Controllable ablative machining of Al/Ti and Ti/Al nano-layers on a Si substrate by single-pulse femtosecond laser irradiation.

Results concerning the controllable ablation of nano-layered thin films (NLTF) by femtosecond laser pulses are presented. Investigated samples were titanium-aluminum bilayers, deposited on a silicon substrate, with the top titanium or aluminum layer of variable thickness on the surface. Irradiation was done in ambient air with single femtosecond laser pulses under standard laboratory conditions. The samples were analyzed by complementary methods of optical and scanning electron microscopy and optical profilometry, exhibiting laser-fluence-dependent ablative removal either of the top layer or the entire bilayer or even partial ablation of the underlying silicon substrate. The removal (spallation) threshold fluences for the topmost layer are scalable versus its thickness almost irrespectively of its material, being rather selective for the Ti-coated samples and much less selective for the Al-coated samples. The removal of the entire bilayers was found to be strongly influenced by electronic properties of the underlying metallic layer, dictating the NLTF-Si adhesion, heat conduction, and capacity in the NLTFs toward the NLTF-Si interface and beyond, as well as by their thermophysical characteristics, e.g., almost twice higher melting temperature and enthalpy for Ti. As a result, precise fs-laser machining of the entire NLTFs is pronounced and selective for the samples with the fusible Al at the low-adhesion Al-Si interfaces, compared with the incomplete NLTF removal from the high-adhesion and refractory Ti-Si interfaces.

VITAMIN D STATUS IN PATIENTS WITH MENTAL DISORDERS: A CROSS-SECTIONAL ANALYSIS OF SINGLE COHORT FROM ROUTINE PRACTICE.

CONTEXT: Clinical research suggests that vitamin D deficiency correlates with mental illnesses. OBJECTIVE: The aim was to prove that the patients from the psychiatric health care service in Serbia had higher vitamin D deficiency than patients from general practice. DESIGN: The study had a cross-sectional design. METHODS: The study included 47 patients aged 19 - 76 of both sexes with different mental disorders. We performed sample size calculation on available data for vitamin D deficiency in patients in health care facilities compared with the general population. The concentrations of vitamin D in serums were measured by HPLC (high performance/pressure liquid chromatography). RESULTS: The mean value of vitamin D (standard deviation) in the whole group of study subjects was 16.27(10.62) ng/mL; 68.1% of the patients had a deficiency of vitamin D (25(OH)D<20 ng/mL). The difference is statistically significant from expected proportion of people with vitamin D deficiency in general practice (p=0.040). Serum concentrations of 25(OH)D were significantly correlated with serum concentrations of phosphorus (ϱ=0.336, p=0.024) and sodium (ϱ=0.304, p=0.038). CONCLUSIONS: The patients of psychiatry health care had significantly higher frequency of vitamin D deficiency than expected. There is a significant association between serum levels of vitamin D, and phosphate and sodium.

The influence of CYP2C8*3 on carbamazepine serum concentration in epileptic pediatric patients.

The aim of the present study was to investigate the distribution of CYP2C8 variants *3 and *5, as well as their effect on carbamazepine pharmacokinetic properties, in 40 epileptic pediatric patients on carbamazepine treatment. Genotyping was conducted using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and allele-specific (AS)-PCR methods, and steady-state carbamazepine plasma concentrations were determined by high performance liquid chromatography (HPLC). The CYP2C8 *3 and *5 polymorphisms were found at frequencies of 17.5 and 0.0%, respectively. After dose adjustment, there was a difference in daily dose in CYP2C8*3 carriers compared to non carriers [mean ± standard deviation (SD): 14.19 ± 5.39 vs. 15.46 ± 4.35 mg/kg; p = 0.5]. Dose-normalized serum concentration of carbamazepine was higher in CYP2C8*3 (mean ± SD: 0.54 ± 0.18 vs. 0.43 ± 0.11 mg/mL, p = 0.04), and the observed correlation between weight-adjusted carbamazepine dose and carbamazepine concentration after dose adjustment was significant only in CYP2C8*3 non carriers (r = 0.52, p = 0.002). However, the population pharmacokinetic analysis failed to demonstrate any significant effect of CYP2C8 *3 polymorphism on carbamazepine clearance [CL L/h = 0.215 + 0.0696*SEX+ 0.000183*DD]. The results indicated that the CYP2C8*3 polymorphism might not be of clinical importance for epilepsy treatment in pediatric populations.

Can a single lactate value predict adverse outcome in critically ill newborn?

OBJECTIVES: The aim of this study was to investigate the role of the lactic acidosis, as an early predictor of significant consequences and/or a fatal outcome in term neonates after a perinatal asphyxia. BACKGROUND: Severe perinatal asphyxia can generate multiple organ dysfunction and neonatal mortality. METHODS: In routine clinical practice, after an admission to the Intensive Care Unit, lactate concentration was determined in capillary blood samples during the first one to six hours after birth in 55 term newborns with the post-asphyxial hypoxic-ischemic encephalopathy. The control group consisted of 36 healthy term neonates randomly selected in the maternity ward at the Gynecology and Obstetrics Clinic. RESULTS: Significantly higher concentrations of lactate (p 8.7 mmol/L with 80 % sensitivity and 82% specificity indicated the development of the hypoxic-ischemic encephalopathy stage II/III, while the lactate level>9.95 mmol/L was a predictor of death, with 75% sensitivity and 74.4% specificity. CONCLUSION: Determination of lactate concentrations in serum of term newborns associated with risk factors for the perinatal asphyxia is a useful tool in diagnosing metabolic disorders and ischemic damage, particularly severe clinical forms (Tab. 2, Fig. 3, Ref. 34).

Total costs of inpatient treatment for COVID-19 in a tertiary hospital in Serbia.

BACKGROUND: Our study aimed to identify the total costs of inpatient treatment for coronavirus disease 2019 (COVID-19) in a tertiary institution in Serbia, an upper-middle-income country in Southeast Europe. METHODS: An observational, retrospective, cost-of-illness study was performed from the perspective of the National Health Insurance Fund and included a cohort of 78 females and 118 males admitted to the COVID-19 ward units of a tertiary center during the first wave of the pandemic. RESULTS: The median of the total costs in the non-survivors subgroup (n =43) was 3,279.16 Euros [interquartile range (IQR): 4,023.34; range: 355.20-9,909.61) which is higher than in the survivors (n =153) subgroup 747.10 Euros (IQR: 1,088.21; 46.71-3,265.91). The cut-off value of 156.46 Euros regarding the total costs per day was estimated to have 95.3 % sensitivity and 91.5 % specificity for predicting patients' dismal prognosis, with the area under the curve (AUC) of 0.968 (95 % confidence interval: 0.940-0.996, p <0.001). CONCLUSIONS: Direct medical inpatient treatment costs for COVID-19 represent a significant economic burden. The link between increased costs and an ultimate unfavorable outcome should be further explored.HIPPOKRATIA 2022, 26 (2):62-69.

Nutrition education in medical schools (NEMS) project: Joining ESPEN and university point of view.

BACKGROUND & AIMS: Nutrition education is not well represented in the medical curriculum. The aim of this original paper was to describe the Nutrition Education in Medical Schools (NEMS) Project of the European Society for Clinical Nutrition and Metabolism (ESPEN). METHODS: On 19 January 2020, a meeting was held on this topic that was attended by 51 delegates (27 council members) from 34 countries, and 13 European University representatives. RESULTS: This article includes the contents of the meeting that concluded with the signing of the Manifesto for the Implementation of Nutrition Education in the Undergraduate Medical Curriculum. CONCLUSION: The meeting represented a significant step forward, moved towards implementation of nutrition education in medical education in general and in clinical practice in particular, in compliance with the aims of the ESPEN Nutrition Education Study Group (NESG).

Ultrasonographic and computed tomography findings in renal suppurations: performance indicators and risks for diagnostic failure.

OBJECTIVES: The main purpose of the study was to identify and quantify clinical variables which predisposed incorrect diagnosis based on ultrasonography (US) and computed tomography (CT) findings in the patients with suppurative renal infections. PATIENTS AND METHODS: A retrospective review of radiological records of patients at 3 tertiary Serbian clinics of urology from 1999 to January 2006 was conducted. The series consisted of 49 women and 26 men, mean age = 56.7 years, ranging from 21 to 78. All patients underwent US examinations. Forty-one patients had undergone CT examinations, on 42 renal units (1 bilateral perirenal infection). The patients were categorized into 4 groups according to the type of suppurative infection: (a) unilocular renal or perirenal abscesses; (b) with pyonephrosis only; (c) with multiple renal or pyonephrosis infections along with extension on perirenal space, and (d) emphysematous infections. RESULTS: Incorrect diagnosis based on US record only depended on the suppurative entity. In the presence of pyonephrosis only, the risk of incorrect diagnosis was reduced for 4 times [odds ratio (OR) = 0.25], and in presence of emphysematous infections the risk increased 19.5 times (OR = 19.49). Perinephric abscesses which were not seen on US were those associated with pyonephrosis, abscesses smaller than 6 cm and gas-forming abscesses. The diagnosis of abscesses considerably varied in the cases of unilocular purulent collections compared to complex purulent collections (chi(2) = 8.177, p = 0.004). Overall, the risk for incorrect diagnosis is about 14 times higher using US only (OR = 14.5), while CT reduced the risk of it for about 37 times (OR = 0.027). CONCLUSIONS: CT was much more reliable than US to correctly identify the pathological entity of renal suppuration. Guiding treatment on US findings only seems hazardous as omission of some pathological processes is very likely.

Qualitative gene profiling: a novel tool in genomics and in pharmacogenomics that deciphers messenger RNA isoforms diversity.

RNA splicing is a tightly regulated process. It is essential for gene expression and, therefore, intervenes in every biological phenomenon in mammals. RNA splicing regulation is cell type-specific in such a way that a cellular situation can be characterised by its repertoire of spliced events, the spliceome. Comparison of the splicing repertoire of two situations identifies alternative exons and introns. This regulation involves cis-acting sequences and transacting factors. Mutations, as well as modifications of signalling pathways, can alter the accuracy of splicing. Since deletion of exons or retention of introns within coding sequences modifies the corresponding proteins and functional domains of proteins are encoded by contiguous exons, identifying changes in the spliceome pinpoints functional domains, which are specifically regulated at the level of RNA splicing. We have developed a new method of gene profiling, qualitative gene profiling, that allows the comparative study of the repertoires of spliced events that characterise distinct physiopathological situations. We present in this review the different uses of this new genomic technique that can help each step of the R&D process in the pharmaceutical industry, and that represents a short cut towards functional genomics and pharmacogenomics.

HLA-DP control of human Schistosoma haematobium infection.

The DPA1 and DPB1 alleles of the major histocompatibility complex (MHC) class II were determined in 110 patients and 120 healthy controls of a Gabonese population from an area endemic for Schistosoma haematobium infection. The MHC-DP alleles of the variable second exons and their human leukocyte antigen (HLA) epitopes were correlated with egg excretion, interleukin-4 and interferon-gamma patterns, and bladder abnormalities, as detected by ultrasonography. A methionine at position 11 of the DP alpha molecule (Met-11) and DPA1*0301 were associated with schistosomiasis when compared with controls (phenotypic gene frequencies = 0.791 versus 0.583 and 0.555 versus 0.375, respectively). Met-11 homozygosity occurred more often in patients, whereas healthy controls were more frequently homozygous for an alanine at position 11 (Ala-11). The combination of the DPB1-epitope DEAV (positions 84-87 of the DP beta molecule) and Met-11 positive DPA1 alleles was more frequent in patients than in controls (0.573 versus 0.316). Two years after antischistosomal treatment, the rate of reinfection as examined in 55 of the 110 former patients was higher in DPA1*0301-positive individuals than in those not possessing this allele (P < 0.001). Ala-11 positive individuals showed less frequently ultrasonographic signs of bladder pathology than Ala-11 negative individuals (P < 0.05). Our results suggest a role of MHC-DP elements in the manifestation of disease in S. haematobium infection.

Pharmacologic characterization of muscarine receptor subtypes in rat gastric fundus mediating contractile responses.

The role of four muscarinic receptor subtypes M1, M2, M3 and M4 which have been characterized pharmacologically was examined in motility control of isolated rat gastric fundus. Acetylcholine produced concentration-dependent tonic contraction of isolated rat fundus (EC50 = 9.64 +/- 0.14 x 10(-8)M). These contractions were concentration-dependently antagonized by atropine (KB = 2.45 x 10(-11)M), M1 selective blockers telenzepine (KB = 6.64 x 10(-11)M) and pirenzepine (KB = 2.3 x 10(-8)M), and hexocyclium (KB = 2.82 x 10(-10)M). M3-selective blocker p-fluoro-hexahydro-sila-difenidol (pFHHSiD) was a less potent antagonist (KB = 2.3 x 10(-8)M), while M2 and M4-selective methoctramine produced only weak blockade of tonic contractions caused by acetylcholine (KB = 4.68 x 10(-6)M). These results suggest that only M1 and M3 muscarinic receptors have functional roles in motility control of rat gastric fundus, M1 receptors being more important.

Serum tryptophan to large neutral amino acid ratio and urinary tryptophan in three patients with phenylketonuria in a family. A clinical and biochemical study.

In this work clinical and biochemical findings are presented in three untreated children with phenylketonuria in a family. Their clinical pictures were not typical for classical phenylketonuria. As a result, diagnosis was missed. It has been shown that patterns of large neutral amino acids in serum and urine were somewhat different. Significantly lower serum TRP/LNAA ratio was observed in all patients with phenylketonuria, compared to the control group. These findings suggest that there was subnormal tryptophan availability in the central nervous system leading to its decreased metabolism through the serotonin and kynurenine pathways. These results may explain decreased children's growth and their mental deficiency.

Plasma and urinary serotonin and 5-hydroxyindol-3-acetic acid in adults with migraine and tension-type headache.

Each headache can be a complex diagnostic, therapeutic, prognostic and social problem. The pain in the head can be connected with many organic and non-organic causes. In this work, the levels of plasma and urinary free 5-HT and 5-HIAA were investigated in eight migraine (aged 23-59 years) and ten tension-type headache suffers (aged 38-61 years). Based on the data obtained and their correlation with clinical features and in comparison with a control group, the following can be stated: (1) there is involvement of serotonin in migraine and tension-type headache during the attacks, although the positive 5-HT values from plasma were small; (2) urinary 5-HT values in migraine and tension-type headache were normal in comparison to the control group; (3) significantly decreased values of 5-HIAA in urine were found both in migraine and tension-type headache groups. These findings show that catabolism of 5-HT is probably decreased during headache periods; (4) visual aura was found in five out of ten subjects with tension-type headache.

Plasma and urinary serotonin and 5-HIAA in children treated with lamotrigine for intractable epilepsy.

Alteration of monoamine levels by some antiepileptic drugs (AEDs) was elucidated in this study. Lamotrigine (LTG) is a new AED, acting the sodium-channels. LTG was given as add-on therapy to 16 patients aged 4.5-18 yrs with intractable epilepsy and comedicated with carbamazepine or valproate. An equal group of epileptics with comparable clinical characteristics and treatment served as control. Plasma and urinary (24 h-samples) serotonin and 5-HIAA were determined before onset of LTG therapy and after 2-3 months. HPLC and electrochemical detection was used for the determination of serotonin (5-HT) and 5-hydroxy indoleacetic acid (5-HIAA). No significant effect of LTG on both urinary 5-HT and 5-HIAA levels was found, whereas plasma 5-HT concentrations significantly decreased in comparison with levels before LTG starting and relevant values in controls. This findings was noted in 7/16 children with favourable response to LTG. Increased serotonin catabolism may be result of LTG action.

Computed tomography image analyzer: 3D reconstruction and segmentation applying active contour models--'snakes'.

Many diagnostic and therapeutic procedures depend on medical images. In order to overcome imperfections of the obtained images, which are due to the acquisition process, and to extract new information from the available images, many techniques have been developed. In this study, a new method of image segmentation and 3D reconstruction based on active contour models ('snakes') was applied in analyzing computed tomography (CT) images in patients with acute head trauma. Using this method, lesion to brain (LBR) and ventricle to brain ratio (VBR) parameters, as well as 3D reconstruction of traumatic lesion, was obtained accurately. In our study group, 215 patients (mean age 42.4+/-23.5 years, 138/215 (64.2%) males) were included. Among them, 72 (33.5%) did not survive during hospitalisation in the Emergency Department. LBR correlated with the Glasgow Coma Score and the intrahospital outcome (r=-0.457 and r=0.515, respectively). Besides, non-survivors had greater LTB values (0.042+/-0.034) than survivors (0.005+/-0.011). However, VBR did not correlate with these clinical parameters. In addition, LBR was significantly higher in the patients with other pathologic CT findings. The proposed methodology, based on extracting maximum information from available CT scans, could be a basis for further medical decision making in patients with acute head trauma.

A pharmacological analysis of the contractile effects of glutamate on rat and human isolated gut smooth muscle strips.

Although the contractile effects of glutamate and related excitatory amino acids on gut smooth muscle strips have been demonstrated, the mechanisms, and particularly the physiological importance of that action, remain unknown. In this study, glutamate, aspartate, AMPA, quisqualate, cis-ACPD and (2R,4R)-APDC evoked concentration-dependent contraction of isolated adult rat gastric fundus, with EC50 values of 210 microM, 150 microM, 20 microM, 33 microM, and 2.7 microM and 7.9 microM, respectively. L-SOP (0.1 microM-1.9 mM) did not change the basal tone of the preparations. The maximal contractions evoked by glutamate (20 mM) were 38.83% compared with those elicited by acetylcholine (20 microM). The glutamate-evoked contractions were not affected by atropine, verapamil and nicardipine, blocked by CNQX (0.01 microM), or potentiated by Mg2+ (0.01-100 microM), ketamine (0.01-100 microM) and DL-AP5 (0.1-100 microM), as well as L-trans-2,4-PDC (1-100 microM). Analysis of glutamate's action on rat rectum (EC50 = 44 microM) could only be carried out at the early stages, as half of the preparations were not affected by glutamate. Only 5 out of 26 human longitudinal and circular smooth muscle preparations taken from the stomach and three segments of the large intestine were very slightly contracted by glutamate, excluding further analysis. The contractile effects of glutamate on rat gut smooth muscles were mediated by multiple GluR (non-NMDA > NMDA > group I/II mGluRs) located primarily on smooth muscle cells but functional GluRs on neurons and/or nerve fibers of myenteric nervous plexuses could not be excluded. To fully understand the physiological significance of glutamate-evoked contractions in the gut, more research is required, most likely using many different methodological approaches.

Human pharmacological investigations of a transdermal nicotine system.

To define the pharmacological properties of a newly developed transdermal nicotine system (TNS) designed to facilitate abstention from smoking, three human pharmacology studies were performed in healthy, nicotine-dependent smokers. The first study, in which cigarette smoking served as the standard mode of nicotine intake, was carried out to evaluate the most suitable non-invasive methods for detecting the pharmacodynamic effects of nicotine and to provide a baseline for comparisons with the results of the subsequent studies to assess the effects of single and repeated applications of the TNS. The pharmacodynamic changes induced by smoking were generally most pronounced after the first cigarette following 10 hours' abstinence. The most sensitive parameters were heart rate, which increased, stroke volume measured by impedance cardiography, which decreased, cutaneous blood flow measured by Laser Doppler flowmetry and skin temperature, which diminished to a statistically significant extent after each cigarette. Increases in blood pressure were not very pronounced. Plasma catecholamines were consistently elevated after each cigarette, but the changes were not statistically significant. Compared with those induced by cigarette smoking, the cardiovascular effect seen after either a single application of the TNS (10, 20 and 40 mg/24 h) or repeated application of a TNS delivering 14 mg nicotine/24 h were minor. A slight increase in blood pressure was detectable only on the first day of application and had disappeared after 10 days' repetitive application, suggesting the development of partial tolerance. Heart rate was slightly increased by 3-7% and stroke volume decreased by 5-12% on the tenth day of TNS application.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholestasis caused by biliary botryoid sarcoma.

A 4-year-old boy with a short history of jaundice and hepatomegaly was studied by endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangiography (PTC). A large obstructing choledochal tumour was found at the level of cystic duct insertion and at surgery, a botryoid sarcoma was removed. Subsequent cytotoxic therapy was complicated by persistent dilatation of the extrahepatic bile ducts which necessitated eventual excision. There was no evidence of persistent tumour.

Computed tomography image analyzer: segmentation applying active contour models--"snakes".

Many diagnostic and therapeutic procedures depend on medical images. In order to overcome imperfections of obtained images which are due to acquisition process and to obtain new information from available images, many techniques have been developed. In this study relatively new method of image segmentation, active contour model--"snakes" was applied in analyzing computed tomography (CT) images in patients with acute head trauma. Using this method, lesion to brain (LBR) and ventricle to brain ratio (VBR) were obtained accurately. Quantitative variable LBR, is significantly higher in patients with other pathologic CT findings and who do not survive during hospitalization. Thus, by applying segmentation "snakes" model it is possible to extract maximum information from available CT scans. These variables could be basis for medical decision making in patients with acute head trauma.