Focal epilepsy is one of the most frequent specific type of epilepsies, with 30% treatment-resistant patients. There are several directions researchers can follow to improve existing treatment of focal epilepsy: synthesis of new compounds with anticonvulsant activity, repurposing drugs approved for other indications, finding drugs targeted to specific genetic and biochemical defects that underlie focal epilepsy syndromes, development of viral vectors for specific gene therapy, creation of devices and methods for suppression of seizures by electrostimulation and development of methods to increase safety of epilepsy surgery. Improvement of efficacy and safety of current therapies is necessary, as well as developing targeted treatment of genetic epilepsy syndromes that will not only suppress seizures, but stop further epileptogenesis.

Single slit diffraction is part of many high-school physics curricula throughout the world. In this study, we aimed to investigate whether high-school physics teachers from Bosnia and Herzegovina, Serbia and North Macedonia are adequately prepared to discuss with their students about various aspects of the single slit diffraction pattern, particularly about vertical length of diffraction fringes. To that end we conducted a written survey which included 57 high-school physics teachers. Besides asking teachers about students’ difficulties in learning about single slit diffraction, we also asked them to specify their own difficulties with this topic and required them to solve a conceptual task. Almost every second teacher believed that vertical length of diffraction fringes can be increased by changing shape or width of the slit and only 1 out of 57 teachers managed to correctly answer why diffraction fringes become shorter when we move away from the central maximum. We concluded that physics teacher education programmes should be changed to develop understanding of both, horizontal and vertical aspects of the diffraction pattern. To that end it is useful to provide learning opportunities which encourage combining ray and wave model of light.

The antidiabetic drug gliclazide is partly metabolized by CYP2C19, the main enzyme involved in omeprazole metabolism. The aim of the study was to explore the interaction between omeprazole and gliclazide in relation to CYP2C19 phenotype using physiologically based pharmacokinetic (PBPK) modeling approach. Developed PBPK models were verified using in vivo pharmacokinetic profiles obtained from a clinical trial on omeprazole-gliclazide interaction in healthy volunteers, CYP2C19 normal/rapid/ultrarapid metabolizers (NM/RM/UM). In addition, the association of omeprazole cotreatment with gliclazide-induced hypoglycemia was explored in 267 patients with type 2 diabetes (T2D) from the GoDARTS cohort, Scotland. The PBPK simulations predicted 1.4–1.6-fold higher gliclazide area under the curve (AUC) after 5-day treatment with 20 mg omeprazole in all CYP2C19 phenotype groups except in poor metabolizers. The predicted gliclazide AUC increased 2.1 and 2.5-fold in intermediate metabolizers, and 2.6- and 3.8-fold in NM/RM/UM group, after simulated 20-day dosing with 40 mg omeprazole once and twice daily, respectively. The predicted results were corroborated by findings in patients with T2D which demonstrated 3.3-fold higher odds of severe gliclazide-induced hypoglycemia in NM/RM/UM patients concomitantly treated with omeprazole. Our results indicate that omeprazole may increase exposure to gliclazide and thus increase the risk of gliclazide-associated hypoglycemia in the majority of patients.

Cytokines and other immune regulatory molecules are critical players in the immune response against cancer. There is growing interest in testing the potential utility of systemic immune biomarkers to track cancer progression and to use them as predictors of effective responses to cancer therapy. The central hypothesis guiding this project is that specific immune biomarkers will serve as predictors of effective vs. ineffective immunotherapy in patients with malignant diseases. The objective of this study was to establish baseline of immune markers in patients already started treatment with immunotherapy (n=10) (T), patients starting, but not yet treated (S) with immunotherapy (n=10) and subjects without diagnosed malignant disease (W) (n=10). Blood was collected and plasma was isolated and used in the biomarker (100 markers) analysis using a protein microarray method (RayBiotech). The biomarkers in the three groups were analyzed by Principal Component Analysis, heat map with clustering, and differential expression based on p value, and Significance Analysis of Microarrays (SAM). Although 15 biomarkers were significantly different between S vs. W groups, based on SAM, only seven were found differentially expressed. Similarly, although 10 biomarkers were significantly different between T vs. W groups, based on SAM, only one biomarker was found differentially expressed. Furthermore, SAM revealed that responders (n=4) vs. stable (n=5) subgroup of patients within the T group exhibited 22 differentially expressed biomarkers. Future larger studies will be needed to evaluate whether immune markers will be able to predict effective vs. ineffective responses to immunotherapy and whether they may have therapeutic potential.

Artificial Intelligence (AI) has been drawing attention in the field of medical devices. However, due to system complexity, the variability of their architecture, as well as ethical and regulatory concerns there is an ongoing need to analyze its application and performance.This study presents a narrative commentary on the applications of artificial neural networks (ANN) and machine learning (ML) algorithms in medical devices, past, current and future perspectives of application. One research focus of this study was on identifying problems and issues related to the implementation of AI in medical devices. The commentary is based on scientific articles published in PubMed, Scopus ad ScienceDirect databases, official publications of international organizations: European Comission (EC), Food and Drug Administration (FDA), and World Health Organisation (WHO) published in 2009 - 2020 period. AI is revolutionizing healthcare, from medical applications to clinical engineering. However, before grasp-ing the full potential ethical, legal and social concerns need to be resolved and its application needs to be harmonized and regulated regarding equitable access, privacy, appropriate uses and users, liability and bias and inclusiveness.

Ibn Sina (Avicenna) is primarily known for his philosophy and medicine, but there is almost no scientific discipline in which this great man didn't leave a significant mark. This paper gives a brief overview of his contribution to medicine and psychology through which his unique scientific and religious approach to the study of the phenomena of human being can be best seen. Medical works of Ibn Sina represent a pinnacle of most important medical achievements of his time. These works contain synthesis of all Greek, Indian and Iranian medical schools, but also new breakthroughs achieved by Muslim scholars through their own experimentation and practice. Although he wrote many medical works, his most important one is El-Kanun fit-tib, which can be translated as The Canon of Medicine. It's made out of five books which systematically show everything known in the area of medicine up until that point in time. In it, Ibn Sina discusses, among other things, the structure of psychological apparatus of human being and the connection of psychological functions with the brain. He considered psychology to be very important for medicine, so in his psychological works he discusses, in great detail, the essence of human soul, consciousness, intellect and other psychological functions. He observed a man in his entirety, taking into consideration all aspects of his existence, paying special attention to spiritual knowledge and spiritual perfection, religiosity, and methods of achieving inner peace and well-being.

BACKGROUND Indoor air quality (IAQ) in classrooms affects children's health and academic perfor-mance. The aim of this pilot study was to determine IAQ in elementary schools different in their inter-nal and external characteristics, in settings of COVID-19 epidemics. METHODS IAQ parameters: fine particulate matter (PM2,5) mass concentration, CO2 concentration, tempera-ture and relative humidity were measured in parallel in four elementary schools/classrooms during October (non-heating season) and four months (including holiday in January) of heating season. IAQ parameters were measured in settings of anti-epidemic restrictions (≤13 students in classroom, frequent ventilation). RESULTS During October, except in one school, PM2,5 concentrations were below the upper recommended value (25 μg/m³), but started rising in all schools in the heating season. The highest concentrations of PM2,5 were registered in two schools with closed or shortly opened windows. CO2 concentrations were mostly in the recommended range (up to 1000ppm) except in the school with constantly closed windows and in three schools in February when concentrations were higher. Except in one, the same school, and in January, both temperature and relative humidity were out of the recommended range (24,0-27,0°C in non-heating; 20,0-24,0°C in heating season; and 45-55%), with temperature mainly above and relative humidity mainly below it in three schools. The largest deviation in temperature and relative humidity were registered in urban schools. Registered differ-ences may be explained by different internal and external characteristics. CONCLUSION Despite anti-epidemic restrictions, most of the measured IAQ parameters were out of the recom-mended values in heating season. In addition, further deterioration of IAQ could be expected if all students had been presented in the classroom. Finally, to assure a healthy school environment in heating season, further optimisation of both indoor and outdoor conditions is needed in both pandemic and non-pandemic settings.

Abstract One of the most important environmental factors, which affects the environment of a healthy life is diet. About 75% of new diseases that have occurred since 2000 in the population of Bosnia and Herzegovina have come from animals or products of animal origin. So-called zoonoses are diseases that can be transmitted from animals to humans most often through food. In addition to zoonoses, contamination of soil, water, air and plants also affects, to a large extent, directly or indirectly the environment of a healthy life. Soil, air, water and plants can be contaminated with pollutants such as heavy metals in the soil or dangerous substances that produce certain types of mushrooms, all of which are transferred in many ways to food production processes. The research define the characteristics of a healthy living environment complemented with healthy food, then explain and demonstrate, on appropriate examples, what are the hazards or hazardous places in food production and show how to reduce the likelihood of their occurrence using the standard and applicable regulations.

A congenital hernia into the umbilical cord (CHUM) is often misinterpreted as a mild form of omphalocele. Herniated content in CHUM can be either the solitary intestinal loop or persistent omphalomesenteric duct (POMD) with the potential for traumatic injury in a case of inadequate examination of the umbilical cord and its clamping in the delivery room. Herein, we report a case of a male newborn with a functional bowel obstruction due to peritonitis caused by necrosis of iatrogenically clamped POMD in the CHUM. A 2-day-old full-term male infant was referred to the emergency department with a 1 day history of bilious vomiting, a gradual increase in abdominal distension, and absence of passage of meconium. The infant was born at 38 weeks’ gestation with a birthweight of 2,885 g. The baby was born following an uncomplicated pregnancy and a normal spontaneous vaginal delivery. The Apgar scores were eight at both 1 and 5 min. On physical examination, his abdomen was slightly distended by an umbilical ligation clip placed approximately 2.5 cm from the enlarged base of the umbilical cord (Fig. 1a). The stump of the umbilical cord was thickened and red. The baby was pale and dehydrated. An abdominal radiograph showed dilated small bowel loops due to small bowel obstruction (Fig. 1b). After resuscitation, a surgical exploration via a circumumbilical incision revealed a clamped POMD in the umbilical cord. The top of the POMD was crushed by the umbilical cord clamp (Fig. 1c). The POMD was resected at its base on the ileal loop. The ileal loop was closed transversely using 5-0 Vicryl by single-layer extra mucosal-interrupted sutures. The postoperative recovery was uneventful at a follow up of 8 years. Evaluation of the umbilical cord is a routine part of every newborn examination in the delivery room. Any suspected abnormal thickening of the base of the umbilical cord or any other malformations found should be further evaluated by a neonatologist or pediatric surgeon. Congenital hernia into the umbilical cord is a type of ventral abdominal wall defect in which the bowel usually herniates into the base of normally inserted umbilical cord through a patent umbilical ring. The condition results from a failure of return of intestine loops following the physiological gut herniation around 10–12 weeks of gestation. Due to similar morphologic features, characterized by coverage of eviscerated abdominal contents with a sac comprising outer amnion and inner peritoneal lining, CHUM may be easily misdiagnosed as a small omphalocele. Unlike an omphalocele, CHUM has an intact abdominal wall with adequate muscle development and a complete umbilical ring covered by a small cuff of skin about ~2.5 cm. Congenital hernia into the umbilical cord is usually not linked to chromosomal abnormalities but cases of trisomy 13 associated with CHUM have been reported in the literature. However, if missed, this condition can lead to intestinal damage by a low-placed umbilical cord clamp as it is shown in our illustrative case. Although very rare, similar complications have been reported in the literature. The prevention of inadvertent bowel injury during cord clamping at delivery is possible with increased awareness and knowledge regarding CHUM. Primary prevention includes the prenatal sonographic CHUM detection characterized by intestinal protrusion only into the base of the hernia. The most important preventive measure if the umbilical cord is broad based is the umbilical cord clamping at a safe distance from the basis (at least 5 cm from the abdominal wall). In conclusion, a careful inspection of the umbilical cord of all newborns in the delivery room is essential to identify any clinically relevant umbilical abnormality (e.g., a persistence of CHUM with POMD). This would prevent any iatrogenic gut injury during umbilical cord clamping. Although these complications are rare, they should be kept in mind when performing umbilical cord clamping.

While the COVID-19 pandemic continues to spread globally, with relistic hope that will be solved with adequate vacination, more and more evidences are collected about the presence of psychi-atric and neurological manifestations and symptoms associated with this diseas. Neurological manifestations, are part of the COVID-19 clinical picture, but questions remain regarding the frequency and severity of centra nervous system symptoms, the mechanism of action underlying neurological symptoms, and the relationship of symptoms with the course and severity of COVID-19. The review of the so far published papers shows that although more and more papers are reporting neuro-logical and psyhiatric manifestations associated with COVID-19, many items remain unclear. The long-term psychological implications of this infectious diseases should not be ignored. In this paper, we aim to present a some of psychological consequences and neurological disorders associat-ed with the SARS-CoV-2 infection, and to emphasize the need a global action that requires close coordination and open-data sharing between hospitals, academic and public health institutions and the fast establishment of harmonised research priorities to face acut and long-term the neurological and psychological consequences.

The volume Remembrance and Forgiveness, edited by Ajlina Karamehić-Muratović and Laura Kromják, brings together a diversity of disciplines, authors, and cultural contexts to discuss the legacies of the post-Holocaust era genocides by focusing on the (de)mobilisation of memory in seeking truth, justice, and forgiveness. The book provides a compendious overview of the social, historical, and political contexts behind the insurgencies and gives a better sense of understanding of (the obstacles to) the healing process and reconciliation in the global frame.

OBJECTIVE   We aimed to confirm whether serum on admission homocysteine level (HCY) and red cell distribution width (RDW) value are independent risk factors for MACE incidence in patients with STEMI myocardial infarction treated by percutaneous coronary intervention (PCI), as well as the possibility of their joint assessment in order to enhance the risk stratification for major adverse cardiac events (MACE). PATIENTS AND METHODS A total of 80 patients with acute myocardial infarction (AMI) were included in the study and tested for blood HCY and RDW values. Patients were followed up for six months after discharge and evaluated for MACE occurrence. RESULTS The RDW value was significantly associated with HCY level (r=0.267, p=0.026). Univariate logistic regression analysis identified both the RDW and HCY as independent predictors of MACE (OR 2.179; CI 95% 1.250 to 3.797; p=0.006 and OR 1.108; CI 95% 1.013 to 1.213; p=0.025, respectively), naming RDW as a stronger predictor of unfavorable prognosis in AMI patients. Addition of HCY to RDW value in receiver operating characteristic (ROC) curve analysis increased the area under the curve (AUC) from 0.705 to 0.730 (p=0.007), while risk prediction model, which also included traditional risk factors, increased AUC up to 0.806, implying this model as good predictor of MACE both in low-risk and high-risk STEMI patients. CONCLUSIONS A high baseline HCY level and RDW value in patients with STEMI undergoing PCI is independently associated with increased risk for MACE outcome. Their joint assessment increases risk prediction ability.

Acacetin, apigenin, chrysin, and pinocembrin are flavonoid aglycones found in foods such as parsley, honey, celery, and chamomile tea. Flavonoids can act as substrates and inhibitors of the CYP3A4 enzyme, a heme containing enzyme responsible for the metabolism of one third of drugs on the market. The aim of this study was to investigate the inhibitory effect of selected flavonoids on the CYP3A4 enzyme, the kinetics of inhibition, the possible covalent binding of the inhibitor to the enzyme, and whether flavonoids can act as pseudo-irreversible inhibitors. For the determination of inhibition kinetics, nifedipine oxidation was used as a marker reaction. A hemochromopyridine test was used to assess the possible covalent binding to the heme, and incubation with dialysis was used in order to assess the reversibility of the inhibition. All the tested flavonoids inhibited the CYP3A4 enzyme activity. Chrysin was the most potent inhibitor: IC50 = 2.5 ± 0.6 µM, Ki = 2.4 ± 1.0 µM, kinact = 0.07 ± 0.01 min−1, kinact/Ki = 0.03 min−1 µM−1. Chrysin caused the highest reduction of heme (94.5 ± 0.5% residual concentration). None of the tested flavonoids showed pseudo-irreversible inhibition. Although the inactivation of the CYP3A4 enzyme is caused by interaction with heme, inhibitor-heme adducts could not be trapped. These results indicate that flavonoids have the potential to inhibit the CYP3A4 enzyme and interact with other drugs and medications. However, possible food–drug interactions have to be assessed clinically.

The critical zone (CZ) is the region of the Earth’s surface that extends from the bottom of the weathered bedrock to the tree canopy and is important because of its ability to store water and support ecosystems. A growing number of studies use active source shallow seismic refraction to explore and define the size and structure of the CZ across landscapes. However, measurement uncertainty and model resolution at depth are generally not evaluated, which makes the identification and interpretation of CZ features inconclusive. To reliably resolve seismic velocity with depth, we implement a Transdimensional Hierarchical Bayesian (THB) framework with reversible‐jump Markov Chain Monte Carlo to generate samples from the posterior distribution of velocity structures. We also perform 2D synthetic tests to explore how well THB traveltime inversion can resolve different subsurface velocity structures. We find that THB recovers both sharp changes in velocity as well as gradual velocity increases with depth. Furthermore, we explore the velocity structure in a series of ridge‐valley systems in northern California. The posterior velocity model shows an increasing thickness of low velocity material from channels to ridgetops along a transect parallel to bedding strike, implying a deeper weathering zone below ridgetops and hillslopes than below channels. The THB method enhances the ability to reliably image CZ structure, and the model uncertainty estimates it yields provides an objective way to interpret deep CZ structure. The method can be applied across other near‐surface studies, especially in the presence of significant surface topography.