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Abstract The aim of the study was to compare the anterior segment parameters after cataract surgery in pseudoexfoliation syndrome (PEX) and control eyes. We conducted a prospective comparative study of 36 eyes (PEX group), 16 eyes (PEXG group) and 46 eyes (control group) of 98 patients after phacoemulsification with intraocular lens implantation. Before surgery, 1 week, 1 month and 3 months postoperatively, anterior chamber parameters were evaluated by swept source anterior segment optical coherence tomography (AS-OCT). Anterior chamber depth (ACD), angle opening distance (AOD500/750), trabecular-iris space area (TISA500/750), trabecular-iris angle (TIA500/750) and lens vault (LV) were assessed at each study visit. Preoperatively, ACD, AOD500/750 and TISA500/750 were significantly smaller, while LV was significantly greater in PEX and PEXG eyes than in controls. 3 months postoperatively all irido-corneal parameters and ACD were significantly greater in all study groups without intergroup differences. ACD and LV significantly increased in PEX group between 1 and 3 months after surgery while being stable in control group. Relative increases in ACD, AOD500, TISA750, TIA500/750 were significantly higher in PEX and PEXG groups than in controls. Our study finds that ACD and iridocorneal parameters in AS-OCT demonstrated significantly greater relative increases 3 months after phacoemulsification in PEX and PEXG groups than in control eyes. Significantly greater deepening of anterior chamber and opening of the irido-corneal angle may be a reason for different refractive outcomes and IOP control in patients with PEX and PEXG after routine cataract surgery.

The cryptoglandular perianal fistula is a common benign anorectal disorder that is managed mainly with surgery and in some cases may be an extremely challenging condition. Perianal fistulas are often characterized by significantly decreased patient quality of life. Lack of fully recognized pathogenesis of this disease makes it difficult to treat it properly. Recently, adipose tissue hormones have been proposed to play a role in the genesis of cryptoglandular anal fistulas. The expression of adipose tissue hormones and epithelial-to-mesenchymal transition (EMT) factors were characterized based on 30 samples from simple fistulas and 30 samples from complex cryptoglandular perianal fistulas harvested during surgery. Tissue levels of leptin, resistin, MMP2, and MMP9 were significantly elevated in patients who underwent operations due to complex cryptoglandular perianal fistulas compared to patients with simple fistulas. Adiponectin and E-cadherin were significantly lowered in samples from complex perianal fistulas in comparison to simple fistulas. A negative correlation between leptin and E-cadherin levels was observed. Resistin and MMP2 levels, as well as adiponectin and E-cadherin levels, were positively correlated. Complex perianal cryptoglandular fistulas have a reduced level of the anti-inflammatory adipokine adiponectin and have an increase in the levels of proinflammatory resistin and leptin. Abnormal secretion of these adipokines may affect the integrity of the EMT in the fistula tract. E-cadherin, MMP2, and MMP9 expression levels were shifted in patients with more advanced and complex perianal fistulas. Our results supporting the idea of using mesenchymal stem cells in the treatment of cryptoglandular perianal fistulas seem reasonable, but further studies are warranted.

Abstract To compare refractive outcomes after cataract surgery in pseudoexfoliation syndrome (PEX) and control eyes and to investigate the accuracy of 3 intraocular lens (IOL) calculation formulas in these eyes. In this prospective comparative study 42 eyes (PEX group) and 38 eyes (control group) of 80 patients were included. The follow-up was 3 months. The refractive prediction error (RPE), mean absolute error (MAE), median absolute error (MedAE) and the percentages of eyes within ± 0.25 D, ± 0.5 D, ± 1.0 D and ± 2.0 D of prediction error were calculated. Three IOL calculation formulas (SRK/T, Barrett Universal II and Hill-RBF) were evaluated. PEX produced statistically significantly higher mean absolute errors and lower percentages of eyes within ± 0.5 D than control eyes in all investigated IOL calculation formulas. There were no statistically significant differences in the median absolute errors between the 3 formulas in either PEX or control eyes. Refractive outcomes after cataract surgery are statistically significantly worse in PEX than in control eyes. All three IOL calculation formulas produced similar results in both PEX and control eyes. Trial registration: ClinicalTrials.gov registration number NCT04783909.

Epilepsy is a neurological disorder involving a number of disease syndromes with a complex etiology. A properly matched antiseizure drug (ASD) gives remission in up to 70% of patients. Nevertheless, there is still a group of about 30% of patients suffering from drug-resistant epilepsy. Consequently, the development of new more effective and/or safer ASDs is still an unmet clinical need. Thus, our current studies were focused on the structural optimization/modifications of one of the leading compounds, KA-11, aiming at the improvement of its antiseizure activity. As a result, we designed and synthesized two close analogs with highly pronounced drug-like physicochemical properties according to in silico predictions, namely KA-228 and KA-232, which were subsequently tested in a panel of animal seizure models, i.e., MES, 6 Hz (32 mA), scPTZ and ivPTZ. Among these compounds, KA-232, which was designed as a water-soluble salt, was distinctly more effective than KA-228 and assured similar antiseizure protection as its chemical prototype KA-11. With the aim of a more detailed characterization of both new molecules, in vitro binding tests were performed to evaluate the potential mechanisms of action. Furthermore, KA-232 was also evaluated in several ADME-Tox studies, and the results obtained strongly supported its drug-like potential. The proposed chemical modification of KA-11 enabled the identification of new pharmacologically active chemotypes, particularly water-soluble KA-232, which, despite the lack of better efficacy than the leading compound, may be used as a chemical prototype for the development of new ASDs, as well as substances potentially active in other neurological or neurodegenerative conditions.

In contrast to the other components of the medium-chain triglycerides ketogenic diet (MCT KD), i.e., caprylic acid (CA8), a comprehensive evaluation of caproic (CA6) and lauric acids’ (CA12) properties in standard chemical and electrical seizure tests in mice has not yet been performed. We investigated their effects in maximal electroshock seizure threshold (MEST), 6 Hz seizure threshold and intravenous (i.v.) pentylenetetrazole (PTZ) seizure tests. Since ketone body production can be regulated by the activation of 5′AMP-activated protein kinase (AMPK), we hypothesized that metformin (an AMPK activator) enhance ketogenesis and would act synergistically with the fatty acids to inhibit convulsions. We assessed the effects of acute and chronic co-treatment with metformin and CA6/CA8 on seizures. CA6 and CA12 (p.o.) increased seizure threshold in the 6 Hz seizure test. CA6 at the highest tested dose (30 mmol/kg) developed toxicity in several mice, impaired motor performance and induced ketoacidosis. Acute and chronic co-treatment with metformin and CA6/CA8 did not affect seizure thresholds. Moreover, we observed the pro-convulsive effect of the acute co-administration of CA8 (5 mmol/kg) and metformin (100 mg/kg). Since this co-treatment was pro-convulsive, the safety profile and risk/benefit ratio of MCT KD and metformin concomitant therapy in epileptic patients should be further evaluated.

An original method for analyzing the influence of the meteorological, as well as physical-geographical conditions on the flooding of stormwater in small urban catchment areas is proposed. A logistical regression model is employed for the identification of the flooding events. The elaborated model enables to simulate the stormwater flooding in a single rainfall event, on the basis of the rainfall depth, duration, imperviousness of the catchment and its spatial distribution within the analyzed area, as well as the density of the stormwater network. The rainfall events are predicted considering the regional convective rainfall model for 32 rain gauges located in Poland, based on 44 years of rainfall data. In the study, empirical models are obtained to calculate the rainfall duration conditioning the flooding of stormwater in a small urban catchment area depending on the characteristics of the examined urban basins. The empirical models enabling to control the urbanization process of catchment areas, accounting for the local rainfall and meteorological characteristics are provided. The paper proposes a methodology for the identification of the areas especially sensitive to stormwater flooding in small urban catchment areas depending to the country scale. By employing the presented methodology, the regions with most sensitive urban catchments are identified. On this basis, a ranking of towns and cities is determined from the most sensitive to flooding in small urban catchment areas to the regions where the risk of flooding is lower. Using the method developed in the paper, maximum impervious catchment area are determined for the selected regions of the country, the exceedance of which determines the occurrence of stormwater flooding.

The G-protein coupled receptor 39 (GPR39) is gaining increasing attention as a target for future drugs, yet there are gaps in the understanding of its pharmacology. Zinc is an endogenous agonist or an allosteric modulator, while TC-G 1008 is a synthetic, small molecule agonist. Zinc is also a positive allosteric modulator for the activity of TC-G 1008 at GPR39. Activation of GPR39 by TC-G 1008 facilitated the development of epileptogenesis in the pentylenetetrazole (PTZ)-induced kindling model of epilepsy. Congruently, TC-G 1008 decreased the seizure threshold in the maximal electroshock seizure threshold (MEST) test. Here, we investigated the effects of TC-G 1008 under the condition of zinc deficiency. Mice were fed a zinc-adequate diet (ZnA, 50 mg Zn/kg) or a zinc-deficient diet (ZnD, 3 mg Zn/kg) for 4 weeks. Following 4 weeks of dietary zinc restriction, TC-G 1008 was administered as a single dose and the MEST test was performed. Additional groups of mice began the PTZ-kindling model during which TC-G 1008 was administered repeatedly and the diet was continued. TC-G 1008 administered acutely decreased the seizure threshold in the MEST test in mice fed the ZnD diet but not in mice fed the ZnA diet. TC-G 1008 administered chronically increased the maximal seizure severity and the percentage of fully kindled mice in those fed the ZnA diet, but not in mice fed the ZnD diet. Our data showed that the amount of zinc in a diet is a factor contributing to the effects of TC-G 1008 in vivo.

The growing demand for energy is accelerating the process of consuming non-renewable energy sources, so special attention should be paid to the development of renewable energy as the energy obtained from renewable energy sources (RES) will reduce the consumption of primary raw materials and reduce emissions of harmful substances entering the atmosphere. The aim of this article is thus to investigate the attitude of Polish consumers towards renewable energy sources and to discover the relationship between the level of awareness and other factors such as age and education. The results of the research revealed that there was a correlation between the age and level of education of the respondents and their willingness to consider the issues related to renewable energy sources and implement solutions in their households that take into account the consumption of natural energy sources (p-value of the significance test for age is 0.0001227, and p-values of independence test for the level of education are 0.00013). The discovery of such correlations will allow knowing in which direction the efforts should be intensified in order to reach the largest part of society.

Neuropsychiatric disorders are anticipated to be a leading health concern in the near future, emphasizing an outstanding need for the development of new effective therapeutics to treat them. Stilbenes, with resveratrol attracting the most attention, are an example of multi‐target compounds with promising therapeutic potential for a broad array of neuropsychiatric and neurological conditions. This review is a comprehensive summary of the current state of research on stilbenes in several neuropsychiatric and neurological disorders such as depression, anxiety, schizophrenia, autism spectrum disorders, epilepsy, traumatic brain injury, and neurodegenerative disorders. We describe and discuss the results of both in vitro and in vivo studies. The majority of studies concentrate on resveratrol, with limited findings exploring other stilbenes such as pterostilbene, piceatannol, polydatin, tetrahydroxystilbene glucoside, or synthetic resveratrol derivatives. Overall, although extensive preclinical studies show the potential benefits of stilbenes in various central nervous system disorders, clinical evidence on their therapeutic efficacy is largely missing. [ABSTRACT FROM AUTHOR]

In the present study, a focused combinatorial chemistry approach was applied to merge structural fragments of well-known TRPV1 antagonists with a potent anticonvulsant lead compound, KA-104, that was previously discovered by our group. Consequently, a series of 22 original compounds has been designed, synthesized, and characterized in the in vivo and in vitro assays. The obtained compounds showed robust in vivo antiseizure activity in the maximal electroshock (MES) test and in the 6 Hz seizure model (using both 32 and 44 mA current intensities). The most potent compounds 53 and 60 displayed the following pharmacological profile: ED50 = 89.7 mg/kg (MES), ED50 = 29.9 mg/kg (6 Hz, 32 mA), ED50 = 68.0 mg/kg (6 Hz, 44 mA), and ED50 = 73.6 mg/kg (MES), ED50 = 24.6 mg/kg (6 Hz, 32 mA), and ED50 = 56.3 mg/kg (6 Hz, 44 mA), respectively. Additionally, 53 and 60 were effective in the ivPTZ seizure threshold and had no influence on the grip strength and body temperature in mice. The in vitro binding and functional assays indicated a multimodal mechanism of action for 53 and 60. These molecules, beyond TRPV1 antagonism, inhibited calcium currents and fast sodium currents in patch-clamp assays. Further studies proved beneficial in vitro ADME-Tox properties for 53 and 60 (i.e., high metabolic stability, weak influence on CYPs, no neurotoxicity, etc.). Overall, 53 and 60 seem to be interesting candidates for future preclinical development in epilepsy and pain indications due to their interaction with the TRPV1 channel.

Several ligands have been proposed for the GPR39 receptor, including the element zinc. The relationship between GPR39 and magnesium homeostasis has not yet been examined, nor has such a relationship in the context of seizures/epilepsy. We used samples from mice that were treated with an agonist of the GPR39 receptor (TC-G 1008) and underwent acute seizures (maximal electroshock (MES)- or 6-hertz-induced seizures) or a chronic, pentylenetetrazole (PTZ)-induced kindling model of epilepsy. MES seizures and PTZ kindling, unlike 6 Hz seizures, increased serum magnesium concentration. In turn, Gpr39-KO mice that underwent PTZ kindling displayed decreased concentrations of this element in serum, compared to WT mice subjected to this procedure. However, the levels of expression of TRPM7 and SlC41A1 proteins—which are responsible for magnesium transport into and out of cells, respectively—did not differ in the hippocampus between Gpr39-KO and WT mice. Furthermore, laser ablation inductively coupled plasma mass spectrometry applied to hippocampal slices did not reveal differences in magnesium levels between the groups. These data show the relationship between magnesium homeostasis and certain types of acute or chronic seizures (MES seizures or PTZ kindling, respectively), but do not explicitly support the role of GPR39 in mediating magnesium balance in the hippocampus in the latter model. However, decreased expression of TRPM7 and increased expression of SLC41A1—which were observed in the hippocampi of Gpr39-KO mice treated with TC-G 1008, in comparison to WT mice that received the same treatment—implicitly support the link between GPR39 and hippocampal magnesium homeostasis.

The research work presents the study of the quality of telecommunications and satellite signals. For this purpose, a proprietary application for mobile devices has been designed, which allowed the collection data. The tests were performed on several models of cell phones and for different operators. The test checked the impact of such things as weather conditions, device architecture, device age, type of terrain. Based on the results, heat maps were created to visualize the research.

We report herein a series of water-soluble analogues of previously described anticonvulsants and their detailed in vivo and in vitro characterization. The majority of these compounds demonstrated broad-spectrum anticonvulsant properties in animal seizure models, including the maximal electroshock (MES) test, the pentylenetetrazole-induced seizure model (scPTZ), and the psychomotor 6 Hz (32 mA) seizure model in mice. Compound 14 showed the most robust anticonvulsant activity (ED50 MES = 49.6 mg/kg, ED50 6 Hz (32 mA) = 31.3 mg/kg, ED50scPTZ = 67.4 mg/kg). Notably, it was also effective in the 6 Hz (44 mA) model of drug-resistant epilepsy (ED50 = 63.2 mg/kg). Apart from favorable anticonvulsant properties, compound 14 revealed a high efficacy against pain responses in the formalin-induced tonic pain, the capsaicin-induced neurogenic pain, as well as in the oxaliplatin-induced neuropathic pain in mice. Moreover, compound 14 showed distinct anti-inflammatory activity in the model of carrageenan-induced aseptic inflammation. The mechanism of action of compound 14 is likely complex and may result from the inhibition of peripheral and central sodium and calcium currents, as well as the TRPV1 receptor antagonism as observed in the in vitro studies. This lead compound also revealed beneficial in vitro ADME-Tox properties and an in vivo pharmacokinetic profile, making it a potential candidate for future preclinical development. Interestingly, the in vitro studies also showed a favorable induction effect of compound 14 on the viability of neuroblastoma SH-SY5Y cells.