Hypomyelination with atrophy of the basal ganglia and cerebellum is a rare leukoencephalopathy that was identified using magnetic resonance imaging in 2002. In 2013, whole exome sequencing of 11 ...patients with the disease revealed that they all had the same de novo mutation in TUBB4A, which encodes tubulin β-4A. We investigated the mutation spectrum in a cohort of 42 patients and the relationship between genotype and phenotype. Patients were selected on the basis of clinical and magnetic resonance imaging abnormalities that are indicative of hypomyelination with atrophy of the basal ganglia and cerebellum. Genetic testing and a clinical inventory were performed, and sequential magnetic resonance images were evaluated using a standard protocol. The heterozygous TUBB4A mutation observed in the first 11 patients was the most common (25 patients). Additionally, 13 other heterozygous mutations were identified, located in different structural domains of tubulin β-4A. We confirmed that the mutations were de novo in all but three patients. In two of these three cases we lacked parental DNA and in one the mutation was also found in the mother, most likely due to mosaicism. Patients showed a phenotypic continuum ranging from neonatal to childhood disease onset, normal to delayed early development and slow to more rapid neurological deterioration. Neurological symptomatology consisted of extrapyramidal movement abnormalities, spasticity, ataxia, cognitive deficit and sometimes epilepsy. Three patients died and the oldest living patient was 29 years of age. The patients' magnetic resonance images showed an absent or disappearing putamen, variable cerebellar atrophy and highly variable cerebral atrophy. Apart from hypomyelination, myelin loss was evident in several cases. Three severely affected patients had similar, somewhat atypical magnetic resonance image abnormalities. The study results were strongly suggestive of a genotype-phenotype correlation. The 25 patients with the common c.745G>A mutation generally had a less rapidly progressive disease course than the 17 cases with other TUBB4A mutations. Overall, this work demonstrates that the distinctive magnetic resonance imaging pattern for hypomyelination with atrophy of the basal ganglia and cerebellum defines a homogeneous clinical phenotype of variable severity. Patients almost invariably have prominent extrapyramidal movement abnormalities, which are rarely seen in patients with hypomyelination of different origin. A dominant TUBB4A mutation is also associated with dystonia type 4, in which magnetic resonance images of the brain seem normal. It is highly likely that there is a disease continuum associated with TUBB4A mutations, of which hypomyelination with atrophy of the basal ganglia and cerebellum and dystonia type 4 are the extremes. This would indicate that extrapyramidal movement abnormalities constitute the core feature of the disease spectrum related to dominant TUBB4A mutations and that all other features are variable.
This study investigated the detailed volatile aroma profile of young white wines of Maraština,
L., produced by spontaneous fermentation. The wines were produced from 10 vineyards located in two ...Dalmatian subregions (Northern Dalmatia and Central and Southern Dalmatia). Volatile compounds from the wine samples were isolated by solid-phase extraction (SPE) and analyzed by an untargeted approach using two-dimensional gas chromatography coupled with time-of-flight mass spectrometry (GC×GC/TOF-MS) and a targeted approach by gas chromatography-tandem mass spectrometry (GC-MS/MS). A comprehensive two-dimensional GC×GC analysis detailed the total volatile metabolites in the wines due to its excellent separation ability. More than 900 compounds were detected after untargeted profiling; 188 of them were identified or tentatively identified. A total of 56 volatile compounds were identified and quantified using GC-MS/MS analysis. The predominant classes in Maraština wines were acids, esters, and alcohols. The key odorants with odor activity values higher than one were
-damascenone, ethyl caprylate, ethyl isovalerate, ethyl 2-methylbutyrate, ethyl caproate, isopentyl acetate, ethyl butyrate, and phenylacetaldehyde. The metabolomics approach can provide a large amount of information and can help to anticipate variation in wines or change winemaking procedures.
BACKGROUNDDue to excessive concerns and focus on weight control and body shape, adolescents often resort to inappropriate behaviours and attitudes towards eating, resulting in physical and ...psychological issues. This study aimed to assess possible relationships and predictor variables between disordered eating and age, BMI, body appreciation, self-esteem, quality of family interactions, psychosocial health and childhood trauma experience in adolescents of both sexes in the city of Mostar (Bosnia and Herzegovina). MATERIALS AND METHODSA cross-sectional study was carried out on a suitable sample of 724 high-school students aged 14-19 years. The following tools have been used: socio-demographic questionnaire, The Eating Attitudes Test (EAT-26), Body Mass Index (BMI), Body Appreciation Scale (BAS), Rosenberg's Self-Esteem Scale, Quality of Family Interaction Scale (KOBI), and Paediatric Quality of Life Inventory, version 4.0 (PedsQLTM) and Childhood trauma Questionnaire (CTQ). Collected data were analyzed in SPSS v. 20.0 software using Pearson's correlation coefficient and multiple regression analysis. RESULTSBody appreciation is the most significant predictor for developing disordered eating across the entire sample of adolescents (β = -0.325, P < 0.05) and individually for male adolescents (β = -0.199, P = 0.010) and female adolescents (β = -0.379, P < 0.001). In addition to this variable, BMI has proved to be a statistically significant predictor in explaining the eating behaviours of female adolescents (β = 0.185, P < 0.001), while this happens to be self-esteem for male adolescents (β = -0.211, P < 0.022). CONCLUSIONThe most significant risk factors for developing disordered eating in adolescents are body appreciation, BMI and self-esteem. Results of this research can contribute to enhancement of intervention programmes which promote a positive body image and aim to prevent disordered eating in adolescents of both sexes.
BACKGROUND:Congenital cytomegalovirus infection (cCMV) is a leading cause of sensorineural hearing loss (SNHL) and neurodevelopmental disabilities in developed countries. Although high cCMV rates ...have been reported in populations with high seroprevalence, the cCMV prevalence in low/middle-income countries in Europe has not been defined.
OBJECTIVE:To determine cytomegalovirus (CMV) seroprevalence and the cCMV prevalence in Bosnia and Herzegovina.
METHODS:Between March 2010 and February 2019, 5222 sera samples from patients seen at the University Clinical Hospital Mostar were tested for CMV IgG. The cord blood samples collected from 2091 infants between July 2011 and January 2013 were analyzed for CMV IgG and CMV DNA. The cCMV prevalence was determined by testing saliva swabs from 1293 infants between November 2015 and October 2016.
RESULTS:The overall CMV IgG prevalence was 81.4% (95% confidence interval0.8–0.82). Significantly higher prevalence was observed among females (84.9%) than in males (77.0%), and the rate increased from 50.8% in the 1 to 5 years group to 97.7% in the group > 65 years old. Most cord blood samples (2091/1925, 92.1%) were CMV IgG positive, and 2 (0.1%) were CMV DNA positive. Of the 1293 saliva swabs, 8 (0.62%; 95% confidence interval0.3–1.2) were CMV positive. All 8 infected infants had asymptomatic cCMV, and none had SNHL at 18 months of age.
CONCLUSIONS:In a highly CMV seropositive population, the prevalence of cCMV was lower compared with that reported from other low/middle-income countries populations. None of the infected infants had symptomatic infection or SNHL at 18 months.
Introduction:
In early 2021, the European Collaborative Haemophilia Network (ECHN) conducted a survey to determine whether the paradigms of care across the European region have changed with the ...introduction of novel therapies for people with hemophilia.
Methods:
We conducted a survey in 19 ECHN centers from 17 countries in the European region. The aim was to track recent changes in the hemophilia treatment landscape, determine the impact of these changes on hemophilia treatment centers and comprehensive care centers in the region, and to look into the future of care as applied to people with hemophilia. The survey was structured to include three key areas: demographics and organization; current challenges and opportunities; and future directions.
Discussion:
Our survey provides a snapshot of the current approach to hemophilia treatment that highlights a move toward preventive, rather than reactive care, but that also raises a number of key concerns related to costs and accessibility (particularly as related to novel therapies), time limitations for clinical research, and ongoing issues regarding human resources (particularly in terms of new doctors entering the field) and availability of laboratory resources as the use of novel therapies (some with unique modes of action and unusual adverse events, some with specialized monitoring requirements) becomes commonplace.
Conclusion:
While our survey suggests that specialized care will continue to play a central role in the management of hemophilia, the standards and protocols, as well as the centers themselves, will have to continue to evolve if they are to continue to provide the highest level of care. To meet this requirement, there is a clear need for engaging, ongoing education programs for healthcare professionals working in the field of hemophilia that can be adjusted to the changing landscape of hemophilia therapy and monitoring.
Lipids are a diverse group of organic compounds that serve essential roles due to their biological functions for all prokaryotic and eukaryotic organisms. Despite the fundamental role of lipid class ...in plants, there is still a relatively low level of knowledge regarding the composition of grape lipids. This research represents the first investigation into the lipids of the Croatian grape variety ‘Maraština’ (Vitis vinifera L.), employing a targeted approach and the UHPLC-MS/MS method to conduct a comprehensive analysis of the lipid profile of grape skins. The study investigated the profile of free fatty acids, glycerolipids, glycerophospholipids, triterpenoids, sphingolipids, and free fatty acid esters in eleven vineyards located along the cultivation area of ‘Maraština’ variety (Dalmatia, Croatia). Grape skins from vineyards that were exposed to more sunlight and higher daily temperature during the vegetation period mainly resulted in a richer profile of free fatty acids. Among lipids, ‘Maraština’ grape skins were characterized mainly by a triterpenoid compound; oleanolic acid (249.49 µg/g of FW), and free fatty acids, especially palmitic acid C16:0 (26.09 µg/g of FW), and lignoceric acid C24:0 (12.40 µg/g of FW). Hierarchical clustering analysis represented valuable insights into the diversity of lipids in ‘Maraština’ grape skin.
Objective A rise in infections with multidrug-resistant Pseudomonas aeruginosa (MDR-PA) is a significant contributor to increased morbidity and mortality of patients with hematologic malignancies. ...The aim of this study was to determine the efficacy and safety of colistin (colistimethate sodium) in the treatment of serious infections caused by MDR-PA in these patients. Patients and Methods A matched pair analysis of renal function, toxicities, and outcome of 26 patients receiving colistin and control subjects was done. All patients had clinical signs of sepsis; P. aeruginosa was isolated from blood in 69% of patients in colistin group and 84% in control group. Patients treated with colistin received 3 million units every 8 hours for a median duration of 13 days. Additionally, patients received at least two additional antimicrobial or antifungal drugs. Results Resolution of infection was achieved in twenty patients (76.9%) receiving colistin and in 17 (65.4%) control subjects. Mortality rate was 11% in both groups. There was no statistically significant difference in the level of serum creatinine, creatinine clearance, or potassium levels before and after treatment between groups. Only one patient receiving colistin developed de novo renal failure and one displayed transient neurologic toxicity. Conclusion Our results suggest that in patients with hematologic malignancies, colistin is effective in treating severe infections caused by MDR-PA while maintaining an acceptable toxicity profile. Prospective randomized studies comparing efficacy and safety of colistin with those of other antipseudomonal drugs are needed.
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