Agricultural chemicals are impacting health nowadays. Recently, promising synergistic antifungal interaction between tacrolimus and some azole compounds was studied. All descriptors and molecular parameters were obtained by the protocols of swissadme. in the result, the following physicochemical and drug-likeness parameters were calculated. Studied triazoles 1 and 2 showed good ADME characteristics and promising toxicity levels suitable to be checked for in vitro toxicology in case of future advanced results in the agricultural field.

Chronic pancreatitis (CP) causes an abdominal pain syndrome associated with poor quality of life. We conducted a clinical trial to further investigate the efficacy and safety of camostat, an oral serine protease inhibitor that has been used to alleviate pain in CP. This was a double-blind randomized controlled trial that enrolled adults with CP with a baseline average daily worst pain score ≥4 on a numeric rating system. Participants were randomized (1:1:1:1) to receive camostat at 100, 200, or 300 mg 3 times daily or placebo. The primary end point was a 4-week change from baseline in the mean daily worst pain intensity score (0-10 on a numeric rating system) using a mixed model repeated measure analysis. Secondary end points included changes in alternate pain end points, quality of life, and safety. A total of 264 participants with CP were randomized. Changes in pain from baseline were similar between the camostat groups and placebo, with differences of least squares means of -0.11 (95% CI, -0.90 to 0.68), -0.04 (95% CI, -0.85 to 0.78), and -0.11 (95% CI, -0.94 to 0.73) for the 100 mg, 200 mg, and 300 mg groups, respectively. Multiple subgroup analyses were similar for the primary end point, and no differences were observed in any of the secondary end points. Treatment-emergent adverse events attributed to the study drug were identified in 42 participants (16.0%). We were not able to reject the null hypothesis of no difference in improvements in pain or quality of life outcomes in participants with painful CP who received camostat compared with placebo. Studies are needed to further define mechanisms of pain in CP to guide future clinical trials, including minimizing placebo responses and selecting targeted therapies. gov, Number: NCT02693093.

The article discusses the problem of the existence of the fundamental non-dispositional intrinsic qualities of matter (quiddities) and arguments for two opposite views, quidditism and dispositionalism (causal structuralism). In support of quidditism, arguments by Howard Robinson, John Foster and Philip Goff are deployed. These arguments highlight the incoherence or unintelligibility of the doctrine that the whole reality is just a network of causal relations without any qualitative filler in the nodes of the network. Sydney Shoemaker’s influential argument for dispositionalism, in the article “Causality and Properties”, is analysed and responded. The case is made that Shoemaker’s objections against the existence of fundamental properties whose identity “consists of something logically independent of their causal potentialities” can be neutralised on the assumption that our world is operated by ontologically fundamental laws of nature in virtue of which quiddities have constant causal potentialities. Quidditism with this assumption makes it possible to know all the same properties of matter as dispositionalism, viz., dispositional properties and spatiotemporal relations. So, pace Shoemaker, it has no “disastrous epistemological consequences”. Although such quidditism expands (as compared with dispositionalism) ontology by attributing matter not only with knowable dispositional properties (causal structures) but also with quiddities, which are in a sense unknowable, this ontological exuberance is justified by the need to avoid the vicious regress of powers entailed by dispositionalism.

Objective: This study was aimed to create a multiple-unit dosage form of isosorbide dinitrate by pressing spherical matrix granules into tablets, selecting the optimal technology parameters and evaluating the obtained tablets. Material and Method: The tablet cores were prepared from mixtures of active matrix granules and shock-absorbing auxiliary granules in various ratios using diverse tabletting forces. The dissolution profiles of the obtained tablet compositions were evaluated in comparison with the reference preparation. Result and Discussion: An optimal ratio of spheroids with the active component with auxiliary granules along with optimal compression parameters were determined. The resulting as multiple-unit tablets exhibited a release profile similar to that of Cardicket Retard. Used technological approach makes it possible to regulate the dissolution profile of tablets by changing the ratio of active granules with different kinetics of the active substance release.

Aim of the study was to characterize the locomotor and cognitive aspects of the behavior of experimental rats under intracerebroventricular colchicine administration in the open field test and the 8-arm radial maze, as well as identify a set of behavioral features of experimental animals that emerged during the study.
 Materials and methods. The study was conducted in two stages on 20 male Wistar rats aged 10–11 months. The first stage involved assessment of initial locomotor activity and cognitive functions in all intact rats. At the next stage, the rats were divided into two experimental groups (n = 10): the first group with intracerebroventricular injection of physiological NaCl solution, and the second group with intracerebroventricular injection of colchicine. In 14 days after the surgery, repeated recording of locomotive and cognitive activity indicators was performed.
 Results. The locomotor activity characteristics did not statistically differ between the animals before the surgical procedures and the rats of the first group. However, in the second group, the activity indicators were significantly higher than in the respective pre-surgery rats. In the intergroup comparison of the rats that entered the second stage of the experiment, it was found that among all the investigated parameters, only the indicator of high activity duration was significantly higher in the second group compared to the first group. At the same time, the animals in the second group showed significant cognitive impairments compared to the first group, as indicated by significantly lower memory index values, the number of correct entries into the maze arms, and a significantly longer time to make the first correct entry into the maze arm.
 Conclusions. Intracerebroventricular administration of colchicine to experimental rats is accompanied by increased locomotor activity and impairment of cognitive functions. The administration of a physiological solution is not accompanied by a statistically significant increase in locomotor activity, but it demonstrates a clear tendency to increase, which may indicate a certain influence of the procedure itself. The applied pharmacological model of neurodegeneration with subsequent comprehensive assessment of animal behavior in an open field and an 8-arm radial maze is legitimate and can be used to study the early development of neuroinflammation, neuroapoptosis, and synaptogenesis disorders in the experiment.

Fetal growth restriction (FGR) is one of the most studied topics in the medicine of the mother and fetus. However, not identified antenatally FGR can have an increased risk of both perinatal morbidity and mortality, as well as adverse long-term consequences. The identification of FGR during pregnancy will contribute to the reduction of both perinatal morbidity and perinatal mortality.
 Aim. Based on a retrospective analysis, assess the obstetric and perinatal consequences of childbirth in women with antenatally undiagnosed fetal growth restriction.
 Materials and methods. An analysis of 488 cases of childbirth in women with singleton pregnancy, who gave birth to a live child, was conducted. In all cases, the gestational age was ≥22 weeks with a fetal weight less than the 10th percentile for the corresponding gestational age. Depending on the antenatally established diagnosis of FGR, two study groups were formed: group I consisted of 204 (41.8 %) cases with antenatally diagnosed FGR, group II – 284 (58.2 %) cases in which signs of FGR were identified after the birth of the child. Maternal characteristics, neonatal outcomes, and evaluation of short-term infant outcomes were analyzed.
 Results. Both groups were dominated by women with first births, the number of which was almost the same. Somatic pathology was almost 2 times more common in women of group I, 17.2 %, compared to 9.2 % of women in group II (p < 0.01), this indicates that the majority of women who were not diagnosed with FGR during pregnancy belong to the low-risk group. Fetuses with impaired blood flow in the umbilical cord arteries were twice as common in group I, 49.5 % versus 23.9 % in group II (p < 0.0001), and the frequency of absent/reversible end flow in the umbilical arteries in group I compared to group II, prevailed 3 times (p < 0.0001), indicating more serious lesions of the placenta and, as a result, early manifestation of the fetal condition disorder. The frequency of premature abdominal delivery was 3.75 times higher in group I compared to group II. The most frequent indication for cesarean delivery in both groups was signs of fetal distress syndrome. Analysis of neonatal outcomes showed that the average birth weight was significantly lower in group I and was 2180 ± 55 g against 2420 ± 61 g in group II (p < 0.0001). The need for hospitalization of newborns in the intensive care unit had no statistical difference between the groups (p > 0.05). However, the complications of the early neonatal period and the total length of stay in the hospital were greater in children of the I group, compared to the II group (p < 0.0001).
 Conclusions. The results of the conducted research indicate a low level of prenatal diagnosis of fetal growth restriction. Most pregnant women with antenatally undiagnosed fetal growth restriction belong to the group of low perinatal risk. The most frequent indication for cesarean section operation, regardless of the date of delivery, in both groups were signs of fetal distress, the frequency of which was 1.5 times higher in the antenatally diagnosed fetal growth retardation group. Newborns with an undetected growth anomaly before delivery have an increased risk of fetal distress, the severity of which is determined by the degree of deterioration of fetal oxygenation, and not by weight percentile, which requires more careful observation of fetuses with signs of growth restriction.

Neonatal osteopenia (KB 61.3 (ICD-11)) – violation of mineral exchange of bone tissue (BT) of premature babies (PB). Predicting and detection of osteopenia is the key to its successful control.
 Aim. The aim of the article was to determine risk factors influencing the formation of neonatal osteopenia of PB and during the term of intensive care / postintensive nursing.
 Materials and methods. Ultrasound densitometer Sunlight Omnisense 9000 was used to measure the ultrasound speed in BT (SOS, m/s) with estimation Z-score (SD) according to gestational age of 56 PB and 20 mature babies (control group) in the early neonatal age. Verification of osteopenia was carried out under the WHO guidelines for radiation methods by Z-score indicator less than SD by -1.0. Estimation of Z-score -2.0 SD and less was attributed to ultra-low indicators. The characteristics of obstetric and gynecological, somatic anamnesis and pregnancy course of premature babies’ mothers, factors of PB postnatal development that influence the formation of BT were studied.
 Results. Children born at 33 weeks or earlier are 3.23 times more likely (OR = 3.23; CI 95 % [1.08; 9.70]) to develop BT demineralization by the corresponding term of birth than other PB. The chances of ultra-low SOS by Z-score are 14.22 times higher (OR = 14.22; CI 95 % [3.29; 61.57]) in PB born at 32 weeks of gestation and earlier. Extragenital diseases, clinical signs of calcium deficiency in mothers, and women’s intake of calcium and vitamin D3 during pregnancy did not have a statistically significant difference (p > 0.05) in the studied PB and control group. The mother’s preeclampsia increases the chances of insufficient BT mineralization by 5.47 times (OR = 5.47; CI 95 % [1.07; 27.93]), second parity pregnancy (and subsequent ones) – by 4.51 times (OR = 4.51, CI 95 % [1.38; 14.80]). The factors of the ratio of the duration of mechanical ventilation relative to the total time of PB treatment, the duration of parenteral feeding have an inverse correlation (moderate (r = -0.42, р < 0.05) and significant (r = -0.51, р < 0.05) respectively) with a decrease in SOS to low Z-score.
 Conclusions. In PB born at 32 weeks of gestation and earlier, the chances of ultra-low SOS indicators by Z-score are 14.22 times higher (OR = 14.22; CI 95 % [3.29; 61.57]). The following factors predicts insufficient mineralization of BT according to SOS indicators according to the Z-score: mother’s second parity pregnancy (and subsequent ones), preeclampsia, parenteral feeding of PB for more than 8 days (Se = 75.00 %, Sp = 71.87 %, p < 0.0001), duration of mechanical ventilation, which is more than 6.48 % of the total time of PB treatment (Se = 86.67 %, Sp = 59.38 %, p < 0.046).

Stroke is found to be one of the global top causes of mortality and the major factor in years of life with a handicap (DALYs). Ischemic strokes contributed to nearly 70% of all strokes worldwide. For endovascular thrombectomy in acute ischemic stroke with large vessel obstruction (AIS-LVO), using stent retrievers and/or reperfusion catheters has become the gold standard of therapy. The methodology involved keyword-based search in databases like PubMed, Embase, and Google Scholar for recent publications on mechanical thrombectomy (MT), AIS, large vessel occlusion (Large Vessel Occlusion (LVO)), screening relevant articles, retrieving full texts, and synthesizing key findings on procedural advancements, patient selection, COVID-19 (coronavirus disease 2019) impact, delay effects, effectiveness, clinical outcomes, and future perspectives. Only people with substantial cerebral artery obstruction may do well from MT. This includes the distal carotid artery and the proximal middle cerebral artery (segment M1). The size of a blocked vessel and NIHSS (National Institute of Health Stroke Scale) score are directly connected. Both the 2018 and 2019 versions of the AHA/ASA (American Heart Association/American Stroke Association) Guidelines for the Early Management of Patients with Acute Ischemic Stroke contained the recommendations that cases with AIS-LVO get endovascular therapy when administered during the time frame of 0–6 h after onset (Grade IA evidence). It is questionable whether this group of patients can be managed without the need for intravenous tissue plasminogen activator at the onset. When functional independence [modified Rankin Scale (mRS) score 2] was present at long-term follow-up, the endovascular intervention was favored. Tenecteplase, which differs from alteplase in terms of genetic variation, has a greater half-life and a higher level of fibrin selectivity, enabling bolus infusion. Studies have also demonstrated its efficacy and safety, as well as its long-term cost-effectiveness.

The purpose of the work – to determine the peculiarities of the response of sportswomen to conflict situations in the conditions of a limited coalition of the volleyball team in order to optimize the process of sports training. Materials and methods. Participants: 30 amateur volleyball players (women), who participated in park and beach volleyball competitions in the 2022-2023 season under the auspices of the Zaporizhzhia Regional Volleyball Federation. Age range: 18-27. Methods: Analysis and systematization of data from scientific and methodical literature and the electronic resource of global information network “Internet”; pedagogical observations; psychological testing according to the method of K. Thomas “Determining the style of behavior in a conflict situation”; pedagogical experiment of controlling orientation; methods of mathematical statistics. Results. The analysis of the experimental indicators allows us to state that the volleyball players of the main group significantly improved the “cooperation” (+6.67%) and “compromise” (+6.67%) indicators, while the “avoidance” indicator significantly decreased (-13.33%). Based on this, we note that the technology for correcting conflict situations in limited coalitions of the volleyball team is quite effective (indicators of volleyball players of the main group). Among the volleyball players of the control group, an increase in indicators according to the “compromise” criteria (+6.67%) and a decrease according to the “avoidance” criterion (-6.66%) were recorded. Conclusion. Modern technologies of psychological training in volleyball, which relate to issues of correction of conflict situations in limited coalitions, are a prerequisite for increasing the effectiveness of the competitive activity of volleyball players. The main ways of applying these technologies in the training process in volleyball are the psychological diagnosis of female athletes taking in to account their personal qualifications, social roles in the limited coalition of the volleyball team; targeted application in competitive micro- or mesocycles of training to increase the effectiveness of training and competitive activities in limited coalitions.

Diabetes mellitus is one of the important independent risk factors for the development of neurological disorders such as ischemic stroke, transient ischemic attacks, vascular dementia and neurodegenerative processes. Hyperglycemia plays a crucial role as a trigger in the pathogenesis of these disorders. In this review, we summarize the existing data on the molecular mechanisms of diabetic encephalopathy development, consider the features of oxidative and nitrosative stresses, changes in the thiol-disulfide system, as well as mitochondrial and endothelial dysfunction in diabetes. We focus on the role of HSP 70 in cellular responses in diabetic encephalopathy. HSP70 protein is an important component of the endogenous system of neuroprotection. It acts as an intracellular chaperone, providing the folding, retention, and transport of synthesized proteins, as well as their degradation under both normoxic and stress-induced denaturation conditions. HSP70 can be considered a molecular marker and a promising therapeutic target in the treatment of diabetes mellitus.