Two Years of Newborn Screening for Cystic Fibrosis in North Macedonia: First Experience.

There is a widely accepted consensus on the benefits of newborn screening (NBS) for cystic fibrosis (CF) in terms of reduced disease severity, improved quality of life, lower treatment burden, and reduced costs. More and more countries in the world are introducing NBS for CF as a national preventive health program. Newborn screening for CF was introduced in the Republic of North Macedonia (RNM) in April, 2019, after a pilot study of 6 months in 2018. A two-step immunoreactive trysinogen (IRT-IRT) algorithm is performed, and then a sweat test for confirmation/exclusion of the CF diagnosis when the IRT values were both over the cutoff (70.0 and 45.0 ng/mL, respectively). In cases with confirmed diagnosis of CF (a sweat chloride concentration >60.0 mmol/L) or with intermediate sweat test results (a sweat chloride concentration of between 30.0 and 59.0 mmol/L), CF transmembrane conductance regulator (CFTR) mutation analysis is performed. By the end of 2020, over a period of 27 months, including the pilot study period, a total number of 43,139 newborns were screened for CF. Seventeen (0.039%) newborns were diagnosed with CF. In all newly discovered CF cases by screening, the diagnosis was confirmed by determination of the CFTR mutations. The most common CFTR mutation, F508del, was found with an overall incidence of 70.6%. Other more frequent mutations were G542X (11.8%) and N1303K (5.9%). Four mutations were found in one CFTR allele each: G1349D, G126D, 457TAT>G and CFTRdupexon22, with the last one being newly discovered with unknown consequences. An incredibly large difference was found in the incidence of the disease between the Macedonian and Albanian neonatal population, with almost four time higher prevalence among Albanians (1:4530 vs. 1:1284).

Hysterosalpingography versus hysterscopy in intrauterine pathology research of infertile patients.

BACKGROUND: The objective of the present paper is to confirm the validity and reliability of hysterosalpingography (HSG) in intrauterine pathology research of infertile female patients by comparing the hysteroscopy (HC) findings to a "gold standard" test. AIM: To analyze HSG and HC findings in infertility patients. MATERIALS AND METHODS: The research was conducted as a prospective study at the Gynecological and Obstetrics Clinic "Narodni front" in Belgrade. RESULTS: HSG indicated pathological findings in 72.5% of patients whereas HC revealed abnormalities of uterine cavity in 77.5%. In 12.5% of patients, HSG demonstrated a normal uterine cavity, and HC confirmed pathological findings, while in 7.5% of patients with filling defects and irregular shapes on HSG images, HC reported normal findings. In 22.5% of patients normal finding as well as endometrial polyps were reported; congenital malformations (anomalies) were found in 32.5%, submucosal myomas in 12.5% and Asherman's syndrome in 10%. CONCLUSION: HC finding was crucial in final diagnosing.

Comparative findings of voice and speech: language processing at an early ontogenetic age in quantitative EEG mapping.

Quantitative EEG mapping in powers of electrical activity, concentration of main powers and area of concentration in relation to the side of presentation (left, right, and bihemisphery) and closer location was done on a 24-day-old infant first, and again when the infant was 2.5 months. EEG responses are analyzed in following acoustic modalities: (1) specific (native language speech of mother and unfamiliar female, unfamiliar female speech of foreign language); (2) unspecific (passive period). Familiar and unfamiliar texts present the contents of speech material. Comparative findings on two different ages showed that the infant maintains the processing scheme of unfamiliar stimulus (passive period, foreign language), and also very similar processing scheme of unfamiliar voice regardless if the text in native language is familiar or unfamiliar. During stimulation with familiar or unfamiliar text in native language, which is read by mother, processing type is significantly changed in relation to the age at the time of examination. While a 24-day-old infant shows a similar scheme in processing the familiar and the unfamiliar voices in native language, at the age of 2.5 months, this scheme of processing is changed, especially for theta rhythm, which now has bihemisphery presentation (at earlier stage it has right-side presentation) in the F-C-P region, what is practically the same region where also delta rhythm is processed. However, the sample of unfamiliar voice in native language observed in subsequent period, when the infant was 2.5 months old, maintains the same processing location as it has at an earlier ontogenetic stage, when the infant was 24 days old, regarding the theta rhythm processed in the F-C-P region with right-side presentation, and delta rhythm processed in C-P region with bihemisphery presentation. Post stimuli periods observed when the infant was 2.5 months old show obviously differentiation of theta and delta rhythms' samples and their electrophysiological parameters. The samples of familiar and unfamiliar texts in native language when read by mother (familiar voice) begin to differentiate regarding to closer location and number of centers for maximal powers in theta rhythm at subsequent ontogenetic period (2.5-month-old infant). The samples of quantitative EEG mapping for a 2.5-months-old infant show the signs of complex processing of different stimuli types: known/unknown voice, foreign language, with stronger inclusion of parietal regions, bihemisphery and an increase in number of maximal powers' centers, compared to the samples when the infant was 42 days old. Quantitative EEG electrophysiological parameters are discussed in relation to side representation and closer regional location with the aim of explaining the processing of complex speech and language stimulation in relation to certain characteristics in its bases.

New technologies in diagnosing occupational asbestosis.

The paper considers the possibilities of applying telemedicine, a relatively new branch combining medicine and telecommunications, in diagnosing occupational asbestosis. Nowadays, telemedicine has been extensively used in an ever-increasing number of areas such as dermatology, oncology, radiology, surgery, cardiology, and psychiatry. The paper gives an example of possible applications in Croatia. Telemedicine is expected to significantly reduce absenteeism and travel expenses incurred by various laboratory tests. Furthermore, the diagnostic procedure would be considerably quicker, thereby improving the overall health condition of the population living in the immediate vicinity of asbestos factories. Our research has been conducted in the southern Croatian town of Ploce with an asbestos plant, but possible application refers to places distant from major hospitals, such as rural areas and the islands.

Structure-affinity relationship studies on D-2/5-HT1A receptor ligands. 4-(2-Heteroarylethyl)-1-arylpiperazines.

With an aim of creating new, mixed D-2/5-HT1A ligands, sixteen different compounds were synthesized. For this purpose 1-arylpiperazines attached through N-4 nitrogen to the dopaminergic pharmacophores of 2-(5-benzimidazole)-ethyl-, 2-(5-benztriazole)-ethyl-, 2-[5-(benzimidazole-2-thione]-ethyl- and 2-[6-(1,4-dihydroquinoxaline-2,3-dione)]-ethyl-type were selected according to their structural diversity (phenyl, substituted phenyl, heteroaryl and naphthyl). All new compounds were checked for in vitro binding affinity at the dopamine (D-1 and D-2) and serotonin (5-HT1A) receptors. Synaptosomal membranes prepared from fresh bovine caudate nuclei and hippocampus were used as a source of dopamine and serotonin receptors, respectively, [3H]SCH 23390 (D-1 selective), [3H]spiperone (D-2 selective) and 8-OH-[3H]DPAT (5-HT1A selective) were employed as the radioligands. All compounds were inactive competitors of [3H]SCH 23390, 1c and 2b being inactive in the two other binding assays, as well. Derivatives of 1-(2-pyridyl)piperazine 1b and 2a and of 1-phenylpiperazine 1a expressed moderate to low affinity for both D-2 and 5-HT1A receptors, while 1-(2-pyridyl)-piperazines 3b and 4b and 4-(1-phenylethyl)-1-(1-naphthyl)-piperazine 10 were moderate [3H]spiperone, but potent 8-OH-[3H]DPAT competitors. Among them, derivatives of 1-(1-naphthyl)-piperazine 1e, 2d and 3e and of 1-(2,3-dimethylphenyl)-piperazine 1d, 2c and 3d were the strongest competitors at both D-2 and 5-HT1A receptors.

[Standardization of diagnostic criteria for occupational asbestosis of the lungs and lung parenchyma]. / Prilog raspravi o ujednacavanju kriterija za priznavanje profesionalne azbestoze plúca i poplucnice.

A reliable method for evaluation of asbestosis-related non-malignant respiratory impairment as occupational disease is described. The method is based on an algorithm which consists of the following elements: a positive full work history, chest radiography (International Labour Organisation), ventilatory lung function measurement, determination of diffusing capacity for carbon monoxide, histopathological examination, computerized tomography, and high resolution computerized tomography for persons with a negative differential diagnosis. The algorithm is meant to contribute to the standardization of diagnostic criteria for assessment of occupational lung diseases. Its use is also proposed for assessment of other occupational diseases.

[Social support and family relations in Graves-Basedow disease]. / Socijalna podrska, odnosi u porodici i Grejvs-Bazedovljeva bolest.

An anamnestic study encompassed 100 new patients with Graves-Basedow's disease and 100 controls matched according to sex, and age (+/-2 years) and place of living (rural/urban). The patients were treated in an out-patient clinic of the Clinical Center of the Medical Faculty, Clinical hospital center "Zvezdara" in Belgrade and in Special institution "Zlatibor" on Zlatibor in the period from May 1st, 1993 to November 1st, 1993. The aim of this study was to estimate the influence of family relationship and social support on the development of Graves-Basedow's disease. The diseased more often lived in an environment of family disharmony (McNemar's test = 3.76; relative risk (RR) = 3.25; 95% confidence limits CL = 1.01-10.68; probability (p) = 0.049) while the controls more often described themselves as nostalgic persons (McNemar's test = 4.96; RR = 0.38; CL (95%) = 0.16-0.89; p = 0.026). The possibility to discuss their personal problems with their relatives and friends (t = 2.29; DF = 99; p = 0.024), the relatives' and friends' interest for their problems and their readiness to help (t = 2.29; DF = 99; p = 0.004) and possibility of the patients to ask for help in case of financial problems (t = 2.78; DF = 99; p = 0.007) were more often present in persons from the control group.

Malignant tumors in an area with an asbestos processing plant.

Incidence rate of malignant tumors of the lung/bronchus, pleura, larynx, pharynx, and peritoneum during the period 1974 to 1987 was studied in a Croatian coastal area with an asbestos processing plant which started to operate in 1954. The study area covers 169 km2 with 11,270 inhabitants: 5590 men and 5710 women (average number during the study period). The calculated number of inhabitants aged 35 and older was 4639 (41.1%), 11.5% were aged 60 or older, and the average age was 32 years. Over the observed 14-year period there were 51 cases of malignant tumors, 40 in men and 11 in women: lung/bronchus cancer, 36-29 men and 7 women; mesothelioma, 5-2 men and 3 women; laryngeal cancer, 5 men; pharyngeal cancer, 4-3 men and 1 women; and peritoneal cancer, 1 man. The results of the study showed that the incidence of lung/bronchus cancer in the studied population was half that in Croatia. There were also fewer malignant tumors of the pharynx and peritoneum in this area than in Croatia. On the other hand, the incidence of primary tumors of the pleura was more than 5 times as high and of laryngeal tumors more than 2 times as high as in Croatia. Evaluation of the data showed that distance from the source of emissions was not crucial for the development of tumors. The incidence of the tumors in the town with the asbestos factory was the lowest. Among and within different towns/villages the tumor incidence varied; in some the observed rate was higher than the expected rate. A more detailed analysis indicated a possible influence of the relief and prevailing wind direction on the environmental contamination with asbestos from the emissions source and consequently on an uneven distribution of the tumor incidence among separate settlements in the area under study.