miRNAs. These molecules are known to play crucial roles in brain development and response to stress through their capacity to suppress gene expression and influence complex biological networks. Through these analyses, we observed more than a hundred differentially expressed miRNAs, including 80 previously reported to be dysregulated in psychiatric disorders. The seven most influential miRNAs associated with pre-treatment exposure, including miR-138-5p, miR-96-5p, miR-34c-5p, miR-1287-5p, miR-497-5p, miR-195-5p, and miR-16-5p, supported by at least 10 negatively correlated mRNA connections, formed hubs in the interaction network with 134 genes enriched with neurobiological function, whereas in the co-treatment condition, miRNA-mRNA interaction pairs were enriched in cardiovascular and immunity-related disease ontologies. Interestingly, 12 differentially expressed miRNAs originated from the DLK1-DIO3 location, which encodes a schizophrenia-associated miRNA signature. Collectively, our findings suggest that early exposure to oxidative stress, before and during prenatal neuronal differentiation, might increase the risk of mental illnesses in adulthood by disturbing the expression of miRNAs that regulate neurodevelopmentally significant genes and networks. Full article

Post-traumatic osteoporosis (PTO) presents a significant challenge in clinical practice, characterized by demineralization and decreased skeletal integrity following severe traumatic injuries. This literature review manuscript addresses the knowledge gaps surrounding PTO, encompassing its epidemiology, pathophysiology, risk factors, diagnosis, treatment, prognosis, and future directions. This review emphasizes the complexity of the etiology of PTO, highlighting the dysregulation of biomineralization processes, inflammatory cytokine involvement, hormonal imbalances, glucocorticoid effects, vitamin D deficiency, and disuse osteoporosis. Moreover, it underscores the importance of multidisciplinary approaches for risk mitigation and advocates for improved diagnostic strategies to differentiate PTO from other musculoskeletal pathologies. This manuscript discusses various treatment modalities, including pharmacotherapy, dietary management, and physical rehabilitation, while also acknowledging the limited evidence on their long-term effectiveness and outcomes in PTO patients. Future directions in research are outlined, emphasizing the need for a deeper understanding of the molecular mechanisms underlying PTO and the evaluation of treatment strategies’ efficacy. Overall, this review provides a comprehensive overview of PTO and highlights avenues for future investigation to enhance clinical management and patient outcomes. Full article

In addressing the challenge of assessing healthy brain aging across diverse interventions, this study introduces the use of MRI-derived Brain Healthcare Quotients (BHQ) for comprehensive evaluation. We analyzed BHQ changes in 319 participants aged 24–69, who were allocated into dietary (collagen peptide, euglena, matcha, isohumulone, xanthophyll) and physical activity (hand massage with lavender oil, handwriting, office stretching, pink lens, clinical art) groups, alongside a control group, over a month. These interventions were specifically chosen to test the efficacy of varying health strategies on brain health, measured through BHQ indices: GM-BHQ for gray matter volume, and FA-BHQ for white matter integrity. Notably, significant improvements in FA-BHQ were observed in the collagen peptide group, with marginal increases in the hand massage and office stretching groups. These findings highlight BHQ’s potential as a sensitive tool for detecting brain health changes, offering evidence that low-intensity, easily implemented interventions can have beneficial effects on brain health. Moreover, BHQ allows for the systematic evaluation of such interventions using standard statistical approaches, suggesting its value in future brain healthcare research. Full article

The gastrointestinal tract is home to trillions of diverse microorganisms collectively known as the gut microbiota, which play a pivotal role in breaking down undigested foods, such as dietary fibers. Through the fermentation of these food components, short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate are produced, offering numerous health benefits to the host. The production and absorption of these SCFAs occur through various mechanisms within the human intestine, contingent upon the types of dietary fibers reaching the gut and the specific microorganisms engaged in fermentation. Medical literature extensively documents the supplementation of SCFAs, particularly butyrate, in the treatment of gastrointestinal, metabolic, cardiovascular, and gut-brain-related disorders. This review seeks to provide an overview of the dynamics involved in the production and absorption of acetate, propionate, and butyrate within the human gut. Additionally, it will focus on the pivotal roles these SCFAs play in promoting gastrointestinal and metabolic health, as well as their current therapeutic implications. Full article

The LPS-induced inflammation model is widely used for studying inflammatory processes due to its cost-effectiveness, reproducibility, and faithful representation of key hallmarks. While researchers often validate this model using clinical cytokine markers, a comprehensive understanding of gene regulatory mechanisms requires extending investigation beyond these hallmarks. Our study leveraged multiple whole-blood bulk RNA-seq datasets to rigorously compare the transcriptional profiles of the well-established LPS-induced inflammation model with those of several human diseases characterized by systemic inflammation. Beyond conventional inflammation-associated systems, we explored additional systems indirectly associated with inflammatory responses (i.e., ISR, RAAS, and UPR) using a customized core inflammatory gene list. Our cross-condition-validation approach spanned four distinct conditions: systemic lupus erythematosus (SLE) patients, dengue infection, candidemia infection, and staphylococcus aureus exposure. This analysis approach, utilizing the core gene list aimed to assess the model’s suitability for understanding the gene regulatory mechanisms underlying inflammatory processes triggered by diverse factors. Our analysis resulted in elevated expressions of innate immune-associated genes, coinciding with suppressed expressions of adaptive immune-associated genes. Also, upregulation of genes associated with cellular stresses and mitochondrial innate immune responses underscored oxidative stress as a central driver of the corresponding inflammatory processes in both the LPS-induced and other inflammatory contexts. Full article