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Background The most common lysosomal storage disorder is Gaucher disease (GD). It is a deficiency of lysosomal glucocerebrosidase (GBA) due to biallelic mutations in the GBA gene, characterized by the deposition of glucocerebroside in macrophage-monocyte system cells. The report targets clinical phenotypes of GD in order to correlate them with GBA gene mutations, as well as to identify GBA gene mutation in patients in Montenegro that are diagnosed with GD. Cases summary Five patients (4 male, 1 female) of type 1 GD (GD1) are reported. The age at diagnosis ranged from 7 to 40. Patients experienced delays of 1-12 years in diagnosis after the original onset of symptoms. The most common mode of presentation was a variable degree of splenomegaly and thrombocytopenia, while other symptoms included bone pain, hepatomegaly, abdominal pain and fatigue. Osteopenia was present in a majority of the patients: 4/5. All patients were found to have an asymptomatic Erlenmeyer flask deformity of the distal femur. On enzyme replacement therapy (ERT), the hematological and visceral parameters showed significant improvement, but no significant progression in bone mineral density was noticed. GBA gene sequencing revealed homozygosity for the N370S mutation in one patient. The genotypes of the other patients were N370S/55bp deletion, N370S/D409H (2 patients), and H255Q/N370S (1 patient). Conclusion The phenotypes of the GD1 encountered in Montenegro were severe but all responded well to ERT.

BACKGROUND Leiomyosarcoma (LMS) of the thyroid gland is a rarely presented tumor that offers poor prognosis. To the best of the authors’ knowledge, there currently exist only 28 known cases described in the literature (limited to English). CASE SUMMARY Herein a case is reported of a 60-year-old female patient who had an LMS of the thyroid, which was accompanied by periodic dysphonia and breathing disorder as well as the feeling of pressure in the chest and neck. At the time the disease was diagnosed, no metastases were detected. Prior to the diagnosis, the patient experienced a uterine adenocarcinoma that had been treated by surgical procedure and radiotherapy. For the LMS, a total thyroidectomy was performed, followed by radiotherapy. Since metastases were also discovered in the lungs, sternum, and femur, chemotherapy was administered as well. Immunohistochemically, the tumor cells in the thyroid indicated positively for alpha smooth muscle actin, calponin, and H-caldesmon, but were negative for CD34, p63, estrogen receptor, progesterone receptor, and Epstein-Barr virus. CONCLUSION Although the etiology of the LMS is as of yet unknown, prior malignancy and radiation should be considered as risk factors.

Introduction/Objective. Cardiovascular diabetic autonomic neuropathy (CDAN) mainly affects heart rhythm through sympathovagal imbalance. The objective of the study is to determine CDAN risk potential regarding electrical complications of acute myocardial ischemia (AMI), including admission glucose profile levels (AGP). Methods. Seventy-six patients suffering from type 2 diabetes mellitus were divided into two age-matched groups related to the presence of CDAN, and the influence of AGP on electrical complications was estimated. Ewing?s tests were used for diagnosis of CDAN. Results. Patients without CDAN have 42.86% risk for developing electrical complication into early post-AMI period. If it is a pre-existing condition, the risk is 63.64%, which is obvious, but not statistically significant. Considering the AGP, levels above 12.25 mmol/L as predictive for post-AMI electrical complications, in CDAN-positive patients with AGP levels above that cut-off value, the risk for electrical complications is raising up to 73.68%. The patients with CDAN who have AGP levels above the cut-off value have statistically higher risk for development electrical complications than those with lower levels (Z = 2.58, p < 0.01). On the other side, those without CDAN and with level of AGP lower than 12.25 mmol/L, the risk for electrical complications developing is as low as 23.08%. Conclusion. CDAN may be an important independent risk factor for electrical complications in postmyocardial ischemia period.

Overhead line energization can be performed under normal or faulty conditions. The latter indicates an occurrence of a fault along the line that exists at the moment of energization. This can lead to significant over-voltages that could endanger proper line operation. The issue gets more complex to protective devices when it comes to high-resistance faults, which impair the ability of relays to react promptly and accurately. Consequently, installation of additional detection devices becomes necessary. This paper proposes a novel method that properly detects and classifies line operating conditions at the moment of energization. The method is designed to be useful for utilities and it can be considered as a low-cost, fast, and accurate detection and classification approach, suitable for dealing with both low-resistance and high-resistance faults. Through comprehensive mathematical modeling it was found that both normal and faulty conditions during line energization are accompanied by the zero-seque...

Introduction: The prevalence of idiopathic hypercalciuria (IH) in healthy pediatric population ranges from 3.0% to 7.0%. There is insufficient data about IH in children with mono-symptomatic enuresis. The aim of this study was to examine calcium excretion in urine (UCa) in patients with primary mono-symptomatic nocturnal enuresis (PMNE). Methods: In patients with PMNE, aged 5 to 17 years, IH was determined in 24-h urine and from second morning spot urine. The completeness of the 24-h urine collections was estimated via measuring 24h-urine creatinine excretion (UCr) of 0.1-0.2 mmol/kg/24h. Results: Sixty patients with PMNE, 32 males and 28 girls, median age of 9 years were enrolled in the study. Only 41.7% patients successfully completed 24 h urine collection. IH, defined as 24-h UCa > 0.1 mmol/kg body weight, was diagnosed in 12% of the patients, while when defined as UCa/UCr > 0.8 mmol/mmol in children 5-7 years and > 0.6 mmol/mmol in those > 7 years, IH was 8.3% and 6.7% from 24hurine and spot urine, respectively. Conclusion: Children and adolescents with PMNE are in risk of hypercalciuria. Therefore, it is useful to examine 24 hours of urine calcium excretion in these patients.

Introduction: The concept of subclinical thyroid disease appeared in the 1980s when sensitive procedures for the measurement of the thyroid-stimulating hormone in the serum were introduced. Subclinical hypothyroidism is defined by the finding of elevated serum TSH concentrations with normal thyroid hormone levels. The incidence of subclinical hypothyroidism with increased cardiovascular risk has not yet been fully clarified. The aim of the study was to identify anthropometric parameters that may indicate an increased cardiometabolic risk in patients with subclinical hypothyroidism. Method: The study will include 140 patients aged 18-65, with 105 patients with subclinical hypothyroidism and a control group of 35 healthy, normally nourished subjects without subclinical hypothyroidism. A program of research will be carried out in all patients and it will include: detailed anamnesis and physical examination, anthropometric measurements (weight measurements, body height, waist circumference, hip circumference, body weight mass measurement by the bioelectrical impedance analysis method (%BFP), calculation of: body mass index (BMI), waist-to-hip circumference ratio (WC/HC), waist-to-height ratio (WC/Ht) and laboratory testing (FT3, FT4, TSH). Results: Examinees with subclinical hypothyroidism had statistically significantly elevated mean TSH values (6.87 + 1.34 mIU/ml) compared to TSH euthyroid examinees (1.9 + .88 mIU/ml). The mean age of subjects with subclinical hypothyroidism was 44.15 ± 11.23 years (MA = 43 years), and in subjects without subclinical hypothyroidism, 33.80 ± 10.60 years (MA = 33 years). In relation to the control group (euthyroid patients), patients with subclinical form of hypothyroidism had higher average mean values and statistically significantly higher incidence of elevated values: BMI (T test = 7.465, p < 0.0001; 2 = 35.977, p < 0.0001), %BFP (T test = 8.594, p < 0.0001; 2 = 44.956, p < 0.0001), WC (T test = 6.262, p < 0.0001; 2 = 48.865, p < 0.0001), and WC/Ht ratio (T test = 7.372, p < 0.0001; 2 = 39.175, p < 0.0001). The WC/HC ratio in the group with subclinical hypothyroidism was higher than in the group without subclinical hypothyroidism, but not statistically significant (T test = -0.946, p = ns; 2 = 0.622, p = 0). Conclusion: In the subclinical form of hypothyroidism, changes in the degree of nutrition and body weight can already be recorded, which, among other things, contributes to the development of increased cardiometabolic risk.

Prevalence of cognitive function decline in end stage renal disease (ESRD) patients undergoing hemodialysis is higher than in the general population. We analyzed risk factors for cognitive function decline in those patients. This study included 93 ESRD patients undergoing hemodialysis two or three times a week in three centers for hemodialysis in Montenegro. The cognitive status of patients was assessed using the mini mental score examination (MMSE) test. All 93 patients have been divided into three groups according to the results of MMSE. Patients in the first group had severe cognitive impairment and MMSE score below 17 (26.88%), patients in the second group with MMSE score 18-23 had moderate cognitive impairment (40.86%) and third group of patients have MMSE >24 and no cognitive impairment (32.26%). There were no significant differences between groups for gender, smoking habits and level of parathyroid hormone. Level of schooling was significantly different between groups of patients (P

Gaucherova bolest (GB) je redak autozomno recesivni nasledni poremecaj nastao kao defekt u sintezi enzima glukocerebrozidaze (GBA), sto uzrokuje manjak ili potpuni nedostatak aktivnosti tog enzima. Glavna karakteristika bolesti je nakupljanje glikosfingolipida glukozilceramida (GL-1) i glikozilsfingozina (LysoGL-1) u lizozomima mononuklearnih fagocita, a mutacije u GBA genu manifestuju se razlicitom klinickom prezentacijom. Kostane manifestacije u klinickoj prezentaciji pacijenata sa GB su ceste kod tipa I i III GB, a javljaju se u vise oblika kao: deformiteti, kostani infarkt, avaskularna nekroza, osteoskleroza i frakture nastale kao posledica osteopenije i osteoporoze, retko akutni osteomijelitis. Kao glavne terapijske opcije prepoznate su primena enzimske terapije i terapija redukcijom supstrata, a bitno mesto zauzimaju i primena biofosfonata, hormonske supstitucione terapije, raloksifena, kalcitonina, stroncijum-ranelata, paratiroidnog hormona. Ortopedske intervencije takođe imaju svoje mesto u terapiji kostanih manifestacija GB, dok je pokazano da splenektomija ima negativan dugorocni uticaj na kostane manifestacije u GB. Patofizioloski mehanizam nastanka kostanih manifestacija u GB jos uvek je nedovoljno razjasnjen, a iste imaju za posledicu smanjenje funkcijske sposobnosti i kvaliteta života pacijenta. Rana dijagnoza kostanih promena u pacijenata sa GB kljuc je za dobre terapijske odluke i sto raniju primenu istih.

Prevalence of cognitive function decline in end stage renal disease (ESRD) patients undergoing hemodialysis is higher than in the general population. We analyzed risk factors for cognitive function decline in those patients. This study included 93 ESRD patients undergoing hemodialysis two or three times a week in three centers for hemodialysis in Montenegro. The cognitive status of patients was assessed using the mini mental score examination (MMSE) test. All 93 patients have been divided into three groups according to the results of MMSE. Patients in the first group had severe cognitive impairment and MMSE score below 17 (26.88%), patients in the second group with MMSE score 18-23 had moderate cognitive impairment (40.86%) and third group of patients have MMSE24 and no cognitive impairment (32.26%). There were no significant differences between groups for gender, smoking habits and level of parathyroid hormone. Level of schooling was significantly different between groups of patients (P 0.001). Laboratory markers observed in this study with significant differences between groups were: IGF 1, IGFBP 3, erythrocytes and hemoglobin (P 0.001, P = 0.004, P 0.001, P = 0.002, respectively). IGF 1 proved to be of great importance for evaluating cognitive status in our study. This marker was statistically different between groups (P 0.001) and Tukey post hoc analysis showed significant differences between all three groups (first and second group P = 0.045, second and third group P = 0.015, first and third group P 0.001). Our data suggest that IGF 1 can be considered as novel biomarker for assessment of cognitive functioning in CKD patients, which can be of huge clinical importance.

Objective: The aim of the study was to determine a correlation between the level of 25-hydroxivitamin D (25-OHD) and the incidence of diabetes. Subjects and Methods: In this prospective observational study, 97 (out of an initial 100) Caucasian women with osteoporosis (OS) were monitored for 2 years for the incidence of diabetes. Logistic regression analysis was used to establish an association with and prognostic value of vitamin D for the onset of type 2 diabetes mellitus, as well as insulin resistance, body mass index (BMI), total cholesterol and triglyceride levels in the development of diabetes. The serum level of 25-OHD was measured using immunochemiluminescence in March and April 2011. Results: Of the 97 patients (mean age 51.64 ± 5.86 years, range 36.0-73.0), 21 (21.65%) were diagnosed with diabetes during the observational period. The study showed that the 22 patients with low levels of vitamin D were more susceptible to diabetes (odds ratio = 0.958). The cut-off value of vitamin D using a receiver operating characteristic curve was 62.36 nmol/l with a sensitivity of 39.5% and a specificity of 90.5%. With an increase in BMI and triglyceride levels, women were, respectively, 1,591 and 2,821 times more likely to get diabetes than those without an increase. Conclusion: This study showed that the patients with postmenopausal OS and hypovitaminosis D, besides a high BMI, elevated triglyceride levels and insulin resistance, had an increased risk of developing type 2 diabetes.

International audience; People are at higher risk of cancer as they get older or have a strong family history of cancer. The potential influence of environmental and behavioral factors remains poorly understood. Earlier population and case control studies reported that upper quartile of circulating IGF-I is associated with a higher risk of developing cancer suggesting possible involvement of the growth hormone (GH)/IGF system in initiation or progression of cancer. Since GH therapy increases IGF-1 levels, there have been concerns that GH therapy in hypopituitarism might increase the risk of cancer. We report a 42-year-old female patient who presented with subacute onset of symptoms of meningitis and with the absence of fever which resulted in death 70 days after the onset of symptoms. The patient together with her younger brother was diagnosed at the age of 5 years with familial congenital hypopituitarism, due to homozygous mutation c.150delA in PROP1 gene. Due to evolving hypopituitarism, she was replaced with thyroxine (from age 5), hydrocortisone (from age 13), GH (from age 13 until 17), and sex steroids in adolescence and adulthood. Her consanguineous family has a prominent history of malignant diseases. Six close relatives had malignant disease including her late maternal aunt with breast cancer. BRCA 1 and BRCA 2 mutational analysis in the patient's mother was negative. Histology after autopsy disclosed advanced ovarian cancer with multiple metastases to the brain, leptomeninges, lungs, heart, and adrenals. Low circulating IGF-1 did not seem to protect this patient from cancer initiation and progression in the context of strong family history of malignancies.

The aim of this study was to compare intrahospital and long-term mortalities after more than 10 years of the follow up after the first acute myocardial infarction (AMI) with patients with and without CDAN and without diabetes mellitus (DM). Methods: The study was based on 76 (43 men and 33 women) with DM type 2, CDAN was detected in 51 patients, and 374 (295 men and 79 women) without DM consecutively hospitalized with the first-ever AMI from January 1998. to December 2000. in Clinical Center of Montenegro Podgorica. Patients were followed until December 31. 2011. CDAN was searched for by standardized five tests evaluating heart rate and blood pressure variations. Results: Intrahospital mortality was presented in 10. 53 % diabetic patients and 5. 61 % nondiabetic patients, this difference is significant (p=0.048). Long-term mortality was presented at 24 (82. 75%) patients with CDAN and 5 (17. 25%) patients without CDAN (p=0.029). Long term mortality rate was significantly higher in diabetic patients 29 (42. 64 %) than in nondiabetic patients 102 (30. 72 %) (p=0.012). Conclusion: Intrahospital mortality was significantly higher in diabetic than in nondiabetic patients. Identically the mortality after more than 10 years of the follow up after the first AMI was significantly higher in diabetic with, than in diabetic patients without CDAN, as in diabetic than in nondiabetic patients.