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Choline and N-acetyl aspartate levels in the dorsolateral prefrontal cortex at the beginning of the recovery phase as markers of increased risk for depressive episode recurrence under different duration of maintenance therapy and after it: a retrospective cohort study
Get PDFAim: To evaluate the relationship between the dynamics of proton magnetic resonance spectroscopy (1H-MRS) brain metabolite levels at the beginning of the recovery phase of the index depressive episode and the time to the recurrence of depression. Methods: This retrospective cohort study analyzed the changes in N-acetyl aspartate (NAA), choline (Cho), and glutamate-glutamine in 48 patients with recurrent depression treated with maintenance antidepressant monotherapy at a stable dose. 1H-MRS was performed at the start of the recovery phase and 6 months later. 1H-MRS parameters, index episode descriptors, and depressive disorder course were analyzed by Cox proportional hazards model. Results: NAA and Cho decrease six months after the beginning of the recovery period were time-independent risk factors for depressive episode recurrence. Hazard ratio associated with NAA decrease was 2.02 (95% confidence interval 1.06-3.84) and that associated with Cho decrease was 2.06 (95% confidence interval 1.02-4.17). These changes were not related to symptoms severity, as Montgomery-Asberg Depression Scale score remained generally unchanged (mean -0.01; standard deviation 1.6) over the first 6 months of recovery. Conclusion: Patients receiving maintenance antidepressant therapy after recovery who experience a decrease in NAA or Cho levels early in the recovery phase have a double risk of depressive episode recurrence. Sustained NAA and Cho levels at the beginning of the recovery phase may indicate increased brain resilience conferred by antidepressant therapy, while NAA and Cho decrease may indicate only the trait-related temporal effect of therapy in another stratum of patients
The attitudes of international medical students toward educational methods and styles applied in a 6-year longitudinal course in fundamentals of medical skills in Croatia
Get PDFAim: To investigate international medical students’ attitudes toward the impact of 6-year longitudinal course, Fundamentals of Medical Skills (FMS), at Medical Studies in English at the University of Zagreb on the development of their practical, clinical, and communication skills. Methods:
This cross-sectional study used a 23-item online survey to collect data from five generations of students attending the FMS course from January 31 to February 3, 2017. First-year students were not included. Invitations and reminders were sent to 202 FMS students by e-mail, SMS, and in closed groups in social networks. Results: The response rate was 69.8% (141/202 students). The majority of students found the course useful (83.7%); favored practical over communication skills (92.9%); found practical skills more useful in higher years (82.3%); thought more time was needed to practice by simulation on mannequins (75.2%); preferred Objective Structured Clinical Examination (OSCE) stations to traditional oral exams (78%); and would recommend a course like FMS to future students or students at other universities (79.4%). Significantly more women than men favored practical over communication skills (P = 0.044). Significantly more 5th and 6th students than students at lower years preferred OSCE stations to traditional learning (P = 0.025) and would recommend a course like FMS to future students or students at other universities (P = 0.001). Conclusion:
Students positively evaluated the FMS course, but underestimated the communication skills aspect
The unexpected effects of L-carnitine supplementation on lipid metabolism in hemodialysis patients
Get PDFBACKGROUND/AIMS: There is a growing body of evidence that the long-term hemodialysis
(HD) treatment leads to disturbances of carnitine homeostasis but the results of L-carnitine
supplementation in HD patients have been conflicting. In the present prospective study, we
investigated the effectiveness of intravenous L-carnitine in mitigating dialysis-related proteinenergy
wasting (PEW) based on pre-treatment albumin levels. ----- METHODS: Fifty patients (46%
male, mean age 63±18.28 years, HD vintage 37.5 (7-288) months) received 1 g L-carnitine
intravenously at the end of every HD session for 12 months. Clinical data were obtained from the
medical records and charts. Intradialytic hypotension periods (defined as a decrease of systolic
blood pressure by ≥ 20 mmHg) were recorded. Dietary habits were evaluated using a selfadministered
questionnaire prior to L-carnitine supplementation. Laboratory parameters were
measured prior to the supplementation and controlled in 6-months intervals. Anthropometric
measurements were performed prior to HD session, including „dry“ body weight and height,
body mass index (BMI), and body composition analysis using bioimpedance spectroscopy.
Malnutrition-inflammation score (MIS) was used as a scoring system representing the severity
of PEW and an indicator of general functional capacity. ----- RESULTS: A significant increase in total
cholesterol, predominantly on the account of LDL was found (p=0.005). Simultaneously, HDL
decreased (p=0.001) while triglyceride levels remained unchanged. Although the rise in serum
prealbumin could be observed, lean tissue index (LTI) decreased and fat tissue index (FTI)
increased which resulted in reduction of the LTI/FTI ratio (p=0.002). When divided into two
groups according to the pre-treatment albumin values (<35 g/L or ≥35 g/L), patients from
the higher albumin group showed significant increase in prealbumin (p=0.005), and improved
MIS (p=0.03). Multivariate regression analysis showed that higher FTI after introduction of
L-carnitine led to greater hemodynamic stability (OR 1.709, 95% CI 1.006-2.905, p=0.048). As there was no differences in HD treatment characteristics, primery kidney disease or residual
diuresis we could conclude that positive energy balance (with an increase in prealbumin and
FTI) eventually led to better hemodynamic stability. ----- CONCLUSION: Our results show significant
effects of L-carnitine supplementation on lipid metabolism. Further clinical trials, as well as
experimental research are needed to define the role of lipid metabolism in CKD population.
Significant benefits of L-carnitine supplementation in patients with better initial serum albumin
levels suggest that this therapy should not be restricted to patients with the worst nutritional
and overall status
Association of polymorphic variants in serotonin re-uptake transporter gene with Crohn's disease: a retrospective case-control study
Get PDFAim: To analyze the distribution of SLC6A4 gene polymorphisms in Crohn's disease (CD) patients and their association with the disease.
Methods: We evaluated the presence/absence of promoter (5-HTTLPR, rs25531) and intron 2 (STin2 VNTR) polymorphic variants of SLC6A4 gene in a retrospective case-control study including 192 CD patients and 157 healthy controls (HC). Genotyping was performed by polymerase chain reaction. The association of polymorphisms with CD and its clinical subtypes was analyzed using χ2 and Fisher exact test, binary logistic regression, and haplotype analysis. Results:
CD patients and healthy controls had similar sex (88 [45.8%] vs 84 [53.5%] women, respectively; P=0.154) and age (41.3±12.8 years vs 41.7±8.8 years, respectively, P=0.091) distribution. Significant differences were observed in the STin2 genotype and allele distribution between CD patients and healthy controls (P=0.003 and P=0.002, respectively) and between the corresponding female subgroups (P=0.004 and P=0.007, respectively), with a significant negative association of biallelic ss (STin2.9 and Stin2.10) STin2 genotype with CD (P=0.013, age- and sex-adjusted odds ratio [OR] 0.5, 95% confidence interval [CI] 0.29-0.86; women: P=0.006, age-adjusted OR 0.32, 95% CI 0.14-0.72) and a significantly higher S-STin2.12 (5-HTTLPR/rs25531: S-STin2: STin2.12) haplotype distribution in CD patients (P=0.004, OR 1.62, 95% CI 1.16-2.26). There was no significant association between 5-HTTLRP and rs25531 genotype or allele frequencies and CD and between any SLC6A4 polymorphic loci with clinical CD subtypes. Conclusion: STin2 VNTR polymorphism of SLC6A4 gene may contribute to CD pathogenesis
Characterization of ADME genes variation in Roma and 20 populations worldwide
Get PDFThe products of the polymorphic ADME genes are involved in Absorption, Distribution, Metabolism, and Excretion of drugs. The pharmacogenetic data have been studied extensively due to their clinical importance in the appropriate drug prescription, but such data from the isolated populations are rather scarce. We analyzed the distribution of 95 polymorphisms in 31 core ADME genes in 20 populations worldwide and in newly genotyped samples from the Roma (Gypsy) population living in Croatia. Global distribution of ADME core gene loci differentiated three major clusters; (1) African, (2) East Asian, and (3) joint European, South Asian and South American cluster. The SLCO1B3 (rs4149117) and CYP3A4 (rs2242480) genes differentiated at the highest level the African group of populations, while NAT2 gene loci (rs1208, rs1801280, and rs1799929) and VKORC1 (rs9923231) differentiated East Asian populations. The VKORC1 rs9923231 was among the investigated loci the one with the largest global minor allele frequency (MAF) range; its MAF ranged from 0.027 in Nigeria to 0.924 in Han Chinese. The distribution of the investigated gene loci positions Roma population within the joined European and South Asian clusters, suggesting that their ADME gene pool is a combination of ancestral (Indian) and more recent (European) surrounding, as it was already implied by other genetic markers. However, when compared to the populations worldwide, the Croatian Roma have extreme MAF values in 10 out of the 95 investigated ADME core gene loci. Among loci which have extraordinary MAFs in Roma population two have strong proof of clinical importance: rs1799853 (CYP2C9) for warfarin dosage, and rs12248560 (CYP2C19) for clopidogrel dosage, efficacy and toxicity. This finding confirms the importance of taking the Roma as well as the other isolated populations`genetic profiles into account in pharmaco-therapeutic practice
The association of semaphorins 3C, 5A and 6D with liver fibrosis stage in chronic hepatitis C
Get PDFSemaphorins are a diverse family of immunoregulators recently recognized to play a major role in various phases of immune responses. Their role in chronic viral hepatitis C (CHC) and contribution to the progression of liver disease is unknown. The aim of this study was to analyse the association of secreted semaphorins with the severity of liver disease in patients with CHC. Serum concentrations of semaphorins were measured in 114 treatment-naive CHC patients and 36 healthy controls. Serum concentrations of SEMA3A, SEMA3C, SEMA5A, SEMA6B and SEMA6D were significantly increased in patients with CHC compared to controls. While serum concentrations of SEMA3C and SEMA6D significantly increased with fibrosis stage in both HCV-g1 and HCV-g3 infections, the concentration of SEMA5A inversely correlated with fibrosis stage in both HCV genotypes. ROC analysis showed that serum concentrations of SEMA3C (>4.0ng/mL, AUC 0.88) and SEMA6D (>4.5, AUC 0.82) had higher AUC than widely used APRI (AUC 0.71) and FIB-4 (AUC 0.74) scores. Serum concentrations of SEMA3C and SEMA6D significantly decreased after DAA and PEG IFN-α/ribavirin therapy, while the serum concentration of SEMA5A significantly increased after DAAs therapy. Immunohistochemistry confirmed the expression of SEMA3C and SEMA5A in hepatocytes, endothelial cells and lymphocytes of cirrhotic livers from CHC patients but not in controls. In conclusion, we provide the first evidence that SEMA3C, SEMA5A and SEMA6D can be considered as markers of liver injury in CHC
Treatment approach to type 2 diabetes: past, present and future
Get PDFType 2 diabetes mellitus (DM) is a lifelong metabolic disease, characterized by hyperglycaemia which gradually leads to the development and progression of vascular complications. It is recognized as a global burden disease, with substantial consequences on human health (fatality) as well as on health-care system costs. This review focuses on the topic of historical discovery and understanding the complexity of the disease in the field of pathophysiology, as well as development of the pharmacotherapy beyond insulin. The complex interplay of insulin secretion and insulin resistance developed from previously known "ominous triumvirate" to "ominous octet" indicate the implication of multiple organs in glucose metabolism. The pharmacological approach has progressed from biguanides to a wide spectrum of medications that seem to provide a beneficial effect on the cardiovascular system. Despite this, we are still not achieving the target treatment goals. Thus, the future should bring novel antidiabetic drug classes capable of acting on several levels simultaneously. In conclusion, given the raising burden of type 2 DM, the best present strategy that could contribute the most to the reduction of morbidity and mortality should be focused on primary prevention
Acute heart failure developed as worsening of chronic heart failure is associated with increased mortality compared to de novo cases
Get PDFAcute heart failure (AHF) emerges either de novo or from worsening of chronic heart failure (CHF). The aim of the present study was to evaluate the association between worsening of CHF and mortality in AHF patients. Out of 152 included AHF patients, 47 (30.9%) were de novo AHF patients and 105 (69%) were AHF patients with worsening of CHF. The proportion dying in hospital (19.0% vs. 4.3%, p = 0.023) and within 3 months after hospitalization (36.6% vs. 6.7%, p < 0.001) was significantly higher in AHF patients with worsening of CHF. Logistic regression analyses also showed a significant positive association of AHF emerging as worsening of CHF with hospital mortality [odds ratio (OR) and 95% confidence interval (CI): 5.29 (1.46-34.10), p = 0.029] and 3-month mortality [8.09 (2.70-35.03), p = 0.001]. While the association with hospital mortality was no longer significant after adjusting for comorbidities and clinical as well as laboratory parameters known to be associated with mortality in heart failure patients, the association with 3-month mortality remained significant. We conclude that compared to de novo AHF, AHF evolved from worsening of CHF is a more severe condition and is associated with increased mortality
A novel PGAP3 mutation in a Croatian boy with brachytelephalangy and a thin corpus callosum
Get PDFBiallelic mutations in the post-GPI attachment to proteins 3 (PGAP3) gene cause hyperphosphatasia with mental retardation syndrome 4 (HPMRS4), which is characterized by elevated serum alkaline phosphatase, severe psychomotor developmental delay, seizures, and facial dysmorphism. To date, 15 PGAP3 mutations have been reported in humans. Here we report a novel homozygous PGAP3 mutation (c.314C>A, p.Pro105Gln) in a Croatian patient and fully describe the clinical features
Leptin/adiponectin ratio in overweight patients – gender differences
Get PDFOBJECTIVE:
Obesity-related atherosclerosis is a systemic disease with a background connected to multiple metabolic-neurohumoral pathways. The leptin/adiponectin ratio has been suggested as an atherosclerotic marker in obese patients. The aim of this study was to assess (1) the significance of the L/A ratio in overweight subjects, (2) the relation with anthropometric/metabolic parameters and (3) gender difference. ----- METHOD:
The study included 80 adult males and females, overweight, non-diabetic patients. Biochemical blood analysis and anthropometric and cardiovascular measurements were performed. Serum leptin levels were measured with a radioimmunoassay test and total adiponectin levels with enzyme-linked immunosorbent assay. Leptin/adiponectin ratios were calculated as ratios between total serum concentrations of leptin and adiponectin. ----- RESULTS:
Differences between leptin, adiponectin serum levels and leptin/adiponectin ratios are presented in overweight persons, where females have a significantly higher leptin/adiponectin ratio than men ( p < 0.001). In men, the leptin/adiponectin ratio showed a positive correlation with total cholesterol levels ( p = 0.011), low-density lipoprotein ( p = 0.013) and triglycerides ( p = 0.032). In females, the leptin/adiponectin ratio correlated with anthropometric parameters of visceral obesity: waist circumference ( p = 0.001) and waist-to-hip ratio ( p = 0.025). ----- CONCLUSION:
The leptin/adiponectin ratio could represent an atherosclerotic risk marker of the early stage of obesity. Gender plays a significant role in pathophysiological changes, with different clinical manifestations, where sex hormones have a crucial effect on neurohumoral adipose tissue activity