Search Results (280)

It has long been accepted that breathing gases that are physiologically inert include helium (He), neon (Ne), nitrogen (N₂), argon (Ar), krypton (Kr), xenon (Xe), and hydrogen (H₂). The term “inert gas” has been used to describe them due to their unusually high chemical stability. However, as investigations have advanced, many have shown that inert gas can have specific biological impacts when exposed to high pressure or atmospheric pressure. Additionally, different inert gases have different effects on intracellular signal transduction, ion channels, and cell membrane receptors, which are linked to their anesthetic and cell protection effects in normal or pathological processes. Through a selective analysis of the representative literature, this study offers a concise overview of the state of research on the biological impacts of inert gas and their molecular mechanisms. Full article

Background: Human metapneumovirus (hMPV) is a respiratory pathogen that causes illness ranging from mild upper respiratory tract infections to severe pneumonia, particularly in individuals with comorbidities. Fatal cases of hMPV-induced hemorrhagic pneumonia are rare and likely under-reported. Diagnosis is often delayed due to overlapping symptoms with other respiratory viruses and the rapid progression of the disease. Case presentation: We report the case of a 55-year-old man with a complex medical history, including liver cirrhosis and diabetes mellitus, who developed acute viral pneumonia. Initial symptoms appeared three days before a sudden clinical deterioration marked by shortness of breath, hemoptysis, and respiratory failure. A nasopharyngeal swab taken on the third day of illness tested positive for hMPV by qRT-PCR. The patient died the following day. Postmortem molecular testing confirmed hMPV in lung tissue and alveolar contents. Autopsy revealed bilateral hemorrhagic pneumonia with regional lymphadenopathy. Histopathological examination showed alveolar hemorrhage, multinucleated cells, neutrophilic infiltration, activated autophagy in macrophages, and numerous cytoplasmic eosinophilic viral inclusions. Conclusions: This is the first documented case of fatal hMPV pneumonia in Armenia. It highlights the potential severity of hMPV in adults with chronic health conditions and emphasizes the need for timely molecular diagnostics. Postmortem identification of characteristic viral inclusions may serve as a cost-effective histopathological marker of hMPV-associated lung pathology. Full article

Malignant mediastinal tumors are a group representing some of the most demanding oncological challenges for early, multi-level, and successful management. The timely identification of any suspicious clinical symptomatology is urgent in achieving an accurate, staged histological diagnosis, in order to follow up with an equally detailed medical therapeutic plan (interventional or not) and determine the principal goals regarding efficient overall treatment in these patients. We report a case of a 24-year-old male patient with an incident-free prior medical history. An initial chest X-ray was performed after the patient reported short-term, consistent moderate chest pain symptomatology, early work fatigue, and shortness of breath. The following imaging procedures (chest CT, PET-CT) indicated the presence of an anterior mediastinal mass (meas. ~11 cm × 10 cm × 13 cm, SUV: 8.7), applying additional pressure upon both right heart chambers. The Alpha-Fetoprotein (aFP) blood levels had exceeded at least 50 times their normal range. Two consecutive diagnostic attempts with non-specific histological results, a negative-for-malignancy fine-needle aspiration biopsy (FNA-biopsy), and an additional tumor biopsy, performed via mini anterior (R) thoracotomy with “suspicious” cellular gatherings, were performed elsewhere. After admission to our department, an (R) Video-Assisted Thoracic Surgery (VATS) was performed, along with multiple tumor biopsies and moderate pleural effusion drainage. The tumor’s measurements had increased to DMax: 16 cm × 9 cm × 13 cm, with a severe degree of atelectasis of the Right Lower Lobe parenchyma (RLL) and a pressure-displacement effect upon the Superior Vena Cava (SVC) and the (R) heart sinus, based on data from the preoperative chest MRA. The histological report indicated elements of a combined, non-seminomatous germ-cell mediastinal tumor, posthuberal-type teratoma, and embryonal carcinoma. The imminent chemotherapeutic plan included a “BEP” (Bleomycin^®/Cisplatin^®/Etoposide^®) scheme, which needed to be modified to a “VIP” (Cisplatin^®/Etoposide^®/Ifosfamide^®) scheme, due to an acute pulmonary embolism incident. While the aFP blood levels declined, even reaching normal measurements, the tumor’s size continued to increase significantly (DMax: 28 cm × 25 cm × 13 cm), with severe localized pressure effects, rapid weight loss, and a progressively worsening clinical status. Thus, an emergency surgical intervention took place via median sternotomy, extended with a complementary “T-Shaped” mini anterior (R) thoracotomy. A large, approx. 4 Kg mediastinal tumor was extracted, with additional RML and RUL “en-bloc” segmentectomy and partial mediastinal pleura decortication. The following histological results, apart from verifying the already-known posthuberal-type teratoma, indicated additional scattered small lesions of combined high-grade rabdomyosarcoma, chondrosarcoma, and osteosarcoma, as well as numerous high-grade glioblastoma cellular gatherings. No visible findings of the previously discovered non-seminomatous germ-cell and embryonal carcinoma elements were found. The patient’s postoperative status progressively improved, allowing therapeutic management to continue with six “TIP” (Cisplatin^®/Paclitaxel^®/Ifosfamide^®) sessions, currently under his regular “follow-up” from the oncological team. This report underlines the importance of early, accurate histological identification, combined with any necessary surgical intervention, diagnostic or therapeutic, as well as the appliance of any subsequent multimodality management plan. The diversity of mediastinal tumors, especially for young patients, leaves no place for complacency. Such rare examples may manifest, with equivalent, unpredictable evolution, obliging clinical physicians to stay constantly alert and not take anything for granted. Full article

Climate change poses an increasing threat to livestock reproduction, with heat stress (HS) known to significantly impair ovarian function. This study aimed to elucidate the impact of HS on ovarian function and circRNA expression profiles in Hu sheep. Twelve ewes were randomly assigned to a control (Con, n = 6) or HS group (n = 6) and exposed to different temperatures for 68 days. Compared with the Con group, HS significantly increased the respiratory rate (108.33 ± 3.72 vs. 63.58 ± 2.42 breaths/min), pulse rate (121.17 ± 3.98 vs. 78.08 ± 3.31 beats/min), and rectal temperature (40.17 ± 0.14 °C vs. 39.02 ± 0.21 °C; p < 0.05). Concurrently, serum antioxidant levels were markedly decreased, including total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px) (p < 0.05). Histological analysis revealed a significant reduction in the numbers of primordial, primary, secondary, and mature follicles, alongside an increase in antral follicles (p < 0.05). TUNEL staining demonstrated enhanced granulosa cell apoptosis (p < 0.05), accompanied by the upregulation of pro-apoptotic genes Bax and Caspase-3 and downregulation of the anti-apoptotic gene Bcl-2, as confirmed by qPCR (p < 0.05). CircRNA sequencing identified 152 differentially expressed circRNAs (120 upregulated, 32 downregulated), and enrichment analyses indicated their involvement in apoptosis, mitophagy, and the FoxO signaling pathway. Collectively, these findings demonstrate that HS impairs ovarian physiology and antioxidant defense, induces follicular damage and cell apoptosis, and alters circRNA expression profiles, providing new insights into the molecular mechanisms underlying HS-induced reproductive dysfunction in Hu sheep. Full article

In South Korea, issues have been raised regarding exposure to humidifier disinfectant products containing certain chemicals postulated to induce lung diseases in consumers. Several rodent studies utilizing whole-body inhalation, which comprises freely moving animals breathing through the nares, and intranasal instillation involving restraint, were conducted by various Korean Governmental Agencies on these products to investigate whether there is a causal relationship between these products and the development of lung diseases. In particular, the humidifier disinfectant product Kathon, containing chloromethylisothiazolinone and methylisothiazolinone (CMIT and MIT), when directly introduced into inhalation chambers at varying concentrations for up to 13 weeks, produced no significant histopathological alterations and no marked changes in pulmonary function parameters. Further, there was no evidence of cytotoxicity; total and differential cell counts did not differ from control. In addition, the levels of cytokine markers of inflammation were not markedly altered. In contrast to published papers utilizing intratracheal and intranasal instillation, where the animal is anesthetized and chemical bypasses the defense mechanisms in the respiratory tract, then reaches the pulmonary region, ignoring recommended dose levels was found to initiate fibrotic responses in mice and rats. However, the usefulness of experimental results to extrapolate to humans obtained following intratracheal and intranasal instillation studies is of limited value because the data generated did not use a realistic design and appropriate dosimetry. Therefore, these findings have significant drawbacks in their use to characterize an inhalation risk for pulmonary fibrosis in humans and cannot be used for the extrapolation of such risk to humans. It is thus evident that the inhalation data generated by the Korean Regulatory Agencies are more realistic and show that exposure to CMIT and MIT does not initiate pulmonary fibrosis. Although inhalation studies still do not fully replicate real-world human exposure scenarios and have limitations for direct extrapolation to humans, they are nevertheless more appropriate than intratracheal or intranasal instillation models. Full article

Early detection of cancer is crucial for improving patient outcomes. Traditional modalities such as mammography and low-dose computed tomography are effective but exhibit inherent limitations, including radiation exposure and accessibility challenges. This review explores innovative, non-invasive cancer screening methods, focusing on liquid biopsy and volatile organic compound (VOC)-based detection platforms. Liquid biopsy analyzes circulating tumor DNA and other biomarkers in bodily fluids, offering potential for early detection and monitoring of treatment response. VOC-based detection leverages unique metabolic signatures emitted by cancer cells, detectable in exhaled breath or other bodily emissions, providing a rapid and patient-friendly screening option. We provide a comprehensive overview of these advanced multi-cancer detection techniques to enhance diagnostic accuracy, accessibility, and patient adherence, and ultimately enhance survival rates and patient outcomes. Full article

Background: Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. Effective screening strategies for early diagnosis that could improve disease prognosis are lacking. Non-invasive breath analysis of volatile organic compounds (VOC) is a potential method for earlier LC detection. This study explores the association of VOC profiles with artificial intelligence (AI) to achieve a sensitive, specific, and fast method for LC detection. Patients and methods: Exhaled breath air samples were collected from 123 healthy individuals and 73 LC patients at two clinical sites. The enrolled patients had LC diagnosed with different stages. Breath samples were collected before undergoing any treatment, including surgery, and analyzed using gas chromatography coupled to ion-mobility spectrometry (GC-IMS). AI methods classified the overall chromatographic profiles. Results: GC-IMS is highly sensitive, yielding detailed chromatographic profiles. AI methods ranked the sets of exhaled breath profiles across both groups through training and validation steps, while qualitative information was deliberately not taking part nor influencing the results. The K-nearest neighbor (KNN) algorithm classified the groups with an accuracy of 90% (sensitivity = 87%, specificity = 92%). Narrowing the LC group to those only in early-stage IA, the accuracy was 90% (sensitivity = 90%, specificity = 93%). Conclusions: Evaluation of the global exhaled breath profiles using AI algorithms enabled LC detection and demonstrated that qualitative information may not be required, thus easing the frustration that many studies have experienced so far. The results show that this approach coupled with screening protocols may improve earlier detection of LC and hence its prognosis. Full article

Background and Objectives: Oral appliances (OAs) are commonly used to manage sleep-disordered breathing conditions, including primary snoring, and offer an alternative treatment for individuals with obstructive sleep apnea (OSA) who cannot tolerate continuous positive airway pressure (CPAP) therapy. Our study analyzed the possible factors associated with higher snoring rates compared with those associated with lower snoring rates. Materials and Methods: A customized dental brace with a tongue compressor was the essential part of the Lin OA (LOA). The compressor is available in various lengths, ranging from 0.5 to 3.0 cm across different versions. The participants wore the LOA throughout the night while sleeping. Their snoring rates were recorded using the SnoreClock app on their cell phones. Results: The analysis included 36 participants, comprising 30 males and 6 females. The participants had a mean age of 44.91 ± 9.96 years, a mean BMI of 26.18 ± 3.50 kg/m², and an average recording duration of 398.27 ± 77.56 min per session. In total, 4052 sleep recordings were analyzed. The number of files for females was less than that for males (563 vs. 3489). In this study, individuals belonging to the highest one-third based on the baseline snoring rate (H group) experienced a significant reduction in snoring, approximately 84.8%, when using the LOA-3 cm device equipped with a 3 cm tongue compressor. The individuals who belonged to the lower two-thirds based on the baseline snoring rate were classified as the L group. Among male participants, snoring decreased by approximately 66.4%. Similarly, among female participants in the L group, snoring decreased by approximately 69.3% when using the LOA-3 cm. Conclusions: In this study, we observed a significant reduction in snoring for the two groups of participants wearing the LOA-3 cm, with the rate decrements ranging from 66.4% to 84.8%. This reduction was more pronounced in the H group than in the male participants in the L group. Further studies are needed to explore the reasons for these findings. Full article

Diabetic kidney disease (DKD) displays a high prevalence of cardiovascular and cerebrovascular disease. Both the kidney and the brain share common pathogenic mechanisms, such as inflammation, endothelial dysfunction, oxidative stress, and mitochondrial dysfunction. The aim of this study was to establish a potential association of cerebral vessel remodeling and its related functional impairment with biomarkers of inflammation, oxidative stress, and mitochondrial dysfunction in the early stages of DKD in type 2 diabetes mellitus (DM) patients. A cohort of 184 patients and 39 healthy controls was assessed concerning serum and urinary stromal cell-derived factor-1 (SDF-1), P-selectin, advanced oxidation protein products (AOPPs), urinary synaptopodin, podocalyxin, kidney injury molecule-1 (KIM-1), and N-acetyl-β-(D)-glucosaminidase (NAG). The quantification of the mitochondrial DNA copy number (mtDNA-CN) and nuclear DNA (nDNA) in urine and peripheral blood was conducted using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Using TaqMan tests, the beta-2 microglobulin nuclear gene (B2M) and the cytochrome b (CYTB) gene, which encodes subunit 2 of NADH dehydrogenase (ND2), were evaluated. The MtDNA-CN is the ratio of mitochondrial DNA to nuclear DNA copies, ascertained through the examination of the CYTB/B2M and ND2/B2M ratios. The intima-media thickness (IMT) measurements of the common carotid arteries (CCAs), along with the pulsatility index (PI) and resistivity index (RI) of the internal carotid arteries (ICAs) and middle cerebral arteries (MCAs), were obtained through cerebral Doppler ultrasonography (US). Additionally, the breath-holding index (BHI) was also measured by cerebral Doppler US. PI-ICAs, PI-MCAs, CCAs-IMT, RI-MCAs, and RI-ICAs demonstrated direct relationships with SDF-1, P-selectin, AOPPs, urine mtDNA, podocalyxin, synaptopodin, NAG, and KIM-1 while showing indirect correlations with serum mtDNA and the eGFR. In contrast, the BHI had negative correlations with SDF-1, P-selectin, AOPPs, urine mtDNA, synaptopodin, podocalyxin, KIM-1, and NAG while showing direct associations with serum mtDNA and the eGFR. In conclusion, a causative association exists among SDF-1, P-selectin, and AOPPs, as well as mitochondrial dysfunction, in early diabetic kidney disease (DKD) and significant cerebrovascular alterations in patients with type 2 diabetes mellitus and normoalbuminuric DKD, with no neurological symptoms. Full article

A study was conducted to assess the efficacy of prebiotic and herbal supplements to relieve transportation stress based on changes in physiological, hematological, and molecular responses in Kenguri sheep. Thirty healthy female sheep were randomly divided into three groups: a control group (CKS) with no supplementation, a prebiotic supplementation group (PKS), and an herbal supplementation group (HKS). The animals were transported 230 km over seven hours during summer conditions, with temperatures ranging from 32.5 °C to 34.9 °C. The groups that received the prebiotic (75.6 breaths/min; 64.8 beats/min) and herbal supplementation (31.0 breaths/min; 66.8 beats/min) had a significantly reduced respiration rate (RR) and pulse rate (PR) compared to those of the control group (38.7 breaths/min; 75.6 beats/min) (p < 0.01 and p < 0.05, respectively), indicating improved physiological stability. The hemoglobin (HGB) and hematocrit (HCT) levels were also significantly lower in the PKS (24.2 g/dL; 24.8%) and HKS (24.7 g/dL; 24.5%) groups than in the CKS (28.1 g/dL; 24.9%) (p < 0.05), highlighting the mitigation of hematological stress. Further, the plasma glucose level was significantly higher (p < 0.01) in the HKS group (80.0 mg/dL) compared to the CKS group (63.5 mg/dL). However, rectal temperature (RT) and skin temperature (ST), red blood cells (RBCs), mean corpuscular volume (MCV), and white blood cells (WBCs) showed no significant differences among the groups. These findings demonstrate that prebiotic and herbal supplementation can effectively reduce transportation-induced stress in Kenguri sheep, offering a practical strategy to improve the welfare and resilience of livestock under challenging environmental conditions. Full article

This study investigated the automotive applicability of parts produced from a newly developed foamed recycled polyethylene terephthalate (rPET). The injection molded part contained a combination of both endothermic and exothermic foaming agents and phosphorus (Exolit OP 1240) (OP)- and melamine polyphosphate (MPP)-based flame retardant agents. The parts were produced using a breathing mold technique to achieve a suitable level of foaming. The aim was to produce lighter parts made of recycled material that also complied with the fire safety automotive industry standards. Computer tomographic scans revealed the foam structure formed successfully, which contributed to an improved strength-to-weight ratio. The scans further showcased that larger cells tended to form in the thicker areas within the part, while smaller cells generally formed in the thinner areas. Finite element simulations showed that the large cell formation in the thicker parts had no effect on the part’s load bearing property, and there were not stress concentration points after the boundary conditions were defined. The sample produced from the material was determined to be a possible replacement of small-sized automotive components. Full article

Exosomes are small extracellular vesicles, ranging from 30 to 150 nm, that are essential in cell biology, mediating intercellular communication and serving as biomarkers due to their origin from cells. Exosomes as biomarkers for diagnosing various illnesses have gained significant investigation due to the high cost and invasive nature of current diagnostic procedures. Exosomes have a clear advantage in the diagnosis of diseases because they include certain signals that are indicative of the genetic and proteomic profile of the ailment. This feature gives them the potential to be useful liquid biopsies for real-time, noninvasive monitoring, enabling early cancer identification for the creation of individualized treatment plans. According to our analysis, the trend toward utilizing exosomes as diagnostic and prognostic tools has raised since 2012. In this regard, the proportion of malignant indications is higher compared with non-malignant ones. To be precise, exosomes have been used the most in gastrointestinal, thoracic, and urogenital cancers, along with cardiovascular, diabetic, breathing, infectious, and brain disorders. To the best of our knowledge, this is the first research to examine all registered clinical trials that look at exosomes as a diagnostic and prognostic biomarker. Full article

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic targets and strategies. The kinase MARK4 (MAP (microtubule-associated proteins)/microtubule affinity-regulating kinase 4) regulates microtubule-associated proteins pivotal for cell polarity, protein stability, and intracellular signaling. Animal models of heart failure revealed elevated MARK4 levels, which correlated with impaired cardiac contractility. However, the involvement of MARK4 and its potential as a molecular drug target has not yet been explored in the myocardium of cardiovascular patients. We investigated the MARK4 mRNA expression in human myocardial biopsies of 152 high-risk cardiovascular patients undergoing cardiac surgery. Comprehensive echocardiography as well as testing for sleep-disordered breathing (SDB), a critical comorbidity in heart failure, were assessed preoperatively. We observed a substantial upregulation of myocardial MARK4 expression in patients with impaired cardiac contractility, resulting in an inverse correlation with the left ventricular ejection fraction. Myocardial MARK4 expression also correlated with echocardiographic E/e’, a central parameter of diastolic dysfunction. Mechanistically, our analyses revealed that MARK4 expression increases in SDB and under hypoxic conditions, as evidenced by significant correlations between myocardial MARK4 expression and factors like mean oxygen saturation, time with oxygen saturation below 90%, and the oxygen desaturation index. Multivariable regression analysis revealed that both left ventricular ejection fraction and mean oxygen saturation were independently associated with dysregulated MARK4 levels, even when controlling for important clinical covariables as potential confounders. Taken together, our findings demonstrate that MARK4 expression is highly increased in the myocardium of cardiovascular high-risk patients, suggesting it is a potential molecular target against cardiovascular diseases. Full article

Objectives: This study assessed the clinical characteristics of pediatric COVID-19 patients across different age groups during the first and second pandemic waves in Jordan. Methods: A retrospective analysis was conducted at Jordan University Hospital, involving 485 patients aged 1 month to 18 years from September 2020 to July 2021. Patients were categorized into preschool (≤5 years), school-aged (6–10 years), and teenagers (>10 years). Patients’ clinical characteristics were analyzed using R (version 2.3.3). Results: The mean age for participants was 10.7 ± 5.7 years. Shortness of breath, abdominal pain, and headaches were significantly more likely among older participants (all p < 0.01). Conversely, younger patients were more likely to experience nasal congestion, decreased activity, and reduced feeding (all p < 0.05). The majority of patients had mild symptom severity. Analysis of physiologic and laboratory parameters demonstrated significant differences among age groups in terms of heart rate, respiratory rate, hemoglobin, neutrophils, lymphocytes, platelets, CRP, and creatinine (all p < 0.05). Respiratory support was mainly observed among younger patients. Antibiotics was the most commonly received medication. In terms of outcomes, two patients had complications during their stay, both of which belonged to the <5 years age group. We observed significant differences in incidence of symptoms and laboratory markers among different pediatric age groups. While younger patients experienced severe complications, their older counterparts exhibited more alarming symptoms and worse counts of immune cells. Conclusions: These findings highlight the importance of age-specific management strategies for COVID-19, emphasizing the need for tailored approaches in both treatment and prevention. Full article

Porcine reproductive and respiratory syndrome (PRRS) is an infectious disease that can cause reproductive disorders in sows and affect the breathing of piglets, seriously endangering pig breeding worldwide. In this study, Lactobacillus plantarum NC8 was used as the expression delivery vector of foreign proteins, and a single-chain antibody was designed based on an mAb-PN9cx3 sequence. Three recombinant strains of Lactobacillus plantarum, namely, NC8/pSIP409-pgsA‘-PN9cx3-scFV(E), NC8/pSIP409-pgsA’-PN9cx3-HC(E), and NC8/pSIP409-pgsA‘-PN9cx3-LC(E), were successfully constructed. In an in vitro test, the viral load of each experimental group was significantly lower than that of the control group (p < 0.01). In the piglet challenge protection test, the percentage of CD3⁺CD8⁺T cells in the blood of piglets given complex lactic acid bacteria was significantly increased before and after the challenge (p < 0.01); the body temperature of piglets in this group was normal, the viral load of each organ was reduced, and the obvious pathological changes in each tissue were alleviated. At the same time, the abundance of Bacteroides, Fusobacterium, and other bacteria in the intestinal tracts of the piglets changed, affecting the metabolism of carbohydrates and amino acids and the differentiation of Th1 and Th2 cells. This experiment provides a feasible strategy and method for the design of a PRRSV vaccine. Full article