HPV E6/E7mRNA association with interleukin 10 (rs1800872) polymorphism in a group of Macedonian women.

Interleukin 10 (IL-10) is an immunosuppressive cytokine and its genetic variants could have an indirect impact on viral biology and human papillomavirus (HPV) E6/E7 messenger RNA (mRNA) expression as well. This study evaluates the association between IL-10-592 C/A (rs1800872) single-nucleotide polymorphism and HPV E6/E7 mRNA expression in a group of women from the Republic of North Macedonia. Using a commercial test, 272 women's cervical samples were analyzed for HPV E6/E7 mRNA and HPV DNA presence. The cases were stratified into three groups: double-positive (n = 108, positive for both tests), negative (n = 51, negative for HPV E6/E7 mRNA and HPV DNA positive), and the control group (n = 113, negative for both tests). The IL-10-592 C/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism. The results showed the CC genotype and the C allele frequencies of IL-10-592C/A were significantly higher in double-positive (59.3% and 78.2%) compared to negative group (39.2% and 65.7%), (p = 0.018, confidence interval [CI] = 2.25; 1.14-4.45 and p = 0.016, CI = 1.88; 1.11-3.16, respectively). The CC genotype and C allele of rs1800872 polymorphism were shown to be associated with HPV E6/E7 mRNA but not with HPV DNA positivity, which implies a possible role of this polymorphism in the course of the infection only after HPV onset, and lack of association with the susceptibility to HPV.

HPV E6/E7 mRNA versus HPV DNA biomarker in cervical cancer screening of a group of Macedonian women.

High risk types of human papillomaviruses E6/E7 oncogenes and their association with tumor suppressor genes products are the key factors of cervical carcinogenesis. This study proposed them as specific markers for cervical dysplasia screening. The aim of the study is to compare the clinical and prognostic significance of HPV E6/E7 mRNA as an early biomarker versus HPV DNA detection and cytology in triage of woman for cervical cancer. The study group consists of 413 women: 258 NILM, 26 ASC-US, 81 LSIL, 41 HSIL, and 7 unsatisfactory cytology. HPV4AACE screening, real-time multiplex PCR and MY09/11 consensus PCR primers methods were used for the HPV DNA detection. The real-time multiplex nucleic acid sequence-based assay (NucliSENS EasyQ HPV assay) was used for HPV E6/E7 mRNA detection of the five most common high risk HPV types in cervical cancer (16, 18, 31, 33, and 45). The results show that HPV E6/E7 mRNA testing had a higher specificity 50% (95% CI 32-67) and positive predictive value (PPV) 62% (95% CI 46-76) for CIN2+ compared to HPV DNA testing that had specificity of 18% (95% CI 7-37) and PPV 52% (95% CI 39-76) respectively. The higher specificity and PPV of HPV E6/E7 mRNA testing are valuable in predicting insignificant HPV DNA infection among cases with borderline cytological finding. It can help in avoiding aggressive procedures (biopsies and over-referral of transient HPV infections) as well as lowering patient's anxiety and follow up period.

Assessment of radiological hazards of soils from the city of Bitola (Macedonia) and its environs.

To establish the radioactivity level of soils and assess the associated radiological impact on residents, 58 samples from the town of Bitola and its environs were collected. After conducting gross alpha and gross beta measurements with a gas-flow proportional counter as a preliminary screening test, subsequent gamma-spectrometry measurements reveal the presence of 40K, 226Ra, 232Th, and 137Cs in the soil samples as radionuclides with the highest impact. The absorbed gamma dose rate, the annual effective dose, radium equivalent activity, external hazard index, gamma index, excess lifetime cancer risk, and annual gonadal dose were calculated using the obtained activity concentrations of the radionuclides. Upon comparison with similar studies conducted in the Balkan countries, the obtained results for radiation hazard indices were found to be the highest in the region. Coloured maps were generated to visually represent the spatial distribution of the absorbed gamma dose rate in air and annual effective dose, clearly indicating the combined influence of geology and human activities, including the nearby thermoelectric power plant operation.

Preventive Measures and Hygiene Habits of Apple Producers in the Prespa Region.

Background: Agriculture is one of the most dangerous industries, both for the employees in that sector and for their families and the environment. The use of personal protective preventive measures and the maintenance of good hygienic practices are the basis for healthy production and healthy workers. The safety and hygiene of food products should be present during all stages of production. Objectives: The study aimed to assess the use of personal protective equipment (PPE) by apple growers during agricultural procedures as well as the hygiene habits of agricultural workers. Subjects and Methods: A cross-sectional study was conducted including 101 farmers from the Prespa region in the Republic of North Macedonia by using a questionnaire with 34 questions. The questions were formulated in order to give us an insight into the protective preventive measures undertaken at work by apple producers and their hygiene. Results: The study included 101 apple growers from the Prespa region. Wearing a completely tidy special PPE when using pesticides was registered in 78.2% of farmers, and when lawn mowing in 42.5%. 16% of the surveyed farmers during agricultural activities did not always wash their hands after going to the toilet, and almost 30% of them did not use soap when washing their hands. Conclusion: There is inadequate hygiene practice/personal hygiene during agricultural activities. In addition, the proper use of PPE is not at a satisfactory level and poses a risk to the health of apple growers.

ALPPS Procedure for the Treatment of Bilobar Multiple Liver Metastasis from Colorectal Cancer: First Case in RN Macedonia.

Introduction: ALPPS (Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy), is a recently developed procedure, first performed by HJ Schlitt in Regensburg, Germany. The technique developed two stages of hepatectomy. The ALPPS procedure has been introduced to increase the volume of future liver remnant, much more than the other technique, such as PVE (portal vein embolization). The first ALPPS in our country was introduced and performed by our team on May 15th, 2018. Results: The 60-year-old patient was previously operated on for rectal cancer in 2017 at another institution. The operation was performed with anterior resection and the patient was in long term adjuvant chemotherapy. One year after surgery, the patient has multiple bilobar liver metastases and increased tumor markers that led to instant admission to our institution for liver resection. In the first stage, we performed four metastasectomies on the left lobe with right portal vein ligation and transection on the Cantlie line. The second stage was performed after a CT evaluation on the eighth day, with significant hypertrophy on the left lobe. Pathological findings reported ten metastases on the right lobe with a diameter 1-3 cm. The patient was on the long-term chemotherapy, and after one year he had other MS in the IVa segment of the liver. We also performed a metastasectomy. The patient died 32 months after ALPPS. Conclusion: ALPPS is a safe and feasible procedure for the treatment of bilobar liver metastasis from colorectal cancer. It could provide long-term survival for patients.

Benefits of Contralateral Patent Processus Vaginalis Closure During Laparoscopic Surgery for Inguinal Hernia in Female Children.

After more than a decade, an accurate description of the current state of pediatric inguinal hernia repair still an issue of contention. Improvement of techniques together with patient-entered intervention that account for the experiences related to individual disease characteristics have become an important factor of which the surgeon must be aware. Therefore, the aim of this study is to analyze a potential treatment for metachronous contralateral inguinal hernia (MCIH) in children during laparoscopic assisted percutaneous internal inguinal ring suturing (PIRS). In a prospective clinical study, carried out at the University Clinic for Pediatric Surgery in Skopje, Republic of North Macedonia, we analyzed the data from 49 female children, aged 1-14 years old, with clinically diagnosed congenital inguinal hernia treated via PIRS. The position of hernias on the right side was 29 (59.2%) on the left side was 19 (38.8%) and on both sides was 1 (2.0%). With intraoperative assessment, it was determined that in 33 (67.3%) participants there was no presence of a hidden hernia, while in 16 (32.7%), there was indeed the presence of a hidden hernia. Of the hidden hernias determined laparoscopically [16 (100%)], 8 (50%) were left and right hidden hernias, all treated laparoscopically. The PIRS technique is a procedure where the basic advanced treatment is exploration. This also included the adequate treatment of other pathologies, such as the prophylactic closure of a contralateral patent processus vaginalis with simultaneous treatment as there is the potential for hernia in future, therefore reducing the number of metachronous inguinal hernias.

A Comprehensive Molecular and Epidemiological Characterization of Influenza Viruses Circulating 2016-2020 in North Macedonia.

Influenza viruses know no boundaries, representing an example of rapid virus evolution combined with pressure exerted by the host's immune system. Seasonal influenza causes 4-50 million symptomatic cases in the EU/EEA each year, with a global death toll reaching 650,000 deaths. That being the case, in 2014 North Macedonia introduced the sentinel surveillance in addition to the existing influenza surveillance in order to obtain more precise data on the burden of disease, circulating viruses and to implement timely preventive measures. The aims of this study were to give a comprehensive virological and epidemiological overview of four influenza seasons (2016-2020), assess the frequency and distribution of influenza circulating in North Macedonia and to carry out molecular and phylogenetic analyses of the hemagglutinin (HA) and neuraminidase (NA) genes of influenza A(H1N1)pdm09, A(H3N2) from ILI and SARI patients. Our results showed that out of 1,632 tested samples, 46.4% were influenza positive, with influenza A(H1N1)pdm09 accounting for the majority of cases (44%), followed by influenza B (32%) and A(H3N2) (17%). By comparing the sentinel surveillance system to the routine surveillance system, we showed that the newly applied system works efficiently and gives great results in the selection of cases. Statistically significant differences (p = < 0.0000001) were observed when comparing the number of reported ILI cases among patients aged 0-4, 5-14, 15-29, and 30-64 years to the reference age group. The phylogenetic analysis of the HA sequences unveiled the resemblance of mutations circulating seasonally worldwide, with a vast majority of circulating viruses belonging to subclade 6B.1A. The PROVEAN analysis showed that the D187A substitution in the receptor binding site (RBS) of the A(H1N1)pdm09 HA has a deleterious effect on the its function. The A(H3N2) viruses fell into the 3C.2a and 3C.3a throughout the analyzed seasons. Molecular characterization revealed that various substitutions in the A(H3N2) viruses gradually replaced the parental variant in subsequent seasons before becoming the dominant variant. With the introduction of sentinel surveillance, accompanied by the advances made in whole-genome sequencing and vaccine therapeutics, public health officials can now modify their approach in disease management and intervene effectively and in a timely manner to prevent major morbidity and mortality from influenza.

The Kapandji Technique of Closed Reduction Using Sommer - Pins in the Treatment of Completely Dislocated Fractures of the Distal Radius in Children.

BACKGROUND: The fractures of the distal radius are one of the most frequent cases in the pediatric population. The primary way of treating these fractures is conservative, with manual reduction and cast immobilisation. In patients where reduction and retention of the fracture cannot be achieved, a surgical approach is the treatment of choice. AIM: To evaluate the benefits of using the minimally invasive surgical treatment of closed reduction using Sommer - pins in the treatment of the fractures of the distal radius in the pediatric population with the method of the Kapandji technique. MATERIAL AND METHODS: In this study, we used cases treated from 2012 to 2017, of 48 completely dislocated fractures of the distal radius in patients ages 6 -14 yrs., where the use of non-surgical treatment proved ineffective. In the surgical treatment, we used one or two Sommer - pins to achieve a correct reduction and fixation. RESULTS: The post-op immobilisation lasted 4 - 7 weeks with an underarm cast. The patients were closely followed in the period of 6 months following the intervention. The anatomic reduction was easily achieved with this type of technique in every case. In the post-op period, there was no significant loss of reduction and another surgical procedure was not needed in any of the cases. CONCLUSION: With the use of the closed reduction Kapandji technique, an easy and good anatomical reduction is achieved with good post-op results in the treatment of completely dislocated fractures in the distal radius in children.

Congenital hydronephrosis: disease or condition?

The aim of this paper is to address the dilemmas of the paediatric surgeon when facing an isolated, unilateral, congenital hydronephrosis and discuss the strategic options for the management of this condition. Congenital hydronephrosis, the most commonly diagnosed uropathy in children, is usually a benign and self-resolving condition. Nonobstructive hydronephrosis does not require operative treatment, while timely treatment is imperative for obstructive hydronephrosis before significant renal damage ensues. Managing congenital hydronephrosis is a challenging task. Thirty-two children with unilateral, isolated hydronephrosis and nonobstructed renography curves were followed up for 3 years. On the initial evaluation according to the grade of hydronephrosis: 22.6% were grade I, 54.8% grade II and 22.6% grade III. After 12 months of follow-up: 30% were grade I, 51 .5% grade II and 18.5% grade III, respectively. After the three-year follow-up, there were no hydroneproses greater than grade II. The mean value of the separate GFR of the affected kidney at initial evaluation was 42.83%, and 40.33% after three years. In three children the treatment was converted from conservative to surgical. Nonobstructive, congenital hydronephrosis is a benign condition not requiring any medical treatment, but aggressive observation is indicated.

Some aspects of culturally competent communication in health care in the republic of macedonia.

AIM: To examine the existing situation, barriers and consequences of the intercultural communication in health institutions and to offer training models for strengthening and improving communication skills of health professionals in the Republic of Macedonia. METHODS: A cross-sectional survey was conducted to assess the relationship between patients and health professionals. A total of 813 health professionals (302 physicians and 511 other medical staff) from different healthcare institutions, and 1016 patients participated in cross-sectional survey performed in autumn 2010. RESULTS: The research has showed that each third examined patient thought that his/her physician or the other medical personnel had no understanding for his/her emotions and gave no answer to all of his/her questions. From the other side, 60% of the physicians declare that they have a good communication with patients speaking other language than their mother tongue. Only 60% of physicians said that they know good the culture of their patient and 52% of the other medical staff said that they adjusted the treatment to the patient culture (religion, attitudes, language, life style). CONCLUSION: There are some gaps in current provision of health care practice in an aspect of effective interactions and communication skills of health professionals to meet patient needs in a multicultural and multilingual setting. A training model is proposed for strengthening communication skills of health professionals.

Laboratory surveillance during pandemic influenza season 2009/2010 in Republic of Macedonia.

OBJECTIVE: To provide virological and epidemiological information on patients laboratory-tested for influenza A/ H1N1pdm during the pandemic season April 2009/May 2010. MATERIALS AND METHODS: Demographic and other data were obtained from the request form arriving with the samples of patients whose symptoms met the clinical definition of influenza A infection. The RNA was tested for the presence of influenza virus using the CDC real-time RT-PCR assay. A total of 3010 suspect patients (pts) were tested from week 18 2009 to week 20 2010. RESULTS: 1632 pts (54.2%) were oositive for influenza. From them 1556 samples were confirmed as H1N1pdm. There was a domination of H1N1pdm positivity among young persons in age groups 5-17 (34.4%) and 18-49 (31.4%) years. The pandemic influenza was presented in two waves. The first wave started on 20 June with the first positive case and peaked early in August (week 32). The second wave started from week 44. The majority of positive cases were between week 45 and week 52. 37.7% of the positive pts were hospitalized--66.7% of pts at age 65+ and 63.3% of children in the age group 0-4 years. The highest percentage of patients with underlying medical conditions were in the age group 50-64 (49.35%) years and 65+ (88.23%) years. 1.15% of the positive pts for H1N1pdm gave data for vaccination with seasonal influenza. CONCLUSIONS: Data obtained from laboratory and epidemiological surveillance of pandemic influenza will serve public health to a full understanding of the pandemic 2009/2010 influenza in R. Macedonia and dealing with future challenges.

The first survey about the antibiotic usage in the Republic of Macedonia.

Development of antibiotic resistance represents a major global and Macedonian public health problem. To assess the opinion and knowledge of the citizens of Macedonia about the usage of antibiotics, voluntary and anonymous survey was realized. A total of 239 persons (age 10-67 years) were interviewed. Following information was obtained: 73.64% get antibiotics with a medical prescription; and 87.03% receiving the antibiotic on time, dosage and prescribed duration. When asked about knowledge about antibiotics, 38% of the interviewed persons gave the right answer, 43.1% of respondents made false statements that antibiotics are effective against viral infections and 25.52% did not express any opinion.