Search

Addressing the worldwide challenge of shortage of nurses contributes to the national and international efforts to enhance the health and well-being of the global population. The main aim of this research is to investigate the level and the relationship between psychological distress, burnout, job satisfaction and intention to quit among primary healthcare nurses in public and private practices while accounting for their socio-demographic characteristics. This was a cross sectional study of 173 primary health care nurses. The Oldenburg Burnout Inventory and General Health Questionairre-12 were used to assess burnout and psychological distress among nursing staff. High psychological distress was present in 21.38% of all respondents and was significantly related to intention to quit. The results indicated a mean job satisfaction score of 3.54 with higher job satisfaction among private vs. public sector nurses. Furthermore, nurses with higher burnout levels and lower job satisfaction were more likely to consider leaving the profession compared with those with lower burnout and higher job satisfaction. The study provides valuable insight for managers of general healthcare practice and healthcare policy makers in effectively managing and retaining primary healthcare nurses.

Background: The aim of this study was to assess the epidemiological profile of unintentional opioid overdoses, the prevalence and number of psychotropic substances involved in opioid overdoses.Methods: This was a descriptive study, in which 180 participants were enrolled, and covered a nine-years-period. For collecting data was used the National patient electronic system “My term”. The variables as gender, age, duration of opioid dependence, number of overdoses, type of substance, number of antidote ampoules, duration of hospitalization were analyzed. Severity of poisoning was made by using the Poison severity score. Results: Opioid overdose cases were significantly higher among males than females. Mean age with standard deviation (SD) was 32.23 ± 6.71 years. Mean years (±SD) of duration of opioid use disorder was 11.60 ± 5.89 years. The most commonly used primary substance was methadone in 68.89% and heroin in 31.11% cases. Twenty patients were treated with mechanical ventilation because of the severe respiratory depression. Poison severity score was moderate in 51.11%, severe in 45.56% and fatal in 3.33% of the cases. Conclusion: Most of the cases, predominantly males used one or two substances. The combination of methadone and benzodiazepine was most frequently used and the most common way was by injecting the abused substances. In most of the subjects PSS score was moderate and severe with no differences between genders.

Aedes albopictus is an invasive mosquito species spreading throughout Europe and its presence in North Macedonia was recorded in 2016. Following the first detection in September 2018, we conducted a two-week mosquito monitoring by ovitraps in order to determine if there were established populations of Aedes albopictus in Skopje, the capital of North Macedonia. Ninety-four Ae. albopictus eggs (0 to 18 eggs per ovitrap per week) were collected from 7 (14%) ovitraps in 3 (30%) municipalities. Thirty-eight eggs (40.4%) successfully hatched and the adult mosquitoes were identified by morphology and PCR. No other potentially invasive species were identified during the monitoring period. Ae. albopictus distribution is expanding and poses a risk for an Aedes-borne disease transmission in North Macedonia. The available data highlight the need for a regular monitoring for tiger mosquitoes to plan adequate control measures.

Next-generation sequencing has sparked the exploration of cancer genomes, with the aim of discovering the genetic etiology of the disease and proposing rationally designed therapeutic interventions. Driver gene alterations have been comprehensively charted, but the improvement of cancer patient management somewhat lags behind these basic breakthroughs. Recently, large-scale sequencing that focused on metastasis, the main cause of cancer-related deaths, has shed new light on the driving forces at work during disease progression, particularly in breast cancer. Despite a fairly stable pool of driver genetic alterations between early and late disease, a number of therapeutically targetable mutations have been found enriched in metastatic samples. The molecular processes fueling disease progression have been delineated in recent studies and the clonal composition of breast cancer samples can be examined in detail. Here we discuss how these findings may be combined to improve the diagnosis of breast cancer to better select patients at risk, and to identify targeted agents to treat advanced diseases and to design therapeutic strategies exploiting vulnerabilities of cancer cells rooted in their ability to evolve and drive disease progression.

α-Selective phosphatidylinositol 3-kinase (PI3K) inhibitors improve outcome in patients with PIK3CA-mutated, hormone receptor-positive (HR+)/Her2- metastatic breast cancer (mBC). Nevertheless, it is still unclear how to integrate this new drug family in the treatment landscape.A total of 649 patients with mBC from the SAFIR02 trial (NCT02299999), with available mutational profiles were selected for outcome analysis. PIK3CA mutations were prospectively determined by next-generation sequencing on metastatic samples. The mutational landscape of PIK3CA-mutated mBC was assessed by whole-exome sequencing (n = 617). Finally, the prognostic value of PIK3CA mutations during chemotherapy was assessed in plasma samples (n = 44) by next-generation sequencing and digital PCR.Some 28% (104/364) of HR+/Her2- tumors and 10% (27/255) of triple-negative breast cancer (TNBC) presented a PIK3CA mutation (P0.001). PIK3CA-mutated HR+/Her2- mBC was less sensitive to chemotherapy [adjusted odds ratio: 0.40; 95% confidence interval (0.22-0.71); P = 0.002], and presented a worse overall survival (OS) compared with PIK3CA wild-type [adjusted hazard ratio: 1.44; 95% confidence interval (1.02-2.03); P = 0.04]. PIK3CA-mutated HR+/Her2- mBC was enriched in MAP3K1 mutations (15% versus 5%, P = 0.0005). In metastatic TNBC (mTNBC), the median OS in patients with PIK3CA mutation was 24 versus 14 months for PIK3CA wild-type (P = 0.03). We further looked at the distribution of PIK3CA mutation in mTNBC according to HR expression on the primary tumor. Some 6% (9/138) of patients without HR expression on the primary and 36% (14/39) of patients with HR+ on the primary presented PIK3CA mutation (P0.001). The level of residual PIK3CA mutations in plasma after one to three cycles of chemotherapy was associated with a poor OS [continuous variable, hazard ratio: 1.03, 95% confidence interval (1.01-1.05), P = 0.007].PIK3CA-mutated HR+/Her2- mBC patients present a poor outcome and resistance to chemotherapy. Patients with PIK3CA-mutated TNBC present a better OS. This could be explained by an enrichment of PIK3CA mutations in luminal BC which lost HR expression in the metastatic setting.SAFIR02 trial: NCT02299999.

Simple Summary Osteosarcoma is the most common form of primary solid bone malignancy, with the highest incidence in adolescence. The therapeutic management includes surgical resection combined with adjuvant/neoadjuvant chemotherapy regimens. Despite this multimodal combination, about two patients out of five are still not cured (5-year overall survival rate at 60%). Complementary therapeutic approaches are required to overcome the frequent resistance to conventional chemotherapy. The aim of the present study was to assess the potential benefit of statins as an adjuvant to chemotherapy. We show that simvastatin synergizes with conventional chemotherapy drugs in terms of cell viability, tumor growth, and dissemination and represents valuable alternative adjuvant therapy that needs further investigation in clinical trials. Abstract Context: Osteosarcoma is the most common primary solid malignancy of the bone, mainly affecting pediatric patients. The main clinical issues are chemoresistance and metastatic spread, leading to a survival rate stagnating around 60% for four decades. Purpose: Here, we investigated the effect of simvastatin as adjuvant therapy on chemotherapy. Methods: Cell viability was assessed by the MTT test, and a combination index was evaluated by an isobologram approach. Cell motility was assessed by wound-healing assay. Cell-derived xenograft models were established in mice. FFPE tumor samples were assessed by immunohistochemistry. Results: In vitro experiments indicate that simvastatin synergized the conventional chemotherapy drugs’ inhibitory effect on cell viability. Functional assays reveal that simvastatin supplementation favored the anticancer mechanism of action of the tested chemotherapy drugs, such as DNA damage through intercalation or direct alkylation and disorganization of microtubules. Additionally, we show that even though simvastatin alone did not modify tumor behavior, it potentiated the inhibitory effect of doxorubicin on primary tumor growth (+50%, p < 0.05) and metastatic spread (+50%, p < 0.05). Our results provide evidence that simvastatin exerted an anti-tumor effect combined with chemotherapy in the preclinical murine model and represents valuable alternative adjuvant therapy that needs further investigation in clinical trials.

Reduction of hearing is the most common sensory impairment among newborns with an incidence of 1-3 per 1000 births. Introduction of an Auditory Newborn screening program allows early identification of hearing impairment. Mainly, congenital hearing loss in early childhood is a result of genetic changes. Due to high frequency of GJB2 pathogenic variants, its molecular characterization among sensorineural hearing reduction cases is already conducted as a routine analysis in many countries. The aim of this study is to show our initial results in the effort to determine whether genetic screening along with the standard hearing screening in newborns is justified. Otoacoustic emission (OAE) method was conducted in 223 newborns at risk of hearing impairment. Among them, 7 did not pass the test in both ears while 9 exhibited one-sided hearing loss. In all 7 children with indication of profound bilateral deafness, the diagnosis was confirmed using auditory brainstem response. Genetic screening of GJB2 gene was performed in 6 of them. Genetic analysis of GJB2 revealed homozygous state of the most common pathogenic variant 35delG in 3 (50%) of the analyzed infants. In the remaining 3 no pathogenic variant was determined. The results indicate that performing auditory OAE together with genetic screening is justified. In newborns who have not passed the hearing screening test and have profound hearing loss, without other syndrome traits, screening for mutations of GJB2 gene should be conducted. Genetic screening enables establishment of early definite diagnosis for deafness and helps in conducting adequate therapy providing timely rehabilitation and social inclusion of deaf child. Key words: hearing loss, genetic screening, auditory screening, GJB2 gene

BACKGROUND: The advanced periodontal disease is characterised by a strongly pronounced loss of attachment and reduction of the alveolar bone support, which leads to luxation, migration of the teeth, functional discomfort and poor facial aesthetics. CASE PRESENTATION: The aim of this paper is to present the case of a 26-year-old female patient, registered at the Clinic of Periodontology with highly expressed gingivitis, unsatisfactory periodontal status, presence of diastemas between the frontal teeth and attachment loss of 5-6 millimetres in different areas. We conducted a thorough classic periodontal treatment, as well as training for proper maintenance of oral hygiene, with frequent professional oral-prophylactic sessions, complemented with orthodontic treatment. Fixed orthodontic appliances were installed, and mild forces were applied for gradual levelling of the teeth, with constant control of the periodontal status. After 20 months of treatment, the patient was in retention. CONCLUSION: Orthodontic therapy of periodontally-affected teeth can begin only after exhaustive administration of a periodontal treatment. Orthodontic treatment as an addition to the periodontal restoration must be gradual with mild forces for an optimal dental response, thus helping to improve function, facial aesthetics and psychological confidence of adult patients.

BACKGROUND: Association of asthma and obesity has been demonstrated in numerous epidemiological studies. However, the underlying mechanisms of the association are not well understood. Both conditions are characterised by chronic tissue inflammation, which includes numerous different inflammatory markers, and possible atopy. AIM: The study aimed to investigate the association between asthma and obesity in children and assess several of potential underlying mechanisms, including the parameters of systemic inflammation (CRP, fibrinogen) and the mechanical effect of obesity on the respiratory system through parameters of lung function. An additional aim was to examine the role of atopy in overweight children with asthma and to investigate the type of respiratory inflammation. MATERIAL AND METHODS: This prospective study included 72 patients in the age group of 7-15 years, including 38 with high body mass index (BMI), 16 with asthma and normal BMI, and 18 with asthma and high BMI for sex and age. Non-specific inflammatory markers (fibrinogen, CRP), eosinophilia, and total serum IgE were investigated. The patients underwent a skin prick test (SPT) with standard inhalant allergen extracts, measurement of fractional exhaled nitric oxide Fe (NO), and an assessment of lung function. RESULTS: In overweight groups of children we determined significantly higher values (p < 0.001) of both acute inflammatory reactants, CRP and fibrinogen, with no difference between children with and without asthma. There was a significant increase in eosinophilia, total IgE, and positive SPT in the asthmatic groups compared to the group of non-asthmatic patients (p < 0.001 for the three parameters). Compared to the group composed of overweight patients without asthma, the asthmatic patients had higher NO values (p < 0.001). No significant difference in the lung function parameters was found between the three groups (p > 0.05). CONCLUSION: A positive association between asthma and obesity with inflammation as an underlying mechanism, eosinophilic one in asthmatic patients and non-eosinophilic one in overweight patients, was determined. It seems that the lung function parameters did not differ between asthmatic patients and overweight patients. No influence of atopy in the association between asthma and obesity was verified. Further analyses of specific inflammatory markers, for an in-depth evaluation of the mechanisms leading to the association of obesity and asthma, are warranted.

Hand spasticity after stroke increases the difficulties of daily living activities and limits the effectiveness of rehabilitation. Radial extracorporeal shock wave therapy (RESWT) has been suggested as an alternative treatment in spasticity reduction.The aim of the study was to evaluate the effectiveness of RESWT on hand spasticity in stroke patients. Material and methods: Controlled clinical trial in which 30patients with post-stroke hand spasticity were assigned in two groups. The examined group received RESWT (6 treatments in a period of two to three days) along with a standard rehabilitation programme. The control group received only standard rehabilitation programme. Clinical evaluations for both groups were performed using the Modified Ashworth Scale (MAS) and the subscore for motor recovery of the Fugl–Meyer assessment for the upper extremity at baseline, immediately after the second, at 6th and 14th week from the start of the rehabilitation.Results: The mean MAS score was significantly decreased inthe examined group after the RESWT.The examined group showed a significant improvement according to Fugl-Meyer test score after treatment. These results lasted 12 weeks after the treatment. Conclusion: RESWT has reduced the hand spasticity and led to a better motor outcome of spastic hand after а stroke., Спастицитетот на шаката по мозочен удар ги зголемува тешкотиите на болните во секојдневното самозгрижување и ја ограничува ефикасноста на рехабилитацијата. Радијалната екстракорпорална терапија со ударни бранови (РЕКТУБ) е предложена како алтернативен третман за редукција на спастицитетот. Целта на истражувањето беше да се евалуираат ефектите од апликација на РЕКТУБ на спастична шака по мозочен удар. Материјал и методи: Контролирана клиничка студија во која беа вклучени 30 пациенти со спастична шака по мозочен удар, поделени во две групи. Испитуваната група беше третирана со РЕКТУБ (6 третмани секој втор или трет ден) и стандардна рехабилитациона програма. Контролната група беше третирана само со стандарднарехабилитациона програма. За клиничка евалуација беа користени Модифицираната Ашфорт Сакала (МАС) и супскорот за моторно закрепнување од Фугл-Мајер тестот за процена на сензомоторната функција на горен екстремитет и тоа пред третманот, по завршување на 2-та, 6-та и 14-та недела од почетокот на рехабилитацијата. Резултати: Средната вредност на оцената на МАС беше значително намалена кај испитуваната група веднаш по РЕКТУБ. Кај испитуваната група се забележа значително подобрување на скорот за моторно закрепнување на Фугл-Мајертестот. Овие резултати се задржаа 12 недели по третманот. Заклучок: РЕКТУБ го намали спастицитетот на шаката по мозочен удар и доведе до нејзино подобро моторно закрепнување.

Objective: We have set as objective to analyze epidemiological data of diagnosed thyroid carcinoma (TC) cases, incidence and prevalence rate by gender, age, histopathological type, and statistical regions in R. of N. Macedonia during the period 1999 to 2015. Material and Methods: Retrospective analysis of medical data collected from the 2 state thyroid departments. Inclusion criteria included newly diagnosed cases of TC in appropriate years for the period 1999 to 2015. We have evaluated: yearly incidence rate, incidence and prevalence by gender, age, the distribution in 8 statistical state regions and histopathological types and subtypes representation. Results: A total number of 422 TC patients were detected, average incidence rate of 1.22/105, with most prevalent papillary TCs79.5%, followed by follicular 10.9%, medullar 4.1%, anaplastic 3.1%, and other rare types with 2.3%. The highest incidence rate was detected in Skopje region, while the lowest in Southeast and the Polog region. The total prevalence rate for the female gender was 32.61/104 and for male 9.27/104 (f/m ratio = 3.52:1), with lowest female/male difference found in the elderly > 65 years (f/m = 2.21/1). Conclusion: Compared with regional epidemiological data we can conclude that Republic of N. Macedonia has very low incidence and prevalence rate, while female/male ratio was similar to that described in the literature. Our low incidence and prevalence rate may be due to 2 possible reasons, 1 would be insufficient diagnosis of only small portion of the real cases in the population, or the second reason may be a real low incidence resulting of specific etiopathogenetic circumstances.

The last two decades have been marked by increased attention towards patient satisfaction as a valuable tool for quality improvement in health care organizations and delivering patient-centred care. However, few articles have investigated the factors of patient's satisfaction among outpatients and inpatients, especially in developing economies. This cross-sectional, quantitative research contributes by analysing patient satisfaction in the context of a developing country and its public health care system among 1318 patients from the Clinic for Plastic and Reconstructive Surgery in Skopje. The study had two main objectives. The first was to analyse factors that influenced patient's satisfaction. The second objective was to analyse the differences in the reported patient satisfaction between outpatients and inpatients within the Clinic for Plastic and Reconstructive Surgery in Skopje. The results indicated higher satisfaction among outpatients scores compared to inpatients. The findings confirm the importance of socio-demographic variables and health status on patient's satisfaction. Improved awareness of these factors may improve the patient experience and increase therapeutic benefits. Furthermore, this research provides an initial insight and understanding into the drivers of patient's satisfaction in the context of developing countries.

Networks of oscillating processes are a common occurrence in living systems. This is as true as anywhere in the energy metabolism of individual cells. Exchanges of molecules and common regulation operate throughout the metabolic processes of glycolysis and oxidative phosphorylation, making the consideration of each of these as a network a natural step. Oscillations are similarly ubiquitous within these processes, and the frequencies of these oscillations are never truly constant. These features make this system an ideal example with which to discuss an alternative approach to modeling living systems, which focuses on their thermodynamically open, oscillating, non-linear and non-autonomous nature. We implement this approach in developing a model of non-autonomous Kuramoto oscillators in two all-to-all weighted networks coupled to one another, and themselves driven by non-autonomous oscillators. Each component represents a metabolic process, the networks acting as the glycolytic and oxidative phosphorylative processes, and the drivers as glucose and oxygen supply. We analyse the effect of these features on the synchronization dynamics within the model, and present a comparison between this model, experimental data on the glycolysis of HeLa cells, and a comparatively mainstream model of this experiment. In the former, we find that the introduction of oscillator networks significantly increases the proportion of the model's parameter space that features some form of synchronization, indicating a greater ability of the processes to resist external perturbations, a crucial behavior in biological settings. For the latter, we analyse the oscillations of the experiment, finding a characteristic frequency of 0.01–0.02 Hz. We further demonstrate that an output of the model comparable to the measurements of the experiment oscillates in a manner similar to the measured data, achieving this with fewer parameters and greater flexibility than the comparable model.

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)., Women are exposed to increased burden of mental disorders during the perinatal period: 13–19% experience postpartum depression. Perinatal psychological suffering affects early mother-child relationship, impacting child’s emotional and cognitive development. Return-to-work brings additional vulnerability given the required balance between parenting and job demands. The MAternal Mental Health in the WORKplace (MAMH@WORK) project aims to develop and evaluate the effectiveness of a brief and sustainable intervention, promoting (a) maternal mental health throughout pregnancy and first 12 months after delivery, and (b) quality of mother–child interactions, child emotional self-regulation, and cognitive self-control, while (c) reducing perinatal absenteeism and presenteeism. MAMH@WORK is a three-arm randomized controlled trial. A short-term cognitive-behavioral therapy-based (CBT-based) psychoeducation plus biofeedback intervention will be implemented by psychiatrists and psychologists, following a standardized procedure manual developed after consensus (Delphi method). Participants (n = 225, primiparous, singleton pregnant women at 28–30 weeks gestational age, aged 18–40 years, employed) will be randomly allocated to arms: CBT-based psychoeducation intervention (including mindfulness); psychoeducation plus biofeedback intervention; and control. Assessments will take place before and after delivery. Main outcomes (and main tools): mental health literacy (MHLS), psychological wellbeing (HADS, EPDS, KBS, CD-RISC, BRIEF COPE), quality of mother–child interaction, child–mother attachment, child emotional self-regulation and cognitive self-control (including PBQ, Strange Situation Procedure, QDIBRB, SGS-II, CARE-Index), job engagement (UWES), and presenteeism. Intention-to-treat and per-protocol analyses will be conducted; Cohen’s d coefficient, Cramer’s V and odds ratio will be used to assess the effect size of the intervention. MAMH@WORK is expected to contribute to mental health promotion during the perinatal period and beyond. Its results have the potential to inform health policies regarding work–life balance and maternal mental health and wellbeing promotion in the workplace., The development of this protocol has benefited from the funding from FCT, under the grants UIDB/04295/2020 and UIDP/04295/2020.

Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/), Self-management of health requires skills to obtain, process, understand, and use health-related information. Assessment of adolescents’ functional health literacy requires valid, reliable, and low-burden tools. The main objective of this study was to adapt and study the psychometric properties of the Newest Vital Sign for the Portuguese adolescents’ population (NVS-PTeen). Classic psychometric indicators of reliability and validity were combined with item response theory (IRT) analyses in a cross-sectional survey, complemented with a 3-month test-retest assessment. The NVS-PTeen was self-administered to students enrolled in grades 8 to 12 (12 to 17 years old) in a school setting. Overall, 386 students (191 girls) from 16 classes of the same school participated in the study (mean age = 14.5; SD = 1.5). Internal reliability of the NVS-PTeen was α = 0.60. The NVS-PTeen total score was positively and significantly correlated with Portuguese (r = 0.28) and mathematics scores (r = 0.31), school years (r = 0.31), and age (r = 0.19). Similar to the original scale (for the U.S.), the NVS-PTeen is composed of two dimensions, reading-related literacy and numeracy. Temporal reliability is adequate, though with a learning effect. IRT analyses revealed differences in difficulty and discriminative capacity among items, all with adequate outfit and infit values. Results showed that the NVS-PTeen is valid and reliable, sensible to inter-individual educational differences, and adequate for regular screening of functional health literacy in adolescents., This research was funded by the Fundação para a Ciência e a Tecnologia (FCT), under the project Health Information of Portuguese Population: Health Knowledge & Perceived Quality and Accessibility of Health Information Sources (Reference: HMSP-IISE/SAU-ICT/0004/2009). The writing of the paper also benefited from funding from the FCT under the grants UIDB/04295/2020 and UIDP/04295/2020. This funding entity had no role in the design or writing of this artic

Copyright © 2021 Candeias, Alarcão, Stefanovska-Petkovska, Santos, Virgolino, Pintassilgo, Pascoal, Costa and Machado. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms., The increasing number of international migrants (ranging from 153 million in 1990 to ~272 million in 2019) brought to attention the wide variation of national contexts concerning the policy measures to protect migrants' rights and ensuring their equal access to basic and essential services, namely in health. Sexual and Reproductive Health (SRH) is a key component to the overall health and quality of life and is impacted by power inequities inherent to society's institutions, environment, economics, and culture. In Portugal, guidelines for intervention in SRH are insufficient, a gap that is more pronounced with migrant populations due to the absence of culturally sensitive indicators to assess and monitor SRH. The aim of this work was 2-fold: to identify good practices in the SRH field, with a particular focus, whenever possible, on migrant populations, and to identify relevant and inclusive indicators to monitor SRH in Portugal. A Delphi panel (via online survey) with 66 experts (researchers, teachers, and health professionals) and 16 stakeholders (non-governmental organizations, civil society, and governmental organizations) was implemented in two rounds. Panelists were asked to state their level of agreement (5-point Likert-type scale) regarding four different SRH areas: Sexual Health, Reproductive Health, Social-Structural Factors, and Good Practices. Items were based on literature review and a World Café with 15 experts and stakeholders. Participation rate was 68% and response rate was 97% on the first round. From the initial list of 142 items, a total of 118 (83%) items were approved by consensus. Findings may provide extended opportunities for the healthcare system to engage in better informed decisions and more inclusive and integrative strategies regarding SRH, contributing to build political measures toward sexual and reproductive justice., This work contributes to the study Fertility, Migration and Acculturation: Intersectional approach to the sexual and reproductive experiences and expectations among Cape Verdean and Portuguese Families (FEMINA project), granted by Fundação para a Ciência e a Tecnologia, I.P. with national funding (PTDC/SOC-SOC/30025/2017). It is also a valuable contribute for the study Promoting citizenship and sexual rights in Immigrant Populations in Portugal: co-production of recommendations and best practices for the reduction of sexual and reproductive inequalities (ProCima project), granted by the Asylum, Migration and Integration Fund (PT/2018/FAMI/356). The writing of this manuscript had also the support of Fundação para a Ciência e a Tecnologia, grant number UIDB/04295/2020 and UIDP/04295/2020.

Background: Sand flies (Diptera: Psychodidae) are medically important vectors of human and veterinary disease-causing agents. Among these, the genus Leishmania (Kinetoplastida: Trypanosomatidae), and phleboviruses are of utmost importance. Despite such significance, updated information about sand fly fauna is missing for Balkan countries where both sand flies and autochtonous leishmaniases are historically present and recently re-emerging. Therefore, a review of historical data on sand fly species composition and distribution in the region was followed by a large-scale entomological survey in eight Balkan countries to provide a recent update on local sand fly fauna. Methods: The literature search involved the period 1910–2019. The entomological survey was conducted at 1189 sampling stations in eight countries (Bulgaria, Bosnia and Herzegovina, Croatia, Kosovo, Montenegro, North Macedonia, Serbia and Slovenia), covering 49 settlements and 358 sampling sites between June and October in the years 2014 and 2016, accumulating 130 sampling days. We performed a total of 1189 trapping nights at these stations using two types of traps (light and CO2 attraction traps) in each location. Sampling was performed with a minimal duration of 6 (Montenegro) and a maximal of 47 days (Serbia) between 0–1000 m.a.s.l. Collected sand flies were morphologically identified. Results: In total, 8490 sand fly specimens were collected. Morphological identification showed presence of 14 species belonging to genera Phlebotomus and Sergentomyia. Historical data were critically reviewed and updated with our recent findings. Six species were identified in Bosnia and Herzegovina (2 new records), 5 in Montenegro (2 new records), 5 in Croatia (2 new records), 9 in Bulgaria (5 new records), 11 in North Macedonia (1 new record), 10 in Serbia (no new records), 9 in Kosovo (3 new records) and 4 in Slovenia (no new records). Conclusions: This study presents results of the first integrated sand fly fauna survey of such scale for the Balkan region, providing first data on sand fly populations for four countries in the study area and presenting new species records for six countries and updated species lists for all surveyed countries. Our findings demonstrate presence of proven and suspected vectors of several Leishmania species. [Figure not available: see fulltext.] © 2020, The Author(s)., European Food Safety Authority, EFSA European Centre for Disease Prevention and Control, ECDC, The work was carried out under the VectorNet project, a European network for sharing data on the geographic distribution of arthropod vectors, transmitting human and animal disease agents (Contract OC/EFSA/AHAW/2013/02-FWC1) funded by the European Food Safety Authority (EFSA) and the European Centre for Disease Prevention and Control (ECDC). Acknowledgements

The Roma Diaspora¿traditionally known as Gypsies¿remains among the least explored population migratory events in historical times. It involved the migration of Roma ancestors out-of-India through the plateaus of Western Asia ultimately reaching Europe. The demographic effects of the Diaspora¿bottlenecks, endogamy, and gene flow¿might have left marked molecular traces in the Roma genomes. Here, we analyze the whole-genome sequence of 46 Roma individuals pertaining to four migrant groups in six European countries. Our analyses revealed a strong, early founder effect followed by a drastic reduction of ~44% in effective population size. The Roma common ancestors split from the Punjabi population, from Northwest India, some generations before the Diaspora started, 50% of their genomes. The linguistic and historical differentiation of Roma in migrant groups is confirmed by the differential proportion, but not a differential source, of European admixture in the Roma groups, which shows a westward cline. In the present study, we found that despite the strong admixture Roma had in their diaspora, the signature of the initial bottleneck and the subsequent endogamy is still present in Roma genomes., This work was supported by the Spanish Ministry of Economy and Competitiveness (Grant No. PID2019-106485GB-I00 and CGL2016-75389-P—MINEICO/FEDER, UE) and “Unidad de Excelencia Maríade Maeztu” (funded by AEI—CEX2018-000792-M) to D.C. and F.C.; and Agència de Gestió d’Ajuts Universitaris i de la Recerca (Generalitat de Catalunya, Grant No. 2017SGR00702). N.F.-P. was supported by a FPU17/03501 fellowship. All samples were collected with informed consent from the participants under the approval of the IRB of the CEIC-Parc Salut Mar 2016/6723/I.

Rapalogs have become standard-of-care in patients with metastatic breast, kidney, and neuroendocrine cancers. Nevertheless, tumor escape occurs after several months in most patients, highlighting the need to understand mechanisms of resistance. Using a panel of cancer cell lines, we show that rapalogs downregulate the putative protein kinase TRIB3 (tribbles pseudokinase 3). Blood samples of a small cohort of patients with cancer treated with rapalogs confirmed downregulation of TRIB3. Downregulation of TRIB3 was mediated by LRRFIP1 independently of mTOR and disrupted its interaction with the spliceosome, where it participated in rapalog-induced deregulation of RNA splicing. Conversely, overexpression of TRIB3 in a panel of cancer cell lines abolished the cytotoxic effects of rapalogs. These findings identify TRIB3 as a key component of the spliceosome, whose repression contributes significantly to the mechanism of resistance to rapalog therapy. Significance: Independent of mTOR signaling, rapalogs induce cytoxicity by dysregulating spliceosome function via repression of TRIB3, the loss of which may, in the long term, contribute to therapeutic resistance.

Summary We performed a retrospective evaluation of the criteria for suspected pulmonary embolism (PE) and requests for computed tomography angiography (CTA) by the emergency room (ER) teams. Simultaneously, we tried to find irregularities in their work. Then we designed new behavioral protocols, and yearly we evaluated the effect on the workload of the computed tomography (CT) unit of the Roentgenology and Radiology at the University Hospital – Pleven and the total impact on the behavior of the teams in cases of suspected for PE. The data from before and after the intervention was evaluated. After the implementation of the protocols, matching the criteria of PE rule-out criteria (PERC), the number of D-dimer testing, echocardiography, and computed tomography pulmonary angiographies (CTPA) was significantly higher. We found that the number of patients urgently transported for primary thrombectomy had increased, and the reduction of PE mortality in the Emergency Unit proves the safety of our intervention. Overall, the intervention in the attitude of the ER teams has a significant positive effect on the management of patients with suspected PE.

Reciprocal chromosomal rearrangements, de novo or inherited, often raise a concern about the foetal health and outcome of the affected pregnancies. The size and origin of the translocated chromosomes could be variable. Cryptic translocations often remain undetected and misdiagnosed. Several studies confirmed that there could be a loss of a certain amount of genomic material within breakpoints, which leads to uncertainties in predicting the pregnancy outcome. A 38 year pregnant woman approached our clinic for a genetic counselling. This was her first pregnancy, with normal foetal growth on ultrasound follow up. The amniocentesis was carried out due to the advanced maternal age. Conventional cytogenetic report showed putative deletion of short arm of chromosome 5. Cordocentesis was done additionally at 18 week of pregnancy due to the discrepancy between normal ultrasonographic finding and karyotype result. MLPA analysis showed that 5p critical region was present. FISH has been performed, using 5p;q probe (Cytocell aquarius, Cat No LPU 013), which showed cryptic de novo translocation 46,XX.ish t(5;17) (p15.1;q25). Decision to terminate the pregnancy was made due to the cytogenetic finding and reduced foetal growth recorded after 20th week. Examination at autopsy showed dysmorphism consistent with some features of cri du chat syndrome-micrognathia, hypertelorism, reduced fetal growth, as well as underdeveloped brain for gestational period. Novel technologies in molecular cytogenetics and array techniques could help in detecting minor imbalances and decrease the risk of the birth of malformed fetus. Combination of several prenatal methods -both ultrasonography and novel genetic techniques, in a small number of cases can help in the process of genetic counselling.

A six-month-old Pomeranian male dog was referred due to a month long history of unformed, soft faeces and mild weight loss. Stool analyses by direct faecal smear, Zinc sulphate flotation and the Baermann concentration method revealed an infection with Strongyloides stercoralis. The dog was initially treated once with a combination drug of praziquantel, pyrantel and febantel (½ Drontal® Plus Tablets for puppies and small dogs; Bayer; i.e. 31.5 mg/kg bodyweight of febantel ). The treatment was repeated after 12 days with the same dosage for 3 consecutive days. The stool analyses performed 14 days and 3 months after the second treatment were negative for S. stercoralis larvae. The results suggest that a repeated treatment with Drontal® Plus Tablets is effective against S. stercoralis in dogs and has no adverse effects.

Ehrlichia canis, the etiologic agent of canine monocytic ehrlichiosis (CME), is mainly transmitted by the brown dog tick Rhipicephalus sanguineus. Clinical signs of the disease can be various, depending on the stage of the disease. Typical changes in hematological and blood biochemical parameters are: severe thrombocytopenia, mild to marked non regenerative anaemia and hypoalbuminemia. In order to present the effects of the treatment protocol on several hematological and biochemistry parameters, 34 Ehrlichia canis positive dogs were compared before and after treatment with doxycycline 10mg/kg/day, in duration of four weeks. Besides the clinical sings and laboratory findings, diagnosis was confirmed by antibody tests (Bionote, Korea, AGROLABO S.p.A., Italy). The most common clinical sings were depression, lethargy, pyrexia, vomiting and anorexia. Hematological analyses were performed on the automatic hematology analyzer Exigo EosVet (Sweden), while biochemistry analyses (alanine aminotransferase, aspartate aminotransferase, urea, creatinine, albumin, total protein, globulin and alkaline phosphatase) were performed using the automatic analyzer ChemWell 2910 (Awareness Technology, INC, USA). Statistically significant difference (pE.canis resulted in significant increase of hematology parameters (red blood cells, hemoglobin, haematocrit and platelets), as well as albumins in serum.

Abnormal cerebrospinal fluid (CSF) pulsatility has been implicated in patients suffering from various diseases, including multiple sclerosis and hypertension. CSF pulsatility results in subarachnoid space (SAS) width changes, which can be measured with near-infrared transillumination backscattering sounding (NIR-T/BSS). The aim of this study was to combine NIR-T/BSS and wavelet analysis methods to characterise the dynamics of the SAS width within a wide range of frequencies from 0.005 to 2 Hz, with low frequencies studied in detail for the first time. From recordings in the resting state, we also demonstrate the relationships between SAS width in both hemispheres of the brain, and investigate how the SAS width dynamics is related to the blood pressure (BP). These investigations also revealed influences of age and SAS correlation on the dynamics of SAS width and its similarity with the BP. Combination of NIR-T/BSS and time-frequency analysis may open up new frontiers in the understanding and diagnosis of various neurodegenerative and ageing related diseases to improve diagnostic procedures and patient prognosis.

Hip dysplasia is one of the most common skeletal disorders. As a late consequence 20–25% of the patients are at risk to develop secondary osteoarthritis and may require total hip replacement early in life. The treatment principles of hip dislocation are (1) concentric reposition, (2) retention, i.e., plaster in human post or Pavlik harness and (3) maturation in abduction flexion orthesis. The Tubingen splint was introduced as a further development of abduction devices for the treatment of (residual) hip dysplasia with stable hips. The advantages are easy handling, adjustment according to growth and safe limitation of abduction. The aim of this study was to determine the success of treatment of unstable hips with use of the Tubingen splint from early diagnosis until final end of therapy hence normal ultrasound findings. From January 2003 to August 2016 79 children with 109 sonographic unstable hips were treated with the Tubingen splint initially consequently 24 h/day. Inclusion criteria were diagnosis of type D, type III a/b or type IV hips according to Graf and beginning of treatment at an age of less or equal 6 weeks, without limitation of abduction on clinical examination. At the time of diagnosis 51 type D (46.8%), 46 type III (42.2%) and 12 type IV (11.0%) hips were noticed. In 30 patients (38.0%) bilateral hip dysplasia (type D–IV) was diagnosed. 104 of 109 hips (95.4%) treated with the Tubingen splint could be transferred in a type I hip after a mean treatment period of 88.9 days (SD ± 26.0). In 5 cases (4.6%, 1 type III and 4 type IV hips) the treatment failed. Our data show, that successful treatment of unstable hips in neonates with the Tubingen splint is a comparably successful treatment modality relative to the Pavlik harness and Fettweis plaster.

This is the third in a planned series of data papers presenting modelled vector distributions produced during the ECDC and EFSA funded VectorNet project. The data package presented here includes those 'Culicoides' vectors species first modelled in 2015 as part of the VectorNet gap analysis work namely 'C. imicola, C. obsoletus, C. scoticus, C. dewulfi, C. chiopterus, C. pulicaris, C. lupicaris, C. punctatus, and C. newsteadi'. The known distributions of these species within the Project area (Europe, the Mediterranean Basin, North Africa, and Eurasia) are currently incomplete to a greater or lesser degree. The models are designed to fill the gaps with predicted distributions, to provide a) first indication of vector species distributions across the project geographical extent, and b) assistance in targeting surveys to collect distribution data for those areas with no field validated information. The models are based on input data from light trap surveillance of adult 'Culicoides' across continental Europe and surrounding regions (71.8°N –33.5°S, – 11.2°W – 62°E), concentrated in Western countries, supplemented by transect samples in eastern and northern Europe. Data from central EU are relatively sparse. Funding statement: This work was carried out with support from the VectorNet framework contract OC/EFSA/AHAW/2013/02-FWC1 funded by the European Centre for Disease prevention and Control (ECDC) and the European Food Safety Agency (EFSA) and the PALE-Blu H2020 Project ID: 727393.

The Roma population is a European ethnic minority characterized by recent and multiple dispersals and founder effects. After their origin in South Asia around 1,500 years ago, they migrated West. In Europe, they diverged into ethnolinguistically distinct migrant groups that spread across the continent. Previous genetic studies based on genome-wide data and uniparental markers detected Roma founder events and West-Eurasian gene flow. However, to the best of our knowledge, it has not been assessed whether these demographic processes have equally affected both sexes in the population. The present study uses the largest and most comprehensive dataset of complete mitochondrial and Y chromosome Roma sequences to unravel the sex-biased patterns that have shaped their genetic history. The results show that the Roma maternal genetic pool carries a higher lineage diversity from South Asia, as opposed to a single paternal South Asian lineage. Nonetheless, the European gene flow events mainly occurred through the maternal lineages; however, a signal of this gene flow is also traceable in the paternal lineages. We also detect a higher female migration rate among European Roma groups. Altogether, these results suggest that sociocultural factors influenced the emergence of sex-biased genetic patterns at global and local scales in the Roma population through time., Tis work was supported by the Spanish Ministry of Economy and Competitiveness (grant numbers CGL2016- 75389-P (MINEICO/FEDER, UE), PID2019-106485GB-I00 (MINEICO), and “Unidad María de Maeztu” (MDM-2014-0370) to DC and FC; and Agència de Gestió d’Ajuts Universitaris i de la Recerca (Generalitat de Catalunya, grant 2017SGR00702). NF-P was supported by a FPU17/03501 fellowship

The most prevalent "rare" disease worldwide, cystic fibrosis (CF), is an autosomal recessive multisystem disease, caused by mutations in the CFTR gene. The knowledge of CFTR mutations present in certain population is important for designing a simple, fast and cost-effective genetic testing approach, also for better management of CF patients, including the administration of novel targeted therapies. Here, we present genetic results of 158 unrelated CF patients from the National CF Registry of the Republic of North Macedonia. Initially, patients were screened for the 11 most common CF mutations. Additional CF mutations and large deletions/duplications in the CFTR gene were analyzed using commercial kits. If the genotype was undetermined, all CFTR exons were analyzed using Sanger DNA sequencing or next generation sequencing (NGS) (since 2014). The most common CF mutation, c.l521_ 1523del (legacy name F508del), was found with an overall incidence of 75.9%. Additionally, 26 other pathogenic variants and three large deletions were identified in the CFTR gene as a genetic cause of CF. Two of these, c.1070 C>T (p.Ala357Val) and c.2779_2788dup CTTGCTATGG (p.Gly930AlafsTer48), were novel. According to the distribution and prevalence of the pathogenic variants detected in our patients, a fast and cost-effective method, based on a single base extension was designed as a first-line CF genetic test with a 90.0% detection rate within our population. Furthermore, the knowledge of CFTR mutation classes in our CF patients represents the first step toward personalized therapy for CF in our country.

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated., Background: The existing knowledge on the interplay between reproductive and sexual health, migration and acculturation is recent and inconsistent, particularly on the sociocultural motives and constraints regarding fertility. Therefore, sexual and reproductive health (SRH) surveys are needed to provide accurate and comparable indicators to identify and address SRH inequalities, with specific focus on under researched aspects, such as the interrelation between migration and gender. FEMINA (FErtility, MIgratioN and Acculturation) aims to investigate intersectional SRH inequalities among Cape Verdean immigrant and Portuguese native families and how they impact on fertility in Portugal. This study will use a comprehensive approach exploring simultaneously the components of SRH, namely regarding identities, perceptions and practices of both women and men among lay people and relevant experts and stakeholders. The project has three main goals: 1) to identify social determinants of SRH among Cape Verdean immigrant and Portuguese native men and women of reproductive age; 2) to gain understanding of the diversity of the sexual and reproductive experiences and expectations of Cape Verdean immigrant and Portuguese native men and women of reproductive age, considering the singularities of their migratory, social and family dynamics; and 3) to produce recommendations for policy makers, employers and service providers on how to better address the SRH needs of Portuguese-born and immigrant populations. Methods: The study will address these goals using a mixed methods approach, including: a cross-sectional telephone survey with a probabilistic sample of 600 Cape Verdean immigrant and 600 Portuguese native women and men (women aged 18 to 49 and men aged 18 to 54), residents of the Greater Lisbon Area; a qualitative research through in-depth interviews with a subsample of 30 Cape Verdean immigrants and 30 Portuguese native men and women; and a Delphi technique for finding consensus on good practices in SRH for the entire population with a special emphasis on immigrants, namely extra-EU migrants. Discussion: Data will be used to produce a comprehensive set of indicators to monitor SRH in Portugal, to foster a greater understanding of its specificities and challenges to policy and decision makers, and to provide targeted recommendations to promote inclusive and migrant sensitive SRH services., The FEMINA project (PTDC/SOC-SOC/30025/2017) was granted by Fundação para a Ciência e a Tecnologia, I.P. with national funding. This publication is supported by Fundação para a Ciência e a Tecnologia project grant and ISCTE-IUL funds.

BACKGROUND: Postmenopausis is a period that starts one year after the last menstruation. Late menopause, after 70 years, is called senile. AIM: To examine the correlation between endometrial thickness and the risk of endometrial malignancy in postmenopausal. MATERIAL AND METHODS: Prospective clinical study involving 120 postmenopausal patients treated at the University Clinic for Gynecology and Obstetrics – Skopje, divided into two groups: control and examination. The control group included 40 postmenopausal patients, hospitalised and operated due to urogenital pathology. The examined group consisted of 80 patients divided into three subgroups according to the ultrasound verified thickness of the endometrium: from 5-8 mm; > 8-11 mm and above 11 mm. A detailed history and intervention were taken in the patients from both groups, and the material was sent for histopathological analysis to determine eventual malignancy. RESULTS: The probability of endometrial malignancy significantly increased by 1.012 times in the group with a thickness of the endometrium from 5-8 mm, 1.769 times in the endometrial thickness group > 8-11 mm and 4.737-fold in the group over 11 mm compared to the control group. CONCLUSION: In postmenopausal patients, the likelihood of endometrial cancer significantly increases with the thickness of the endometrium.

Aim To assess the association between azoospermia factor c microrearrangements and semen quality, and between Y-chromosome background with distinct azoospermia factor c microrearrangements and semen quality impairment. Methods This retrospective study, carried out in the Research Center for Genetic Engineering and Biotechnology “Georgi D. Efremov,” involved 486 men from different ethnic backgrounds referred for couple infertility from 2002- 2017: 338 were azoospermic/oligozoospermic and 148 were normozoospermic. The azoospermia factor c microrearrangements were analyzed with sequence tagged site and sequence family variant markers, quantitative fluorescent polymerase chain reaction, and multiplex ligation probe amplification analysis. The Y-haplogroups of all participants were determined with direct single nucleotide polymorphism typing and indirect prediction with short tandem repeat markers.Results Our participants had two types of microdeletions: gr/gr and b2/b3; three microduplications: b2/b4, gr/gr, and b2/b3; and one complex rearrangement gr/gr deletion + b2/b4 duplication. Impaired semen quality was not associated with microrearrangements, but b2/b4 and gr/ gr duplications were significantly associated with haplogroup R1a (P < 0.001 and P = 0.003, respectively) and b2/b3 deletions with haplogroup E (P = 0.005). There were significantly more b2/b4 duplication carriers in Albanians than in Macedonians with haplogroup R1a (P = 0.031). Conclusion Even though azoospermia factor c partial deletions/duplications and Y-haplogroups were not associated with impaired semen quality, specific deletions/ duplications were significantly associated with distinct haplogroups, implying that the Y chromosome background may confer susceptibility to azoospermia factor c microrearrangements.

Osteosarcoma is the most prevalent primary bone malignancy in children and young adults. Resistance to chemotherapy remains a key challenge for effective treatment of patients with osteosarcoma. The aim of the present study was to investigate the preventive role of metallothionein-2A (MT2A) in response to cytotoxic effects of chemotherapy. A panel of human and murine osteosarcoma cell lines, modified for MT2A were evaluated for cell viability, and motility (wound healing assay). Cell-derived xenograft models were established in mice. FFPE tumour samples were assessed by IHC. In vitro experiments indicated a positive correlation between half-maximal inhibitory concentration (IC50) for drugs in clinical practice, and MT2A mRNA level. This reinforced our previously reported correlation between MT2A mRNA level in tumour samples at diagnosis and overall survival in patients with osteosarcoma. In addition, MT2A/MT2 silencing using shRNA strategy led to a marked reduction of IC50 values and to enhanced cytotoxic effect of chemotherapy on primary tumour. Our results show that MT2A level could be used as a predictive biomarker of resistance to chemotherapy, and provide with preclinical rational for MT2A targeting as a therapeutic strategy for enhancing anti-tumour treatment of innate chemo-resistant osteosarcoma cells.

Objectives The aim of our study was to evaluate the survival rate of all thyroid carcinomas (TCs) diagnosed in the 1999–2015 period in the Republic of North Macedonia and to analyze the prognostic influence of several characteristics on development of distant metastases, as well as to analyze the prognostic effect of seven clinical and constitutional features on mortality. Material and methods A retrospective analysis of medical data from all TCs diagnosed in 1999–2015 was performed. The survival rate of all types of TCs was estimated using the Kaplan Meier method. Univariate and multivariate logistic regression analysis was applied for evaluation of the predictive role of seven clinical and constitutional characteristics for development of distant metastases, and the univariate Cox-proportional model was applied for evaluation of the predictors for mortality. Results A total of 422 TC cases were diagnosed in the 17-year period, with an average survival time of 212.99 months. Results of the univariate regression analysis showed that dimension at initial ultrasound and histopathological type of tumor were significantly predictive variables for distant metastases. Multifocal tumors vs. unifocal tumors < 15 mm significantly increased the probability of distant metastases by 7.401 (p = 0.005, 95% CI = 1.817–30.190) times. Age, initial lymph node involvement, number of radioiodine therapies, and histopathology of the tumor were selected as independent significant predictors for mortality. Conclusion Our results showed an excellent overall prognosis of thyroid tumors in the Macedonian population. The dimension of the tumor, multifocality, and histopathological type were the most relevant prognostic predictive features for development of distant metastases.

Taenia solium and Taenia saginata are food-borne parasites of global importance. In eastern Europe only fragmented information is available on the epidemiology of these zoonotic parasites in humans and animal populations. In particular for T. solium, on-going transmission is suspected. The aim of this systematic review was to collect the available data and describe the current knowledge on the epidemiology of T. solium and T. saginata in eastern Europe.Literature published in international databases from 1990 to 2017 was systematically reviewed. Furthermore, local sources and unpublished data from national databases were retrieved from local eastern European experts. The study area included 22 countries.Researchers from 18 out of the 22 countries provided data from local and unpublished sources, while no contacts could be established with researchers from Belarus, Kosovo, Malta and Ukraine. Taeniosis and human cysticercosis cases were reported in 14 and 15 out of the 22 countries, respectively. Estonia, the Former Yugoslav Republic of Macedonia, Lithuania, Moldova, Poland, Romania, Serbia, and Slovakia reported cases of porcine cysticercosis. Croatia, Czech Republic, Estonia, Former Yugoslav Republic of Macedonia, Moldova, Poland, Romania, Serbia, Slovakia, and Ukraine reported bovine cysticercosis.There is indication that taeniosis and cysticercosis are present across eastern Europe but information on the occurrence of T. solium and T. saginata across the region remains incomplete. Available data are scarce and species identification is in most cases absent. Given the public health impact of T. solium and the potential economic and trade implications due to T. saginata, notification of taeniosis and human cysticercosis should be implemented and surveillance and notification systems in animals should be improved.

Simple Summary Accumulating evidence supports a key function for Tribbles proteins in oncogenesis, both in leukemia and solid tumors. However, the exact role of these proteins is hard to define since in a context-dependent manner they can function as both oncogenes and tumor suppressors. Their complex role arises from the capacity to interact with a wide range of target molecules thereby acting as molecular scaffolds and signaling regulators of multiple pathways. This review focuses on one particular Tribbles family member, namely, TRIB3, addressing its gene and protein expression, as well as its role in cancer development and progression. Abstract The first Tribbles protein was identified as critical for the coordination of morphogenesis in Drosophila melanogaster. Three mammalian homologs were subsequently identified, with a structure similar to classic serine/threonine kinases, but lacking crucial amino acids for the catalytic activity. Thereby, the very weak ATP affinity classifies TRIB proteins as pseudokinases. In this review, we provide an overview of the regulation of TRIB3 gene expression at both transcriptional and post-translational levels. Despite the absence of kinase activity, TRIB3 interferes with a broad range of cellular processes through protein–protein interactions. In fact, TRIB3 acts as an adaptor/scaffold protein for many other proteins such as kinase-dependent proteins, transcription factors, ubiquitin ligases, or even components of the spliceosome machinery. We then state the contribution of TRIB3 to cancer development, progression, and metastasis. TRIB3 dysregulation can be associated with good or bad prognosis. Indeed, as TRIB3 interacts with and regulates the activity of many key signaling components, it can act as a tumor-suppressor or oncogene in a context-dependent manner.

Introduction: Most of the patients feel pain 4 hours after the arch applying, gaining the highest level after 24 hours and its lowering in the next few days. Literature reports show that the fear of pain is a very important reason for discouraging the patient to agree for this kind of orthodontic treatment The aim of this study was to evaluate the effectiveness of the biostimulative laser treatment in pain reduction in patients with fixed orthodontic appliances. Materials and methods. Fifteen patients were treated with low energy level biostimulative diode laser, used 2 minutes per quadrant immediately after placement of fixed orthodontic appliances and in the following four days. The control group of 15 patients received analgesic therapy for period of five days. The pain was assessed subjectively as strong, medium or no pain. The pain disappeared in 20% of the subjects in the examined group after the first day, while in 60% and 26.6% of the subjects medium and isolated pain was still present at day 2 and 3, respectively. Results. The pain disappeared in all the patients treated with laser at day 5. In the control group, strong pain was present in all the subjects the first day, decreasing to 60% of strong pain and 20% medium pain the second day. After day three, the control group demonstrated medium localized pain in 40% of the cases, which dropped to 26.6% after the fourth day, suggesting delayed pain reduction, compared to the laser treated group. Conclusion. Our results suggest that the low energy laser treatment can successfully be used for pain reduction during the initial discomfort period after placing fixed orthodontic appliances.

Background Osteosarcoma is the most prevalent primary bone malignancy in children and young adults. These tumors are highly metastatic, leading to poor outcome. We previously demonstrated that Cysteine-rich protein 61 (CYR61/CCN1) expression level is correlated to osteosarcoma aggressiveness in preclinical model and in patient tumor samples. The aim of the present study was to investigate the CYR61-induced intracellular mechanisms leading to the acquisition of an invasive phenotype by osteosarcoma cells. Methods Modified murine and human osteosarcoma cell lines were evaluated for cell adhesion, aggregation (spheroid), motility (wound healing assay), phenotypic markers expression (RT-qPCR, western blot). Cell-derived xenograft FFPE samples and patients samples (TMA) were assessed by IHC. Results CYR61 levels controlled the expression of markers related to an Epithelial-mesenchymal transition (EMT)-like process, allowing tumor cells to migrate acquiring a competent morphology, and to be able to invade the surrounding stroma. This phenotypic shift indeed correlated with tumor grade and aggressiveness in patient samples and with the metastatic dissemination potential in cell-derived xenograft models. Unlike EGFR or PDGFR, IGF1Rβ levels correlated with CYR61 and N-cadherin levels, and with the aggressiveness of osteosarcoma and overall survival. The expression levels of IGF1Rβ/IGF1 axis were controlled by CYR61, and anti-IGF1 neutralizing antibody prevented the CYR61-induced phenotypic shift, aggregation, and motility abilities. Conclusions Taken together, our study provides new evidence that CYR61 acts as a key inducing factor in the metastatic progression of osteosarcoma by playing a critical role in primary tumor dissemination, with a process associated with IGF1/IGFR stimulation. This suggests that CYR61 may represent a potential pivotal target for therapeutic management of metastases spreading in osteosarcoma, in correlation with IGF1/IGFR pathway. Electronic supplementary material The online version of this article (10.1186/s12885-019-5282-4) contains supplementary material, which is available to authorized users.

BackgroundThe quantitative fluorescent polymerase chain reaction (QF-PCR) has proven to be a reliable method for detection of common fetal chromosomal aneuploidies. However, there are some technical shortcomings, such as uncertainty of aneuploidy determination when the short tandem repeats (STR) height ratio is unusual due to a large size difference between alleles or failure due to the presence of maternal cell contamination (MCC). The aim of our study is to facilitate the implementation of the QF-PCR as a rapid diagnostic test for common fetal aneuploidies.MethodsHere, we describe an in-house one-tube multiplex QF-PCR method including 20 PCR markers (15 STR markers and 5 fixed size) for rapid prenatal diagnosis of chromosome 13, 18, 21, X and Y aneuploidies. In order to improve the aneuploidy classification of a given diallelic STR marker, we have employed a multilevel logistic regression analysis using "height-ratio" and "allele-size-difference" as fixed effects and "marker" as a random effect. We employed two regression models, one for the 2:1 height ratio (n = 48 genotypes) and another for the 1:2 height ratio (n = 41 genotypes) of the trisomic diallelic markers while using the same 9015 genotypes with normal 1:1 height ratio in both models. Furthermore, we have described a simple procedure for the treatment of the MCC, prior DNA isolation and QF-PCR analysis.ResultsFor both models, we have achieved 100% specificity for the marker aneuploidy classification as compared to 98.60% (2:1 ratio) and 98.04% (1:2 ratio) specificity when using only the height ratio for classification. Treatment of the MCC enables a successful diagnosis rate of 76% among truly contaminated amniotic fluids.ConclusionsAdjustment for the allele size difference and marker type improves the STR aneuploidy classification, which, complemented with appropriate treatment of contaminated amniotic fluids, eliminates sample re-testing and reinforces the robustness of the QF-PCR method for prenatal testing.

The impact of plant growth regulators (PGRs) “Stimpo” and “Regoplant” on Miscanthus x giganteus (Mxg) biomass parameters was investigated when the plant was grown in military soils with different properties from Dolyna, Ukraine and Hradcany, Czech Republic. The results showed that PGRs positively influenced the biomass parameters when the plant was grown in soil in Dolyna with good agricultural characteristics, the influence of “Regoplant” was higher and the best results were obtained with combined treatment: application to rhizomes before planting and spraying on the biomass during vegetation. Using of PGRs did not improve the biomass parameters when the plant was grown in poor soil in Hradcany. In parallel the peculiarities of the metals uptake process were studied for the following metals: chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), zinc (Zn), strontium (Sr) and lead (Pb). The uptake behavior of the monitored elements differed based on the soil quality. According to the bioconcentration factor uptake of the abiogenic elements, Cr and Pb, was dominant in the plant roots in both soils, whereas Ni was not detected in any plant tissues. The behavior of biogenic elements (Mn, Cu, Zn) and their analogs (Sr) was different. Those elements were more intensively taken up in shoot tissues in low-nutrient sandy Hradcany soils, while they were mainly taken up in plant roots in fertile Dolyna soils. The unusual behavior of biogenic elements in the low-nutrient soils may be explained by the effect of stress. However, more research is needed focused mainly on soil properties and nutrient availability in order to confirm or disprove this hypothesis and to explore the cause of the stress. The summarized results here show that soil properties influenced Mxg biomass parameters, affected the uptake behavior of metals significantly and tested PGRs cannot be utilized universally in the production of Mxg in the poor military soils.

© 2018 Santos, Lopes, Virgolino, Stefanovska-Petkovska, Dinis, Ambrósio and Heitor. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms., Background: Epidemiologic evidence highlights the harmful consequences of unemployment on health and well-being. This emphasizes the need to design low-cost interventions to prevent the adverse mental health effects of unemployment. The main aim of this study was to create expert-consensus regarding development and implementation of a brief, sustainable, and effective intervention program for promoting mental health among unemployed. Methods: The Delphi technique entailed a selected panel of 75 experts from various relevant professional backgrounds. Panel members were asked to state their level of agreement (5-point Likert scale) regarding (a) required characteristics for an effective mental health intervention for unemployed people and (b) key variables for assessing the effectiveness of that intervention. Consensus was obtained throughout two rounds of data collection through e-mail contact, with structured questionnaires. Items of the questionnaire were based on literature reviews about community-based interventions for unemployed individuals. Results: Overall, 46 experts collaborated with the Delphi process (final participation rate: 61.3%). Based on a review of the literature, 185 items were identified and grouped into two broad categories (set of characteristics of the intervention and set of variables for effectiveness assessment), aggregating a total of 11 dimensions. The two Delphi rounds resulted in the selection of 35 characteristic items for the intervention program and 54 variables for its effectiveness assessment. Brief group interventions were considered to be effective and sustainable for mental health promotion in unemployment conditions if targeting mental health literacy, training interpersonal skills, and job-search skills. Conclusion: As agreed by the panel of experts, a brief, sustainable and effective intervention can be developed and implemented by accounting for unemployed capacity-building for mental health self-care and adequate job-searching attitudes and skills. These results should be further implemented in community and multisector-based standardized interventions, targeting mental health among unemployed people, ensuring adequate conditions for its effectiveness assessment., This study is part of the Healthy Employment project, granted by the Public Health Initiatives Programme (PT06) and financed by EEA Grants Financial Mechanism 2009–2014.

The therapy of erosive lichen planus (ELP) has been particular problem in the treatment of oral lesions. This case of ELP in male patient 29 years old was treated with topic application of the NBF gingival gel, three times a day after meal, previously rinsed with Clorhexidine gluconate 0.12%. After 5 days of treatment, initial improvements were recorded, and after two weeks of application of the NBF gingival gel we observed significant improvement. Clinical monitoring after the fifth day showed mild epithelialization of the eroded mucosa, yet still present erythematous base of the lesion. After the second week the erythema area was significantly reduced and the eroded surfaces of the mucosa were minimal, measured less than 0.5 mm. After the third week there were no erosions to detect on the oral mucosa, yet still present vague redness, which completely pulled after the fourth week. Treatment ended after the fifth week when the topical application of the NBF gingival gel was terminated, and therapy was done, and clinically achieved effects remained stable even after the third month of the treatment. Topic application of the NBF gingival gel with ELP patients showed positive clinical effects in relatively short time period.

Cytochrome P450 2D6 (CYP2D6) is an enzyme of great importance for the metabolism of clinically used drugs. More than 100 variants of the CYP2D6 gene have been identified so far. The aim of this study was to investigate the allele distribution of CYP2D6 gene variants in 100 individuals of each of the Macedonian, Albanian and Romany population, by genotyping using long range polymerase chain reaction (PCR) and a multiplex single base extension method. The most frequent variants and almost equally distributed in the three groups were the fully functional alleles *1 and *2. The most common non functional allele in all groups was *4 that was found in 22.5% of the Albanians. The most common allele with decreased activity was *41 which was found in 23.0% of the Romany ethnic group, in 11.0% of the Macedonians and in 10.5% of the Albanians. Seven percent of the Albanians, 6.0% of the Romani and 4.0% of the Macedonians were poor metabolizers, while 5.0% of the Macedonians, 1.0% of Albanians and 1.0% of the Romanies were ultrarapid metabolizers. We concluded that the CYP2D6 gene locus is highly heterogeneous in these groups and that the prevalence of the CYP2D6 allele variants and genotypes in the Republic of Macedonia is in accordance with that of other European populations.

Background Taenia solium and Taenia saginata are food-borne parasites of global importance. In eastern Europe only fragmented information is available on the epidemiology of these zoonotic parasites in humans and animal populations. In particular for T. solium, on-going transmission is suspected. The aim of this systematic review was to collect the available data and describe the current knowledge on the epidemiology of T. solium and T. saginata in eastern Europe. Methods Literature published in international databases from 1990 to 2017 was systematically reviewed. Furthermore, local sources and unpublished data from national databases were retrieved from local eastern European experts. The study area included 22 countries. Results Researchers from 18 out of the 22 countries provided data from local and unpublished sources, while no contacts could be established with researchers from Belarus, Kosovo, Malta and Ukraine. Taeniosis and human cysticercosis cases were reported in 14 and 15 out of the 22 countries, respectively. Estonia, the Former Yugoslav Republic of Macedonia, Lithuania, Moldova, Poland, Romania, Serbia, and Slovakia reported cases of porcine cysticercosis. Croatia, Czech Republic, Estonia, Former Yugoslav Republic of Macedonia, Moldova, Poland, Romania, Serbia, Slovakia, and Ukraine reported bovine cysticercosis. Conclusions There is indication that taeniosis and cysticercosis are present across eastern Europe but information on the occurrence of T. solium and T. saginata across the region remains incomplete. Available data are scarce and species identification is in most cases absent. Given the public health impact of T. solium and the potential economic and trade implications due to T. saginata, notification of taeniosis and human cysticercosis should be implemented and surveillance and notification systems in animals should be improved.

OBJECTIVE To assess the performance of laser Doppler flowmetry (LDF) in measuring blood perfusion from darkly-pigmented skin, i.e. skin with high melanin concentration. LDF provides for the noninvasive monitoring of microvascular blood flow dynamics. It has been used extensively on light-skinned subjects, i.e. on skin with low melanin concentration, in both the healthy and pathological states. Because the optical properties of human skin might affect the reliability of optically-based diagnostic equipment, the effectiveness of LDF needs to be checked and evaluated on dark skin, too, if this method is to be useful in global healthcare. APPROACH Thirteen dark-skinned subjects and ten light-skinned subjects were included in the study. Microvascular blood flow dynamics was measured on both the right and left ankles using LDF with a laser diode of wavelength 780 nm. The characteristics of time-varying blood flow oscillations were investigated by wavelet analysis, nonlinear mode decomposition and wavelet phase coherence. An electrocardiogram (ECG), skin temperature, and respiratory effort were measured simultaneously with the LDF for each subject. MAIN RESULTS No significant differences were observed between the groups in the mean blood perfusion (p > 0.1), or wavelet power (p > 0.6). The instantaneous heart rate (IHR), extracted from the LDF at each of the recording sites, and from the ECG, did not differ significantly between the groups (p > 0.8). Nor did the wavelet power of the IHR differ (p > 0.8) between the groups. The only significant difference found between the groups lay in left/right ankle blood flow coherence near the cardiac frequency, attributable to known ethnic physiological differences. SIGNIFICANCE These results indicate that high melanin concentrations in skin exert no significant influence on the ability of LDF to monitor microvascular blood flow dynamics when using a laser diode of wavelength 780 nm. Hence LDF can help in the diagnosis and exploration of the pathogenesis of diseases such as diabetes, hypertension, or malaria in darkly pigmented patients across sub-Saharan Africa.

Recently, Balkan virus (BALKV, family Phenuiviridae, genus Phlebovirus) was discovered in sand flies collected in Albania and genetically characterised as a member of the Sandfly fever Naples species complex. To gain knowledge concerning the geographical area where exposure to BALKV exists, entomological surveys were conducted in 2014 and 2015, in Croatia, Bosnia and Herzegovina (BH), Kosovo, Republic of Macedonia and Serbia. A total of 2830 sand flies were trapped during 2014 and 2015 campaigns, and organised as 263 pools. BALKV RNA was detected in four pools from Croatia and in one pool from BH. Phylogenetic relationships were examined using sequences in the S and L RNA segments. Study of the diversity between BALKV sequences from Albania, Croatia and BH showed that Albanian sequences were the most divergent (9–11% [NP]) from the others and that Croatian and BH sequences were grouped (0.9–5.4% [NP]; 0.7–5% [L]). The sand fly infection rate of BALKV was 0.26% in BH and 0.27% in Croatia. Identification of the species content of pools using cox1 and cytb partial regions showed that the five BALKV positive pools contained Phlebotomus neglectus DNA; in four pools, P neglectus was the unique species, whereas P. tobbi DNA was also detected in one pool. We report here (i) the first direct evidence that the Balkan virus initially described in coastal Albania has a much wider dissemination area than originally believed, (ii) two real-time RT-PCR assays that may be useful for further screening of patients presenting with fever of unknown origin that may be caused by Balkan virus infection, (iii) entomological results suggesting that Balkan virus is likely transmitted by Phlebotomus neglectus, and possibly other sand fly species of the subgenus Larroussius. So far, BALKV has been detected only in sand flies. Whether BALKV can cause disease in humans is unknown and remains to be investigated.

Altered cellular energy metabolism is a hallmark of many diseases, one notable example being cancer. Here, we focus on the identification of the transition from healthy to abnormal metabolic states. To do this, we study the dynamics of energy production in a cell. Due to the thermodynamic openness of a living cell, the inability to instantaneously match fluctuating supply and demand in energy metabolism results in nonautonomous time-varying oscillatory dynamics. However, such oscillatory dynamics is often neglected and treated as stochastic. Based on experimental evidence of metabolic oscillations, we show that changes in metabolic state can be described robustly by alterations in the chronotaxicity of the corresponding metabolic oscillations, i.e. the ability of an oscillator to resist external perturbations. We also present a method for the identification of chronotaxicity, applicable to general oscillatory signals and, importantly, apply this to real experimental data. Evidence of chronotaxicity was found in glycolytic oscillations in real yeast cells, verifying that chronotaxicity could be used to study transitions between metabolic states.

Prenatal screening and diagnosis are routinely offered at antenatal care clinic visits, and are im-portant in decision making about the continuation of pregnancies affected by genetic conditions for which there are no cures, and prevention through therapeutic abortion is a reasonable option. Prenatal screening is offered to all pregnant women and include fetal ultrasonography and maternal se-rum biochemistry to select the pregnancies at-risk for chromosomal abnormalities. However, these methods have limited sensitivities (60.0-75.0%) and specificities (false positive rate of 5.0%). Even when used in combination and taking into account maternal age, the identification rate of affected fe-tuses does not exceed 90.0% [one]. Prenatal diag-nosis is usually preformed for detection of chromo-somal aneuploidies or monogenic diseases in “high risk” pregnancies. Diagnostic testing currently requires a sample of fetal cells obtained either by chorionic villus sampling (CVS) between 10 and 14 weeks gestation or by amniocentesis after 15 weeks of gestation. However, these invasive procedures carry a risk of miscarriage of around 1.0% [2].

We apply wavelet-based time-localized phase coherence to investigate the relationship between blood flow and skin temperature, and between blood flow and instantaneous heart rate (IHR), during vasoconstriction and vasodilation provoked by local cooling or heating of the skin. A temperature-controlled metal plate (approximate to 10 cm(2)) placed on the volar side of the left arm was used to provide the heating and cooling. Beneath the plate, the blood flow was measured by laser Doppler flowmetry and the adjacent skin temperature by a thermistor. Two 1 h datasets were collected from each of the ten subjects. In each case a 30 min basal recording was followed by a step change in plate temperature, to either 24 degrees C or 42 degrees C. The IHR was derived from simultaneously recorded ECG. We confirm the changes in the energy and frequency of blood flow oscillations during cooling and heating reported earlier. That is, during cooling, there was a significant decrease in the average frequency of myogenic blood flow oscillations (p < 0.05) and the myogenic spectral peak became more prominent. During heating, there was a significant (p < 0.05) general increase in spectral energy, associated with vasodilation, except in the myogenic interval. Weak phase coherence between temperature and blood flow was observed for unperturbed skin, but it increased in all frequency intervals as a result of heating. It was not significantly affected by cooling. We also show that significant (p < 0.05) phase coherence exists between blood flow and IHR in the respiratory and myogenic frequency intervals. Cooling did not affect this phase coherence in any of the frequency intervals, whereas heating enhanced the phase coherence in the respiratory and myogenic intervals. This can be explained by the reduction in vascular resistance produced by heating, a process where myogenic mechanisms play a key role. We conclude that the mechanisms of vasodilation and vasoconstriction, in response to temperature change, are oscillatory in nature and are independent of central sources of variability.