Comparative research on substance abuse and self-perception among adolescents with physical handicap

The research on substance (alcohol, tobacco and drug) abuse and on self-perception was done by comparing a test group of physically disabled adolescents and a test group of non-disabled adolescents. The respondents of the experimental group were students of the only special high school for physically handicapped persons in Croatia, Zagreb. The respondents of the control group were the students of two regular high schools in the capital of Croatia. The instrument used in this research was a self-reported, anonymous questionnaire. The respondents completed the questionnaire in the classroom. The data analysis regarding alcohol abuse indicated that physically disabled adolescents drink more often and out of quite different motives than their non-disabled peers. Regarding the prevalence, frequency, quantity and motives for smoking, no statistically significant difference has been found between the tested groups. On the contrary, significant differences between handicapped and non-disabled adolescents were evident regarding drug abuse. Only one physically disabled examinee used a drug--marijuana, only a few times a year. On the other hand, almost one quarter of the non-disabled adolescents use at least one, five at the most, type of drug sometimes or often. The results on the self-perception scale show that adolescent with physical disabilities have a much more negative attitude toward themselves than non-disabled controls. Their self-esteem and self-confidence are seriously diminished. Described findings could have a mighty impact on ways of preventing substance abuse, and on ways of increasing self-esteem among disabled and non-disabled adolescents.     

The effectiveness of a 40-year long iodine prophylaxis in endemic goitre region of Grobnik, Croatia

The region of Grobnik, in the north west of Croatia, 15 km away from the Adriatic coast and 400 meters above the sea level, used to be known as a centre of endemic goitre. Iodine prophylaxis of 10 mg KJ added per kilo salt started in Croatia during the year 1953 and it was increased to 25 mg KJ per kilo in 1996. During 1961, the prevalence of goitre among Grobnik school children was 63%, while in the adult population it was 34%. In 1981, 18% of goitrous school children and 11% of goitrous adults were found in the same region, which shows the fall in goitre prevalence in the twenty-year period, from a severe to a mild one. The aim of this study was to estimate the effectiveness of iodine prophylaxis in goitre eradication and to compare the obtained results to those found in the same region 20 and 40 years ago, namely, in 1961 and 1981. The research was conducted in 2001. We examined 472 Grobnik inhabitants, 378 children (196 girls and 182 boys, aged 7-15 years) and 94 adults. Regarding their size thyroid glands were graded according to WHO and PAHO classification. Data regarding lifestyles and health conditions were collected by individual and family questionnaires. The prevalence of goitre in 2001 was 6.6% in school children and 6.4% in adults. In relation to 1981, we found a statistically significant fall of goitre in school children at the level of p < 0.01 (chi2 = 23.65), but the prevalence change was not statistically significant in adults (p > 0.01, chi2 = 1.419). The frequency of thyroid gland hereditary diseases in native inhabitants was high, 11.7%. There were no statistically significant differences in the prevalence of goitre or thyroid hereditary diseases between groups of native and newcomers' children. According to our results, in the year 2001 the area of Grobnik was still was a region of a mildly expressed endemic goitre. This study presents final results of a 40-year long follow up of endemic goitre eradication, demonstrating the long-term effectiveness of iodine prophylaxis.     

Minimized combinatorial CRISPR screens identify genetic interactions in autophagy

Combinatorial CRISPR-Cas screens have advanced the mapping of genetic interactions, but their experimental scale limits the number of targetable gene combinations. Here, we describe 3Cs multiplexing, a rapid and scalable method to generate highly diverse and uniformly distributed combinatorial CRISPR libraries. We demonstrate that the library distribution skew is the critical determinant of its required screening coverage. By circumventing iterative cloning of PCR-amplified oligonucleotides, 3Cs multiplexing facilitates the generation of combinatorial CRISPR libraries with low distribution skews. We show that combinatorial 3Cs libraries can be screened with minimal coverages, reducing associated efforts and costs at least 10-fold. We apply a 3Cs multiplexing library targeting 12,736 autophagy gene combinations with 247,032 paired gRNAs in viability and reporter-based enrichment screens. In the viability screen, we identify, among others, the synthetic lethal WDR45B-PIK3R4 and the proliferation-enhancing ATG7-KEAP1 genetic interactions. In the reporter-based screen, we identify over 1,570 essential genetic interactions for autophagy flux, including interactions among paralogous genes, namely ATG2A-ATG2B, GABARAP-MAP1LC3B and GABARAP-GABARAPL2. However, we only observe few genetic interactions within paralogous gene families of more than two members, indicating functional compensation between them. This work establishes 3Cs multiplexing as a platform for genetic interaction screens at scale.     

Lacustrine basin to delta evolution in the Zagorje Basin,a Pannonian sub-basin (Late Miocene: Pontian,NW Croatia)

Pontian deposits of the Zagorje Basin constitute a coarsening-upward succession, which reflects the infilling style of this Pannonian sub-basin, i.e. the progradation of clastic systems into the brackish lake. Six facies differentiated correspond to lake floor, channelled slope, distal and proximal pro-delta, distal and proximal mouth bars, and lagoon/bay to swamp and alluvial environments. The deposition in the mouth-bar area was dominated by frictional forces. The upper-stage plane-bed sands are the main mouth-bar facies, which is uncommon in the geological record. The main factors for the origin of such bars include an abundant sand supply by the high-energy fluvial system(s), low-energy of the receiving basin and shallow depositional depth. Prolonged, catastrophic floods generated sustained hyperpycnal flows, which bypassed the mouth-bar area and fed the slope/pro-delta. The high ratio between sediment supply and subsidence rate resulted in a fast moving progradational wave, which involved the entire SW Pannonian Basin, including the Zagorje Basin.     

Differential diagnostic relevance of high resolution magnetic resonance in patients with possible multiple system atrophy (MSA) - A case report

Multiple system atrophy (MSA) is sporadic, progressive neurodegenerative disorder characterized clinically by autonomic dysfunction, Parkinsonism (MSA-P), and cerebellar ataxia (MSA-C) in any combination. Parkinsonism is present in the majority of patients (80%). Early in the course of the disease autonomic dysfunctions are present in approximately 40% of patients, while the domination of cerebellar symptoms is present in 20% of all patients. According to second consensus statement on diagnosis of MSA, to make the diagnosis of possible MSA, except Parkinsonism or a cerebellar syndrome, there must be one feature involving autonomic dysfunction plus one other additional that can include findings on history, clinical examination or changes in structural or functional imaging. We present a case of 60-year old male with Parkinsonism and cerebellar symptoms accompanied with signs of autonomic nervous system involvement. Level of autonomic dysfunction was not the level required for the diagnosis of probable MSA. On initially performed 1.5T MRI, the most prominent neurodegenerative feature of brain stem, cerebellum and basal ganglia was atrophy, however features like "hot-cross bun" sign, "slit-like" putaminal rim and middle cerebellar peduncle hyperintensities were detected only after MR imaging on higher resolution (3T) device. Our case points to the possibility that some typical structural changes that can help in diagnostic process may not be clearly visible on 1.5 T MRI devices. In such cases we suggest using 3T MRI device, if feasible, in order to demonstrate findings that may help in establishing the diagnosis of possible MSA.     

Henoch-Schönlein purpura complicated by appendicitis, intussusception and ureteritis

Henoch-Sch?nlein purpura (HSP) is the most common childhood systemic small-vessel vasculitis with skin, joint, gastrointestinal (GI) and renal involvement. Uncommon GI complications are intussusception, bowel perforation and rarely reported appendicitis. HSP-associated stenosing ureteritis represents a rare and potentially serious complication. We present a 5-year-old boy with severe and prolonged course of HSP and three very rare complications that occurred sequentially: appendicitis, intussusception and ureteritis. Only three days after admission, he developed clinical signs of acute appendicitis indicating surgical intervention. Histological analysis of excised appendix showed inflammation but without signs typical for vasculitis. Two weeks later, with the reccurence of HSP he again developed clinical picture of acute abdomen. Ultrasound and radiologic evaluation demonstrated ileo-ileal intussusception and the second laparotomy was undertaken. Histological analysis of the resected bowel tissue showed typical signs of leucocytoclastic vasculitis. In the fourth week of his illness, serial urinalysis showed nephritic urinary sediment indicative of renal involvement. Unexpectedly, control abdominal ultrasound demonstrated mild hydronephrosis of the left kidney, not seen on previous ultrasound evaluations. Undertaken excretory urography and computed tomography (CT) scan showed stenosis of upper/ midureter with mild dilation of upper part of the left ureter suggesting unilateral HSP-associated stenosing ureteritis. Eventually, the patient was discharged and closely followed-up for the next two years. He had no further reccurence of HSP, the urinalysis normalized after six months, while mild unilateral hydronephrosis remained unchanged. Our search of the literature did not show reports of HSP complicated by appendicitis, intussusception and ureteritis, and to our knowledge this is the first case with three different illness events that occured sequentially. We emphasize the necessity of repeated ultrasound evaluations in the course of HSR especially in cases with severe GI and renal invovement.     

Chain Assembly and Disassembly Processes Differently Affect the Conformational Space of Ubiquitin Chains

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