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Background: Higher levels of thyroid autoantibodies in follicular fluid (FF) of thyroid autoimmunity (TAI) positive women are strongly correlated with serum levels and may have effect on the post-implantation embryo development. Literature highlights that levothyroxine (LT4) treatment may attenuate the risk of adverse pregnancy outcomes. The aim of the study was to estimate the pregnancy and newborn outcomes in women with FF thyroid autoantibodies undergoing assisted reproductive technology (A RT). Methods: The study population included 24 women with confirmed clinical pregnancy, 8 TAI positive and 16 TAI negative women. LT4 supplementation was applied in 20.8% patients, TAI positive. Results: Pregnancy outcomes were: twin pregnancy rate 4 1 .7 % , early miscarriage rate 8.3% , late miscarriage rate 4.2% , preterm birth rate 16.7% , term birth rate 70.8% , live birth rate 96.0% . There was significant difference in serum and in FF TgAbs (p< 0.001)betw een the groups according to TAI, while serum fT 3 was lower in the group with TAI (p = 0 .0 4 7 ). Serum P 4 was higher in LT4 treated group (p = 0 .0 0 5 ), with TAI, and newborns in this group had higher birth weight (p = 0.001) and height (p = 0 .0 0 8 ). Maternal complications occurred in 23.8% of patients. No congenital malformations in newborns were noted. Conclusions: Thyroid autoantibodies present in FF may have an effect on the post-implantation embryo development, but have no effect on further course of pregnancy. The special benefit of LT4 treatment for successful A R T outcome was demonstrated for newborn anthropometric parameters.

Today, infertility is not only a serious health but also a psycho-social problem, one that is on the rise in the world. Thyroid autoimmunity (TAI) is the most common disease of the thyroid gland in the reproductive period, which can affect spontaneous conception as well as conception through assisted reproduction technology (ART), but also the maintenance of healthy pregnancy. It can also cause numerous maternal and fetal complications. There is a wide array of publications on the topic of the mechanisms of association between TAI and reproduction, with the question of whether thyroid autoantibodies are solely tissue-specific antibodies, whether and when to start levothyroxine treatment, and that we require more fundamental research on the direct effect of thyroid autoantibodies starting from folliculogenesis to embryogenesis and implantation as well as the post-implantation embryo development, but also the composition of the follicular fluid as a microenvironment of enormous importance for the maturation of the oocytes which thyroid autoantibodies reach via the blood-follicle barrier.

The aim of this study is to show how public health surveillance of travel-associated Legionnaires' disease was conducted in Europe, as well as in Montenegro. The estimations of the European Centre for Disease Prevention and Control (ECDC) indicate that every year about one thousand tourists from Europe get infected by legionellae during their holiday and stay at hotels across the continent. The European Legionnaires' Disease Surveillance Network (ELDSNet) was established with the aim to detect, control and prevent cases, clusters and sources of outbreaks of travel-associated Legionnaires' disease within the European Union (EU) and European Economic Area (EEA), and to assist with detection and response to outbreaks outside the EU/EEA. Sharing information leads to concrete and timely actions of member states of ELDSNet, so that residents of the EU/EEA who travel abroad are protected. ECDC recommends a set of measures that should be followed by public health authorities and tourist sector of the country which was visited by the traveler who caught this disease. If the measures are not carried out, information is published online and European tour operators can use the information when booking holiday packages abroad. Operating procedures provide a set of common measures which should be followed by all EU/ EEA member states involved in the protection of their residents against Legionnaires' disease. Each case of Legionnaires' disease which is reported in tourists, who stayed in Montenegro, is epidemiologically analyzed according to the operating procedures of ELDS Network.

Obesity is an epidemic that has led to a rise in the incidence of many comorbidities: among others, reduced fertility is often under-evaluated in clinical practice. The mechanisms underlying the link between reduced fertility and obesity are numerous, with insulin resistance, hyperglycaemia and the frequent coexistence of polycystic ovary syndrome being the most acknowledged. However, several other factors concur, such as gut microbiome alterations, low-grade chronic inflammation and oxidative stress. Not only do women with obesity take longer to conceive, but in vitro fertilization (IVF) is also less likely to succeed. We herein provide an updated state-of-the-art regarding the molecular bases of what we could define as dysmetabolic infertility, focusing on the clinical aspects, as well as possible treatment.

Leishmaniosis (or leishmaniasis) is a neglected parasitosis most commonly transmitted by the sandfly bite. Changes in temperature, precipitation, and humidity can greatly affect the vectors and reservoir hosts. This study aimed to determine the association between temperature, air humidity, and weather conditions with the incidence of leishmaniasis in Montenegro during a seven-decade period (1945–2014) and to statistically compare and correlate the obtained data. In the studied period, there were 165 registered cases of leishmaniosis, 96.4%, in the coastal and central region of Montenegro, with an average incidence rate of 0.45/100.000. The visceral form of leishmaniosis predominated (99% of the cases), with only one case of cutaneous disease. Climate factors (average temperature, air humidity, and precipitation) had an impact on the occurrence of leishmaniosis in Montenegro. Air temperature elevated by 1 °C in all regions of Montenegro was significantly correlated with an increased incidence of leishmaniosis, by 0.150 (0.013 to 0.287; p < 0.05). In order to improve prevention and control of this disease, it is also necessary to investigate other factors with a possible impact on the number of cases of this neglected parasitosis.

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.

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.

Background: In 2009, an improved influenza surveillance system was implemented and weekly reporting to the World Health Organization on influenza-like illness (ILI) began. The goals of the surveillance system are to monitor and analyse the intensity of influenza activity, to provide timely information about circulating strains and to help in establishing preventive and control measures. In addition, the system is useful for comparative analysis of influenza data from Montenegro with other countries. Aim: We aimed to evaluate the performance and usefulness of the Moving Epidemic Method (MEM), for use in the influenza surveillance system in Montenegro. Methods: Historical ILI data from 2010/11 to 2017/18 influenza seasons were modelled with MEM. Epidemic threshold for Montenegro 2017/18 season was calculated using incidence rates from 2010/11–2016/17 influenza seasons. Results: Pre-epidemic ILI threshold per 100,000 population was 19.23, while the post-epidemic threshold was 17.55. Using MEM, we identified an epidemic of 10 weeks’ duration. The sensitivity of the MEM epidemic threshold in Montenegro was 89% and the warning signal specificity was 99%. Conclusions: Our study marks the first attempt to determine the pre/post-epidemic threshold values for the epidemic period in Montenegro. The findings will allow a more detailed examination of the influenza-related epidemiological situation, timely detection of epidemic and contribute to the development of more efficient measures for disease prevention and control aimed at reducing the influenza-associated morbidity and mortality.

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.

From 2004 to 2014, 106 cases of Human haemorrhagic fever with renal syndrome were notified in Montenegro, with a peak in 2014. Most of the cases occurred in summer, in the North-east and Central Montenegro, a hilly/mountainous area, that provides suitable habitats for the main rodent carriers. Cases were mainly males (71) and exposures were often working outdoor or spending time visiting mountains and lakes. Incidence correlated with average annual temperature increase and average annual rainfalls decrease, but not with land cover. Environment and climate effects on HFRS in Montenegro need further investigation to get insight into future trends.

Obesity and overweight are contributing factors for diseases such as type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and ultimately, cardiovascular (CV) disease. Obesity is imposing an increasing health burden in rich and poor nations, with almost 30% of people globally now either obese or overweight - a staggering 2.1 billion. The link between obesity and T2DM is widely held to involve two adverse effects: obesity-induced insulin resistance and β-cell failure. This "unified field theory" raises questions about whether defects favoring progressive weight gain and metabolic impairment also contribute to β-cell decompensation. The concept of weight-centric management of T2DM is considered justified because of the strong negative impact of obesity on the effects of treatment of diabetes. Two pharmacotherapy options are considered: drugs developed primarily for blood glucose control that also exert a favorable effect on body weight and drugs developed primarily to induce weight loss that also have a favorable effect on glycemia. Treating hunger counter-regulatory mechanisms will have an additional effect on glucose control in T2DM. This narrative review addresses advances in pharmacotherapy for the management of obesity and obesity-related co-morbidities, with a focus on T2DM. It is also important to identify the correct balance between weight-centric and glucose-centric management of T2DM.

The study aim was to analyze the epidemiology and clinical characteristics of severe acute respiratory infection (SARI) cases and to compare demographic and clinical characteristics as well as outcomes of influenza-positive SARI cases to those of influenza-negative SARI cases in Montenegro.SARI surveillance was established in 2014 in nine healthcare institutions. Retrospective analysis of case-based surveillance data pertaining to all reported SARI cases during three seasons was conducted.Among the 90 identified SARI cases, 64 (71%) were influenza positive. Death outcome was reported in 25 (28%) of all registered SARI cases. Cardiovascular disease was more prevalent among the patients in the influenza-positive SARI group (36% vs. 12%, p = .021), as was concurrence of two or more chronic medical conditions (57% vs. 30%, p = .042). These patients were also more likely to be immunocompromised (16% vs. 0%, p = .057) and have viral pneumonia (14.4% vs. 20.3%, p = .017), compared to those in the influenza-negative SARI group. Younger age, presence of cardiovascular disease and being immunocompromised were patient characteristics independently associated with SARI related to influenza.Continued and extended monitoring of SARI is necessary in order to fully assess the burden of flu disease, define risk groups and establish better control measures.

Graves’ ophthalmopathy (GO) is an autoimmune disease affecting ocular and orbital tissues. Overproduction of tumor necrosis factor  (TNF-) in rheumatoid arthritis (RA) and GO has destructive consequences. The subject of this paper is a case of a female patient initially diagnosed with primary hypothyroidism substitution with levothyroxine, and subsequent diagnosis of RA with insufficient therapeutic efficacy of a standard medication. Three years later, the patient presented symptoms and signs of GO. Etanercept was administrated for RA, and after four months, an improvement of the eye symptoms and reduced exophthalmos were observed and confirmed using visual methods. Graves’ ophthalmopathy association with primary hypothyroidism is uncommon. The treatment of RA using etanercept led to clinical improvement of GO symptoms, which indicates that RA and GO may share similar pathogenic features. The paper suggests that etanercept may suppress the symptoms and clinical signs of GO. However, controlled trials are needed to further evaluate the effect of TNF- inhibitors, particularly etanercept, and to compare its side effects with the current options for medical treatment.

Objective Although there are substantial data linking thyroid autoimmunity (TAI) and infertility, data regarding assisted reproductive technology (ART) outcomes and TAI markers in follicular fluid (FF) of women undergoing ART are scarce. Objective of the study was to assess the association of the levels of thyroid autoantibodies in FF and ART outcome expressed as the achieved pregnancies. Methods This study enrolled 52 women undergoing ART (26 TAI positive subjects and 26 age and body mass index matched TAI negative controls). Blood samples were drawn before the initiation of protocol for controlled ovarian stimulation, and thyrotropin (TSH), free triiodothyronine (fT3), free thyroxine (fT4), thyroid peroxidase antibodies (TPOAbs) and thyroglobulin antibodies (TgAbs) levels were measured. TSH, fT4, TPOAbs, TgAbs and progesterone levels were also measured in FF. Results There were no significant differences between the groups regarding mean levels of FF TSH and FF fT4. Statistically significant correlation was discovered regarding the levels of serum and FF TPOAbs (0,961, p

Introduction The diseases caused by Leishmania are spread worldwide and represent a significant public health problem. Objective The aim of this study was to present the results of epidemiological surveillance of leishmaniasis in humans in Montenegro in the period from 1992 to 2013. Methods The study was planned and realized as a descriptive epidemiological study. The sample included patients of leishmaniasis in Montenegro in the period from 1992 to 2013. The health and demographic data were collected from medical records. The disease was microbiologically proven in the patients. For statistical analysis the χ2-test was used, which examined the significance of the incidence rate. Results During this period, 66 cases of leishmaniasis were identified (40 men and 26 women) aged 0 to 62 (mean 15.61±16.76 years). A visceral form of the disease was diagnosed in 65 (98%) patients, and one patient was diagnosed with cutaneous leishmaniasis. The average incidence rate for the abovementioned period is 0.48 per 100,000 inhabitants. The highest average incidence rate was identified in patients up to seven years of age (3.50 per 100,000 inhabitants). The highest average incidence rates of leishmaniasis were identified in the coastal region of Montenegro, while seasonal distribution indicates that the disease occurs throughout the year with predominance in late spring and summer. Conclusion The research has shown that Montenegro is among the countries with low incidence of leishmaniasis. Nevertheless, because of leishmaniasis re-emergence in the entire Mediterranean Basin, a comprehensive research of ecological and epidemiological characteristics of leishmaniasis, including better monitoring and notification system, is required., Uvod Oboljenja izazvana lajšmanijama su rasprostranjena širom sveta i značajan su zdravstveni problem. Cilj rada Cilj rada je bio da se predstave rezultati epidemiološkog istraživanja lajšmanijaze kod ljudi na području Crne Gore u periodu 1992-2013. godine. Metode rada Istraživanje je planirano i realizovano kao deskriptivna epidemiološka studija. Uzorak istraživanja su činili oboleli od lajšmanijaze u Crnoj Gori od 1992. do 2013. godine. Zdravstveni i demografski podaci prikupljeni su iz medicinske dokumentacije. Kod svih obolelih bolest je mikrobiološki dokazana. Za statističku analizu rezultata korišćen je χ2-test, kojim je ispitana značajnost stopa incidencije. Rezultati U navedenom periodu od lajšmanijaze je obolelo 66 osoba (40 muškaraca i 26 žena) starih do 62 godine (prosečno 15,61±16,76 godina). Kod 65 (98%) bolesnika dijagnostikovan je visceralni oblik oboljenja, a kod jednog bolesnika kožni tip lajšmanijaze. Prosečna stopa incidencije bila je 0,48 obolelih na 100.000 stanovnika. Najviša prosečna stopa incidencije bila je u uzrastu do sedam godina (3,50 na 100.000 stanovnika). Prosečne stope incidencije lajšmanijaze s najvišom vrednosti bile su u priobalju Crne Gore, dok sezonska distribucija ukazuje na to da se bolest javlja tokom cele godine s predominacijom s kraja proleća i na leto. Zaključak Naše istraživanje je pokazalo da je Crna Gora među državama s niskom stopom incidencije obolevanja od lajšmanijaze. Ipak, zbog ponovnog pojavljivanja ove bolesti u Mediteranskom basenu i značaja za narodno zdravlje, potrebno je sveobuhvatno istraživanje ekoloških i epidemioloških odlika lajšmanijaze, uključujući bolji monitoring i sistem registracije.

Introduction: Thyroid nodular goiter Nodular goiter is clinically recognizable restricted structure changes of the thyroid gland. Numerous studies show the relationship between thyroid autoimmunity and differentiated thyroid cancer in patients with nodular thyroid goiter. One of the important clinical marker in defining thyroid autoimmunity are antibodies to thyroid peroxidase. Objective: The aim of this study was to analyze the relationship between antibodies anti peroksidaznih ii thyroid malignancies in patients with thyroid altered thyroid. Material and Methods: We retrospectively reviewed the 248 reports of thyroid FNA cytology of samples obtained by puncture of patients with nodular thyroid goiter, at Department of thyroid gland, Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia in the period from October 2007. by January 2010. year. We analyzed the relationship between findings of cytopathological diagnostic categories and serum concentrations of anti peroxidase antibodies. The data were statistically processed using the computer program SPSS 12.0 software package. Results: Of total 248 patients, 148 patients (59.7%) had anti-TPO antibody values in a reference limits (30 IU/ml), and 40.3% elevated anti-TPO antibodies (over 30 IU/ml). In the group of patients with elevated values of anti-TPO antibodies 7% (7/100) of patients had malignant cytologic findings, and in the group of patients with anti-TPO antibody values in the normal range only 1.4% (2/148) of patients had malignant cytologic findings. Conclusion: Defining the relationship between thyroid autoimmune disease and differentiated thyroid cancer, providing new insights in the field of immunotherapy of thyroid carcinoma. Enlightening the molecular mechanisms link autoimmune thyroid disease and thyroid cancer development in patients with thyroid nodule help find new therapeutic strategies against thyroid cancer.

Introduction: Nodular goiter is clinically recognizable restricted structure changes of the thyroid gland. FNA is the first line diagnostic test for an enlarged thyroid gland. TSH is known as a thyroid growth factor, but the pathogenic role of this hormone in thyroid oncogenesis is unclear. Objective: The aim of this study is to analyze the relationship between elevated serum TSH concentartions and thyroid malignancies in patients with nodular thyroid goiter. Material and Methods: We retrospectively reviewed the 637 reports of thyroid FNA cytology of samples obtained by puncture of patients with nodular thyroid goiter, at Department of thyroid gland, Department of Endocrinology, Diabetes and Metabolic Diseases, Clinical Center of Serbia in the period from October 2007. by January 2010. year. We analyzed the relationship between findings of cytopathological diagnostic categories and serum concentrations of TSH. The data were statistically tested using Kruskal Wallis test of differences using the computer program SPSS 12.0 software package. Results: Of total 637 patients 3.45% (22/637) had a malignant, and 4.87% patients (31/637) cytopathological indeterminate findings. 91.52% (583/637) patients were with benign findings, and only one puncture failed. The average value of TSH in a group of patients with a diagnosis of malignancy was 9.83 ± 17.48 mmol/l with a median 3.31mmol/l. In all three diagnostic categories (benign, malignant and unspecified) most patients are with the normal concentrations of serum TSH , but there is a relatively large proportion of 27.3% (6/22) of patients with malignant cytopathological findings in the group of patients with elevated TSH concentartion. Statistically significant differences between diagnostic categories by group TSH values (χ²=8.136,p=0.017). Conclusion: It is concluded that the risk of developing thyroid malignancy increases in patients with elevated serum TSH concentrations. TSH should be used as an additional diagnostic tool in identifying high-risk patients who require further investigation and / or surgical treatment.

Program for tuberculosis in Montenegro is a framework for the implementation, monitoring and evaluation of TB control strategy in Montenegro, in accordance with WHO guidelines. The objective of the present study was to assess TB knowledge of selected doctors in Montenegro. A cross-sectional study was conducted in 18 primary health care institutions in Montenegro. The study included 315 selected doctors for adults, children and women, which makes 83% of the total numbers of medical doctors. In the last two years, 48% of respondents indicated that they did not have any patient suffering from tuberculosis, while 17.5% of respondents had one patient suffering from tuberculosis. There were statistically significant differences between selected doctors regarding the incidence rates among different age groups (p=0.023). About half of health care workers gave the correct answer that, on average, 5-10% of people infected by M. tuberculosis develop TB (p=0.005). Regarding group of questions related to infectivity only a third of respondents gave the correct answer and statistically significant differences were observed between health care workers according to infectivity (p

Figure1. A 30 year old women underwent in vitro fertilization (IVF) for four times, with no success (always poor ovarian response, double embryo transfer). Hashimoto thyroiditis and subclinical hypothyreoidismus were diagnosed. Levothyroxine substitution was started. Repeatedly elevated prolactin level in the morning, but preserved circadian rhythm and daily values ​​in the referent range. NMR sellar region shown microadenoma in the right half. No adequate cortisol answer in insulin tolerance test, but normal prolactine and growth hromone. In thyrotropin relasing hormone test no paradoxal response. Husband has the oligoasthenospermia, the varicocele surgically removed and normal karyotype (46, XY). Patient’s karyotype testing shown a mosaic monosomy X (46, XX/45, X0), with 5% of analyzed cells caracterized by monosomy X, but no syndrome fenotype characteristics, entered puberty at the time, regular menstrual cycles and no echocardiography dysgenetic ovarian caracteristics. During the last IVF no follicle on folitropine stimulation was found, and for the first time higher FSH value and lower AMH value were found, indicating premature ovarian insuffuciency; antiovarian antibodies were negative exluding immune-mediated process. A year later, menstrual cycles became irregular. Two years later she presented with sings of hypocorticismartralgia, hyperpigmentation, fatigue, hypotension and low corisol level, but normal electrolyte level, hydrocortisone substitution was started (Figure 1,2). PTH was in referent range. Positive anti GAD and anti IA2 antibodies were demonstrated, oral glucose tolerance test was normal. Patient is now in oocyte donation process. Polyglandular autoimmune syndrome type II (PGA-II) is the most common immunoendcrinopathy syndrome, characterized by the obligatory occurrence of Addison disease in combination with thyroid autoimmune diseases and/or type 1 diabetes mellitus. This case report presents coexistence of mosaic Turner syndrome and pituitary micoradenoma in patient with PGA-II.