Hyperbaric Oxygenation: Can It Be a Novel Supportive Method in Acute Kidney Injury? Data Obtained from Experimental Studies.

Despite constant achievements in treatment, acute kidney injury (AKI) remains a significant public health problem and a cause of mortality in the human population. In developed countries, AKI is a significant and frequent hospital complication, especially among patients admitted to intensive care units, where mortality rates can reach up to 50%. In addition, AKI has been implicated as an independent risk factor for the development of chronic kidney disease. Hyperbaric oxygenation (HBO) has been used as a primary or adjunctive therapy for the past 50 years, both in experimental and clinical studies. HBO is a treatment in which the patient is occasionally exposed to 100% oxygen at a pressure greater than atmospheric pressure at sea level. However, despite decades of extensive research, the potentially beneficial effects of this therapeutic approach are still not fully understood, although many potential mechanisms have been proposed, such as antioxidative, anti-inflammatory, anti-apoptotic, etc. Furthermore, the low cost and insignificant adverse events make HBO a potentially important strategy in the prevention and treatment of different diseases. Considering all of this, this review highlights the potential role of HBO in maintaining cellular homeostasis disrupted due to AKI, caused in different experimental models.

Liver phospholipid fatty acid composition in response to chronic high-fat diets.

Liver phospholipid fatty acid composition depends on the dietary lipid intake and the efficiency of hepatic enzymatic activity. Our study aimed to simultaneously investigate the liver phospholipid fatty acid composition in response to chronic linseed, palm, or sunflower oil diets. We used adult female C57/BL6 mice and randomly divided them into control and three groups treated with 25 % dietary oils. Prior to treatment, we analyzed the fatty acid profiles in dietary oils and hepatocytes and, after 100 days, the fatty acid composition in the liver using gas-liquid chromatography. Linseed oil treatment elevated alpha-linolenic, eicosapentaenoic, and docosapentaenoic acids and reduced arachidonic and docosatetraenoic acids, consequently lowering the n-6/n-3 ratio. Palm oil treatment increased linoleic acid and decreased docosahexaenoic acid, contributing to an elevated n-6/n-3 ratio. Sunflower oil treatment elevated total monounsaturated fatty acids by increasing palmitoleic, oleic, and vaccenic acids. The estimated activity of Δ9 desaturase was significantly elevated in the sunflower oil group, while Δ5 desaturase was the highest, and Δ6 desaturase was the lowest after the linseed oil diet. Our findings demonstrate that chronic consumption of linseed, palm, or sunflower oil alters the distribution of liver phospholipid fatty acids differently. Sunflower oil diet elevated total monounsaturated fatty acids, proposing potential benefits for liver tissue health. Considering these outcomes, a substantial recommendation emerges to elevate linseed oil intake, recognized as the principal ALA source, thereby aiding in reducing the n-6/n-3 ratio. Moreover, modifying dietary habits to incorporate specific vegetable oils in daily consumption could substantially enhance overall health.

The impact of six-week dihydrogen-pyrroloquinoline quinone supplementation on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals with mild cognitive impairment: a randomized controlled trial.

OBJECTIVES: To assess the impact of medium-term supplementation with dihydrogen and pyrroloquinoline quinone (PQQ) on mitochondrial biomarkers, brain metabolism, and cognition in elderly individuals diagnosed with mild cognitive impairment. DESIGN: A parallel-group, randomized, placebo-controlled, double-blind experimental design, maintaining a 1:1 allocation ratio between the experimental group (receiving the dihydrogen-producing minerals and PQQ) and the control group (receiving the placebo) throughout the trial. SETTING AND PARTICIPANTS: Thirty-four elderly individuals with mild cognitive impairment (mean age 71.9 ± 3.8 years; 28 females) voluntarily provided written consent to participate in this trial. Participants were assigned in a double-blind parallel-group design to receive either a dihydrogen-PQQ mixture (Alpha Hope®, CalerieLife, Irvine, CA) or placebo twice daily for a 6-week intervention period. METHODS: The primary endpoint was the change in serum brain-derived neurotrophic factor (BDNF) from baseline to the 6-week follow-up; secondary outcomes included cognitive function indices, specific metabolites in brain tissue, brain oxygenation, and the prevalence and severity of side effects. Interaction effects (time vs. intervention) were evaluated using two-way ANOVA with repeated measures and Friedman's 2-way ANOVA by ranks, for normally distributed data with homogeneous variances and non-homogeneous variances, respectively. RESULTS: Dihydrogen-PQQ resulted in a significant elevation in serum BDNF levels at the six-week follow-up (P = 0.01); conversely, no changes in BDNF levels were observed in the placebo group throughout the study duration (P = 0.27). A non-significant trend in the impact of interventions on BDNF levels was observed (treatment vs. time interaction, P = 0.14), suggesting a tendency for dihydrogen-PQQ to upregulate BDNF levels compared to the placebo. A significant interaction effect was observed for the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog) scores in the orientation domain (P = 0.03), indicating the superiority of dihydrogen-PQQ over placebo in enhancing this cognitive aspect. Cerebral oxygenation saturation exhibited a significant increase following the administration of the dihydrogen-PQQ mixture, from 48.4 ± 7.2% at baseline to 52.8 ± 6.6% at 6-week post-administration (P = 0.005). In addition, brain N-acetyl aspartate levels significantly increased at seven out of thirteen locations post-intervention in participants receiving the mixture (P ≤ 0.05). CONCLUSIONS: Despite the limited number of participants included in the study for interpreting clinical parameters, the dihydrogen-PQQ mixture blend shows promise as a potential dietary intervention for enhancing mental orientation and brain metabolism in individuals with age-related mild cognitive decline.

The Impact of Chronic Magnesium Deficiency on Excitable Tissues-Translational Aspects.

Neuromuscular excitability is a vital body function, and Mg2+ is an essential regulatory cation for the function of excitable membranes. Loss of Mg2+ homeostasis disturbs fluxes of other cations across cell membranes, leading to pathophysiological electrogenesis, which can eventually cause vital threat to the patient. Chronic subclinical Mg2+ deficiency is an increasingly prevalent condition in the general population. It is associated with an elevated risk of cardiovascular, respiratory and neurological conditions and an increased mortality. Magnesium favours bronchodilation (by antagonizing Ca2+ channels on airway smooth muscle and inhibiting the release of endogenous bronchoconstrictors). Magnesium exerts antihypertensive effects by reducing peripheral vascular resistance (increasing endothelial NO and PgI2 release and inhibiting Ca2+ influx into vascular smooth muscle). Magnesium deficiency disturbs heart impulse generation and propagation by prolonging cell depolarization (due to Na+/K+ pump and Kir channel dysfunction) and dysregulating cardiac gap junctions, causing arrhythmias, while prolonged diastolic Ca2+ release (through leaky RyRs) disturbs cardiac excitation-contraction coupling, compromising diastolic relaxation and systolic contraction. In the brain, Mg2+ regulates the function of ion channels and neurotransmitters (blocks voltage-gated Ca2+ channel-mediated transmitter release, antagonizes NMDARs, activates GABAARs, suppresses nAChR ion current and modulates gap junction channels) and blocks ACh release at neuromuscular junctions. Magnesium exerts multiple therapeutic neuroactive effects (antiepileptic, antimigraine, analgesic, neuroprotective, antidepressant, anxiolytic, etc.). This review focuses on the effects of Mg2+ on excitable tissues in health and disease. As a natural membrane stabilizer, Mg2+ opposes the development of many conditions of hyperexcitability. Its beneficial recompensation and supplementation help treat hyperexcitability and should therefore be considered wherever needed.

Eight-Week Creatine-Glucose Supplementation Alleviates Clinical Features of Long COVID.

Preliminary studies demonstrated beneficial effects of dietary creatine across different post-viral fatigue syndromes. Creatine is often co-administered with glucose to improve its potency yet whether glucose boost the efficacy of creatine in long COVID remains currently unknown. In this report, we investigate the effects of 8-wk creatine intake with and without glucose on patient-reported outcomes, exercise tolerance, and tissue creatine levels in patients with long COVID. Fifteen male and female long COVID adult patients (age 39.7±16.0 y; 9 women) with moderate fatigue and at least one of additional long COVID-related symptoms volunteered to participate in this randomized controlled parallel-group interventional trial. All patients were allocated in a double-blind parallel-group design (1 : 1 : 1) to receive creatine (8 g of creatine monohydrate per day), a mixture of creatine and glucose (8 g of creatine monohydrate and 3 g of glucose per day), or placebo (3 g of glucose per day) t.i.d. during an 8-wk intervention interval. Two-way ANOVA with repeated measures (treatment vs. time interaction) revealed significant differences in changes in total creatine levels between the groups, showing an interaction effect at two brain locations (right precentral white matter F=34.740, p=0.008; partial η2=0.72; left paracentral grey matter F=19.243, p=0.019; partial η2=0.88), with creatine and creatine-glucose outcompeted placebo to elevate creatine levels at these two locations. Several long COVID symptoms (including body aches, breathing problems, difficulties concentrating, headache, and general malaise) were significantly reduced in creatine-glucose group at 8-wk follow-up (p≤0.05); the effect sizes for reducing body aches, difficulties concentrating, and headache were 1.33, 0.80, and 1.12, respectively, suggesting a large effect of creatine-glucose mixture for these outcomes. Our preliminary findings suggest that supplying exogenous creatine with glucose could be recommended as an effective procedure in replenishing brain creatine pool and alleviating long COVID features in this prevalent condition.

Hyperbaric Oxygen Reduces Oxidative Stress Impairment and DNA Damage and Simultaneously Increases HIF-1α in Ischemia-Reperfusion Acute Kidney Injury.

The central exacerbating factor in the pathophysiology of ischemic-reperfusion acute kidney injury (AKI) is oxidative stress. Lipid peroxidation and DNA damage in ischemia are accompanied by the formation of 3-nitrotyrosine, a biomarker for oxidative damage. DNA double-strand breaks (DSBs) may also be a result of postischemic AKI. γH2AX(S139) histone has been identified as a potentially useful biomarker of DNA DSBs. On the other hand, hypoxia-inducible factor (HIF) is the "master switch" for hypoxic adaptation in cells and tissues. The aim of this research was to evaluate the influence of hyperbaric oxygen (HBO) preconditioning on antioxidant capacity estimated by FRAP (ferric reducing antioxidant power) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) assay, as well as on oxidative stress parameter 3-nitrotyrosine, and to assess its effects on γH2AX(S139), HIF-1α, and nuclear factor-κB (NF-κB) expression, in an experimental model of postischemic AKI induced in spontaneously hypertensive rats. The animals were divided randomly into three experimental groups: sham-operated rats (SHAM, n = 6), rats with induced postischemic AKI (AKI, n = 6), and group exposed to HBO preconditioning before AKI induction (AKI + HBO, n = 6). A significant improvement in the estimated glomerular filtration rate, eGFR, in AKI + HBO group (p < 0.05 vs. AKI group) was accompanied with a significant increase in plasma antioxidant capacity estimated by FRAP (p < 0.05 vs. SHAM group) and a reduced immunohistochemical expression of 3-nitrotyrosine and γH2AX(S139). Also, HBO pretreatment significantly increased HIF-1α expression (p < 0.001 vs. AKI group), estimated by Western blot and immunohistochemical analysis in kidney tissue, and decreased immunohistochemical NF-κB renal expression (p < 0.01). Taking all of these results together, we may conclude that HBO preconditioning has beneficial effects on acute kidney injury induced in spontaneously hypertensive rats.

Peak Resembling N-acetylaspartate (NAA) on Magnetic Resonance Spectroscopy of Brain Metastases.

Background and Objectives: Differentiating between a high-grade glioma (HGG) and solitary cerebral metastasis presents a challenge when using standard magnetic resonance imaging (MRI) alone. Magnetic resonance spectroscopy (MRS), an advanced MRI technique, may assist in resolving this diagnostic dilemma. N-acetylaspartate (NAA), an amino acid found uniquely in the central nervous system and in high concentrations in neurons, typically suggests HGG over metastatic lesions in spectra from ring-enhancing lesions. This study investigates exceptions to this norm. Materials and Methods: We conducted an MRS study on 49 histologically confirmed and previously untreated patients with brain metastases, employing single-voxel (SVS) techniques with short and long echo times, as well as magnetic resonance spectroscopic imaging (MRSI). Results: In our cohort, 44 out of 49 (90%) patients demonstrated a typical MR spectroscopic profile consistent with secondary deposits: a Cho peak, very low or absent Cr, absence of NAA, and the presence of lipids. A peak at approximately 2 ppm, termed the "NAA-like peak", was present in spectra obtained with both short and long echo times. Among the MRS data from 49 individuals, we observed a peak at 2.0 ppm in five brain metastases from mucinous carcinoma of the breast, mucinous non-small-cell lung adenocarcinoma, two metastatic melanomas, and one metastatic non-small-cell lung cancer. Pathohistological verification of mucin in two of these five cases suggested this peak likely represents N-acetyl glycoproteins, indicative of mucin expression in cancer cells. Conclusions: The identification of a prominent peak at 2.0 ppm could be a valuable diagnostic marker for distinguishing single ring-enhancing lesions, potentially associated with mucin-expressing metastases, offering a new avenue for diagnostic specificity in challenging cases.

Body composition, pulmonary function tests, exercise capacity, and quality of life in chronic obstructive pulmonary disease patients with obesity.

PURPOSE OF THE STUDY: Larger proportions of chronic obstructive pulmonary disease (COPD) patients are currently overweight or with obesity than underweight, and the combination of COPD and obesity is increasing. The purpose of this study was to investigate differences in the body composition, pulmonary function tests, exercise capacity, and health-related quality of life among normal weight, overweight, and obese patients with COPD. STUDY DESIGN: A total of 514 patients with COPD were included in the study. According to the World Health Organization criteria for body mass index, the patients were classified as normal weight, overweight, and obese. Evaluations included fat-free mass, fat-free mass index, phase angle, pulmonary function tests, and 6-minute walk test. Dyspnea was assessed using the modified Medical Research Council dyspnea scale, and the health-related quality of life was evaluated using COPD Assessment Test and St. George's Respiratory Questionnaire. Values were compared among the three groups. RESULTS: There were 315 male and 199 female patients, with a mean age of 66.7 ± 8.4 years. Fat-free mass, fat-free mass index, and phase angle values were significantly higher in COPD patients with obesity than in other patients (P < .001, P < .001, P < .001). Forced expiratory volume in 1 s, forced expiratory volume in 1 s/forced vital capacity, and diffusing capacity of lung for carbon monoxide value in pulmonary function tests were significantly higher in COPD patients with obesity than in other patients (P = .046, P < .001, P < .001), while the forced vital capacity values were similar in all groups. Exercise capacity (6-min walk test distance), dyspnea symptoms (modified Medical Research Council scale), and health-related quality of life (COPD Assessment Test and St. George's Respiratory Questionnaire) did not differ significantly between groups. CONCLUSIONS: According to our study, obesity has no negative effect on pulmonary function tests, dyspnea perception, exercise capacity, and health-related quality of life.

Effects of six-month creatine supplementation on patient- and clinician-reported outcomes, and tissue creatine levels in patients with post-COVID-19 fatigue syndrome.

Dietary creatine has been recently put forward as a possible intervention strategy to reduce post-COVID-19 fatigue syndrome yet no clinical study so far evaluated its efficacy and safety for this perplexing condition. In this parallel-group, randomized placebo-controlled double-blind trial, we analyzed the effects of 6-month creatine supplementation (4 g of creatine monohydrate per day) on various patient- and clinician-reported outcomes, and tissue creatine levels in 12 patients with post-COVID-19 fatigue syndrome. Creatine intake induced a significant increase in tissue creatine levels in vastus medialis muscle and right parietal white matter compared to the baseline values at both 3-month and 6-month follow-ups (p < .05). Two-way analysis of variance with repeated measures revealed a significant difference (treatment vs. time interaction) between interventions in tissue creatine levels (p < .05), with the creatine group was superior to placebo to augment creatine levels at vastus medialis muscle, left frontal white matter, and right parietal white matter. Creatine supplementation induced a significant reduction in general fatigue after 3 months of intake compared to baseline values (p = .04), and significantly improved scores for several post-COVID-19 fatigue syndrome-related symptoms (e.g., ageusia, breathing difficulties, body aches, headache, and difficulties concentrating) at 6-month follow-up (p < .05). Taking creatine for 6 months appears to improve tissue bioenergetics and attenuate clinical features of post-COVID-19 fatigue syndrome; additional studies are warranted to confirm our findings in various post-COVID-19 cohorts.

Differences in nutritional status of patients with chronic obstructive pulmonary disease between Mediterranean and non-Mediterranean regions in Croatia.

The nutritional status of patients with chronic obstructive pulmonary disease (COPD) is a significant factor that influences the prognosis of the disease. This observational study aimed to analyse the nutritional status of COPD patients and assess the associations between nutritional status, disease severity, and exercise capacity in four different regions of Croatia. In this multicentre study, 534 COPD patients were recruited and evaluated concerning fat-free mass (FFM), fat-free mass index (FFMI), skeletal muscle mass index (SMMI), phase angle (PhA), pulmonary function tests, and the 6-minute walk test (6MWT). There were 325 (60.9%) male and 209 (39.1%) female patients with a mean age of 66.7±8.4 years. Most patients (73.2%) exhibited a moderate to severely abnormal obstructive pattern and had a reduced 6MWT distance (396.5±110.8 m). Among the participants, 32.8% were overweight and 22.3% were obese, and they had satisfactory values for nutritional status variables (FFM, FFMI, SMMI, PhA). There were no statistical differences between the centres in terms of nutritional status variables. There was a significantly positive correlation of FEV1 with BMI (r=0.148, p=0.001), PhA (r=0.256, p=0.00), FFM (r=0.365, p=0.00), and SMMI (r=0.238, p=0.00). However, there was no significant correlation of the 6MWT with BMI (r=-0.049, p=0.254), FFM (r=0.065, p=0.133), and SMMI (r=-0.007, p=0.867). The data analysis demonstrated that our patients were not underweight and that there was no significant difference between the centres in terms of BMI, FFM, FFMI, SMMI, and PhA. This lack of significant difference was observed even though one of the regions studied was Mediterranean.

SLUG and SNAIL as Potential Immunohistochemical Biomarkers for Renal Cancer Staging and Survival.

Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial-mesenchymal transition, a process important during embryogenesis but also involved in tumor progression. We examined Slug and Snail immunohistochemical expression in patients with different stages of renal cell carcinomas with the aim to investigate their potential role as staging and prognostic factors. A total of 166 samples of malignant renal cell neoplasms were analyzed using tissue microarray and immunohistochemistry. Slug and Snail expressions were evaluated qualitatively (presence or absence), in nuclear and cytoplasmic cell compartments and compared in relation to clinical parameters. The Kaplan-Meier survival analysis showed the impact of the sarcomatoid component and Slug expression on the survival longevity. Cox regression analysis separated Slug as the only independent prognostic factor (p = 0.046). The expression of Snail was associated with higher stages of the disease (p = 0.004), especially observing nuclear Snail expression (p < 0.001). All of the tumors that had metastasized showed nuclear immunoreactivity (p < 0.001). In clear cell RCC, we showed a significant relationship between a high nuclear grade and nuclear Snail expression (p = 0.039). Our results suggest that Slug and Snail could be useful immunohistochemical markers for staging and prognosis in patients suffering from various RCCs, representing potential targets for further therapy strategies of renal cancer.

Molecular hydrogen modulates brain glutamate/GABA-glutamine cycle in overweight humans.

Introduction: We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Methods: A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results: The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. Conclusions: We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens.

Hypomyelination caused by a novel homozygous pathogenic variant in FOLR1: complete clinical and radiological recovery with oral folinic acid therapy and review of the literature.

BACKGROUND: Neurodegeneration due to cerebral folate transport deficiency is a rare autosomal recessive disorder caused by biallelic pathogenic variants in FOLR1. Onset typically occurs in late infancy and is characterized by psychomotor regression, epilepsy, and a hypomyelinating leukodystrophy on magnetic resonance imaging. If left untreated, progressive neurodegeneration occurs. However, early treatment with folinic acid has been shown to stabilize or reverse neurological features. Approximately thirty patients have been described worldwide. Here, we report the first two cases with genetically proven cerebral folate transport deficiency from South-Eastern Europe, describe the effect of oral folinic acid therapy on clinical and neuroradiological features and review the literature. RESULTS: Two siblings presented in childhood with clinical and radiological findings consistent with a hypomyelinating leukodystrophy. Exome sequencing revealed a novel homozygous pathogenic variant in FOLR1 (c.465_466delinsTG; p.W156G), confirming the diagnosis of neurodegeneration due to cerebral folate transport deficiency. Folinic acid treatment was promptly initiated in both patients. The younger sibling was treated early in disease course at 2 years of age, and demonstrated complete recovery in clinical and MRI features. The older sibling, who was 8 years of age at the time of diagnosis and treatment, demonstrated partial but substantial improvements. CONCLUSION: We present the first account in the literature that early treatment initiation with oral folinic acid alone can result in complete neurological recovery of both clinical and radiological abnormalities in neurodegeneration due to cerebral folate deficiency. Moreover, through the report of these patients along with review of the literature, we provide information about the natural history of the disease with comparison of treatment effects at different stages of disease progression. This report also reinforces the importance of universal access to genetic testing to ensure prompt diagnoses for treatable disorders.

Are We Missing the Opportunity to Disseminate GOLD Recommendations Through AECOPD Discharge Letters?

Introduction: Acute exacerbations in chronic obstructive pulmonary disease (AECOPD) lead to poor outcomes and increased burden for patients and healthcare systems. The Global Initiative for COPD (GOLD) includes specific recommendations for AECOPD interventions, discharge criteria, and follow-up. Aligning the AECOPD discharge letters (DL) with GOLD guidelines could facilitate dissemination of recommendations among general practitioners (GPs). Purpose: This study was conducted to assess the compliance of DL with the GOLD recommendations in Croatia. Methods: Pre-pandemic DL of patients presenting for AECOPD to emergency room (ER) were analyzed and stratified by clinical decision to hospitalize (HDL) or discharge patients for outpatient treatment (ERDL). Experienced pulmonologists checked the information from DL against guidelines by using online study-specific questionnaires. Results: In total, 225 HDL and 368 ERDL were analyzed. In most cases, the GOLD ABCD categories (85% HDL, 92% ERDL) or the spirometry-based degree of severity (90% HDL, 91% ERDL) were not included. The number of AEs in the previous year was recorded, but the specific frequent exacerbator phenotype not explicitly stated. The AE phenotype was included in two thirds of HDL and one third of ERDL. The blood eosinophil count was frequently available, but not considered decision-relevant information. Adjustments of previous maintenance therapy, mostly escalation, were recommended in 58.4% HDL and 27.9% ERDL, respectively. Education on proper use of inhalers was recommended only in 15.6% of HDL. Smoking cessation measures were advised in 23.1% HDL and 7.9% ERDL; pulmonary rehabilitation in 35.6% HDL and 0.8% ERDL. Early follow-up was frequently advised (>50%), but rarely appointed. Conclusion: Significant deficiencies in compliance with the GOLD guidelines were identified, translating into a missed opportunity for GPs to become acquainted with GOLD recommendations. These findings emphasize the necessity to increase compliance with guidelines first at specialist level and consequent standardization of DL.

Immunohistochemical Pattern of Histone H2A Variant Expression in an Experimental Model of Ischemia-Reperfusion-Induced Acute Kidney Injury.

Ischemia-reperfusion injury (IRI) is a frequent cause of AKI, resulting in vasoconstriction, cellular dysfunction, inflammation and the induction of oxidative stress. DNA damage, including physical DNA strand breaks, is also a potential consequence of renal IRI. The histone H2A variants, primary H2AX and H2AZ participate in DNA damage response pathways to promote genome stability. The aim of this study was to evaluate the immunohistochemical pattern of histone H2A variants' (H2AX, γH2AX(S139), H2AXY142ph and H2AZ) expression in an experimental model of ischemia-reperfusion-induced acute kidney injury in spontaneously hypertensive rats. Comparing the immunohistochemical nuclear expression of γH2AX(S139) and H2AXY142ph in AKI, we observed that there is an inverse ratio of these two histone H2AX variants. If we follow different regions from the subcapsular structures to the medulla, there is an increasing extent gradient in the nuclear expression of H2AXY142ph, accompanied by a decreasing nuclear expression of γH2AX. In addition, we observed that different structures dominated when γH2AX and H2AXY142ph expression levels were compared. γH2AX was expressed only in the proximal tubule, with the exception of when they were dilated. In the medulla, H2AXY142ph is predominantly expressed in the loop of Henle and the collecting ducts. Our results show moderate sporadic nuclear H2AZ expression mainly in the cells of the distal tubules and the collecting ducts that were surrounded by dilated tubules with PAS (periodic acid-Schiff stain)-positive casts. These findings may indicate the degree of DNA damage, followed by postischemic AKI, with potential clinical and prognostic implications regarding this condition.

The simultaneous action of acute paradoxical sleep deprivation and hypothyroidism modulates synaptosomal ATPases and acetylcholinesterase activities in rat brain.

BACKGROUND: Thyroid dysfunctions as well as sleep abnormalities are usually followed by neurological, psychiatric and/or behavioral disorders. On the other hand, changes in the brain adenosine triphosphatases (ATPases) and acetylcholinesterase (AChE) activities show significant importance in pathogenetic pathways in the evolution of numerous neuropsychiatric diseases. METHODS: This study aimed to evaluate the in vivo simultaneous effects of hypothyroidism and paradoxical sleep deprivation for 72 h on synaptosomalATPases and AChE activities of whole rat brains. In order to induce hypothyroidism, 6-n-propyl-2-thiouracil was administrated in drinking water during 21 days. The modified multiple platform method was used to induce paradoxical sleep deprivation. The AChE and ATPases activities were measured using spectrophotometric methods. RESULTS: Hypothyroidism significantly increased the activity of Na+/K+-ATPase compared to other groups, while at the same time significantly decreased AChE activity compared to the CT and SD groups. Paradoxical sleep deprivation significantly increased AChE activity compared to other groups. The simultaneous effect of hypothyroidism and sleep deprivation reduced the activity of all three enzymes (for Na+/K+-ATPase between HT/SD and HT group p < 0.0001, SD group p < 0.001,CT group p = 0.013; for ecto-ATPases between HT/SD and HT group p = 0.0034, SD group p = 0.0001, CT group p = 0.0007; for AChE between HT/SD and HT group p < 0.05, SD group p < 0.0001, CT group p < 0.0001). CONCLUSIONS: The effect of simultaneous existence of hypothyroidism and paradoxical sleep deprivation reduces the activity of the Na+/K+-ATPase, ecto-ATPases, and AChE, what is different from individual effect of hypothyroidism and paradoxical sleep deprivation itself. This knowledge could help in the choice of appropriate therapy in such condition.

Prognostic Role of Monocyte Distribution Width, CRP, Procalcitonin and Lactate as Sepsis Biomarkers in Critically Ill COVID-19 Patients.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic and one group of patients has developed a severe form of COVID-19 pneumonia with an urgent need for hospitalization and intensive care unit (ICU) admission. The aim of our study was to evaluate the prognostic role of MDW, CRP, procalcitonin (PCT), and lactate in critically ill COVID-19 patients. The primary outcome of interest is the 28 day mortality of ICU patients with confirmed SARS-CoV-2 infection and sepsis (according to Sepsis 3 criteria with acute change in SOFA score ≥ 2 points). Patients were divided into two groups according to survival on the 28th day after admission to the ICU. Every group was divided into two subgroups (women and men). Nonparametric tests (Mann-Whitney) for variables age, PCT, lactate, and MDW were lower than alpha p < 0.05, so there was a significant difference between survived and deceased patients. The Chi-square test confirmed statistically significant higher values of MDW and lactate in the non-survivor group. We found a significant association between MDW, lactate, procalcitonin, and fatal outcome, higher values were reported in the deceased group.

The environmentally friendly approaches based on the heterojunction interface of the LaFeO3/Fe2O3@g-C3N4 composite for the disposable and laboratory sensing of triclosan.

Triclosan (TCS) is a polychlorinated phenoxy phenol (PCPPs) used as a disinfectant and a broad-spectrum antibacterial and antifungal agent in personal hygiene products. TCS easily forms diphenyl ethers and dioxins, which are persistent organic pollutants. This work used a double approach for the TSC sensing: a) screen-printed (SPE) electrochemical platform for on-site application, modified with lanthanum iron oxide and graphitic carbon nitride composite (LaFeO3/Fe2O3@g-C3N4/SPE); and b) carbon paste electrode (CPE), modified with the same material and used in laboratory conditions. Linear range from 0.1 µM to 10 µM, the limit of detection (LOD) of 29 nM and the limit of quantification (LOQ) of 91 nM were obtained for CP electrode in BRBS pH 8. SPE showed the best analytical parameters in BRBS at pH 3, with a linear range from 0.3 µM to 7 µM, LOD of 0.09 µM and LOQ of 0.28 µM. Furthermore, the influence of potential interferents was investigated and proven to be negligible. Determination of TSC was performed to estimate the environmental impact of this compound as well as the practical usefulness of the proposed sensor in the real sample analysis, confirmed with a HPLC analysis.

Clinicopathological Relevance of PAX8 Expression Patterns in Acute Kidney Injury and Chronic Kidney Diseases.

Transcription factor PAX8, expressed during embryonic kidney development, has been previously detected in various kidney tumors. In order to investigate expression of PAX8 transcription factor in acute kidney injury (AKI) and chronic kidney diseases (CKD), immunohistochemical analysis was performed. Presence, location and extent of PAX8 expression were analyzed among 31 human kidney samples of AKI (25 autopsy cases, 5 kidney biopsies with unknown etiology and 1 AKI with confirmed myoglobin cast nephropathy), as well as in animals with induced postischemic AKI. Additionally, expression pattern was analyzed in 20 kidney biopsy samples of CKD. Our study demonstrates that various kidney diseases with chronic disease course that results in the formation of tubular atrophy and interstitial fibrosis, lead to PAX8 expression in the nuclei of proximal tubules. Furthermore, patients with PAX8 detected within the damaged proximal tubuli would be carefully monitored, since deterioration in kidney function was observed during follow-up. We also showed that myoglobin provoked acute kidney injury followed with large extent of renal damage, was associated with strong nuclear expression of PAX8 in proximal tubular cells. These results were supported and followed by data obtained in experimental model of induced postischemic acute kidney injury. Considering these findings, we can assume that PAX8 protein might be involved in regeneration process and recovery after acute kidney injury. Thus, accordingly, all investigation concerning PAX8 immunolabeling should be performed on biopsy samples of the living individuals.