This study aimed to investigate the effect of lifestyle intervention (LSI) on diagnosed infertility in overweight and obese women. A systematic review and meta-analysis were conducted. A literature search was performed on the following databases from September 2022 to December 2022: PubMed, Web of Science, and SPORTDiscus. The inclusion criteria were the following: women between 18 and 45 years of age, BMI over 25.0 kg/m2, diagnosed with infertility, a weight loss intervention, and control group part of RCTs. In total, 15 studies were identified and included. The meta-analysis shows a beneficial effect of LSI on reducing weight, waist circumference, and BMI and increasing infertility. A significantly beneficial effect of lifestyle intervention on weight reduction was observed for participants who initially had a higher BMI, while a non-significant effect was observed for individuals with a BMI above 35 kg/m2. The meta-analysis showed a beneficial effect of lifestyle intervention on ovulation incidence and sex hormone-binding globulin. The lifestyle intervention group had 11.23 times more ovulatory incidence than the control group, which in turn increased the ability to conceive. As robust evidence for the effect of lifestyle interventions on infertility in obese and overweight women was found, it is advised to integrate similar interventions into future infertility treatment processes.

For over two decades, the acronym PAPA syndrome has been used to describe an autoinflammatory condition caused by missense mutations in the PSTPIP1 (proline-serine-threonine phosphatase interacting protein 1) gene and clinically characterized by the presence of pyogenic arthritis, pyoderma gangrenosum (PG), and acne (1,2). Due to the involvement of the PSTPIP1 gene in the regulation of innate immunity, mutations of this gene cause abnormal activation of inflammasomes, complexes of NLRP3/ASC/caspase-1 proteins. As a result, production of interleukin-1β, a key molecule that triggers synthesis of cytokines necessary for the recruitment of neutrophils, is significantly increased (2,3). Additionally, the levels of other pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interferon-γ (INF-γ) and interleukin 17 (IL-7) are also elevated, which further disrupts inflammatory mechanisms in the microenvironment (4). Since hyperproduction of IL-1 and other involved cytokines is the predominant event in the pathogenesis, these molecules are promising targets in the treatment of PAPA syndrome. Corticosteroids and biologics are currently the most commonly used agents for inducing and hastening remission of symptoms (5). A substantial step forward in the treatment of PAPA syndrome has been the introduction of medications blocking the cytokines crucial in the pathogenesis of this disorder, with TNF-α and IL-1 inhibitors being the most frequent choice of such biological therapy (6). We report the case of a 22-year-old male patient with PAPA syndrome who was referred to our department 18 months ago due to exacerbation of skin changes. Initial presentation and subsequent evolution of disease in this patient matched the typical clinical pattern of PAPA syndrome. The first symptoms occurred at the age of two in the form of unspecific joint disease that was diagnosed as juvenile idiopathic arthritis. Subsequently, in the early adolescence the patient presented with new skin changes manifesting as severe acne and persistent pyoderma gangrenosum-like ulcers. At the same time, severity of joint involvement gradually decreased. After the characteristic phenotype of the disease had fully developed, suspicion of possible syndromic origin of symptoms arose. For this reason, genetic analysis was performed as requested by attending pediatricians at the University Clinical Center in Sarajevo, and E250Q mutation of the PSTPIP1 gene was detected. Thus, the diagnosis of PAPA syndrome was confirmed. Throughout the duration of the disease, several types of medication had been introduced in the treatment with varying success. Earliest joint symptoms were alleviated with non-steroidal anti-inflammatory drugs, while repeated courses of corticosteroids were the mainstay of the therapy during a decade-long period. As a consequence of prolonged steroid therapy, growth disorder, among various other side-effects, had been especially pronounced. Acting as a classic steroid-sparing immunosuppressive agent, methotrexate had also been part of the patient's treatment regimen. Lastly, biologics, including both TNF-α and IL-a inhibitors, had been separately administered as the remaining treatment options. However, adalimumab expressed a predominant effect on joint symptoms, whereas re-activation of previously undetected Hepatitis-B infection occurred during the subsequent therapy with anakinra. Due to this adverse reaction, anakinra treatment was discontinued. At the initial examination, the patient presented with multiple erythematous, partially excoriated papules and nodules, along with residual post-inflammatory hyperpigmented patches and scars on the skin of the whole back, chest, shoulders, and upper arms (Figure 1, Figure 2). The presence of postoperative scars on the elbows, resulting from previously performed surgical procedures of persistently affected joints with the goal of achieving pain relief and functional improvement, was also observed. Several smaller ulcers with undermined edges (Figure 3), as well as residual hyperpigmentation and cicatrices (Figure 4) were visible on the lower extremities. Additionally, the patient reported appearance of pustules and non-healing ulcers after minor trauma, which corresponds to the pathergy phenomenon, a common feature of PAPA syndrome. In contrast to the severity of cutaneous changes, the joint symptoms were mild. After thorough assessment of the patient's medical history and current condition, a multi-agent regimen was initiated, consisting of adalimumab, isotretinoin, and prednisone. Regular check-ups during the 12 months of treatment showed that the applied agents stabilized the patient's condition, alleviated more severe and acute skin changes, and slowed down further exacerbation of symptoms. Due to the rarity of PAPA syndrome, data on its treatment is scarce. Official guidelines are non-existing, and available information is based on case reports, case series, and a few smaller retrospective studies (5,7). In general, response to therapy remains inconsistent between patients, despite introduction of novel drugs. Furthermore, single treatment regimens are often not equally effective for all manifestations of the disease, which in a number of cases results in the administration of multi-agent treatment (2). As described in our case report, we opted for a multi-agent regimen not only due to specific individual role of each drug in the treatment of PAPA syndrome but also because of the possible augmented effect of combined therapy. Initially, a short course of systemic corticosteroid (prednisone 30 mg/day for 3 weeks) was introduced in order to alleviate acute symptoms until other agents started showing their effects. The initial dose of administered corticosteroid was gradually tapered by 5 mg every week and soon discontinued. Adalimumab (40 mg every 2 weeks for 12 months) was chosen since its previous administration was without significant adverse effects and with more acceptable end results, unlike therapy with anakinra (8). In addition, TNF-α inhibitors, such as adalimumab, etanercept, and infliximab, have been generally regarded as a more effective treatment option for cutaneous changes, while anakinra, an anti-IL-1 agent, has been more beneficial in alleviating joint symptoms (9-11). Since the skin of our patient was significantly more affected than the joints, adalimumab was a preferred option for biological treatment. Finally, isotretinoin (0.5 mg/kg/day for 6 months) also found a place in our multi-agent therapy plan as a specific, supportive treatment agent for acne (12). Due to the fact that our national health insurance system covered the costs of treatment with TNF-α inhibitors for only 12 months, adalimumab had to be discontinued after the end of this period. Episodes of acute exacerbation that the patient experienced after the cessation of multi-agent regimen were addressed with systemic corticosteroids and symptomatic therapy. Based on case reports, corticosteroids are usually one of the first agents to be administered in patients diagnosed with PAPA syndrome. They are frequently effective in alleviating joint symptoms, but, on the other hand, high doses of corticosteroids can worsen acne lesions (6). Moreover, due to the multiple side-effects of corticosteroids, such as electrolyte abnormalities, hypertension, hyperglycemia, osteoporosis, growth suppression, and adrenal insufficiency (13), a steroid-sparing agent is typically introduced into treatment together with or after corticosteroid therapy. A substantial step forward in the treatment of PAPA syndrome has been achieved with the introduction of medications targeting cytokines crucial in the pathogenesis of this disorder. The two most commonly used groups of such biological drugs have been those that block TNF-α and IL-1. A longer lasting improvement of symptoms has been achieved in a number of cases with both types of agents. Since other medications have often failed to establish long-term control of PAPA syndrome, such effects can be seen as a valuable accomplishment (6,14). Regardless of this observation, the response to treatment still differs between patients. More variable effects have been documented for IL-1 inhibitors, such as anakinra, while TNF-α inhibitors, such as adalimumab, infliximab, and etanercept, have been associated with more steady responses (4,6,10). The inconsistent effect of biologic therapies could be explained by the fact that PSTPIP1 protein is involved in various biochemical processes in different cells of the immune system. Thuse, none of the medications has an adequate spectrum of activity to control all involved immunological pathways (5,15). Overall, due to scarcity of valid information and guidelines, there is an increasing need for multicentric randomized controlled trials that would provide evidence-based data on effective treatment options for PAPA syndrome. Despite the rarity of this disorder, extensive research should be performed in order to discover therapies that could successfully manage all different manifestations of PAPA syndrome. Consequently, such efforts and breakthroughs would lead to decreased mortality and improved quality of life for patients suffering from this debilitating disease. The case described herein shows that PAPA syndrome can remain undiagnosed for longer periods of time, resulting in delayed treatment. Furthermore, the available therapeutic options are not sufficient to achieve long-term remission in many patients. Thus, continuous and comprehensive research is vital for ensuring adequate care of patients with PAPA syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE The medicinal plants Salvia officinalis, Trifolium pratense, Agrimonia eupatoria, Cichorium intybus and Vinca minor are traditionally used for the prevention and treatment of numerous diseases, including diabetes. AIM OF THE STUDY Type 2 diabetes (T2D) is one of the most common diseases nowadays, often accompanied by oxidative stress and microbial infections. The aim of our work was to examine the antidiabetic, antioxidant, and antimicrobial properties of ethanol extracts of five medicinal plants for the purpose of their possible use in the treatment of T2D. MATERIALS AND METHODS The polyphenolic profile of the plant extracts was analyzed by Ultra-High Performance Liquid Chromatography with a diode array detector configured with a triple quadrupole mass spectrometer (UHPLC/DAD/(-)HESI-MS2). In vitro antidiabetic activity of extracts was determined by measuring the percentage of α-amylase and α-glucosidase inhibition. The antioxidant activity of the extract was determined by different spectrophotometric methods, while the antimicrobial activity was determined by agar dilution and disc diffusion methods. RESULTS A. eupatoria extract contains the highest percentage of flavonoids (94%, with isoquercetin, vitexin, and rutin as the most abundant) in relation to the concentration of total phenolic compounds and exhibits excellent antidiabetic, antioxidant, and antimicrobial activity. S. officinalis extract contains 60% flavonoids (predominately cirismaritin and epigallocatechin gallate) and 40% phenolic acids (with rosmarinic acid being the most abundant from this group) and exhibits weak antidiabetic activity, significant antioxidant activity, and excellent antibacterial activity. A 45% percentage of flavonoids (with isoquercetin as the most abundant one) and 55% of phenolic acids (with ferulic acid as the most abundant) were measured in the extract of T. pratense, which had excellent antidiabetic activity but weaker antioxidant and antimicrobial activity. A similar percentage of flavonoids (52%, with epigallocatechin gallate in the highest concentration) and phenolic acids (48%, with chlorogenic acid as the most abundant) was measured in the extract of C. intybus which showed moderate antidiabetic, antioxidant, and antimicrobial properties. The extract of V. minor was the richest in phenolic acids (80%, with the most abundant chlorogenic acid), which resulted in weaker antidiabetic and antioxidant activities (except for Fe2+ chelating ability) and antimicrobial activity. CONCLUSION The results indicate that specific phenolic compounds are responsible for the different biological activities of the plant extracts. Among the investigated plants, the extract of A. eupatoria has the greatest potential for applications in the treatment of T2D.

To compare clinical, radiographic, biological and technical long-term outcomes of two types of dental implants over a period of 10 years. Ninety-eight implants were placed in 64 patients, randomly allocated to one of two manufacturers (AST and STM). All implants were loaded with fixed restorations. Outcome measures were assessed at implant insertion (Ti), at baseline examination (TL), at 1, 3, 5, 8 and 10 (T10) years. Data analysis included survival, bone level changes, complications and clinical measures. Re-examination was performed in 43 patients (23 AST and 20 STM) at 10 years. The implant level analysis was based on 37 (AST) and 32 (STM) implants. Survival rates of 100% were obtained for both groups. The median changes of the marginal bone levels between baseline and T10 (the primary endpoint) amounted to a loss of 0.07 mm for group AST and a gain of 0.37 mm for group STM (intergroup p = 0.008). Technical complications occurred in 27.0% of the implants in group AST and in 15.6% in group STM. The prevalence of peri-implant mucositis was 29.7% (AST) and 50.1% (STM). The prevalence of peri-implantitis amounted to 0% (AST) and 6.3% (STM). Irrespective of the implant system used, the survival rates after 10 years were high. Minimal bone level changes were observed, statistically significant but clinically negligible in favor of STM. Technical complications were more frequently encountered in group AST, while group STM had a higher prevalence of peri-implant mucositis.

(1) Background: With the ever-increasing number of polymer materials and limited data on polymer gear calculations, designers are often required to perform extensive experimental testing in order to establish reliable operational data for specific gear applications. This research investigates the potential of a Polyvinyldene fluoride (PVDF) polymer material in gear applications, considering various loading conditions and different types of gear transmission configurations, including both self-mated mesh and steel/PVDF mesh. (2) Methods: PVDF gear samples were tested on a specially designed test rig that enables active torque control and temperature monitoring in order to obtain the necessary design parameters and failure modes. Each test for certain load conditions was repeated five times, and to fully investigate the potential of PVDF gear samples, comparative testing was performed for Polyoxymethylene (POM) gear. (3) Results: Tribological compatibility, tooth load capacity, and lifespan assessment, along with the types of failure, which, for some configurations, include several types of failures, such as wear and melting, were determined. Temperature monitoring data were used to estimate the coefficient of friction at the tooth contact of analyzed gear pairs, while optical methods were used to determine a wear coefficient. (4) Conclusions: The tribological compatibility of polymer gear pairs needs to be established in order to design a gear pair for a specific application. PVDF gear samples mated with steel gear showed similar lifespan properties compared to POM samples. Temperature monitoring and optical methods serve as a basis for the determination of the design parameters. PVDF is an appropriate material to use in gear applications, considering its comparable properties with POM. The particular significance of this research is reflected in the establishment of the design parameters of PVDF gear, as well as in the analysis of the potential of the PVDF material in gear applications, which gives exceptional significance to the current knowledge on polymer gears, considering that the PVDF material has not previously been analyzed in gear applications.

Šumske ceste kao trajni građevinski objekti zahtijevaju ispunjene minimalno propisane kvalitete i standarda tijekom izgradnje. Prema dostupnim podacima prosječni troškovi gradnje šumskih cesta u F BiH za 2019. godinu iznosili su 22.282,19 € po dužnom kilometru (Anon 2019a). Ovako niski troškovi gradnje nameću opravdano pitanje kvalitete novoizgrađenih šumskih cesta i potrebno mu je posvetiti odgovarajuću pozornost. Na području F BiH, zbog niza razloga, sve se više grade prilazne ili tzv. tehnološke šumske ceste, koje se zbog činjenice da se radi o vrsti šumskih cesta bez izvedene kolničke konstrukcije mogu koristiti samo po suhom vremenu te zbog toga ne ulaze u obračun klasične otvorenosti šuma. Osim toga, zbog nedostatka odvodnih jaraka i prevelikog uzdužnog nagiba nivelete na ovim cestama mogu nastati nesagledive ekološke posljedice. S obzirom da postojeća otvorenost šuma u F BiH nije na zadovoljavajućoj razini, cilj svih šumarskih poduzeća je njeno povećanje. Kako se gradnjom šumskih cesta bez izvedene kolničke konstrukcije ne utječe na povećanje otvorenosti, količina cesta koju je potrebno izgraditi za dostizanje ciljane klasične otvorenosti ostaje nepromijenjena. Kao rješenje za riješavanje navedene situacije, u praksi se u posljednje vrijeme sve više grade šumske ceste s elementima koji čine kombinaciju sporednih i prilaznih šumskih cesta. U ovom radu je izvršena analiza tehničkih i konstruktivnih elemenata za novoizgrađenu šumsku cestu „Braćinac - Doljanske stijene“ stacionaže 1,72 km. Na osnovi dobivenih rezultata, došlo se do saznanja o elementima koje na ovoj cesti treba unaprijediti kako bi se ista očuvala, odnosno kako bi se omogućilo njeno dugogodišnje korištenje. S tim u vezi evidentirana su odstupanja uzdužnog nagiba nivelete u odnosu na propisane veličine na 41% od ukupne dužine, na 26% od ukupne dužine nagibi škarpi usjeka nisu prilagođeni kategoriji materijala u kojoj su izgrađene, duž cijele šumske ceste nisu izgrađeni odvodni kanali. Navedena odstupanja daju za rezultat propadanje kolničke konstrukcije, s obzirom da su na 24% evidentirana manja, a na 9% veća oštećenja. Imajući u vidu da su mjerenja na terenu urađena samo godinu dana nakon izgradnje šumske ceste, nameće se zaključak da niska kvaliteta gradnje i nepridržavanje tehničkih propisia rezultira ubrzanim propadanje ceste.

The selection of unmanned aerial vehicles for different purposes is a frequent topic of research. This paper presents a hybrid model of an unmanned aerial vehicle (UAV) selection using the Defining Interrelationships Between Ranked criteria (DIBR), Full Consistency Method (FUCOM), Logarithm Methodology of Additive Weights (LMAW) and grey - Evaluation based on Distance from Average Solution (G-EDAS) methods. The above-mentioned model is tested and confirmed in a case study. First of all, in the paper are defined the criteria conditioning the selection, and then with the help of experts and by applying the DIBR, FUCOM and LMAW methods, the weight coefficients of the criteria are determined. The final values of the weight coefficients are obtained by aggregating the values of the criteria weights from all the three methods using the Bonferroni aggregator. Ranking and selection of the optimal UAV from twenty-three defined alternatives is carried out using the G-EDAS method. Sensitivity analysis confirmed a high degree of consistency of the solutions obtained using other MCDM methods, as well as changing the criteria weight coefficients. The proposed model has proved to be stable; its application is also possible in other areas and it is a reliable tool for decision-makers during the selection process.

This research focuses on the use of electric vehicles (EVs) to transport visitors and cargo within Bosnia and Herzegovina’s Kozara National Park. Reduced air pollution and the preservation of natural resources are required to help protect this aerial spa. Together with the expert employees of this NP, the EV that would best suit their needs was chosen. The process of decision-making combines subjective and objective methods. Employees first chose the criteria and alternatives and then weighed their importance. On that occasion, Z-numbers were used to include uncertainty in the decision, because it is not always possible to make decisions with complete certainty. Furthermore, the weight of these criteria was determined using the fuzzy PIPRECIA (PIvot Pairwise Relative Criteria Importance Assessment) method. Range (C1) became the most important criterion, followed by vehicle cost (C2), and the technical specifications of these EVs were used to compare them. Because these specifications vary, a rough set was used in which the minimum and maximum EV characteristics were taken based on specific criteria. To rank the alternatives, the R-CRADIS (Rough Compromise Ranking of Alternatives with Distance to Ideal Solution) method was used. According to the research results, the Mercedes eVito Tourer 90 kWh is the highest ranked EV and the validation of the results confirmed these findings. According to the research results, the Mercedes eVito Tourer 90 kWh is the highest ranked EV and the validation of the results confirmed these findings. The sensitivity analysis revealed that if criterion C1 is not as important, the other EVs are ranked higher. This research`s methodology has demonstrated flexibility, therefore it is recommended for use in similar research.

We study the local dynamics and global character of third-order polynomial difference in the first octant of initial conditions with infinite number of prime period-three solutions (three cycles). It is also presented the case when the observed difference equation may be extended to the whole ℝ𝟑.