Urban logistics implementation causes environmental pollution; therefore, it is necessary to consider the impact on the environment when carrying out such logistics. Electric vehicles are alternative vehicles that reduce the impact on the environment. For this reason, this study investigated which electric vehicle has the best indicators for urban logistics. An innovative approach when selecting such vehicles is the application of a fuzzy–rough method based on expert decision making, whereby the decision-making process is adapted to the decision makers. In this case, two methods of multi-criteria decision making (MCDM) were used: SWARA (stepwise weight assessment ratio analysis) and MARCOS (measurement alternatives and ranking according to compromise solution). By applying the fuzzy–rough approach, uncertainty is included when making a decision, and it is possible to use linguistic values. The results obtained by the fuzzy–rough SWARA method showed that the range and price of electric vehicles have the greatest influence on the selection of an electric delivery vehicle. The results of applying the fuzzy–rough MARCOS method indicated that the Kangoo E-Tech Electric vehicle has the best characteristics according to experts’ estimates. These results were confirmed by validation and the application of sensitivity analysis. In urban logistics, the selection of an electric delivery vehicle helps to reduce the impact on the environment. By applying the fuzzy–rough approach, the decision-making problem is adjusted to the preferences of the decision makers who play a major role in purchasing a vehicle.
Exclusive semileptonic b hadron decays (b → uℓν) serve as a sandbox for probing strong and electroweak interactions and for extracting the CKM element Vub. Instead, this work investigates their underexplored potential to reveal new short-distance physics. Utilizing SMEFT as a conduit to chart territory beyond the SM, we demonstrate that substantive new physics contributions in b → uℓν are necessarily linked to correlated effects in rare neutral-current b decays, neutral B meson mixing or high-mass Drell-Yan tails. We find that measurements of the latter processes strongly restrict the allowed deviations in the former. A complete set of tree-level mediators, originating from a perturbative ultraviolet model and matching at dimension 6, is thoroughly explored to support this assertion. As a showcase application, we examine the feasibility of a new physics interpretation of the recent tension in exclusive |Vub| extraction from B → Vℓν where V = (ρ, ω).
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.
AIMS The aim of this study was to estimate cutoff values of mid-upper arm circumference (MUAC) and calf circumference (CC) for reduced muscle mass and analyze their accuracy in identifying malnutrition among individuals of 65 years of age or older in Bosnia and Herzegovina. MATERIALS AND METHODS The study is a secondary analysis dataset assessing nutritional risk and malnutrition among 446 community-dwellers and nursing home residents in Bosnia and Herzegovina. Malnutrition assessment included phenotypic criterions (weight loss, low body mass index, and reduced muscle mass) and etiologic criterions (inadequate food intake, disease-related inflammation, or albumin levels) according to recommendations of the Global Leadership Initiative on Malnutrition (GLIM). Receiver operating curves were used to calculate MUAC and CC's cutoff values as compared to the Mini Nutritional Assessment (MNA). RESULTS The optimal cutoff value for MUAC in men was 24 cm (AUC = 0.910, sensitivity 100%, specificity 77%), and in women 23 cm (AUC = 0.792, sensitivity 64%, specificity 83%). Optimal cutoff value of CC in men was 31 cm (AUC = 0.818, sensitivity 100%, specificity 67%) and in women 29 cm (AUC = 0.882, sensitivity 86%, specificity 74%). Two hundred fifty nine elderly individuals were categorized as malnourished/at risk for malnutrition per MNA. The prevalence of malnutrition based on GLIM criteria ranged from 19% to 30%. CONCLUSIONS The study suggested that MUAC and CC may be used as the alternative indicators of muscle mass when other assessment methods are unavailable. Future validation and reliability studies for GLIM using anthropometric parameters as a proxy of reduced muscle mass are needed.
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.
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.
Clinoidal meningiomas are meningiomas arising from or in the vicinity of the anterior clinoid process.1 Despite advanced microsurgical techniques, clinoidal meningiomas remain challenging.2 Extradural anterior clinoidectomy with optical unroofing remains an important tool in skull base surgery, which provides a safe operative corridor, facilitating greater extent of resection and enhancing overall outcome, particularly visual function.2-13 A 66-year-old female presented with history of visual disturbances. MRI revealed dural-based tumor consistent with a large left clinoidal meningioma, with tumor wrapping (encircling) around left trunk and internal carotid artery (ICA) bifurcation, elevating the left middle cerebral artery M1 segment, and invading the left optic canal. Left cranio-orbital craniotomy with pretemporal exposure was used.1,9 High-speed diamond drill with irrigation completed the extradural anterior clinoidectomy and optical canal unroofing. Use of 1mm Kerrison rongeur should be used with utmost care. The tumor was unwrapped via meticulous piecemeal removal. Final dissection and ICA unwrapping was done when the tumor was debulked enough that dissecting it off the artery was safe and under less tension. Due to its obscurity, final decompression of the left optic nerve with incision and opening of the falciform ligament was performed at the end of the procedure.10 Postoperative neuro-ophthalmologic exam showed grossly unchanged left visual field with some visual acuity improvement. Resection of tumor encircling the ICA has been described previously14; however, to the best of our knowledge, this is the first video describing removal of tumor surrounding ICA ("unwrapping") the left ICA trunk and its bifurcation. The patient consented to publication.
Abstract Idiopathic dilatation of the right atrium is a rare condition with an unknown etiology. It is characterized by a significant enlargement of the right atrium without the presence of other valvopathies, intracardiac shunts, or pulmonary hypertension. This report presents the case of a 50-year-old woman with a significantly enlarged right atrium that was identified at birth; however, a definitive diagnosis was made later in life. The patient did not have any genetic diseases. Through the help of regular follow-up, anticoagulant therapy, previous radio-frequency ablation, and antiarrhythmic medications, she was able to carry a pregnancy to full term and live a regular life.
Abstract Introduction The optimal reperfusion technique in patients with isolated posterior cerebral artery (PCA) occlusion is uncertain. Previous studies in LVO and MeVO have demonstrated a correlation between good clinical outcomes and the first pass effect (FPE, eTICI 2c/3 on the first pass) but no differences in FPE rates or clinical outcomes between first‐line endovascular therapy techniques.1‐6 We compared clinical and technical outcomes with first‐line stent‐retriever (SR), contact aspiration (CA), or combined techniques in patients with isolated PCA occlusion. Methods This international cohort study was conducted at 30 sites in Europe and North America and included consecutive patients with isolated PCA occlusion and pre‐stroke modified Rankin Scale (mRS) 0‐3, presenting within 24 hours of time last seen well from January 2015 to August 2022.7 The primary outcome was the first‐pass effect (FPE), defined as eTICI 2c/3 on the first pass. Secondary outcomes included final successful reperfusion (eTICI 2b‐3), 90‐day excellent outcome (mRS 0 to 1), 90‐day functional independence (mRS 0 to 2), sICH, and 90‐day mortality. Patients treated with SR, CA, or combined technique were compared with multivariable logistic regression. This study was registered under NCT05291637. Results There were 326 patients who met inclusion criteria, consisting of 56.1% male, median age 75 (IQR 65‐82) years and median NIHSS 8 (5‐12). Occlusion segments were PCA P1 (53.1%), P2 (40.5%), and other (6.4%). Intravenous thrombolysis was administered in 39.6%. First‐line technique was SR, CA, and combined technique in 43 (13.2%), 106 (32.5%), and 177 (54.3%) patients, respectively; FPE was achieved in 62.8%, 42.5%, and 39.6%, respectively. Compared to SR, FPE was lower in patients treated with first‐line combined technique and similar in patients treated with first‐line CA (combined vs. SR: aOR 0.35 [0.016‐0.80], p=0.01; CA vs. SR: aOR 0.45 [0.19‐1.06], p=0.07). Final successful reperfusion (eTICI 2b‐3) was present in 81% of cases with no differences between treatment groups. Excellent outcome (mRS 0‐1) occurred in 30.7% of patients and functional independence (mRS 0‐2) occurred in 50.0% of patients. There were lower odds of functional independence in the first‐line CA versus SR alone group (aOR 0.52 [0.28‐0.95], p=0.04). FPE was associated with higher rates of favorable outcomes (mRS 0‐2: 58% vs. 43.4%, p=0.01; mRS 0‐1: 36.6% vs. 25.8%, p=0.05). sICH was observed in 5.6% (18/326) and mortality in 10.9% (35/326) with no differences between first‐line technique. Conclusion In patients with isolated PCA occlusion undergoing EVT, first line SR was associated with a higher rate of FPE compared to CA or combined techniques with no difference in final successful reperfusion. Functional independence at 90‐days was more likely with first‐line SR compared to CA in adjusted analyses. FPE was associated with higher rates of 90‐day excellent outcomes and functional independence. No difference in sICH or mortality was noted across the three techniques. As the endovascular field evolves to treat patients with distal vessel occlusion and milder severity of stroke, optimizing the efficacy and safety of the procedure is essential.8
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