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Introduction: This study aimed to investigate the effects of normobaric hypoxia (NH) and hypobaric hypoxia (HH) on associative memory performance for emotionally valenced stimuli., Methods: Two experiments were conducted. In Study 1, n = 18 undergraduates performed an associative memory task under three NH conditions (FiO 2 = 20.9 %, 15.1 %, 13.6 %) using a tent with a hypoxic generator. In Study 2, n = 20 participants were assessed in a field study at various altitudes on the Himalayan mountains, including the Pyramid Laboratory (5000 m above sea level), using functional Near-Infrared Spectroscopy (fNIRS) and behavioral assessments., Results: Study 1 revealed no significant differences in recognition accuracy across NH conditions. However, Study 2 showed a complex relationship between altitude and memory for emotionally valenced stimuli. At lower altitudes, participants more accurately recognized emotional stimuli compared to neutral ones, a trend that reversed at higher altitudes. Brain oxygenation varied with altitude, indicating adaptive cognitive processing, as revealed by fNIRS measurements., Conclusions: These findings suggest that hypoxia affects associative memory and emotional processing in an altitude-dependent manner, highlighting adaptive cognitive mechanisms. Understanding the effects of hypobaric hypoxia on cognition and memory can help develop strategies to mitigate its impact in high-altitude and hypoxic environments., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Oxylipins are powerful signalling compounds derived from polyunsaturated fatty acids (PUFAs) and involved in regulating the immune system response. A mass spectrometry-based method was developed and validated for the targeted profiling of 52 oxylipins (e.g., isoprostanoids, prostaglandins, epoxy- and hydroxy-fatty acids, specialized pro-resolving mediators) and 4 PUFAs in small urinary extracellular vesicles (uEVs). Ultrasound-assisted extraction using a 50:50 v/v MeOH:H 2 O mixture ensured optimal analytical performances. Limits of detection ranged between 10 and 400 pg/mL for oxylipins and 0.10-3 ng/mL for PUFAs. Satisfactory recoveries (85-116 %) and good intra- and inter-day precisions (RSD ≤15 %) were obtained for all the analytes. The reliability of the procedure was tested in a real case scenario by monitoring ultramarathon runners during the world Tor des Géants® (TDG) race. Both F 2 - and E 2 -isoprostanes were detected in small uEVs of the ultramarathon runners, suggesting the onset of an oxidant insult. 5-F 2t -IsoP exhibited significant pre- to post-race variations, thus potentially representing a non-invasive marker of in-vivo lipid peroxidation. The presence of specialized pro-resolving mediators suggests the activation of pro-resolution signalling cascade resolving inflammation. These outcomes may help manage post-exercise recovery and improve training., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: The environment can alter the homeostasis of humans and human microbiota. Oral health is influenced by high altitude through symptoms of periodontitis, barodontalgia, dental barotrauma, and a decrease in salivary flow. Microbiota and inflammatory state are connected in the oral cavity. This study aimed to explore the effect of acute high-altitude exposure on the salivary microbiome and inflammatory indicators. Methods: Fifteen healthy expeditioners were subjected to oral examination, recording the plaque index (PII), gingival index (GI), the simplified oral hygiene index (OHI-S), and the number of teeth; unstimulated saliva samples were collected at an altitude of 1191 m (T1) and 4556 m (T2). TNF-α, sICAM1, ROS, and the oral bacterial species Porphyromonas gingivalis ( Pg ) and Fusobacterium nucleatum ( Fn ) were quantified. Results: At T2, slCAM, TNF, and ROS increased by 85.5% (IQR 74%), 84% (IQR 409.25%), and 53.5% (IQR 68%), respectively, while Pg decreased by 92.43% (IQR 102.5%). The decrease in Pg was greater in the presence of low OHI-S. The increase in slCAM1 correlated with the reduction in Fn . Individuals with high GI and OHI-S had a limited increase in TNF-α at T2. Conclusion: Short-term exposures can affect the concentration of pathogenic periodontal bacteria and promote local inflammation.

Background and Objectives : This study aimed to compare the effects and safety of boldine combined with Phyllanthus niruri and Ononis spinosa plus tamsulosin vs. tamsulosin alone in medical expulsive therapy (MET) for distal ureteral calculi. Materials and Methods : This retrospective cohort study was conducted on 159 renal colic patients with distal ureteric stones (≤10 mm). Patients aged between 18 and 70 years or older with distal ureteral (below the sacroiliac joint) stones ≤10 mm (defined by the largest diameter in three planes) confirmed by urinary ultrasonography and/or native computed tomography (CT). Patients were divided into two groups: A and B. Patients in Group A received tamsulosin 0.4 mg plus boldine combined with Phyllanthus niruri and Ononis spinosa , while those in Group B received tamsulosin 0.4 mg. The rate of stone expulsion, duration of stone expulsion, the dose and the duration of nonsteroidal anti-inflammatory drugs (NSAIDs), analgesic use, and adverse effects of drugs were recorded. Results : No differences were reported in demographic profiles between the two groups. The stone expulsion rate in Group A (84.8%) was higher in comparison to Group B (52.5%); the mean time of stone expulsion was 16.33 ± 4.75 days in Group A and 19.33 ± 6.42 days in Group B. The mean requirement time of analgesia was significantly less in Group A, 2.42 ± 2.56, than in Group B, 6.25 ± 3.05. Drug-related adverse effects (headache, dizziness, nausea, vomiting, postural hypotension, backache, and running nose) were comparable between the two groups. Conclusions : Tamsulosin plus boldine combined with Phyllanthus niruri and Ononis spinosa as medical expulsion therapy is more effective for distal ureteric stones with less need for analgesics and a shorter stone expulsion time than tamsulosin alone.

The prevalence of chronic kidney disease (CKD) continues to rise globally, paralleled by an increase in associated morbidity and mortality, as well as significant implications for patient quality of life and national economies. Chronic kidney disease often progresses unrecognized by patients and physicians, despite diagnosis relying on two simple laboratory measures: estimated glomerular filtration rate (eGFR) and urine analysis. GFR measurement has been grounded in renal physiology, specifically the concept of clearance, with creatinine identified as a suitable endogenous marker for estimating creatinine clearance (CrCl). On this foundation, various equations have been developed to calculate CrCl or estimated GFR (eGFR) using four variables that incorporate creatinine and certain demographic information, such as sex and age. However, creatinine measurement requires standardization to minimize assay variability across laboratories. Moreover, the accuracy of these equations remains contentious in certain patient subgroups. For these reasons, additional mathematical models have been devised to enhance CrCl estimation, for example, when urine collection is impractical, in elderly or debilitated patients, and in individuals with trauma, diabetes, or obesity. Presently, eGFR in adults can be immediately measured and reported using creatinine-based equations traceable through isotope dilution mass spectrometry. In conclusion, leveraging insights from renal physiology, eGFR can be employed clinically for early diagnosis and treatment of CKD, as well as a public health tool to estimate its prevalence., (Copyright by Società Italiana di Nefrologia SIN, Rome,Italy.)

Exposure to high altitude might cause the body to adapt with negative energy and fluid balance that compromise body composition and physical performance. In this field study involving 12 healthy adults, sex-balanced, and aged 29 ± 4 years with a body mass index of 21.6 ± 1.8 kg/m 2 , we investigated the effects of a 4-day trekking up to 4556 m a.s.l. on Monte Rosa (Alps, Italy). The food intake was recorded using food diaries and nutrient averages were calculated. The bio-impedance analysis was performed at low and high altitudes, and a wearable biosensor (Swemax) was used to track hydro-saline losses in two participants. Daily total energy intake was 3348 ± 386 kcal for males and 2804 ± 415 kcal for females (13%-14% protein, 35% fat, 44%-46% carbohydrates). Although there was a significant body weight loss (65.0 ± 9.3 vs. 64.2 ± 9.10 kg, p  < 0.001, d  = 1.398), no significant changes in body composition parameter were found but a trend in the increase of the bioelectrical phase angle in males ( p  = 0.059, d = -0.991). Body water percentage significantly changed ( p  = 0.026, η 2 p   = 0.440), but the absolute water did not, suggesting that the weight loss was not due to water loss. Salivary and urinary osmolality did not change. A reduction in sweat rate at higher altitudes was observed in both participants. Interestingly, salivary leptin increased ( p  = 0.014, η 2 p   = 0.510), and salivary ghrelin decreased ( p  = 0.036, η 2 p  = 0.403). Therefore, the 4-day trekking at altitude of hypoxia exposure induced changes in satiety and appetite hormones. High altitude expeditions require more specific nutritional guidance, and using multiplex analysis could help in monitoring fluid balance and body composition., Competing Interests: Matteo Beccatelli, Pierluigi Lodi Rizzini, Davide Seletti, Rocco Mecca, and Tommaso Beccatelli were employee or collaborators of the company Biometrica S.r.l., Parma, Italy (which provided the device SWEMAX and the technical assistance) while engaged in the research project. The other authors declare there are no competing interests.

Phthalates are chemical compounds, mainly used as additives in plastics, which are known to induce harmful impacts to the environment and human health due to their ability to act as hormone-mimics. Few studies have been reported on the relationship between human exposure to phthalates and the level of circulating microRNAs (miRs), especially those miRs encapsulated in extracellular vesicles/exosomes or exosome-like vesicles (ELVs). We examined the relationship of ELV-miR expression patterns and urine of adult men with five phthalate metabolites (i.e., mono isobutyl phthalate, mono-n-butyl phthalate, mono benzyl phthalate, mono-(2-ethyl-5-oxohexyl) phthalate, mono-(2-ethylhexyl) phthalate) to identify potential biomarkers and relevant pathways. We found significant positive associations which were further confirmed by multivariable analysis. Overall, our analyses showed that the Σ phthalate metabolite concentration was associated with a significant increase in the expression level of two miRs found in ELV: miR-202 and miR-543. Different pathways including cancer and immune-related responses were predicted to be involved in this relationship. Analyzing the specific downstream target genes of miR-202 and miR-543, we identified the phosphatase and tensin homolog (PTEN) as the key gene in several converging pathways. In summary, the obtained results demonstrate that exposure to environmental phthalates could be related to altered expression profiles of specific ELV-miRs in adult men, thereby demonstrating the potential of miRs carried by exosomes to act as early effect biomarkers.

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a demanding medical condition for patients and society. It has raised much more public awareness after the COVID-19 pandemic since ME/CFS and long-COVID patients share many clinical symptoms such as debilitating chronic fatigue. However, unlike long COVID, the etiopathology of ME/CFS remains a mystery despite several decades' research. This review moves from pathophysiology of ME/CFS through the compelling evidence and most interesting hypotheses. It focuses on the pathophysiology of skeletal muscle by proposing the hypothesis that skeletal muscle tissue offers novel opportunities for diagnosis and treatment of this syndrome and that new evidence can help resolve the long-standing debate on terminology., (© 2024 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)