High dose rate brachytherapy as monotherapy for localised prostate cancer

Background and purpose

To evaluate the oncological outcome of a three-implant high dose rate (HDR) brachytherapy (BRT) protocol as monotherapy for clinically localised prostate cancer.

3-D Source Localization of Epileptic Foci Integrating EEG and MRI Data

This study evaluates the utility of 3-D localization of interictal spike activity on the electroencephalographs (EEG) superimposed on magnetic resonance imagery (MRI) in a pediatric population with extra-temporal lesional epileptic foci. 3-D software programming based on the CURRY platform (a multimodal neuro-imaging software) was adapted for analyzing scalp EEG data and reconstructing superimposed images in 10 children who underwent extensive pre-surgical evaluation for intractable partial seizures. The results of 3-D spike source localization were assessed in relationship to focal lesions evident on the patient's MRI scans. Calculated spike sources were closest to the lesions during intervals corresponding to the spike peaks. The information was useful in surgical planning in six children that underwent successful resections.     

Postantibiotic effect of colistin alone and combined with vancomycin or meropenem against Acinetobacter spp. with well defined resistance mechanisms

Previous studies found short postantibiotic effect of colistin on Acinetobacter baumannii. Many studies have evaluated the potential for synergy between colistin and other antibiotics against A. baumannii. The aim of this study was to determine in vitro synergy and postantibiotic effect (PAE) of colistin alone and combined with other antibiotics (vancomycin or meropenem) against eight carbapenem-non-susceptible Acinetobacter spp. strains with defined resistance mechanisms. It was hypothesised that vancomycin or meropenem would prologue the PAE of colistin since it was previously found that they exert synergism with colistin in time-kill kinetics and chequerboard analysis. After exposure of 1?hour colistin alone exhibited the negative (???0.07?hour) (OXA-143), short (0.2–1.82?hours) (OXA-24, OXA-58, OXA-72, VIM-1+OXA-23, OXA-58+NDM-1, ISAba1/OXA-69) or moderate PAE (3.2?hours) for OXA-23 positive strain. When combined with vancomycin, the PAE was moderate (1.7–4?hours) with OXA-23, OXA-23+VIM-1, OXA-72 and OXA-24 positive strains while with OXA-58, OXA-143, OXA-58/NDM-1 and ISAba1/OXA-69 positive strains, it was not possible to calculate mean duration of PAE because there was no regrowth after exposure to antibiotics or it was longer than 5?hours. The combination with meropenem resulted in short (0.2?hours) (OXA-143), moderate (2.4–3.73?hours) (OXA-24, OXA-58, OXA-23, OXA-23+VIM-1), long PAE of 5?hours (OXA-23) or longer than 5?hours (OXA-58+VIM-1, ISAba1/OXA-69). From the clinical point of view, the prolongation of colistin PAE when combined with other antibiotics could provide a rationale for the modification of the dosing interval and could be important for the optimization of the treatment regimen and the minimization of drug-induced side effects.     

Induction of CYP1A2 by heavy coffee consumption in Serbs and Swedes

Objectives To investigate the influence of coffee consumption on CYP1A2 enzyme activity controlling for the effects of smoking and oral contraceptive (OC) use among Serbs and Swedes and to compare CYP1A2 activity between the two populations. Methods Data on oral contraceptive use, habitual coffee consumption and smoking habits were obtained from 100 Serbian and 149 Swedish healthy volunteers using a detailed questionnaire. CYP1A2 activity was estimated by plasma paraxanthine/caffeine (17X/137X) ratio analysed by reversed-phase HPLC after oral administration of 100 mg caffeine. Results Daily consumption of at least three cups of coffee significantly increased CYP1A2 enzyme activity in both Serbs (P = 0.0002) and Swedes (P < 0.0001). Among non-smokers and non-OC users, heavy coffee consumption significantly increased CYP1A2 activity in Serbs (mean difference 0.11; 95% CI of the mean difference 0.04, 0.18; P = 0.003) and Swedes (mean difference 0.07; 95% CI of the mean difference 0.01, 0.12; P = 0.02). Significantly higher 17X/137X ratio was detected in Serbian smokers compared to non-smokers. There was no significant gender difference in CYP1A2 activity in Serbs. Controlling for the effect of smoking, heavy coffee consumption habit and oral contraceptive use, significantly lower 17X/137X ratio was observed in Serbs than in Swedes (P = 0.0003). Conclusions Habitual heavy coffee consumption increases CYP1A2 activity. Polycyclic aromatic hydrocarbons formed during roasting of coffee beans might partly be responsible for this effect. The reason for the observed lower CYP1A2 activity in Serbs as compared to Swedes remains to be investigated.     

Supplementation with Guanidinoacetic Acid in Women with Chronic Fatigue Syndrome

A variety of dietary interventions has been used in the management of chronic fatigue syndrome (CFS), yet no therapeutic modality has demonstrated conclusive positive results in terms of effectiveness. The main aim of this study was to evaluate the effects of orally administered guanidinoacetic acid (GAA) on multidimensional fatigue inventory (MFI), musculoskeletal soreness, health-related quality of life, exercise performance, screening laboratory studies, and the occurrence of adverse events in women with CFS. Twenty-one women (age 39.3 ± 8.8 years, weight 62.8 ± 8.5 kg, height 169.5 ± 5.8 cm) who fulfilled the 1994 Centers for Disease Control and Prevention criteria for CFS were randomized in a double-blind, cross-over design, from 1 September 2014 through 31 May 2015, to receive either GAA (2.4 grams per day) or placebo (cellulose) by oral administration for three months, with a two-month wash-out period. No effects of intervention were found for the primary efficacy outcome (MFI score for general fatigue), and musculoskeletal pain at rest and during activity. After three months of intervention, participants receiving GAA significantly increased muscular creatine levels compared with the placebo group (36.3% vs. 2.4%; p < 0.01). Furthermore, changes from baseline in muscular strength and aerobic power were significantly greater in the GAA group compared with placebo (p < 0.05). Results from this study indicated that supplemental GAA can positively affect creatine metabolism and work capacity in women with CFS, yet GAA had no effect on main clinical outcomes, such as general fatigue and musculoskeletal soreness.     

Emerging Trends in the Epidemiology of COVID-19: The Croatian ‘One Health’ Perspective

During the four pandemic waves, a total of 560,504 cases and 10,178 deaths due to COVID-19 were reported in Croatia. The Alpha variant, dominant from March 2021 (>50% of positive samples), was rapidly replaced by Delta variants (>90%) by August 2021. Several seroprevalence studies were conducted in different populations (general population, children/adolescents, professional athletes, healthcare workers, veterinarians) and in immunocompromised patients (hemodialysis patients, liver/kidney transplant recipients). After the first pandemic wave, seroprevalence rates of neutralizing (NT) antibodies were reported to be 0.2–5.5%. Significantly higher seropositivity was detected during/after the second wave, 2.6–18.7%. Two studies conducted in pet animals (February-June 2020/July–December 2020) reported SARS-CoV-2 NT antibodies in 0.76% of cats and 0.31–14.69% of dogs, respectively. SARS-CoV-2 NT antibodies were not detected in wildlife. Environmental samples taken in the households of COVID-19 patients showed high-touch personal objects as most frequently contaminated (17.3%), followed by surfaces in patients’ rooms (14.6%), kitchens (13.3%) and bathrooms (8.3%). SARS-CoV-2 RNA was also detected in 96.8% affluent water samples, while all effluent water samples tested negative. Detection of SARS-CoV-2 in humans, animals and the environment suggests that the ‘One Health’ approach is critical to controlling COVID-19 and future pandemics.     

Oxidative stress in response to xenobiotics in the blue mussel Mytilus edulis L.: evidence for variation along a natural salinity gradient of the Baltic Sea

Blue mussels (Mytilus edulis L.) collected at three sampling sites in each of three geographical regions (South, Middle, North) along the permanent longitudinal South-North salinity gradient of the Baltic Sea, were exposed for 10 days to copper (35ppb) or 95 octane petrol (0.3 per thousand). During the experiment, they were maintained at the respective sampling site salinity. Scope for growth (SFG) was determined, and biochemical stress markers (protein carbonyl groups, disulfide bond formation, and glutathione transferase (GST), and catalase (CAT) activities) were investigated in gill tissue upon termination of the experiment. Treatment and regional effects for SFG and protein carbonyl groups were all significant for petrol. The largest increase in protein carbonyl groups was observed in the North. Mussels from the southern, more saline ( approximately 7 per thousand) region had the highest SFG, and displayed the largest SFG decrease in response to treatment, indicating that they had the most energy available for allocation to stress response. They also displayed the least increase in the level of protein carbonyl groups. Mussels from the Northern, less saline ( approximately 5%) region had the highest degree of protein carbonyl groups in response to both treatments, and lowest average SFG. Silver stained diagonal gels for samples from one sampling site in South and North, respectively, demonstrated differences in disulfide bond profiles for both stress treatments. There was also a regional difference in the number of protein disulfides observed on diagonal gels. The most diverse protein disulfide response was found in South. No treatment related effects on GST and CAT activities were observed. We suggest that both SFG and protein carbonyl groups show that geographical difference in stress susceptibility, previously established between the North and the Baltic Seas, also apply on a regional scale within the Baltic Sea, along the salinity gradient.     

Effect of potassium channel opener pinacidil on the contractions elicited electrically or by noradrenaline in the human radial artery

In order to discover an agent that can prevent spasm of the human radial artery, the aim of our study was to evaluate the effect of the K⁺ channel opener, pinacidil, on contractions in the radial artery. Contractions of the radial artery were evoked by exogenously applied noradrenaline or by electrical field stimulation (EFS, 20 Hz, neurogenic). Pinacidil induced concentration-dependent inhibition of both EFS- and noradrenaline-evoked contractions of the radial artery. Glibenclamide, a selective blocker of ATP-sensitive K⁺ channels (Kir6.x containing subunit) antagonized in the same manner the pinacidil-induced inhibition of neurogenic contractions and contractions evoked by exogenous noradrenaline. The inhibition of pinacidil relaxation by tetraethylammonium (TEA), a blocker of Ca-sensitive K⁺ (K_Ca) channels, was more pronounced in EFS-contracted preparations. A blocker of voltage-sensitive K⁺ (K_V) channels, 4-aminopyridine (4-AP), inhibited pinacidil relaxation only in EFS-contracted preparations. In order to test the presence of different K⁺ channels, immunohistochemistry of K⁺ channels expression in the radial artery was performed. The vascular wall of the human radial artery showed variable positivity with the following applied antibodies: Kv1.2, Kv1.3, Kir6.1, and K_Ca1.1. The antibodies against Kv1.6, Kv2.1, and Kir6.2 channel subunits were completely negative. These results suggest that the inhibitory effect of pinacidil on contractions of the human radial artery might be postsynaptic and associated with opening of smooth muscle Kir6.1-containing K_ATP channels. TEA- and 4-AP-sensitive K⁺ channels may also contribute to pinacidil effect in the human radial artery.