The effect of neutron irradiation of Si-Ge/Si film structures obtained by gas-phase epitaxy on the processes of charge carrier generation and the magnitude of the dark short-circuit current and open-circuit voltage caused by it is studied, it is shown that their magnitude practically does not change with time. The results obtained indicate that all types of structural defects, both associated with dopant impurities and radiation exposure, contribute to the generation of charge carriers in heated silicon structures with the participation of deep energy levels, which indicates the applicability of neutron processing of silicon materials to create thermal energy converters, operating at high temperatures.

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

A simple and sensitive liquid chromatography-tandem mass spectrometry (LC– MS/MS) method has been developed for the simultaneous determination of atorvastatin (ATOR), ezetimibe (EZM) and their three metabolites including o-hydroxyl atorvastatin (o-OH ATOR), p-hydroxyl atorvastatin (p-OH ATOR), and ezetimibe-glucuronide (EZM-G) in human plasma using benzyl paraben (BP) as internal standard (IS). The analytes and IS were ionized using ESI positive ion mode (ATOR, o-OH ATOR, and p-OH ATOR), ESI negative ion mode (EZM, EZM-G, and BP), and operated in multiple reaction monitoring (MRM) mode. They were next extracted by salting-out assisted liquid–liquid extraction with acetonitrile, and then analyzed by liquid chromatography on a reversed-phase chromatographic column (50 mm × 4.6 mm; 3.5 µm), using a mixture of ac-etonitrile and an acetic acid solution (0.5%) as the mobile phase, showing high extraction effi-ciency (>70%), and a minimized matrix effect. The method was satisfactorily validated, and showed excellent linearity over wide concentration ranges of 0.06–15 ng/mL, 0.6–150 ng/mL, 0.4–100 ng/mL, 0.12–30 ng/mL, and 0.05–3 ng/mL for EZM, EZM-G, ATOR, o-OH ATOR, and p-OH ATOR, respectively.

BackgroundIt is unclear what underpins the large global variations in the prevalence of fluoroquinolone resistance in gram-negative bacteria. We tested the hypothesis that different intensities in the use of quinolones for food-animals plays a role. MethodsWe used Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in human infections with Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa was correlated with the use of quinolones for food producing animals. Linear regression was used to assess the relative contributions of country-level quinolone consumption for food-animals and humans on fluoroquinolone resistance in these 4 species. ResultsThe prevalence of fluoroquinolone resistance in each species was positively associated with quinolone use for food-producing animals (E. coli [ρ=0.55; P<0.001], K. pneumoniae [ρ=0.58; P<0.001]; A. baumanii [ρ=0.54; P=0.004]; P. aeruginosa [ρ=0.48; P=0.008]). Linear regression revealed that both quinolone consumption in humans and food animals were independently associated with fluoroquinolone resistance in E. coli and A. baumanii. ConclusionsReducing quinolone use in food-producing animals may help retard the spread of fluoroquinolone resistance in various gram negative bacterial species.

In this paper, the notion of θ∗-weak contraction is introduced, which is utilized to prove some fixed point results. These results are helpful to give a positive response to certain open question raised by Kannan [Amer. Math. Monthly 76:1969] and Rhoades [Contemp. Math. 72:1988] on the existence of contractive definition which does not force the mapping to be continuous at the fixed point. Some illustrative examples are also given to support our results. As applications of our result, we investigate the existence and uniqueness of a solution of non-linear matrix equations and integral equations of Volterra type as well.

Different contact materials along with optimization of the deposition techniques expand the possibilities to obtain high performance room temperature CdTe-based X/γ-ray detectors. The heterostructures with ohmic (MoOx) and Schottky (MoOx, TiOx, TiN, and In) contacts, created by DC reactive magnetron sputtering and vacuum thermal evaporation, as well as In/CdTe/Au diodes with a p-n junction, formed by laser-induced doping, were developed and investigated. Depending on the pre-treatment of the surface of semi-insulating p-CdTe crystals, deposition of a MoOx film formed an ohmic or Schottky contact. Based on the calculations and IV characteristics of the fabricated Mo-MoOx/р-CdTe/MoOx-Mo, In/CdTe/MoOx-Mo, Ti-TiOx/р-CdTe/MoOx-Mo, and Ti-TiN/р-CdTe/MoOx-Mo Schottky-diode detectors, the current transport processes were described in the models of the carrier generation-recombination within the space-charge region (SCR) at low bias voltages, and space-charge limited current at higher voltages, respectively. The energies of generation–recombination centers, density of trapping centers, and carrier lifetimes were determined. A sharp increase in the reverse current in the Mo-MoOx/р-CdTe/MoOx-Mo, Ti-TiOx/р-CdTe/MoOx-Mo, and Ti-TiN/р-CdTe/MoOx-Mo heterostructures at high bias was discussed in frames of the Poole–Frenkel emission model. Nanosecond laser irradiation of the In electrode, pre-deposited on the p-CdTe crystals, resulted in an increase in the voltage range, corresponding to the carrier generation-recombination in the SCR, in the IV characteristics of the In/CdTe/Au diodes. Such In/CdTe/Au p-n junction diodes demonstrated high energy resolutions (7%@59.5 keV, 4%@122 keV, and 1.6%@662 keV).

Arabidopsis contains eight different h-type thioredoxins (Trx) being distributed in different cell organelles. Although Trx h2 is deemed to be localized in mitochondria, its subcellular localization and function remains a matter of debate. Here, Trx h2 localization and function were investigated using cell fractionation studies and reverse genetics. Differential centrifugation and immunodetection showed the Trx h2 protein to be distributed to the microsomal fraction rather than to mitochondrial preparations. To analyze whether Trx h2 has different roles than mitochondrial Trxs, Arabidopsis mutants lacking Trx h2 were compared with mutants deficient in mitochondrial Trx o1 and double mutants with joint deficiencies in both Trxs. Under constant medium light, trxh2 grew as the wild type, while trxo1 and trxo1h2 mutants showed impaired growth. This was accompanied by differences in the metabolite profiles. The trxo1 and trxo1h2 mutants clustered differently from the wild type during the night, revealing a decrease in ascorbate and glutathione redox states. In fluctuating light intensities, genotypic differences in growth rates were attenuated. Compared to the wild type, the fluctuating-light induced decrease in the NADPH/NADP ratio was diminished in the mutants, with the trxo1h2 double mutant showing the strongest effect. This was accompanied by an increase in the photosynthetic efficiency of the trxo1h2 mutant, specifically in the high light phases of fluctuating light. Conclusively, these results support the view that Trxs o1 and h2 are localized in different subcellular compartments, and have different effects on ascorbate and glutathione redox states and growth in medium light, but cooperatively affect NADP(H) redox state and photosynthetic efficiency in fluctuating light.

Transforming growth factor beta (TGF-β) is a determinant for inflammation and fibrosis in cardiac and skeletal muscle in Chagas disease. To determine its regulatory mechanisms, we investigated the response of T. cruzi-infected cardiomyocytes (CM), cardiac fibroblasts (CF) and L6E9 skeletal myoblasts to TGF-β. Cultures of CM, CF and L6E9 were infected with T. cruzi (Y strain) and treated with TGF-β (1–10 ng/mL, 1h or 48 h). Fibronectin (FN) distribution was analyzed by immunofluorescence and Western blot (WB). Phosphorylated SMAD2 (PS2), phospho-p38 (p-p38), and phospho-c-Jun (p-c-Jun) signaling were evaluated by WB. CF and L6E9 showed an increase in FN from 1 ng/mL of TGF-β, while CM displayed FN modulation only after 10 ng/mL treatment. CF and L6E9 showed higher PS2 levels than CM, while p38 is less stimulated in CF than CM and L6E9. After T. cruzi infection, localized FN disorganization was observed in infected CF and L6E9. T. cruzi induced an increase in FN in CF cultures, mainly in uninfected cells. Infected CF cultures treated with TGF-β showed a reduction in PS2 and an increase in p-p38 and p-c-Jun levels. Our data suggest that p38 and c-Jun pathways may be participating in the fibrosis regulatory process mediated by TGF-β after T. cruzi infection.

In this paper, we investigate a new $q$-analogue of the higher order degenerate Changhee polynomials and numbers, which are called the Witt-type formula for the $q$-analogue of degenerate Changhee polynomials of order $r$. We can derive some new interesting identities related to the degenerate $(h,q)$-Changhee polynomials and numbers.

In this paper, we investigate a new $q$-analogue of the higher order degenerate Changhee polynomials and numbers, which are called the Witt-type formula for the $q$-analogue of degenerate Changhee polynomials of order $r$. We can derive some new interesting identities related to the degenerate $(h,q)$-Changhee polynomials and numbers.

In this paper, we study the p-adic integral representation on Z_p of q-Bernoulli numbers arising from two variable q-Bernstein polynomials and investigate some properties for the q-Bernoulli numbers. In addition, we give some new identities of q-Bernoulli numbers.

In the present paper, we introduce (p, q)-extension of Apostol type Frobenius-Euler polynomials and numbers and investigate some basic identities and properties for these polynomials and numbers, including addition theorems, difference equations, derivative properties, recurrence relations and so on. Then, we provide integral representations, explicit formulas and relations for these polynomials and numbers. Moreover, we discover (p, q)-extensions of Carlitz's result [L. Carlitz, Mat. Mag., 32 (1959), 247–260] and Srivastava and Pintér addition theorems in [H. M. Srivastava, A. Pinter, Appl. Math. Lett., 17 (2004), 375–380].

Background. National surveys reported on variable prevalence of chronic kidney disease (CKD) due to differences in characteristics of population, design, equations used to estimate glomerular filtration rate (eGFR) and definitions. The EH-UH 2 survey is the first study evaluating CKD prevalence, characteristics and awareness in Croatia. Methods. This was a cross-sectional nationwide observational study designed to assess the prevalence and cardio-kidney-metabolic risk factors in Croatia which included 1765 randomly selected subjects. We estimated the prevalence of CKD by means of albumin-to-creatinine ratio (ACR) and eGFR (CKD EPI equation). Comorbidities, anthropometric and social factors related to the prevalence of CKD were analyzed, and CV risk profile was evaluated. Results. The weighted prevalence of CKD (any stage), CKD stage ≥ G3A A2, and CKD defined only as eGFR < 60 ml/min/1.73 m2 were estimated at 17.1%, 9.8% and 7.9%, respectively. The prevalence was higher in men than in women (11.8% vs. 7.9%; p 30 mg/g was 15.1%. Older age, male gender, diabetes, ePWV, and uric acid were independently associated with CKD prevalence. The awareness of CKD of 9.5%. Unaware were older with lower income, less educated, having more frequently diabetes, hypertension (less frequently controlled) and milder renal impairment. Conclusion. In Croatia, the estimated prevalence of CKD is high, being more frequently presented in men than in women. CKD patients have unfavorable CV risk profile. The awareness of CKD is very low reflecting poor health literacy in general population but also in health care workers.

Background. IgA nephropathy (IgAN) is associated with chronic inflammation. Platelet-related parameters, such as platelet (PLT) count, platelet-to-albumin ratio (PAR) and platelet-to-lymphocyte ratio (PLR), were examined as potential prognostic indicators for renal and cardiovascular (CV) outcomes in IgAN. Methods. 150 IgAN patients were devided into two groups based on the cut-off value of PAR. All-cause mortality, major CV events and end-stage renal disease were the primary combined endpoints. Secondary endpoints, such as CV or renal endpoints, were also analyzed separately. Results. The patient’s mean age was 43.7 ± 13.5 years, and the follow-up time was 124 ± 67 months. The K-M curve showed that PLR, PAR and PLT were strongly associated with primary combined (p = 0.002, p = 0.004, p = 0.001) and renal outcomes (p < 0.001, p < 0.001, p < 0.001), but not with CV outcomes in IgAN. However, when combined with left ventricular hypertrophy (LVH) or metabolic syndrome (MetS) PAR was found to be a significant predictor of both primary (p < 0.001, p < 0.001) and secondary outcomes (p = 0.001 and p = 0.038; p = 0.001 and p = 0.015). Additionally, PLR correlated with microalbuminuria (r = -0.165, p = 0.033) and LVH (r = -0.178, p = 0.025), while PLT correlated with eGFR (r = 0.158, p = 0.040). Conclusion. Elevated PAR and PLR may predict progression to end-stage kidney disease, but in combination with LVH and MetS, they showed CV events also in IgAN. The determination of PAR and PLR can be useful and cost-effective parameters for assessing both cardiovascular and renal risks in CKD.

Renal uric acid (UA) reabsorption is mainly mediated by urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9). Dotinurad selectively inhibits URAT1 and do not inhibit other UA transporters such as GLUT9, ATP-binding cassette transporter G2 (ABCG2) and organic anion transporter1/3 (OAT1/3). We discovered that dotinurad improved metabolic parameters and renal function in hyperuricemic patients. We consider a significance of high selectivity in inhibiting URAT1 by dotinurad for metabolic syndrome, chronic kidney disease (CKD), and cardiovascular disease (CVD). Dotinurad inhibits selectively URAT1 and increases UA in the proximal tubules, and UA may compete with glucose for GLUT9, reducing glucose reabsorption. The inhibition of UA entry via URAT1 to liver and adipose tissues by dotinurad increased energy expenditure and decrease lipid synthesis and inflammation in rats. The inhibition of URAT1 in kidney, liver and adipose tissues improve metabolic parameters. CKD patients accumulate uremic toxins such as indoxyl sulfate (IS) in the body. ABCG2 regulates renal and intestinal excretion of IS which strongly affects CKD. OAT1/3 inhibitors suppress IS uptake into kidney, increasing plasma IS, which produces oxidative stress, inducing vascular endothelial dysfunction in CKD patients. The high-selective inhibition of URAT1 by dotinurad may be beneficial for metabolic syndrome, CKD and CVD.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are common in middle aged and elderly individuals. DM may accelerate the aging process, and the age-related declines in the estimated Glomerular Filtration Rate (eGFR), can pose a challenge to diagnose diabetic kidney disease (DKD) using standard diagnostic criteria especially with absence of severe albuminuria among the elderly. In the presence of CKD and DM, elderly patients may need multidisciplinary care due to susceptibility to various health issues e.g., cognitive decline, auditory or visual impairment, various comorbidities, complex medical regimens, and increased sensitivity to medication adverse effects. As a result, it can be challenging to apply recent therapeutic advancements for the general population to the elderly. We review the evidence that the benefits from these newer therapies apply equally to elderly and non-elderly patients and propose a framework for the management of DKD by discussing the nonpharmacological measures and pharmacological management with renin angiotensin system inhibitors (RASi), Sodium Glucose Co-Transporter two inhibitors (SGLT2i), non-steroidal mineralocorticoids receptor antagonists (MRAs), and Glucagon Like Peptide 1 Receptor Agonists (GLP1-RAs).

The 30-day postoperative outcome after elective endovascular aneurysm repair (EVAR) was evaluated and the possible predictors were identified. Demographics, medical history, laboratory values, length of hospitalization (LOH), intensive care unit (ICU) admission and 30-day complications, classified as major [major adverse cardiovascular events (MACE), acute kidney injury (AKI) and death of any cause] and minor [post-implantation syndrome (PIS), postoperative delirium (POD), urinary tract infection (UTI) and technical graft failure] were documented, respectively. We included 322 patients (median LOH 4 days). One-hundred and twenty one (37.5%) complications, mostly minor (n=103, 31.9%), were recorded. Eleven patients (3.4%) evolved MACE, 5 (1.6%) AKI and 2 patients (0.6%) died in ICU. Seventy-seven patients (23.9%) suffered from PIS, eleven from POD, 11 from UTI and 4 from technical graft failure. Multivariate logistic regression analysis revealed that aneurysm diameter (p=0.01) and past smoking (p=0.003) were predictors for postoperative complications. PAD was an independent predictor of MACE (p=0.003), preoperative neutrophil to lymphocyte ratio (NLR) value of AKI (p=0.003) and past smoking of PIS (p=0.008), respectively. Our study showed that 30-day morbidity after EVAR exceeded 35%. However, the majority of complications were classified as minor and the associated mortality was low. Aneurysm diameter and past smoking were independent predictors for postoperative outcome.

Background: This study analyzes sex-based differences in renal structure and response to the Angiotensin-Converting Enzyme (ACE) inhibitor enalapril in a mouse model of atherosclerosis. Methods: ApoE-/- mice (8 weeks old) received enalapril (5 mg/kg/day, subcutaneous) or PBS as a control for an additional 14 weeks. Each group consisted of six males and six females. Results: Females exhibited elevated LDL-cholesterol levels, while males presented higher creatinine levels and proteinuria. Enalapril effectively reduced blood pressure in both groups, but proteinuria decreased significantly only in females. Plaque size analysis and assessment of kidney inflammation revealed no significant sex-based differences. However, males displayed more severe glomerular injury, with increased mesangial expansion, mesangiolysis, glomerular foam cells and activated parietal epithelial cells (PECs). Enalapril mitigated mesangial expansion, glomerular inflammation (particularly in females), and the hypertrophy of PECs in males. Conclusion: This study demonstrates sex-based differences in the response to enalapril in a mouse model of atherosclerosis. Males exhibited more severe glomerular injury, while enalapril provided renal protection, particularly in females. These findings suggest potential sex-specific considerations for ACE inhibitor therapy in chronic kidney disease and atherosclerosis cardiovascular disease. Further research is needed to elucidate the underlying mechanism behind these observations.

Automated medical diagnosis is one of the important machine learning applications in the domain of healthcare. In this regard, most of the approaches primarily focus on optimizing the accuracy of classification models. In this research, we argue that unlike general-purpose classification problems, medical applications, such as chronic kidney disease (CKD) diagnosis, require special treatment. In the case of CKD, apart from model performance, other factors such as the cost of data acquisition may also be taken into account to enhance the applicability of the automated diagnosis system. In this research, we have proposed two techniques for cost-sensitive feature ranking. An ensemble of decision tree models is employed in both the techniques for computing the worth of a feature in the CKD dataset. An automatic threshold selection heuristic is also introduced which is based on the intersection of features’ worth and their accumulated cost. A set of experiments are conducted to evaluate the efficacy of the proposed techniques on both tree-based and non-tree based classification models. The proposed approaches are also evaluated against several comparative techniques. Furthermore, it is demonstrated that the proposed techniques select around 1/4^th of the original CKD features while reducing the cost by a factor of 7.42 of the original feature set. Based on the extensive experimentation it is concluded that the proposed techniques employing feature-cost interaction heuristic tend to select feature subsets that are both useful and cost-effective.

Purpose: Acute kidney injury (AKI) is a severe symptom of the 2019 novel coronavirus disease (COVID-19), especially for patients in a critical condition.This study explored the potential mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on AKI at the single-cell level. Methods: 15 normal human kidney samples were collected and analyzed using single-cell RNA sequencing (scRNA-seq). Subsequently, we analyzed the components and proportions of kidney cells expressing the host cellular receptor ACE2 and the key protease TMPRSSs family, and analyzed the expression differences in Occidental and Asian populations. Results: We drafted the currently available world's largest human kidney cell atlas with 42,589 cells and identified 19 clusters through unsupervised hierarchical clustering analysis. ACE2 and TMPRSSs genes were significantly co-expressed in podocytes and proximal convoluted tubules as potential host cells targeted by SARS-CoV-2. Comparative analysis showed that ACE2 expression in kidney cells was no less than that in the lung, esophagus, small intestine and colon, suggesting that the kidney may be an important target organ for SARS-CoV-2. In addition, given the high expression of ACE2 and kidney disease-related genes in Occidental donors relative to Asian donors, Occidental populations with SARS-CoV-2 infection might be a higher risk of of kidney injury.

Healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence on the benefits of physical activity and other health-related behaviors in the early-stage CKD. This study aimed to explore the association between health-related behaviors and end-stage renal disease (ESRD) and mortality in the early stages of CKD. The National Health Insurance Service (NHIS) database from January 1st, 2009 to December 31st, 2016 was used to screen 83,470 subjects with early stage CKD. Cox proportional hazard regression analysis was used to evaluate the association between health-related behaviors and ESRD and death. Kaplan-Meier curves for mortality and ESRD were plotted according to the physical activity, smoking status and alcohol consumption pattern. Risk of death decreased significantly in subjects who engaged in sufficient physical activity (adjusted Hazard Ratio (HR) 0.73; 95% CI: 0.64-0.83; p < 0.001). Risk of ESRD and death increased significantly in the current smoker with adjusted HR of 1.44 (95% CI: 1.06-1.95; p < 0.02) and 1.61 (95% CI: 1.44-1.80; p < 0.001) respectively. Therefore, systematic interventions to encourage physical activity and smoking cessation need to be actively considered in the early stages of CKD.

Background: Kidney transplantation is considered the first-choice therapy in ESRD patients. Despite recent improvements in terms of outcomes and graft survival in recipients, postoperative complications still concern health-care providers involved in the management of those patients. Particularly challenging are cardiovascular complications. Perioperative goal-directed fluid-therapy (PGDT) and hemodynamic optimization are widely used in high-risk surgical patients, and are associated with a significant reduction in postoperative complication rates and length of stay (LOS). The aim of this work is to compare the effects of perioperative goal-directed therapy (PGDT) with conventional fluid therapy (CFT), and to determine whether there are any differences in major postoperative complications rates and delayed graft function (DGF) outcomes. Methods: Prospective study with historical controls. Two groups, a PGDT- and a CFT- group were used: the stroke volume (SV) optimization protocol was applied in PGDT group throughout the procedure. Conventional fluid therapy with fluids titration at a central venous pressure (CVP) 8-12 mmHg and mean arterial pressure (MAP) >80mmHg was applied to the control-group. Postoperative data collection including vital signs, weight, urinary output, serum creatinine, blood urea nitrogen, serum potassium, and assessement of volemic status and the signs and symptoms of major postoperative complications occurred at 24h, 72h, 7 days and 30 days after transplantation. Results: Among the 66 patients enrolled, 33 were in each group and both groups had similar physical characteristics. Good fuctional recovery was evident in the 94% of patients. The statistical analysis has showed a difference in postoperative complications as follows: significant reduction of cardiovascular complications, DGF episodes (p<0.05) and surgical complications (p<0.01). There were no significant differences in pulmonary or other complication. Conclusions: PGDT and SV optimization effectively influenced the rate of major postoperative complications, reducing the overall morbidity and thus the mortality in patients receiving kidney transplantation.

Tspo is a receptor involved in the regulation of cellular proliferation, apoptosis and mitochondrial functions. Previous studies showed the expression of TSPO protein correlated positively with tumour malignancy and negatively with patient survival. The aim of this study was to determine the transcription of Tspo mRNA in various types of normal and cancer tissues. In situ hybridization was performed to localise the Tspo mRNA in various human normal and cancer tissues. The relative level of Tspo mRNA was quantified using fluorescent intensity and visual estimation of colorimetric staining. RT-PCR was used to confirm these mRNA levels in normal lung, lung cancer, liver cancer and cervical cancer cell lines. There was a significant increase in the level of transcription in liver, prostate, kidney and brain cancers while a significant decrease was observed in cancers of the colon and lung. Quantitative RT-PCR confirmed that the mRNA levels of Tspo are higher in a normal lung cell line than in a lung cancer cell line. An increase in the expression levels of TSPO makes it a good diagnostic biomarker and TSPO could serve as a target for anticancer drug development.

Soil water balance (SWB) in woody crops is sometimes difficult to estimate with one-dimensional models because these crops do not completely cover the soil and usually have a deep root system, particularly when cropped under rainfed conditions in a Mediterranean climate. In this study, the actual crop evapotranspiration (ETc act) is estimated with the soil water balance model SIMDualKc which uses the dual-Kc approach (relating the fraction of soil cover with the crop coefficients) to improve the estimation of the water requirements of a rainfed vineyard, using data from a deep soil profile. The actual basal crop coefficient (Kcb act) obtained using the SIMDualKc model was compared with the Kcb act estimated using the A&amp;P approach, which is a simplified approach based on measurements of the fraction of ground cover and crop height. Spectral vegetation indices derived from Landsat-5 satellite data were used to determine the fraction of ground cover (fc VI) and thus, the density coefficient (Kd). The SIMDualKc model was calibrated using soil water content (SWC) measurements down to a depth of 1.85 meters, which significantly improved the conditions for using a SWB estimation model. The test of the model was performed using a different SWC dataset. A good agreement between simulated and field measured SWC was observed for both data sets along the crop season, with RMSE&lt;12.0 mm, NRMSE &lt;13%. The calibrated Kcb values were 0.15, 0.60 and 0.52 for the initial, mid-season, and end season, respectively. The ratio between actual (ETc act) and crop evapotranspiration (ETc) was quite low between veraison and maturity (mid-season), corresponding to 36%, indicating that the rainfall was not sufficient to satisfy the vineyards water requirements. Spectral vegetation indices used to compute fc VI were unable to fully track the plants’ conditions when water stress. However, ingestion of data from remote sensing showed promising results that could be used to support decisions making in irrigation scheduling. Further studies on the use of the A&amp;P approach using remote sensing data are required.

Photovoltaic materials convert light into electrical voltages. So far, most research in the field are focused on how to refine/improve the existing or standard photovoltaic cells to yield more efficient electricity, to reduce weight, to make more flexible shape, or to minimize costs under standard and uniform sunlight illuminations. In this project, we explore and demonstrate a hypothesis that non-uniform light illumination photovoltages can also be generated due to photo doping induced mobile charge carrier density gradient between light and dark areas in either p-type or n-type photo doping semiconductors. The term non-uniform light illumination was coined to refer to subjecting our photo sensing thin film devices to areas of high and low intensities of light illumination simultaneously, with an intention of creating a charge density gradient and therefore a voltage. Specifically, a polymeric composite thin film composed of P3HT (p-type photo doping semiconductor) and PCBM (photo doping electron acceptor and trap) at varying p-doping levels were studied. We observed that the fabricated photovoltaic cells with about 80% PCBM doped P3HT thin film devices exhibited 0.5-1.2 volts photovoltages under non-uniform light illuminations.

Background. ADHD is a neurodevelopmental disorder that is accompanied by executive deficits. Objectives. To obtain evidence of the usefulness of the BRIEF-P and to analyse the possible ceiling and floor effect of its scores in the assessment of executive function in preschoolers with signs compatible with a possible diagnosis of ADHD. Methods. Seven articles were selected from 2538 potentially eligible articles from different databases. We included studies assessing samples of individuals with symptoms compatible with ADHD, with age range 2-6 years, published in English or Spanish, during the period 2012-2022. References published in: Science Direct, NCBI (PubMed), ProQuest Education Journals in the last decade. Risk of bias was assessed using the QUADAS-2 questionnaire. The main variables were: age and executive functioning. Conclusions. Executive deficits in early-life individuals with ADHD-compatible symptoms are more extensive than deficits in working memory. BRIEF-P is an instrument that facilitates obtaining a sensitive and discriminative executive profile. It should be used in combination with other neuropsychological performance tests, finding a floor effect in tests associated with warm executive functions and a ceiling effect in cold executive functions. This requires using a variety of tests to assess executive performance in preschoolers with symptoms compatible with ADHD and designing intervention proposals in line with them...

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.

Films prepared from poly(3-hydroxybutyrate-co-4-hydroxybutyrate) copolymers produced by Aneurinibacillus sp. H1 using an automatic film applicator were homogeneous and had a defined thickness, which allowed a detailed study of physicochemical properties. Their properties were compared with a poly (3-hydroxybutyrate) homopolymer film prepared by the same procedure, which proved to be significantly more crystalline by DSC and XRD. Structural differences between samples had a major impact on their properties. With increasing 4-hydroxybutyrate content, the ductility and release rate of the model hydrophilic active ingredient increased significantly. Other observed properties, such as the release of the hydrophobic active substance, the contact angle with water and ethylene glycol, or the surface morphology and roughness, were also affected by the composition. The identified properties predetermine these copolymers for wide use in areas such as biomedicine or smart biodegradable packaging for food or cosmetics. The big advantage is the possibility of fine-tuning properties simply by changing the fermentation conditions.

It is unclear how important it is to reduce fluoroquinolone consumption in the general population to prevent the spread of fluoroquinolone resistance in Neisseria gonorrhoeae (bystander selection). Methods We assessed bystander selection by using Spearman’s correlation to assess if the country-level prevalence of fluoroquinolone resistance in N. gonorrhoeae was correlated with the prevalence of fluoroquinolone resistance in four other gram-negative species - Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. Results Fluoroquinolone resistance in N. gonorrhoeae was positively associated with homologous resistance in all 4 species - A. baumanii. (ρ=0.61, P=0.0003, E. coli (ρ=0.67, P<0.0001), K. pneumoniae (ρ=0.52, P=0.0004) and P. aeruginosa (ρ=0.40, P=0.0206). Positive associations were also found between the national prevalence of fluoroquinolone resistance and fluoroquinolone consumption in the general population in the preceding year for 4 of the 5 species. Conclusions Gonococcal fluoroquinolone resistance can be productively viewed as being part of a syndemic of fluoroquinolone resistance. Strengthening antimicrobial stewardship programs may help retard the spread of fluoroquinolone resistance in N. gonorrhoeae.

Dendrobium okinawense is an endangered epiphytic orchid, and there has been no scientific report so far on its propagation. Protocorm is mass of cell, and protocorm-like bodies (PLBs) look alike protocorm produced by vegetative explants in vitro. Regeneration of PLBs is the most efficient technique for the orchids micro-propagation. We used different light emitting diodes (LEDs) for the efficient PLB organogenesis of D. okinawense. PLBs regenartion under green and red LED surpassed respectively 81.1% and 71.6% in numbers, and respectively 80.8% and 57.8% in fresh weight over white fluorescent light. We manipulated the culture media by different concentrations of PCIB and HMI. PLBs organogenesis promoted by low concentration, it increased respectively 35.9% and 19.3% over control by 0.01 mg/L PCIB and 0.01 ml/L HMI in numbers. Green LED and PCIB independently produced mostly similar numbers of new PLBs. Interestingly, culture media with 0.01 mg/L of PCIB further increased 8.5% of the numbers of PLBs under green LED, whereas the culture media with 0.01 mg/L HMI reduced the number of PLBs under green LED. PLBs culture under green LED with very low concentrations of PCIB manipulated culture media can significantly increase their organogenesis of D. okinawense.

The circuitry of the summarized "floating" differential stages (FDS) based on complementary field-effect transistors with a control p-n junction (CJFET), intended for use in low-noise analog microcircuits, for example, operational amplifiers. The results of modeling the flow characteristics of one of the CJFET FDSs in the LTSpice XVII environment at low temperatures (down to -197 ⁰С) and exposure to a neutron flux in the range of 1e13 ÷ 1e15 n / cm² are presented.

The article introduces a new solution approach to grid-connected single-stage three-phase PV inverter whereby a dc-link voltage can successfully achieve the desired performance. As a single-stage, the variable output of perturb and observe maximum power point tracking (P&O based-MPPT) is fully utilized as dc-link voltage reference in inverter control scheme. As a result, it is challenging for the dc-link voltage to preserve energy balance by tracking its variable dc-link voltage reference under unpredictable environmental changes. To overcome this challenge, an adaptive reference proportional-integral (ARPI) controller, self-tuning, is designed and implemented to compel the dc-link voltage tracking its voltage reference to be equal as closely as possible; hence, the capability of the dc-link under abnormal events substantially guarantees the best energy balance and transient performance enhancement. To verify the validity of the method, simulation results for multiple events scenarios on 250 KW single-stage grid-connected PV systems show the effectiveness of the ARPI controller compared with PI controller.

Quorum Sensing (QS) and Machine Learning (ML) hybrid systems represent a groundbreaking innovation in synthetic biology, offering unprecedented control and adaptability in microbial gene regulation and metabolic processes. QS, a microbial communication mechanism, is crucial for coordinating gene expression in response to population density, impacting behaviors such as biofilm formation, virulence, and resource optimization. However, traditional QS systems are constrained by their reliance on static, pre-programmed feedback loops, limiting their flexibility in dynamic, complex environments. This review highlights how integrating advanced ML algorithms—such as reinforcement learning and deep learning—into QS systems can overcome these limitations by enabling real-time data processing, predictive modeling, and dynamic feedback control. Through these innovations, QS-ML systems can autonomously adjust gene expression and metabolic outputs, making them more efficient and scalable in applications ranging from pathogen control to precision medicine and industrial biomanufacturing. Key case studies illustrate the successful deployment of QS-ML systems to combat antimicrobial resistance, optimize bio-production, and enhance therapeutic precision in cancer and immune modulation. Despite the clear advantages, challenges remain in data integration, system robustness, and regulatory oversight. Addressing these hurdles through interdisciplinary collaboration and developing scalable, multi-omics data platforms will be critical for advancing QS-ML systems from experimental settings to real-world applications. This review underscores the transformative potential of QS-ML systems in revolutionizing synthetic biology, with profound implications for personalized medicine, sustainable biomanufacturing, and environmental health.Quorum Sensing (QS) and Machine Learning (ML) hybrid systems represent a groundbreaking innovation in synthetic biology, offering unprecedented control and adaptability in microbial gene regulation and metabolic processes. QS, a microbial communication mechanism, is crucial for coordinating gene expression in response to population density, impacting behaviors such as biofilm formation, virulence, and resource optimization. However, traditional QS systems are constrained by their reliance on static, pre-programmed feedback loops, limiting their flexibility in dynamic, complex environments. This review highlights how integrating advanced ML algorithms—such as reinforcement learning and deep learning—into QS systems can overcome these limitations by enabling real-time data processing, predictive modeling, and dynamic feedback control. Through these innovations, QS-ML systems can autonomously adjust gene expression and metabolic outputs, making them more efficient and scalable in applications ranging from pathogen control to precision medicine and industrial biomanufacturing. Key case studies illustrate the successful deployment of QS-ML systems to combat antimicrobial resistance, optimize bio-production, and enhance therapeutic precision in cancer and immune modulation. Despite the clear advantages, challenges remain in data integration, system robustness, and regulatory oversight. Addressing these hurdles through interdisciplinary collaboration and developing scalable, multi-omics data platforms will be critical for advancing QS-ML systems from experimental settings to real-world applications. This review underscores the transformative potential of QS-ML systems in revolutionizing synthetic biology, with profound implications for personalized medicine, sustainable biomanufacturing, and environmental health.

Introduction: This review explores the literature and presents institutional cases of concurrent robotic multisite surgery—in particular, robot-assisted radical prostatectomy (RARP) and robot-assisted partial nephrectomy (RAPN) for synchronous prostate and kidney cancers. We highlight dual-console synchronous robotic procedures, emphasizing the unique docking tech-nique developed. Aim: The aims of the study were to evaluate the feasibility, safety, and clinical outcomes of concurrent RARP and RAPN for synchronous prostate cancer and small renal tumors, as well as other concurrent robotic multisite surgeries, and to compare institutional findings with the existing literature. Materials and Methods: We describe the unique docking technique used in our procedures, which facilitates atraumatic transitions between surgeries using the same port sites. Additionally, eligible studies on concurrent robotic multisite surgery that were published in English were retrieved from the MEDLINE, Embase, and Cochrane Library databases. Data on operative time, blood loss, complications, and postoperative outcomes were extracted. Results: Eight cases from our institution demonstrated the feasibility and safety of the proposed approach, which is consistent with previous reports. The unique docking technique and dual-console setup enhance surgical precision, offering significant benefits in patient outcomes. As part of the litera-ture review, nine retrospective studies involving 40 cases of concurrent RARP and RAPN were reviewed. Additionally, eleven retrospective studies involving 392 cases of concomitant RARP and robotic transabdominal preperitoneal inguinal hernia repair (RTAPPIHR) were analyzed. Conclusions: Concurrent RARP and RAPN for synchronous prostate and kidney tumors is a viable and effective approach. Our early experience suggests that this and other combined procedures can optimize patient care and reduce costs. Prospective trials are needed to validate these findings and further refine the techniques.

Background: In this investigation, we explored the effects of pharmacological cholinergic stimulation on cardiac function and renal inflammation following acute myocardial infarction (AMI) in spontaneously hypertensive rats (SHRs). Methods: Adult male SHRs were randomized into three experimental groups: sham-operated; AMI+Veh (infarcted, treated with vehicle); and AMI+PY (infarcted, treated with the cholinesterase inhibitor pyridostigmine bromide (PY) - 40 mg/kg, once daily for seven days). Rats were euthanized 7 or 30 days post-surgery. Clinical parameters were assessed on the day before euthanasia. Subsequent to euthanasia, blood samples were collected and renal tissues were harvested for histological and gene expression analyses aimed to evaluate inflammation and injury. Results: Seven days post-surgery, the AMI+PY group demonstrated improvements in left ventricular diastolic function and autonomic regulation, and a reduction in renal macrophage infiltration compared to the AMI+Veh group. Furthermore, there was a notable downregulation of pro-inflammatory gene expression and an upregulation of anti-inflammatory gene expression. Analysis 30 days post-surgery showed that PY treatment had a sustained positive effect on renal gene expression, correlated with a decrease in biomarkers indicative of subclinical kidney injury. Conclusion: Short-term cholinergic stimulation with PY provides both cardiac and renal protection by mitigating the inflammatory response after AMI.

Gut microbiota dysfunction is a key factor affecting chronic kidney disease (CKD) susceptibility. Puerariae Lobatae Radix (PLR), a traditional Chinese medicine and food homologous herb, is known to promote gut microbiota homeostasis, however, its role in renoprotection remains unknown. This study aimed to investigate the efficacy and potential mechanism of PLR to alleviate CKD. An 8-week 2% NaCl-feeding murine model was applied to induce CKD and evaluate the therapeutic effect of PLR supplementary. After gavage for 8 weeks, PLR significantly alleviated CKD-associated creatinine, urine protein increasement and nephritic histopathological injury. Moreover, PLR protected kidney from fibrosis by reducing inflammatory response and down-regulating the canonical Wnt / β-catenin pathway. Further, PLR rescued gut microbiota dysbiosis and protected high salt-induced gut barrier dysfunction. We found enrichment of Akkermansia and Bifidobacterium after PLR intervention, the relative abundance of which were in positive correlation with normal maintenance of renal histology and function. Next, fecal microbiota transplantation experiment verified that the positive effect of PLR on CKD was at least partially exerted through gut microbiota reestablishment and down-regulation of the Wnt / β-catenin pathway. Our study provides evidence for new function of PLR on kidney protection and put forward a potential therapeutic strategy target for CKD.

Overhydration (OH) is a prevalent medical problem occuring in patients with kidney failure, but a specific marker has still not been found. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function such as NT-pro-BNP, GFR or creatinine levels. New serum markers, including but not limited to Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are presently under research, displaying promising results. The necessity to ascertain a more precise marker of overhydration is urgent mainly because physical examination is exceptionally imprecise. Signs and symptoms of fluid overload, like edema or gradual increase of body mass, are not always present, notably in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation, focusing specifically on kidney diseases.

Pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab in immunocompromised patients has reduced the risk of breakthrough infection, disease, hospitalization, and COVID-19 related mortality. However, the advent of the Kraken variant (XBB.1.5) has limited the use of this monoclonal antibody, based on poor efficacy in in vitro studies The objective of the study was to evaluate the risk of breakthrough infection, symptomatic disease, hospitalization, intensive care admission and COVID-19 related death in kidney transplanted recipients receiving pre-exposure prophylaxis with Tixagevimab/Cilgavimab for COVID-19 in the era of the Kraken variant (XBB.1.5). In a prospective, observational study, we enrolled kidney transplant patients undergoing pre-exposure prophylaxis for COVID-19 with Tixagevimab/Cilgavimab at the Division of Infectious Diseases of Federico II University of Naples between February 2023 and August 2023. Each patient subsequently underwent a six-month follow-up with symptom monitoring and surveillance nasopharyngeal swab for SARS-CoV-2 RNA detection every 30 days, regardless of symptoms. Thirty-four kidney transplant patients were enrolled and in the follow-up period, only one tested positive for the nasopharyngeal swab for SARS-CoV-2 research with asymptomatic infection and virological recovery on the eighth day from the diagnosis of infection. Therefore, no patient developed disease and no patient needed hospitalization and no death occurred. No adverse drug reaction to Tixagevimab/Cilgavimab occurred. Our data, although derived from a limited and uncontrolled sample, show the potential of Tixagevimab/Cilgavimab as a valid and viable therapeutic strategy in pre-exposure prophylaxis for immunocompromised patients. These findings highlight the importance of conducting clinical studies on this topic.

Hemodialysis (HD) patients experience significant psychological stress related HD. Coping strategies are utilized to help these patients cope with this stress. Prevalence of different types of coping strategies in relation with differential levels of HD-related stress scores and by demographics were assessed. HD patients aged 18 years and above who were seeking regular treatment in a specific HD-unit of a hospital in the upper Midwest, were surveyed between March 2020 and July 2020. Descriptive statistics, correlational analyses, and regression analyses were performed. Females could be expected to have emotional coping scores 8 units greater than males, as B = 8.017 for sex in the model, p =.000. Females could be expected to have coping scores 6.4 points higher than males when adjusted for stress levels, as: B = 6.351, p =.001 for sex in the model. For each 1point increase in Stress Score, the Coping Score could be expected to: increase 6.8 points when adjusted for Sex, where B = 6.751 and p =.000. Increased prevalence of emotional pre-occupation was only observed among female patients which increased with the increase in stress. Psychological interventions in female HD patients should be strongly considered in addressing emotional pre-occupation coping.

Background: Pre-treatment with lipopolysaccharide (LPS) protected the kidney against a later lethal ischemia. To reveal the mechanisms of renal cross-tolerance and septic acute kidney injury we investigated the effects of LPS on miRNA expression in the kidney. Methods: Male NMRI mice were injected with 40 and 10 mg/kg LPS ip. and sacrificed at 1.5 and 6 hours (early preconditioning, EP) and at 24 and 48 hours (late preconditioning, LP). The miRNA profile was established using miRCURY LNA™ microarray and confirmed with qPCR. Results: Plasma urea concentration peaked at 24 hours after LPS and decreased thereafter. Renal TNF-α and IL-6 mRNA were extremely elevated at all time-points. miRNome changes were mild at 1.5 hours, most miRNAs were altered at 6 and 24 hours and declined by 48 hours. Not all miRNAs could be assayed or validated by qPCR. In EP miR-762 was newly identified and validated and was the most elevated miRNA with both methods. In LP miR-21a-5p was the most influenced miRNA followed by miR-451a, miR-144-3p and miR-146a-5p. MiR-21a-3p increased significantly in both EP and LP. Conclusion: miR-762 might attenuate the LPS-induced immune response during EP and the miR-144/451 cluster is involved in LPS-induced renal preconditioning.

We have collected theoretical arguments supporting the functional role of nano-metallic coatings of solar cells, which enhance their efficiency via by plasmon strengthening of absorption of sun-light photons and reduction of binding energy of photo-excitons. The quantum character of plasmonic effect related with the absorption of photons (called as optical plasmonic effect) is described in terms of Fermi golden rule for quantum transitions of semiconductor band electrons induced by plasmons from a nano-metallic coating. The plasmonic effect related with the lowering of exciton binding energy (called as electrical plasmonic effect) is also quantumly characterized with particular significance for metalized perovskite solar cells. Quantum coupling between plasmons in nanoparticles from a coating with band electrons in a semiconductor substrate significantly modifies material properties (dielectric functions) both of particles and of a semiconductor, beyond the ability of a classical electrodynamics description.

Recent algorithmic-based research in the stock market has predominantly focused on ultra-high-frequency trading and index estimation. We developed an improved algorithm to address the need for a low-frequency, real-world trading model to build on the existing high hit-ratio and low maximum drawdown. We utilized established price indicators, Stochastic and Williams %R, and introduced a volume factor to increase the model's safety to enhance the model's performance. This improved algorithm demonstrated superior returns while maintaining high hit-ratio and low maximum drawdown. Specifically, we leveraged the existing algorithm to trade using 2X and 3X signals, incorporating volume data, the 52-week average, standard deviation, and other factors. The data set comprised SPY ETF price and volume from 2010 to 2023, covering over 13 years. Our enhanced algorithmic trading model outperformed both the benchmark and previous results, achieving a hit rate of over 90%, a maximum drawdown of less than 1%, an average of 1.5 trades per year, a total return of +519.3%, and an annualized return (AnnR) of +15.1%. The analysis demonstrates that the model's simplicity, ease of application, and comprehensibility can assist investors in making informed investment decisions albeit the past performance does not guarantee future returns.

The aim of this work was to investigate a new, simple one-pot combustion synthesis technique for creating sulphur-based CuS/ZnS p-n heterojunction nanocomposite photocatalysts. The study examined the photocatalytic activity and reusability of these nanocomposites in removing rhodamine B (RhB) dye under visible light irradiation. Various methods of characterisation were employed to determine the properties of the materials, including particle morphology, crystalline phases and bandgap energy. The intrinsic reaction parameters, such as catalyst loading, pH level of the solution, and initial pollutant concentration, were varied to establish the optimal photo-degradation conditions. The results showed that a binary CuS/ZnS catalyst with a 10 gL-1 loading, at pH 5, degraded 97% of 5 ppm RhB dye after 270 minutes of visible light irradiation. Addition-ally, this composite catalyst exhibited excellent chemical stability and reusability, achieving 83% RhB dye removal after five recycling runs. Scavenger tests identified the photogenerated holes (h+) and superoxide free radicals (•O2) as the primary reactive species responsible for degradation. This study provides valuable insight into the design of highly efficient nanomaterials for removing organopollutants in wastewater, and a possible reaction mechanism is proposed.

In many practical applications, it is more convenient to characterize the quality of production processes or service operations throughout the count of nonconformities. In the context of SPC, nonconformities are usually assumed to appear according to the binomial probability model. The conventional way for monitoring nonconformities involves Shewhart-type control procedures based on both constant and time-varying sample sizes. In this article, an EWMA scheme is proposed for monitoring the fraction of nonconforming items with time-varying sample sizes. The proposed control chart is referred to as the EWMAG-B and can be easily adapted to work with a constant sample size by fixing it at a needed value. By means of simulation, it was found out that the EWMAG-B chart outperforms the conventional p control chart in Phase II while detecting changes in the process level is wanted.

The thermoelectric generator (TEG) stands out in many energy harvesters due to its simple structure, small size, etc. However, previous studies rarely probe into the influence of TEG internal resistances on extracting maximum power from TEG, and tracking efficiency is limited. By analyzing the relationship between the tracking efficiency and the TEG internal resistances, a time exponential rate perturbation and observation (P&amp;O) technology is proposed to achieve maximum power point tracking (MPPT) for a wide resistance range of TEG. Using the time exponential rate P&amp;O, the MPPT circuit observes the power change by comparing PMOS on-time and perturbs the power by adjusting NMOS on-time exponentially. The MPPT circuit is implemented in a 110nm CMOS process. The tracking efficiency keeps a high level from 98.9 to 99.5%. The applicable range of the TEG resistance is from 1 to 12Ω, which is enhanced at least 2.2 times.

The cellular stress response corresponds to the molecular changes that cell undergoes in response to various environmental stimuli. It induces drastic changes in the regulation of gene expression, at transcriptional and post-transcriptional levels. Actually, translation is strongly affected with a blockade of the classical cap-dependent mechanism, whereas alternative mechanisms are activated to support translation of specific mRNAs. One of the major mechanisms involved in stress-activated translation is the internal ribosome entry site (IRES)-driven initiation. IRESs, first discovered in viral mRNAs, are present in cellular mRNAs coding for master regulators of cell responses, whose expression must be tightly controlled. IRESs allow translation of these mRNAs in response to different stresses, including DNA damage, amino-acid starvation, hypoxia or endoplasmic reticulum stress, as well as to physiological stimuli such as cell differentiation or synapse network formation. Importantly, cellular mRNA IRESs are regulated by IRES trans-acting factor (ITAFs), exerting their action by at least nine different mechanisms. This review presents an update of the reported ITAFs regulating cellular mRNA translation and of the different mechanisms allowing them to control translation initiation in specific conditions. The impact of ITAFs on coordinated expression of mRNA families and consequences in cell physiology and diseases are also highlighted.

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood-brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure-activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, q²_CV = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80–0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany and the retraction of phenformin (N-Phenethylbiguanide) because of the letal complication of acidosiss,metformin (1-1-dimethylbiguanide) was first released in France in 1959 and then in the USA in 1995 for oral treatment of diabetes type 2. Acute gastrointestinal side effects often lead to dose reduction and strongly limit adherence to therapy.Main long-term consequences are deficency of vitamin B12 and of iron and sometimes also acidosis development. Intravenously injected F18-labelled glucose in metformin-treated type 2 diabetics accumulates in the the small and even more in the large intestine.The densitometry picture observed in metformin-treated diabetics is similar to that observed in patients after bowel-cleansing or chronically taking different types of laxatives where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to „attraction“ of glucose from the hepatocyte to the intestine,possibly through its secretion into the bile.Metformin is not different from the other biguanides ,synthalin B and phenformin.The mechanism of action,and the side effects are comparable to those of laxatives.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in activities of daily living. Fractures in the elderly people are associated with bone fragility, which is influenced by diabetes and chronic kidney disease. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Many countries are facing the advent of super-aging societies, where sarcopenia and frailty will become emerging problems. Elderly people suffer from various diseases, such as diabetes, heart failure, chronic kidney disease and dementia. The prevalence of comorbidities is a major problem in countries with aged populations. Underlying diseases, such as diabetes, heart failure, chronic kidney disease and also dementia are associated with sarcopenia and frailty, and they are frequent causes of falls, fractures, and a decline in ADL. Fractures in the elderly people are associated with bone fragility. Diabetes and chronic kidney disease are associated with bone fragility. Nutritional support for chronic disease patients and sarcopenic individuals with adequate energy and protein intake, vitamin D supplementation, blood-glucose-level management for individuals with diabetes, obesity prevention, nutritional education for healthy individuals, and the enlightenment of society could be crucial to solving the problems in super-aging societies.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, like empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1β, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate–induced VC in mouse VSMCs to investigate the mechanisms underlying empagliflozin’s therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE−/− mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate–induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE−/− mice on a high-phosphate diet.

The aim of this study was to assess the key laboratory features displayed by coronavirus disease 2019 (COVID-19) inpatients which associated with mild, moderate, severe and fatal course of the disease and, through longitudinal follow-up, to understand the dynamics of COVID-19 pathophysiology. All SARS-CoV-2 positive patients admitted to the University Hospital in Motol between March and June 2020 were included in this study. Severe course of COVID-19 was associated with elevation of proinflammatory markers, efflux of immature granulocytes into peripheral blood, activation of CD8 T cells, which infiltrate lungs, and transient liver disease. In particular, the elevation of serum gamma-glutamyl transferase (GGT) and histological signs of cholestasis were highly specific for patients with severe disease. In contrast, patients with fatal course of COVID-19 failed to upregulate markers of inflammation, showed dyscoordination of immune response and progressed towards acute kidney failure. COVID-19 is a disease with multi-organ affinity characterized by activation of innate and cellular adaptive immunity. Biliary lesion with elevation of GGT and organ-infiltration of IL-6 producing cells are defining characteristic for patients with fulminant disease.

Increased platelet activity is a risk factor of thrombotic events in cardiovascular patients. We studied the relationship between platelet function, platelet size and content of reticulated platelets (RP) in patients with coronary heart disease (CHD, n = 55) and acute coronary syndrome (ACS, n = 95) receiving acetylsalicylic acid + clopidogrel or ticagrelor respectively. Control group consisted of patients with risk factors for CHD, but no CHD/ACS and free of antiplatelet drugs (n = 66). Platelet function was evaluated by exposure of activated glycoprotein (GP) IIb-IIIa and P-selectin. In the control group, platelets were activated by TRAP (Thrombin Receptor Activating Peptide) 10 µM, ADP 20, 5, 2.5 µM and in CHD/ACS groups, by TRAP 10 µM, ADP 20, 5 µM (+/- epinephrine 20 µM). Platelet size was assessed by mean volume, % large forms and forward scattering. RP were stained by thiazole orange. In the control group activated GP IIb-IIIa and P-selectin correlated with platelet size and RP content after platelet activation by all agonists. Despite the decrease of platelet activity by antiplatelet drugs, most correlations (primarily for activated GP IIb-IIIa) were preserved in CHD/ACS patients. In conclusion, increased platelet size and RP content are associated with increased platelet activity and reduced efficacy of antiplatelet therapy.

To improve the understanding of soil–pile interaction of laterally loaded piles, the quasi-static test of pile group foundation in silty clay with 5 foundation piles arranged in cross shape is carried out. The direct measurement-based p–y curves at different depths showed nonlinear behavior, in which the initial stiffness and ultimate soil reaction increased as the depth increased. The loading displacement amplitude corresponding to the failure of each foundation pile in the high axial compression reinforced concrete pile group foundation is given as follows: the front-end nappe foundation pile (#3 pile) is 6mm, the middle pile is 16mm, the front-end nappe foundation pile is 20mm, and the loading displacement amplitude of side pile is 24mm. In silty clay, due to the existence of pile group effect, the edge effect has little effect on the horizontal foundation bed coefficient of foundation pile in pile group, while the influence of masking effect on the horizontal foundation bed coefficient of each foundation pile in pile group is not related to the position of pile, but only to the existence of masking effect, and the influence of different columns of masking effect on the horizontal foundation bed coefficient is the same.

Diabetic kidney disease (DKD) is regarded as a silent assassin due to its delayed signs. It is a progressive illness that can appear in various ways, from mild to severe. The severity of DKD must be determined in order to make educated treatment decisions and understand the hazards that the patient may encounter. DKD is one of the primary causes for death and morbidity among noncommunicable illnesses, affecting 10% to 15% of the global population. Timely prediction of DKD is expected to improve patients' health and reduce mortality. This study aims to predict DKD using machine learning models like Decision Trees, Random Forest, Logistic Regression, Bagging Tree Model and Support Vector Machine, to help in timely detection and cure of this deadly disease. Clinical data required for model training were taken from Kaggle's public repository and additional samples of 50 individuals were collected from local hospital, Coimbatore, Tamil Nadu. Meta-heuristic algorithms based on Swarm Intelligence, such as Particle Swarm Optimization, Ant Colony Optimization, and Firefly Optimization, were employed to optimize the selected models. The main aim of this study is to compare the predictions of different models and identify models that best agree with the given scenario.

Therapeutic measures aimed at optimising organ function prior to transplantation - whether by conditioning the donor after determination of brain death or by improving organ preservation after kidney removal - have the potential to enhance outcomes after transplantation. The particular advantage is that, unlike any optimised immunosuppressive therapy, a positive effect can be achieved without side effects for the organ recipient. In recent years, several such measures have been tested in controlled clinical trials on large patient cohorts following kidney transplantation. Hypothermic pulsatile machine perfusion in particular has become the focus of interest, but interventions in the donor prior to organ removal, such as the administration of low-dose dopamine until the start of cold perfusion as an example of conditioning antioxidant therapy, and therapeutic donor hypothermia in the intensive care unit after brain death confirmation have also significantly reduced the frequency of dialysis after transplantation with far less effort and cost. With regard to a favourable effect on graft survival in the long-term, the database for all procedures is less clear and controversial. The aim of this review article is to re-evaluate the available clinical evidence on the basis of the large multicentre controlled trials, which have also significantly influenced later meta-analyses, and to assess the significance for use in routine clinical practice.

Background and purpose: Chronic kidney disease (CKD) is a common chronic disease usually associated with cardiovascular disease (CVD), and premature death and millions of people are at increased risk for CKD. As this disease is extremely complex, multidisciplinary care (MDC) is needed to provide complete and continuous care. Usually, the nephrology units need coopera-tion from several other Healthcare Professionals (HCPs) such as cardiologists, nutritionists, ob-stetricians, and so forth. All modalities of treatments, peritoneal dialysis (PD) and Hemodialysis (HD) require HCPs and patients to develop a variety of skills to effectively deliver and manage dialysis tasks in the center or at home. Information and Communication Technology (ICT) in-terventions can offer tools that provide HCPs and patients with tools that facilitate the manage-ment of kidney patients in centers or at home. ICT interventions can allow to automate registra-tions, videoconferencing, minimize the geographic burden and resource cost savings. ICT can be the best way to promote cost saving on health spending and ensure the sustainability of the health system and, the environment as well. In the Iberian Peninsula, kidney patients consume about 3% of the total cost of healthcare. The cost of kidney transplants and dialysis is around 1.8 billion euros annually, and 75 % of this amount goes to dialysis treatment. Objective: This study aimed to evaluate and analyze the opinion of Healthcare Professionals (HCP) in Nephrology units about the Intervention of ICT in nephrology care and the Clinical benefits results from the use of ICT in Nephrology Services and dialysis Units in Portugal and Spain. Thus we collected the opinion of Health care professionals concerning the role of ICT intervention in nephrology. Understanding HCPs' feelings and attitudes is essential to understand if such technologies are correctly adjusted to the workflow and really bring huge benefits for the clinical practice of nephrology and also what features need improvement and what should be implemented in the future. ICT intervention has been implemented to promote better healthcare in nephrology units and improve patient outcomes. In the Survey, we intended to evaluate nephrology HCPs' opinions concerning the ICT interventions, in nephrology, represented by several tools that al-low the HCPs to implement solutions such as Remote Patient Monitoring(RPM); Remote Moni-toring of Treatment (RMT); Tele homecare; Telehealth (Tele-nephrology); Home Dialysis; mHealth; mobile App; Web Portal, Telemedicine, and so forth. Key Points: In many countries particularly in the Iberian Peninsula (Portugal and Spain) the incidence of CKD is substantially high. The “treatments” for kidney disease have not improved substantially over the past 50 years, leaving too many kidney patients with a poor quality of life and reduced life expectancy. This situation is associated with staggering aggregate annual costs amounting to €140 billion per year in Europe, more than the annual healthcare costs of cancer or diabetes [1]. The increased daily use of information and communication technologies may lead to the need for healthcare professionals to incorporate technology use competencies into practice.

Chronic kidney disease (CKD) is a progressive condition of kidney dysfunction due to diverse causes of injury. In healthy kidneys, protein-bound uremic toxins (PBUTs) are cleared from the systemic circulation by proximal tubule cells through the concerted action of plasma membrane transporters that facilitate their urinary excretion, but the endogenous metabolites are hardly removed with kidney dysfunction and may contribute to CKD progression. Accumulating evidence suggests that senescence of kidney tubule cells influences kidney fibrosis, the common endpoint for CKD with an excessive accumulation of extracellular matrix (ECM). Senescence is a special state of cells characterized by permanent cell cycle arrest and limitation of proliferation, which promotes fibrosis by releasing senescence-associated secretory phenotype (SASP) factors. The accumulation of PBUTs in CKD causes oxidative stress and increases the production of inflammatory (SASP) factors that could trigger fibrosis. Recent studies provide some clues that PBUTs may also promote senescence in kidney tubular cells. This review provides an overview on how senescence contributes to CKD and the involvement of PBUTs in this process, and how kidney senescence can be studied, Finally, some suggestions for future therapeutic options for CKD while targeting senescence are given.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

In this work, we studied light-output properties, efficiency function as well as PSD capability of p-Terphenyl scintillator. The selected solid cylindrical scintillation detector has a size of (45 x 45) mm with PSD properties. Recently presented studies of light-output functions have been meas-ured only for low neutron energies. Our motivation has been to determine more accurate the light output function for p-Terphenyl scintillator over a wider neutron energy range. The measurements have been carried out with mono-energetic neutron beams in the wide energy range from 2.5 to 19 MeV. The neutron-gamma spectrometric system, which we developed has been used for the measurement. The input analogue signal from the detector is digitized with fast 12-bits analogue to digital converter with sampling frequency of 1 GHz. Measured data from the detector are processed into gamma and neutron spectra. The light output function for protons has been determined by finding the position of the protons for given neutron energies. The more accurate light output function for p-Therphenyl scintillator has been calculated. The pulse-shape discrimination capability as well as efficiency of p-Terphenyl scintillator in comparison with NE-213 equivalent detector is lower.

Silica aerogels and their derivatives have outstanding thermal properties with exceptional values in the thermal insulation industry. However, the brittle nature restricts its large-scale commercialization. Thus, enhancing their mechanical strength without affecting their thermal insulating properties is essential. Therefore, for the first time, highly thermally stable Poly(acrylamide-Co-acrylic acid) partial sodium salt is used as a reinforcing polymer to synthesize hybrid P(AAm-CO-AAc)-silica aerogels via epoxy ring-opening polymerization in the present study. Functional groups in P(AAm-CO-AAc) partial sodium salts, such as CONH2 and COOH, acted as nucleophiles for the epoxy ring-opening reaction with (3-glycidyloxypropyl)trimethoxysilane, which resulted in a seven-fold enhancement in mechanical strength compared to that of a pristine silica aerogel while maintaining the thermal conductivity at less than 30.6 mW/mK and porosity of more than 93.68%. Moreover, the hybrid P(AAm-CO-AAc)-silica aerogel demonstrated improved thermal stability up to 343 ⁰C owing to the synergetic effect between P(AAm-CO-AAc) and the silica aerogel, corresponding to thermal stability and strong covalent bonding among them. These excellent results illustrate that this new synthetic approach for producing hybrid P(AAm-CO-AAc)-silica aerogels is useful for enhancing the mechanical strength of a pristine silica aerogel without impairing its thermal insulating property and shows potential as an industrial heat insulation material.

In this paper, a study of modeling PV cell (solar cell), PV module (solar modules) and PV array solar array) using Matlab/Simulink software is presented. This study is focused on the study to design photovoltaic cell, photovoltaic modules, photovoltaic panels and PV array (solar array) and to analyze the change in PV performance according to changes in different parameters such temperature, solar irradiation, reverse saturation current, series resistance and shunt resistance. This study shows the PV and IV characteristics curve for each model from which MPP (maximum power point) is determined. In this study, different PV and IV characteristic curves are gained for varying temperatures with specified solar irradiation conditions,s and then the MPP is tracked. The highest power output is also compared between the designed PV module and the selected PV module (MX Solar USA MX60-245)

The main goal of the present paper is to construct some families of the Carlitz’s q-Bernoulli polynomials and numbers. We firstly introduce the modified Carlitz’s q-Bernoulli polynomials and numbers with weight (α, β) and investigate their some explicit properties and identities arising from the bosonic q-Volkenborn integral on ℤ_p. We then define the modified degenerate Carlitz’s q-Bernoulli polynomials and numbers with weight (α, β) and obtain some recurrence relations and other identities. Moreover, we derive some correlations with the modified Carlitz’s q-Bernoulli polynomials with weight (α, β), the modified degenerate Carlitz’s q-Bernoulli polynomials with weight (α, β), the Stirling numbers of the first kind and second kind.

This paper explores the pivotal role of personalized product recommendations in enhancing the e-commerce experience. As online shopping becomes increasingly prevalent, the demand for tailored user experiences has surged, prompting the development of sophisticated recommendation systems. This study presents a comprehensive analysis of various methodologies employed to deliver personalized suggestions, including collaborative filtering, content-based filtering, and hybrid approaches. The implementation of a user-centric recommendation engine demonstrates significant improvements in user engagement, satisfaction, and conversion rates. Furthermore, the paper discusses the importance of real-time adaptation mechanisms and user feedback loops in optimizing recommendations. By providing insights into the challenges and solutions associated with recommendation systems, this research aims to equip e-commerce businesses with the tools necessary to leverage personalization effectively, ultimately leading to enhanced customer experiences and increased sales.

This comprehensive review examines the role of fenoldopam, a selective dopamine-1 receptor agonist, in preventing and treating acute kidney injury (AKI) during cardiac surgery. AKI remains a significant complication in cardiac surgery, associated with increased morbidity, mortality, and healthcare costs. The review explores fenoldopam's pharmacological properties, mechanism of action, and clinical applications, synthesizing evidence from randomized controlled trials, meta-analyses, and observational studies. While some studies have shown promising results in improving renal function and reducing AKI incidence, others have failed to demonstrate significant benefits. The review discusses these conflicting findings, explores potential reasons for discrepancies, and identifies areas requiring further research. It also compares fenoldopam to other renoprotective strategies, including dopamine, diuretics, and N-acetylcysteine. The safety profile of fenoldopam, including common side effects and contraindications, is addressed. Current guidelines and recommendations for fenoldopam use in cardiac surgery are presented, along with a cost-effectiveness analysis. The review concludes by outlining future research directions and potential new applications of fenoldopam in cardiac surgery. By providing a thorough overview of the current state of knowledge, this review aims to facilitate informed decision-making for clinicians and researchers while highlighting areas for future investigation.

Introduction: ophthalmological assessment of the retinal circulation and the level of VEGF-A is currently considered a non-invasive and safe diagnostic tool to assess the peripheral microcircu-lation Objective: to study retinal hemodynamics and VEGF-A levels in patients with type 1 diabetes mellitus after pancreas transplantation Settings and Design: A prospective, single-stage, single-center, non-randomized clinical trial Methods: 79 patients (158 eyes) with type 1 diabetes mellitus and end-stage diabetic nephropathy participated in the study. Patients were divided into 3 groups: group 1, potential recipients of pancreas and kidney transplant from the waiting list; group 2, patients after kidney transplanta-tion; and group 3, patients after simultaneous pancreas and kidney transplantation. Ophthalmo-logical examination included measuring the macular hemoperfusion density. The level of VEGF-A was examined in the patients' tear by enzyme immunoassay. Results: retinal hemoperfusion density and VEGF-A concentration were expected to correlate with the severity of diabetic changes in the fundus of patients. A lower index of retinal hemoperfusion density and a high level of VEGF-A were noted in patients with proliferative ret-inopathy and macular oedema. Group 3 showed the lowest frequency of the active phase of the proliferative retinopathy and retinal macular oedema, characterized by a higher retinal hemoperfusion density in the foveal and the parafoveal zone of the macular region, and low VEGF-A concentration in tear. Conclusion: measurement of retinal hemoperfusion density and determination of tear VEGF-A concentration are informative objective methods for diagnosing the severity of diabetic changes of the fundus.

Background: This practice guideline was developed by the Chronic Kidney Disease (CKD) Task Force, which was composed of clinical and methodological experts. The Saudi Arabian Ministry of Health and its Health Holding Company commissioned this guideline project to support the realization of the Vision 2030's healthcare transformation pillar. Methods: The guideline synthesis was guided by the GRADE-ADOLOPMENT methodology. Results: The final adoloped guideline addressed 12 clinical questions on blood pressure management in patients with CKD through a set of recommendations and performance measures. The recommendations included antihypertensive agents in children, non-renin angiotensin system inhibition (Non-RASi) vs RASi in adults, intensive vs standard blood pressure targets, early vs late assessment for kidney replacement therapy (KRT), late vs early preparation strategy for KRT, CKD symptoms during assessment for KRT or conservative management, initiation of KRT in patients with deteriorating CKD, choice of KRT modality or conservative management in certain CKD patient groups, changing or discontinuing KRT modalities, review frequency for KRT or conservative management, and Information, education and support. Conclusions: These conditional recommendations were based on low to very low certainty of evidence that highlights the need for high-quality randomized trials comparing different antihypertensive agents in patients with CKD.

Acute kidney injury (AKI), especially if recurring represents a risk factor for future chronic kidney disease. In intensive care units, increased intraabdominal pressure is well-recognized as a significant contributor of AKI. However, the importance of transiently increased intra-abdominal pressures procedures is less commonly appreciated during laparoscopic surgery, the use of which has rapidly increased over the last few decades. Unlike the well-known autoregulation of the renal cortical circulation, medulla perfusion is modulated via partially independent regulatory mechanisms and strongly impacted by changes in venous and lymphatic pressures. In our review paper, we will provide a comprehensive overview of this evolving topic, covering a broad range from basic pathophysiology up to and including current clinical relevance. Key regulators of oxidative stress such as ischemia-reperfusion injury, the activation of inflammatory response and humoral changes interacting with procedural pneumoperitoneum formation and AKI risk will be recounted. Moreover, we present an in-depth review of the interaction of pneumoperitoneum formation with general anesthetic agents and animal models of congestive heart failure. A better understanding of the relationship between pneumoperitoneum formation and renal perfusion will support basic and clinical research, leading to improved clinical care and collaboration among specialists.

Background: The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the unknown risk of severity and mortality in COVID-19 patients with underlying kidney and liver diseases. Method: We retrieved data on the clinical features and primary composite end point of COVID-19 patients released from inception till 16^th of April 2020 from Medline and Embase. The data on two comorbidities, liver diseases and chronic kidney disease, present in COVID-19 were pooled and statistically analysed to explain the associated severity and mortality rate. Results: 142 abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and CKD were 3% (95%CI; 2%-3%) and 1% (95%CI; 1%-2%) respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) cases were severe with 17.65% mortality. While in CKD patients with COVID-19, 83.93% (47/56) severity and 53.33% (8/15) mortality were reported. Conclusion: This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases and CKD. This will allow for better clinical management and inform more stringent preventative measures for this group of patients.

The dynamic and never exactly repeatable tumor transcriptomic profile of people affected by the same form of cancer requires a personalized and time-sensitive approach of the gene therapy. The Gene Master Regulators (GMRs) were defined as genes whose highly controlled expression by the homeostatic mechanisms commands the cell phenotype by modulating major functional pathways through expression correlation with their genes. The Gene Commanding Height (GCH), a measure that combines the expression control and expression correlation with all other genes, is used to establish the gene hierarchy in each cell phenotype. We developed the experimental protocol, the mathematical algorithm and the computer software to identify the GMRs from transcriptomic data in surgically removed tumors, biopsies or blood from cancer patients. The GMR approach is illustrated with applications to our microarray data on human kidney, thyroid and prostate cancer samples, and on thyroid, prostate and blood cancer cell lines. We proved experimentally that each patient has his/her own GMRs, that cancer nuclei and surrounding normal tissue are governed by different GMRs, and that manipulating the expression has larger consequences for genes with higher GCH. Therefore, we launch the hypothesis that silencing the GMR may selectively kill the cancer cells from a tissue.

Congenital anomalies of the kidney and urinary tract (CAKUT) are common birth defects deriving from abnormalities in renal differentiation during embryogenesis. CAKUT is the major cause of end-stage renal disease and chronic kidney diseases in children, but its genetic causes remain largely unresolved. Here we discuss advances in the understanding of how MAPK/ERK activity contributes to the regulation of ureteric bud branching morphogenesis, which dictates the final size, shape, and nephron number of the kidney. Recent studies also demonstrate that MAPK/ERK pathway is directly involved in nephrogenesis, regulating both the maintenance and differentiation of the nephrogenic mesenchyme. Interestingly, aberrant MAPK/ERK signaling is linked to many cancers, and recent studies suggest it also plays a role in the most common pediatric renal cancer, Wilms’ tumor.

Epigenetic mechanisms, including histone post-translational modifications (PTMs), play a critical role in regulating pain perception and the pathophysiology of burn injury. However, the epigenetic regulation and molecular mechanisms underlying burn injury-induced pain remain insufficiently explored. Spinal dynorphinergic (Pdyn) neurons contribute to heat hyperalgesia induced by severe scalding-type burn injury through p-S10H3-dependent signaling. Beyond p-S10H3, burn injury may impact various other histone H3 PTMs. Double immunofluorescent staining and histone H3 protein analyses demonstrated significant hypermethylation at H3K4me1 and H3K4me3 sites and hyperphosphorylation at S10H3 within the spinal cord. By analyzing Pdyn neurons in the spinal dorsal horn, we found evidence of chromatin activation with a significant elevation in p-S10H3 immunoreactivity. We used RNA-seq analysis to compare the effects of burn injury and forma-lin-induced inflammatory pain on spinal cord transcriptomic profiles. We identified 98 DEGs for burn injury and 86 DEGs for formalin-induced inflammatory pain. A limited number of shared differentially expressed genes (DEGs) suggest distinct central pain processing mechanisms between burn injury and formalin models. KEGG pathway analysis supported this divergence, with burn injury activating Wnt signaling. This study enhances our understanding of burn injury mechanisms and uncovers converging and diverging pathways in pain models with different origins.

Alpha-methyl-p-tyrosine (AMPT; also referred as metyrosine) is an approved medication for the treatment of pheochromocytoma. As a tyrosine hydroxylase inhibitor AMPT may be a potential candidate for the treatment of diseases involving catecholamine alterations. However, only small-scale clinical trials have tested AMPT repurposing in few other illnesses. Chronic fatigue syndrome (CFS) is an heterogenous disorder with genetically associated vulnerability of catecholamine metabolism (e.g. catechol O-methyltransferase polymorphisms) holding an important impact of environmental factors. The current case report compiles genetic and longitudinal biochemical data for over a year follow-up of one patient sequentially diagnosed with sustained overstress, neurasthenia, CFS, and POTS (postural orthostatic tachycardia syndrome) over a 10-year period, and reports patient’s symptom improvement in response to low-medium doses of AMPT.

Motivated by Kurt's work [Filomat 30 (4) 921-927, 2016], we first consider a class of a new generating function for (p, q)-analog of Apostol type polynomials of order a including Apostol-Bernoulli, Apostol-Euler and Apostol-Genocchi polynomials of order a. By making use of their generating function, we derive some useful identities. We also introduce (p, q)-analog of Stirling numbers of second kind of order v by which we construct a relation including aforementioned polynomials.

Inflammatory diseases are common pathological processes caused by various acute and chronic factors and some of them are autoimmune diseases. Exosomes are fundamental extracellular vesicles secreted by almost all cells, which contain a series of constituents, i.e. cytoskeletal and cytosolic proteins (actin, tubulin, histones), nucleic acids (mRNA, miRNA, DNA), lipids (diacylglycerophosphates, cholesterol, sphingomyelin, ceramide), and other bioactive components (cytokines, signal transduction proteins, enzymes, antigen presentation and membrane transport/fusion molecules, adhesion molecules). This review would be a synopsis of the actual knowledge on the contribution of exosomes from different cell sources as possible therapeutic agents against inflammation, focusing on several inflammatory diseases, neurological diseases, rheumatoid arthritis and osteoarthritis, intestinal bowel disease, asthma, liver and kidney injuries. Current knowledge indicates that the role of exosomes in therapy of inflammation and in inflammatory diseases could be distinctive. Main limitations to their clinical translation are still production, isolation, and storage. Additionally, there is an urgent need to personalize the treatments in terms of selection of exosomes, their dosages and routes of administration, and a deeper knowledge about their biodistribution, type and incidence of adverse events and long-term effects of exosomes. In conclusion, exosomes can very promising next generation therapeutic option, superior to synthetic nanocarriers and cell therapy, and can represent a new strategy of effective, safe, versatile and selective delivery systems in the future.

Adult X-linked hypophosphatemia (XLH) patients present with specific symptoms, including enthesopathies (e.g., ossification of the longitudinal ligament (OPLL), osteophytes around the large joint, and enthesopathy in the Achilles tendon), the development of severe secondary and tertiary hyperparathyroidism (SHPT/THPT) and the subsequent progression of chronic kidney disease (CKD). In addition, these patients exhibit the typical phenotypes of osteomalacia, such as pseudofracture and fracture in weight-bearing bones, odontitis, and tooth abscess. The mechanism underlying enthesopathy development is unknown; however, a common underlying mechanism among XLH and autosomal recessive hypophosphatemic rickets, ARHR1.2, due to mutations in PHEX, DMP1, and ENPP1, is assumed. Clarification of the pathogenesis and drug discovery for this complication is an urgent issue to address, as many adult XLH patients suffer subsequent debilitating nervus symptoms or impingement syndrome, and existing treatments are ineffective. Severe SHPT and THPT are associated with conventional therapy, including active vitamin D and phosphate supplementation, and complicated and careful adjustment of the dosage by experienced clinicians is required to avoid SHPT/THPT. Burosumab is a very effective therapy without risk for the development of SHPT/THPT. However, the indication of this drug should be carefully considered along with the cost-effectiveness, guidelines or recommendations and health care system of each country.

The goal of the manuscript is to design a relatively best control structure for the noise suppression of a drone’s camera gimbal action. The gimbal’s movement can be simplified as a rest-to-rest reorientation system that can achieve the boundary result of a dynamic system. Six different control architectures are proposed and evaluated based on their ability to control the trajectory of the dynamic-system position and speed, their running time, and quadratic cost. The robustness of the control architecture to uncertainties in inertia and sensor noise is also analyzed. Monte Carlo figures are used to assess the performance of the six control systems. The conditions for applying different architectures are identified through this analysis. The analysis and experimental tests reveal the most suitable control of the drone’s camera gimbal rotation.

All severe cases of SARS-CoV-2 infections are characterized by a high risk of disease progression towards ARDS, leading to bad outcome. Respiratory symptoms in COVID-19 patients often do not correspond to disease’s worsening. A dysregulated host response to the large viral load could play a key role in the disease progression. In our sample median age was 74 years (72-75) and 54% were men. Median period of hospitalization was 9 days. Firstly, we observed an asynchronous trend of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) in 764 selected among 963 patients who were consecutively recruited in two hospitals (Cannizzaro, S. Marco) in Catania, Italy. NLR values in deceased patients showed an increase from baseline over time. By contrast, CRP tended to fall from baseline to median day of hospitalization in all four subgroups, but steeply increased at the end of hospitalization only in ICU-admitted patients. Then we evaluated the relationships between NLR and CRP as continuous variables with PaO2/FiO2 ratio (P/F). Finally, we made mediation and moderation analyses to determine the link between inflammation (CRP), immune system (neutrophils and lymphocytes) and respiratory failure (P/F). CRP, neutrophils and P/F are linked in the same pathogenetic chain leading to respiratory failure.

This article analyzes and compares the integration of two different maximum power point tracking (MPPT) control methods, which are tested under partial shading and fast ramp conditions. These MPPT methods are designed by Improved Particle Swarm Optimization (IPSO) and a combination technique between Neural Network and Perturb & Observe method (NN_P&O). These two methods are implemented and simulated for photovoltaic systems (PV), where various system responses, such as: voltage and power are obtained. The MPPT techniques were simulated using Matlab/Simulink environment. A comparison of the performance of IPSO and NN_P&O algorithms is carried out to confirm the best accomplishment of the two methods in terms of speed, accuracy and simplicity.

Tumor vasculature proliferates rapidly, generally lacks pericyte coverage, and is uniquely frag-ile making it an attractive therapeutic target. A subset of small-molecule tubulin binding agents cause disaggregation of the endothelial cytoskeleton leading to enhanced vascular permeability generating increased interstitial pressure. The resulting vascular collapse and ischemia cause downstream hypoxia, ultimately leading to cell death and necrosis. Thus, local damage gener-ates massive amplification and tumor destruction. The tumor vasculature is readily accessed and potentially a common target irrespective of disease site in the body. Development of a therapeutic approach and particularly next generation agents benefits from effective non-invasive assays. Imaging technologies offer varying degrees of sophistication and ease of implementation. This review considers technological strengths and weaknesses with examples from our own laboratory. Methods reveal vascular extent and patency, as well as insights into tissue viability, proliferation and necrosis. Spatiotemporal resolution ranges from cellular mi-croscopy to single slice tomography and full three-dimensional views of whole tumors and measurements can be sufficiently rapid to reveal acute changes or long-term outcomes. Since imaging is non-invasive, each tumor may serve as its own control making investigations par-ticularly efficient and rigorous. The concept of tumor vascular disruption was proposed over 30 years ago and it remains an active area of research.

Materials based on platinum metals with very good catalytic activity were tested in the reduction of p–nitrophenol (pNP) to p–aminophenol (pAP). The majority of presented catalytic materials are based on the adsorption of p–nitrophenol on the surface of the catalyst simultaneously with molecular hydrogen, coming from sodium borohydride in an aqueous medium, which reduces it. In the present paper, a catalytic material based on osmium dispersed in n–decanol or n–dodecanol is presented, which also works as an emulsion membrane, for the absorption of p–nitrophenol and molecular hydrogen at the n–alcohol aqueous solution interface. The hydrogenation of p–nitrophenol is carried out in a reaction and separation column in which the acid receiving phase emulsion is dispersed in the osmium nanodispersion, in n–alcohols. This emulsion circulates from the base of the column to its upper part in co-current or counter-current with the source phase consisting of p–nitrophenol and sodium borohydride. Experiments show that the circulation of counter-current phases is superior to that in co-current, and the emulsion based on n–decanol is more efficient than the one based on n–dodecanol. The increase in the pH difference between the source and receiving phases leads to the increase in the conversion of p–nitrophenol to p–aminophenol. The efficiency of separation of the reaction product in the receiving phase is lower than the conversion at the same operating time. The apparent catalytic rate constant (kapp) of the new catalytic material based on the emulsion membrane with nanodispersion of osmium nanoparticles (0.1×10−3 for n–dodecanol and 0.9×10−3 for n-decanol) is lower by an order of magnitude compared to those based on adsorption on catalysts from platinum metal group. The advantage of the tested membrane catalytic material is that it extracts p–aminophenol in the acid receiving phase. The paper proposes a mechanism of the studied reduction system.

The development of mineral resources in China has gradually entered the stage of deep mining. Rock burst, collapse and other ground pressure disasters caused by deep high stress have become major hidden dangers restricting mine safety production. Microseismic monitoring technology is an important means of ground pressure risk prediction. In this paper, the wavelet coefficient threshold denoising method in time-frequency domain, STA/LTA method, AIC method, Skew and Kurtosis method are studied, and the automatic P-phase onset time picking model based on noise reduction and multiple detection indexes is established. Through the effect analysis of microseismic signals collected by microseismic monitoring system of coral Tungsten Mine in Guangxi, automatic P-phase onset time picking is realized. the reliability of the P-phase onset time picking method proposed in this paper based on noise reduction and multiple detection indexes is verified. The picking accuracy can still be guaranteed under the severe signal interference of background noise, power frequency interference and manual activity underground mine, Which is of great significance to the data processing and analysis of microseismic monitoring.

proposal for a fundamental theory is described in which classical and quantum physics as a representation of the universe as a gigantic dendrogram are unified. The latter is the explicate order structure corresponding to the purely number-theoretical implicate order structure given by p-adic numbers. This number field was zero-dimensional, totally disconnected, and disordered. Physical systems (such as electrons, photons) are sub-dendrograms of the universal dendrogram. Measurement process is described as interactions among dendrograms; in particular, quantum measurement problems can be resolved using this process. The theory is realistic, but realism is expressed via the the Leibnitz principle of the Identity of Indiscernible. The classical-quantum interplay is based on the degree of indistinguishability between dendrograms (in which the ergodicity assumption is removed). Depending on this degree, some physical quantities behave more or less in a quantum manner (versus classic manner). Ideologically, our theory is very close to Smolin’s dynamics of difference and Rovelli’s relational quantum mechanics. The presence of classical behavior in nature implies a finiteness of the Universe-dendrogram. (Infinite Universe is considered to be purely quantum.) Reconstruction of events in a four-dimensional space type is based on the holographic principle. Our model reproduces Bell-type correlations in the dendrogramic framework. By adjusting dendrogram complexity, violation of the Bell inequality can be made larger or smaller.

The toxin-antitoxin (TA) systems have been attracting attention due to their role in regulating prokaryotic cell responses to stress and their biotechnological potential. Much recognition has been given to type II TA system of mesophiles, but so far, limited attention has been given to thermophiles. Here, we are presenting the putative type II TA families encoded on the genomes of four Geobacillus strains. We employed the TA finder tool to mine for TA-coding genes and manually curated the results using various tools. We identified 28 putative TA pairs, distributed over 8 TA families. Among the identified TAs, 15 represent putative novel toxins and antitoxins that have been overlooked or annotated as hypothetical proteins in their genome records. We also identified a potentially new TA composite, AbrB-ParE. Furthermore, we are suggesting the Geobacillus acetyltransferase toxin-antitoxin (GacTA) family which potentially represents one of the unique TA families that has a reverse gene order. Moreover, we are proposing a hypothesis on the regulation of the xre-cog2856 gene expression, which seems to involve c-di-AMP. This study aims for highlighting the significance of studying TAs in Geobacillus, since they have special features. It also aims for facilitating future experimental research.

In the present paper, the (p,q)-Hermite based Apostol type Frobenius-Euler polynomials and numbers are firstly considered and then diverse basic identities and properties for the mentioned polynomials and numbers, including addition theorems, difference equations, integral representations, derivative properties, recurrence relations. Moreover, we provide summation formulas and relations associated with the Stirling numbers of the second kind.

We present here a case of complex uterine anomaly – Obstructed HemiVagina with Ipsilateral Renal Agenesis (OHVIRA), also known as Herlyn-Werner-Wunderlich syndrome in a 13-year-old girl with the history of recurrent urinary tract infections (rUTI). In emergency room, trans-abdominal sonography revealed ovarian cyst and renal agenesis, without any suspicion of vaginal obstruction. This led to delay in the diagnosis of this uncommon anomaly. Finally, MRI findings confirmed the presence of OHVIRA syndrome. As the congenital anomalies of kidney and urinary tract (CAKUT) are in almost one third of cases associated with genital malformations, urologist should carefully search for patients with rUTI. The patient underwent simultaneous laparoscopy and vaginoscopy, what was in our opinion the most appropriate therapeutic decision. In this article we are also going to discuss the role of laparoscopy in the management of OHVIRA syndrome as well as other surgical techniques described in the literature.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today we are talking about a new paradigm - cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies.

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p&lt;0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p&lt;0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p&lt;0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.

The hospital indoor environment plays a significant role in shaping the microbial exposures that humans encounter. Resistance to antibiotics is one of the mechanisms employed by bacteria to develop resilience against stress in indoor environments. The extensive usage of antibiotics has been a key factor in driving changes in the ecological function of antibiotic resistance genes (ARGs) and their acquisition by pathogenic bacteria. By integrating the 16S rRNA Illumina sequencing and high throughput-qPCR approaches with water and air dust samples across seven departments at Peking University Shenzhen Hospital, China, this study yielded intriguing findings regarding the department-specific variation, transmission, and correlation of bacteria, ARGs and MGEs within the hospital indoor environment. One notable observation was that the seasonal variation played a vital role in shaping the bacterial composition in the overall hospital indoor environment across seven studied departments. Nevertheless, a similar significant seasonal impact was only observed in the blood test room and emergency departments, rather than in the other five departments. Another intriguing finding was the correlation between ARGs and MGEs abundance. This correlation was evident in the overall hospital indoor environment, which was conversely not found in the emergency, pneumology and gynecology departments. Additionally, while there was no significant relationship that occurred between bacterial communities and ARGs/MGEs within the hospital, the gynecology department demonstrated a close link between bacterial communities and the presence of ARGs/MGEs. Notably, the gynecology department also stood out as an important source of bacteria and ARGs/MGEs for other departments. This study underscores the need for careful surveillance and monitoring of antibiotic resistance, particularly in Legionella spp. in man-made water systems. The findings also show the importance of monitoring and understanding the genetic elements such as Tp614 involved in gene transfer and recombination, as well as their impact on antimicrobial treatment efficacy.

Polyhydroxyalcanoates (PHAs) are biodegradable polymers synthesized in cytoplasmic granules in bacteria, such as Cupriavidus necator (Ralstonia eutropha), Alcaligenes latus, Pseudomonas spp., Comamonas spp. and other species. PHAs accumulation occurs in response to stress conditions, i.e. under high carbon and low nitrogen (24:1 ratio). PHA can be synthesized using recombinant microorganisms (provided with the operon phbA/phbB/phbC), escaping the constrains of nutrient request, except addition of high amount of sugar (glucose, lactose, fructose). In this study; E. coli was genetically modified for PHB production in biofermentors. The production of PHA at industrial scale requires a continuous supplementation of fermentable sugars to support the availability of nutrients and to assess the level of the exponential growth phase; since sugars are required either for bacterial growth either for PHA synthesis and energy storage. The biofermentors need to be run in automated system. Sensors are used at many points in fermentators; in the evaluation of parameters: consumption of sugars; cell density; quantification of PHB synthesis. The need of operational control during the fermentation has prompted us to application of three measurements; one unit linked to a Nanodrop to evaluate OD; one linked to a reaction chamber to measure sugars consumed by enzyme based fluorescence detection; and one for bacteria Nile Blue staining and fluorescence intensity reads. The growth of bacteria on three different plant by-products was monitored and PHB production in four days using a banana by-product feed was optimised. These detectors will make possible to exploit the full potential of bioreactors optimizing the time of use and maximizing the number of bacteria synthesizing PHA.

A mass mortality event of Asian seabass Lates calcarifer juveniles occurred in Zhuhai, the main Asian seabass cultured area in mainland China. The fish samples were pooled for pathogen identification and both high viral loads of ISKNV and NNV were detected by real-time microfluidic quantitative PCR. Immunohistochemistry and immunofluorescence showed that strong ISKNV signals were examined in spleen and liver, while strong NNV signals were detected in brain and eye. The multi-tissue homogenates were inoculated into MFF-1 cell and SSN-1 cell, respectively. After several viral passages, both ISKNV and NNV were purely isolated from each other, and designated as ASB-ISKNV-23 and ASB-NNV-23, respectively. The whole genome sequences of ASB-ISKNV-23 and ASB-NNV-23 were determined and annotated. The result showed that ASB-ISKNV-23 and ASB-NNV-23 are composed of 112,236 bp and 4,538 bp, respectively. Phylogeny analysis showed that ASB-ISKNV-23 belongs to ISKNV-II sub-genotype and ASB-NNV-23 belongs to RGNNV genotype. Collectedly, coinfection of ISKNV-II and RGNNV were firstly documented in mass mortality of Asian seabass in mainland China. Importantly, both ISKNV-II and RGNNV were purely isolated using two different permissive cell lines. Our study provides useful information for better understanding the complex pathogenesis regarding the coinfection with ISKNV and NNV in farmed fish.

We present a new mathematical model of disease spread reflecting specialties of covid-19 epidemic by elevating the role social clustering of population. The model can be used to explain slower approaching herd immunity in Sweden, than it was predicted by a variety of other mathematical models; see graphs Fig. \ref{GROWTH2}. The hierarchic structure of social clusters is mathematically modeled with ultrametric spaces having treelike geometry. To simplify mathematics, we consider homogeneous trees with $p$-branches leaving each vertex. Such trees are endowed with algebraic structure, the $p$-adic number fields. We apply theory of the $p$-adic diffusion equation to describe coronavirus' spread in hierarchically clustered population. This equation has applications to statistical physics and microbiology for modeling {\it dynamics on energy landscapes.} To move from one social cluster (valley) to another, the virus (its carrier) should cross a social barrier between them. The magnitude of a barrier depends on the number of social hierarchy's levels composing this barrier. As the most appropriate for the recent situation in Sweden, we consider {\it linearly increasing barriers.} This structure matches with mild regulations in Sweden. The virus spreads rather easily inside a social cluster (say working collective), but jumps to other clusters are constrained by social barriers. This behavior matches with the covid-19 epidemic, with its cluster spreading structure. Our model differs crucially from the standard mathematical models of spread of disease, such as the SIR-model. We present socio-medical specialties of the covid-19 epidemic supporting our purely diffusional model.

(1) Background: donor-derived circulating free DNA (dd-cfDNA) is an innovative biomarker with great potential for the early identification and prevention of graft damage; (2) Methods: Prospective study to analyze dd-cfDNA plasma levels in 30 kidney transplant patients during their post-transplant follow-up (15 days, 3, 6 and 9 months), to determine if the result could be of interest in the identification of possible adverse events, specially allograft rejection. In addition, the aim is also to verify the obtained data on sensitivity, specificity, NPV and PPV; (3) Results: Plasma levels of dd-cfDNA could be considered a novel biomarker of graft rejection after first term post-transplant up to several months before its clinical presentation, mainly in TCMR or ABMR. In this study, it appears to have no positive predictive value for borderline rejection or TCMR IA. Our results show a low NPV of the technique because other pathologies or biological post-transplant complications can also affect dd-cfDNA levels and they must be considered in the interpretation of the result.; (4) Conclusions: dd cfDNA could allow, together with other additional biomarkers in the context of a future score, avoid invasive biopsies in most cases, mainly in the case of suspected TCMR or ABMR.

We extended our model of the S1 tubular segment to address the mechanisms by which SGLT1 interacts with lateral Na/K pumps and tight junctional complexes to generate isosmotic fluid reabsorption via tubular segment S3. The strategy applied allowed simulation of laboratory experiments. Reproducing known experimental results constrained the range of acceptable model outputs and contributed to minimizing the free parameter space. 1. In experimental conditions, published Na and K concentrations of proximal kidney cells were found to deviate substantially from their normal physiological levels. Analysis of the mechanisms involved suggested insufficient oxygen supply as the cause and indirectly, that a main function of the Na/H exchanger (NHE3) is to extrude protons stemming from mitochondrial energy metabolism. 2. The water path from the lumen to the peritubular space is through aquaporins on the cell membrane and claudin-2 at paracellular tight junctions, with a smaller additional contribution to water transport by the coupling of 1 glucose:2 Na:200 H2O in SGLT1. 3. A Na+-uptake component passed through paracellular junctions by solvent drag in Na- and water-permeable claudin-2, thus bypassing the Na/K-pump, in agreement with the findings of early studies. 4. Electrical cross talk between apical rheogenic SGLT1 and lateral rheogenic Na/K pumps results in tight coupling of luminal glucose uptake and transepithelial water flow. 5. Isosmotic transport is achieved by Na-mediated ion recirculation at the peritubular membrane.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults, characterized by abnormal growth of mature B cells in the blood, bone marrow, and lymphoid tissues. Although CLL primarily affects the hematopoietic system and lymph nodes, renal involvement is exceptionally rare and presents diagnostic and treatment challenges. Potential causes of renal failure in CLL patients include sepsis, dehydration, tumor lysis syndrome (TLS), compression of the ureter by enlarged lymph nodes, and side effects of cancer therapy. This report presents a case of CLL with renal infiltration leading to severe renal failure, discussing the clinical presentation, diagnostic workup, and management of this condition.

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones etc. and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host's protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases etc. and the list is increasing gradually. In this review, we summarize NETs mediated pathophysiology of different diseases, focus on some updated potential therapeutic approaches against NETs and share our future perspectives.

Diffuse type of gastric cancer (GC) has an increasing prevalence worldwide, especially in Western countries, is usually diagnosed at advanced stages, and has no efficacious treatment options. Epidemiological studies have reported an increased mortality from GC after occupational exposure to well-studied pro-carcinogen that are metabolically activated by Cyp P450 enzymes through aryl hydrocarbon receptor (AhR). Substantial studies support the involvement of AhR in gastric carcinogenesis. However, little is known about the role of AhR in diffuse GC, as compared to intestinal GC. In a cohort of 29 gastric tumors, we described a significantly increased AhR protein and mRNA expression levels in GCs, independently of subtypes and clinical parameters. AhR and RhoA mRNA expression were correlated in diffuse GC. Further, our study characterized how AhR affects gene expression in diffuse GC. Using qRT-PCR, we compared the expression levels of AhR, Cyp1A1 and Cyp1B1 to the expression of genes in a panel previously described. In diffuse GC, Cyp1A1 expression correlated with genes involved in IGF signalling, EMT (VIM), migration (MMP2). In an in vitro assay using the poorly differentiated KATOIII epithelial cell line, two well-known ligands for AhR (TCDD and BaP) induced mRNA expression of CYP1A1, IL1b, as well as UGT1, NQO1 and AhRR to a lower extent. We also observed a strong increase in Cyp1B1 expression in diffuse GC, along with a lower TCDD-increased Cyp1B1 expression as compared to Cyp1A1 in KATOIII cells, and immunostaining in stromal cells. In intestinal GC, Cyp1B1 inversely correlated with several genes including IDO1 (generating endogenous kynurenin-e AhR ligand). Our data provide evidence for a major role of AhR in GC, as an environmental xenobiotics receptor, through different mechanisms and pathways in diffuse and intestinal GC. Our results support continued efforts to clarify the identities of exogenous AhR ligands in diffuse GC in order to define new therapeutic strategies.

Background: Fullerenes and metallofullerenes can be considered promising nanopharmaceuticals themselves and as a basis for chemical modification. As reactive oxygen species homeostasis plays a vital role in cells, the study of their effect on genes involved in oxidative stress and anti-inflammatory response is of particular importance. Methods: Human fetal lung fibroblasts were incubated with aqueous dispersions of C60, C70, and Gd@C82 in concentrations of 5 nM and 1.5 µM for 1, 3, 24, and 72 hours. Cell viability, intracellular ROS, NOX4, NFκB, PRAR-γ, NRF2, heme oxygenase 1, and NAD(P)H quinone dehydrogenase 1 expression have been studied. Results &amp; conclusion: The aqueous dispersions of C60, C70, and Gd@C82 fullerenes are active participants in ROS homeostasis. Low and high concentrations of AFDs have similar effects. C70 was the most inert substance, C60 was the most active substance. All AFDs have both a “prooxidant” and “antioxidant” effect, but with a different balance. Gd@C82 was a substance with more pronounced antioxidant and anti-inflammatory properties, while C70 had more pronounced “prooxidant” properties.

Following Smolin, we proceed to unification of general relativity and quantum theory by operating solely with events, i.e., without appealing to physical systems and space-time. The universe is modelled as a dendrogram (finite tree) expressing the hierarchic relations between events. This is the observational (epistemic) model; the ontic model is based on p-adic numbers (infinite trees). Hence, we use novel mathematics—not only space-time but even real numbers are not in use. Here, the p-adic space (which is zero dimensional) serves as the base for the holographic image of the universe. In this way our theory relates to p-adic physics; in particular, p-adic string theory and complex disordered systems (p-adic representation of Parisi matrix for spin glasses). Our Dendrogramic-Holographic (DH) theory matches perfectly with the Mach’s principle and Brans-Dicke theory. We found surprising informational interrelation between the fundamental constants, h, c, G, and their DH-analogues, h(D), c(D), G(D). DH-theory is part of Wheeler’s project on the information restructuring of physics. It is also a step towards the Unified Field theory. The universal potential V is nonlocal, but this is relational DH-nonlocality. V can be coupled to the Bohm quantum potential by moving to the real representation. This coupling enhanced the role of the Bohm potential.