Background: Acute intracranial stenting for the treatment of patients with large vessel occlusion in case of failed reperfusion or severe stenosis is a growing practice. Our aim was to explore the clinical and radiological outcome in a large multicenter and international registry. Methods: The RESISTANT registry is a multicenter and international retrospective registry of patients with large vessel occlusion stroke that underwent intracranial stenting due an acute stroke from 2016 to 2023. Primary endpoints was clinical outcome at 90 days. Secondary efficacy endpoints were final reperfusion (mTICI 2b-3), and stent patency at 24 hours. Safety outcomes included procedural complications, symptomatic intracranial hemorrhage and in-hospital mortality. Results: Among 890 patients enrolled, 862 fulfilled inclusion criteria. Median age was 67.0 years (IQR 59.0-77.0), 558 (64.7%) were males and median NIHSS was 12 (IQR 7.0-19.0). Occlusion location was proximal in 758 (87.9%) patients and anterior circulation was affected in 613 (71.1%) patients (390 M1-MCA, 142 terminal ICA). The indication for intracranial stenting was failed reperfusion (mTICI 0-2a) in 456 patients (52.9%). After intracranial stenting, successful recanalization was achieved in 764 (88.6%) with a reocclusion rate during admission of 11.9% and missing controls of 17.7%. The rate of symptomatic intracranial hemorrhage was 8.1%. At 90 days, the median mRS was 3 (IQR 1-6). Successful recanalization and regular flow after stenting were predictors of functional outcome at 90 days. No variables were independently associated with early reocclusion or symptomatic intracranial hemorrhage. Conclusion: Acute intracranial stenting was an effective therapy for patients with failed reperfusion or severe stenosis. Successful reperfusion and regular flow after stenting predicted functional outcome. Prospective studies are warranted to confirm efficacy and safety.

Background: There are limited therapy options in case of failed reperfusion after stent-retriever and/or aspiration based endovascular treatment (EVT) for acute ischemic stroke. Despite the absence of data supporting its use, rescue angioplasty (RA; with or without stent implantation) is often utilized in such cases. Studies are limited to large vessel occlusions, while the outcomes and complications after RA in medium/distal vessel occlusions (MDVOs) have not been reported. This study aims to report the outcomes of RA in MDVO stroke patients. Methods: We performed a retrospective sub-analysis of the “Blood pressure and Antiplatelet medication management after reScue angioplasty after failed Endovascular treatment in Large and distal vessel occlusions with probable IntraCranial Atherosclerotic Disease” (BASEL ICAD) registry. All MDVO stroke patients were included in the analysis. Results: Out of 718 patients, 92 (12.8%) presented with an MDVO. Sixty-one patients (65.9%) presented with an occlusion of the M2 segment of the middle cerebral artery. Rescue stenting (RS) was performed in 83 patients (90.2%) and balloon angioplasty alone was performed in 9 patients (9.8%). Successful reperfusion (modified thrombolysis in cerebral infarction (mTICI) score ≥ 2b) before RA was achieved in 34 patients (36.9%) and after RA in 76 (82.6%) patients. Symptomatic intracranial hemorrhage (sICH) occurred in 8 patients (9.1%) and post-treatment stent occlusion in 14 patients (16.7%). 90 days mortality was 24.1%. Twenty-nine patients (34.9%) achieved functional independence at 90 days (modified Rankin Scale 0 – 2). Conclusion: Rescue Angioplasty might be a viable treatment option in case of failed reperfusion after conventional EVT in selected MDVO patients. However, safety concerns remain.

Background: Intracranial stenting is increasingly performed after thrombectomy failure. Stent selection and procedural strategies are heterogenous between centers. Our aim is to evaluate the clinical and radiological impact of stent design among these patients. Methods: The RESISTANT registry is a multicenter, international, retrospective study of patients with acute ischemic stroke who underwent intracranial stenting from 2016 to 2023. This analysis compares outcomes based on stent type and evaluates the role of pre- and post-stenting angioplasty. The primary endpoint was 90-day good clinical outcome defined as modified Rankin Scale 0 to 2. Secondary outcomes included final reperfusion, and early stent patency (within 48 hours). Safety outcomes included procedural complications, symptomatic intracranial hemorrhage, and in-hospital mortality. Results: Among 859 patients in the RESISTANT registry, 176 underwent intracranial stenting with balloon-mounted stent (BMS) and 683 with self-expandable stent (SES). The Vertebrobasilar location was more frequent in patients who received BMS (46.6% vs 24.0%, p<0.001); other baseline variables were similar between groups. Angioplasty was performed more frequently before (SES: 54.0% vs BMS: 39.2%, p<0.001) and after SES (SES: 21.1% vs BMS: 9.2%, p<0.001). Successful reperfusion (mTICI 2b-3) was similar between groups (BMS: 91.2% vs SES: 89.1%) and the rate of residual intracranial stenosis was higher in SES patients (57.1% vs 35.6%, p<0.001). Reocclusion, procedural complications and symptomatic intracranial hemorrhage rates were similar between groups. At 90 days, the rate of good clinical outcome was higher among those patients treated with SES (44.7% vs 29.5%, aOR 1.74 (95%ICI 1.07-2.82)). Conclusions: Among patients who underwent rescue intracranial stenting, patients treated with self-expandable stents had a better outcome than patients treated with balloon-mounted stent at 90 days despite similar rates of symptomatic intracranial hemorrhage, successful recanalization and early reocclusion.

OBJECTIVES Many rheumatoid arthritis (RA) patients continue to experience persistent pain even after successful management of joint inflammation. Clinical data indicate that RA patients treated with the JAK inhibitor baricitinib consistently achieve pain relief that cannot be entirely attributed to its anti-inflammatory effects. In this study, we investigated the antinociceptive properties of baricitinib using the collagen antibody-induced arthritis (CAIA) model in which mechanical hypersensitivity persists long after resolution of joint inflammation. METHODS The effects of baricitinib, etanercept (tumour necrosis factor inhibitor), and LP-922761 (adaptor protein-2 (AP2) associated kinase 1 (AAK1) inhibitor) on pain-like behaviour in CAIA mice were examined. Tissue samples from the late, low-grade inflammatory phase were examined for the effect of the treatments. Additionally, in vitro experiments using dorsal root ganglion (DRG) cells were conducted to assess baricitinib's influence on neuronal excitability and cell morphology. RESULTS Baricitinib reduced CAIA-induced joint inflammation, but its antinociceptive effects were most pronounced during the late phase when etanercept was ineffective. Administering baricitinib both early and late significantly decreased CAIA-induced bone loss, synovial innervation, and baseline STAT3 phosphorylation in ankle joints and DRGs. Unlike etanercept, baricitinib effectively reduced pain-like behaviour and synovial hyperinnervation when administered exclusively in the late phase. Additionally, baricitinib modulated glial cell morphology and neuronal excitability in vitro. Notably, it inhibited AAK1 signalling in DRGs, with AAK1 kinase activity blockade providing an antinociceptive effect in the CAIA model. CONCLUSIONS Our data suggests that baricitinib has antinociceptive effects by targeting not only immune cells but also neurons and glia cells via inhibition of 2 signalling pathways linked to chronic pain.

Background: Three-dimensional printing is used in veterinary medicine to produce precise physical models for education, research, and training. As simulation-based approaches in veterinary education continually improve, we are exploring the applicability of three dimensional (3D) printing technology for this purpose. Aim: The aim of this study was to evaluate the level of student satisfaction, motivation, and confidence with the introduction of 3D-printed models in veterinary clinical training. Methods: A total of 57 students from the University of Sarajevo–Veterinary Faculty were included in the study. The groups were created according to the previous clinical training: third-year students with dominant observational and little active participation, fourth-year students with modest active participation, and fifth-year students with high prominent active participation in the clinical work. The students attended the theoretical review and practical presentation prior to their work on 3D printing models. Upon completion of the activity, students were given a survey that included questions divided into four categories: general satisfaction, comparison with traditional teaching methods, interactivity and practical application, and technical characteristics. Results: Students exhibited a positive attitude toward the use of the three dimensional printing (3DP) models as clinical simulators. This innovative approach could reduce stress when transitioning to work with live animals while enhancing interest in clinical work. Conclusion: The significant benefits of the 3DP include enhanced durability, low production costs, and a significant reduction in the number of cadavers needed for educational purposes.

Background Tumor-associated macrophages (TAMs) constitute an important part of the tumor microenvironment of breast cancer (BC), and they play an essential role in modulating tumor growth and invasion. However, the role of TAMs in neoadjuvant chemotherapy (NAC) has not been fully elucidated. Therefore, the aim of this study was to assess the function of TAM subtypes and investigate their role in the response to NAC in BC. Methods Presence of TAMs was examined immunohistochemically (IHC) in pre- and post- NAC treatment tumor tissue in a cohort of 138 BC patients. IHC staining with monoclonal antibodies for CD68 and CD163 were performed. Positivity was defined as staining > 1% TAMs in stroma and tumor cell nests. Response to NAC was evaluated according to tumor size change and Residual Cancer Burden (RCB) index. Results CD68+ and CD163+ TAMs decreased significantly in both the stroma and tumor nests (TN) after NAC. The median CD68+ TAMs in the stroma decreased significantly from 5% to 1% (p < 0.005), while CD163+ TAMs showed a marked reduction from 20% to 5% (p < 0.001). Post-NAC, the persistence of CD68+ and CD163+ TAMs in the stroma was strongly correlated with larger residual tumor size (p < 0.005 and p < 0.001, respectively). Changes in CD163+ TAM levels in the stroma were significantly associated with RCB classes (p < 0.005). Pre-NAC, CD163+ TAMs in the stroma and TN showed a significant association with TILs; however, no correlations with TILs were observed post-NAC. Conclusion This study highlights the critical role of TAMs dynamics in shaping NAC response in BC. Notably, CD163+ TAMs may emerge as pivotal players in mechanisms of chemotherapy resistance and response, underscoring their potential as biomarkers and therapeutic targets in breast cancer treatment.

The language we speak shapes our reality. In this paper, we shed light on the fact that by inventing and normalizing phrases such as the "U.K. variant", "Chinese virus", or the "Spanish flu", we are not only endorsing discriminative narratives that could deepen divisions within society, harming people's mental health, but also distracting the public's attention from the most important issue amid the pandemic-how to stall or stem COVID-19 in a timely matter. Furthermore, we also make a call to actions for media professionals, health experts, and government officials to stop creating and popularizing discriminative COVID-19 terms, so that we can reduce the divisions between societies and better focus on controlling the pandemic.

Background/Objectives: Post-infectious syndromes, including Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease, are associated with overlapping clinical features and autonomic dysfunction. Despite shared symptoms such as fatigue and orthostatic intolerance, the underlying pathophysiology and specific patterns of autonomic dysfunction may differ. This study aimed to evaluate and compare autonomic nervous system function in these syndromes using multiple diagnostic modalities to identify unique characteristics and improve differentiation between these conditions. Methods: This cross-sectional study included 758 patients, which were divided into four groups: Post-COVID syndrome, Chronic Fatigue Syndrome following Post-COVID syndrome, Chronic Fatigue Syndrome unrelated to COVID-19, and late-stage Lyme disease. Autonomic nervous system function was assessed using cardiovascular reflex tests, the Head-Up Tilt Test, beat-to-beat analysis, five-minute electrocardiogram recordings, 24 h Holter electrocardiogram monitoring, and 24 h ambulatory blood pressure monitoring. Statistical analyses compared parameters across the groups, focusing on patterns of sympathetic and parasympathetic dysfunction. Results: The patients with Lyme disease showed distinct autonomic patterns, including a higher prevalence of orthostatic hypotension (53.4%) and changes in heart rate variability during the Head-Up Tilt Test suggestive of adrenergic failure. Compared to the other groups, patients with Lyme disease exhibited reduced baroreceptor sensitivity and diminished changes in frequency domain heart rate variability parameters during orthostatic stress. Parasympathetic dysfunction was less prevalent in the Lyme disease group, while the Post-COVID syndrome and Chronic Fatigue Syndrome groups showed more pronounced autonomic imbalances. Conclusions: The patients with Post-COVID syndrome, Chronic Fatigue Syndrome, and late-stage Lyme disease exhibited varying degrees and types of autonomic dysfunction. Late-stage Lyme disease is characterized by adrenergic failure and distinct hemodynamic responses, differentiating it from other syndromes. The functional assessment of autonomic nervous system function could aid in understanding and managing these conditions, offering insights for targeted therapeutic interventions.

The COVID-19 pandemic has significantly reshaped work dynamics, pushing remote work to the forefront. This study explores the impact of transformational leadership on employee performance in remote working environments. Conducted among 231 respondents from various sectors in Bosnia and Herzegovina, the research investigates how leadership styles affect employee performance in a post-pandemic period. The findings highlight that transformational leadership significantly enhances employee performance across all dimensions. Remote working benefits, however, show negligible impact on performance, while remote working disadvantages and job autonomy have medium to large effects. These results underline the importance of effective leadership and autonomy in optimizing employee performance in remote work settings. These insights highlight the need for organizations to adapt their leadership strategies to the evolving digital work environment, ensuring that remote work remains a viable and productive option for the future. Research provides valuable guidance for businesses aiming to navigate the new normal successfully, emphasizing the crucial role of transformational leadership in the digital age.

Summary Existing research has proven difficult to understand the interplay between upstream signaling events during NLRP3 inflammasome activation. Additionally, events downstream of inflammasome complex formation such as cytokine release and pyroptosis can exhibit variation, further complicating matters. Cell Painting has emerged as a prominent tool for unbiased evaluation of the effect of perturbations on cell morphological phenotypes. Using this technique, phenotypic fingerprints can be generated that reveal connections between phenotypes and possible modes of action. To the best of our knowledge, this was the first study that utilized Cell Painting on human THP-1 macrophages to generate phenotypic fingerprints in response to different endogenous and exogenous NLRP3 inflammasome triggers and to identify phenotypic features specific to NLRP3 inflammasome complex formation. Our results demonstrated that not only can Cell Painting generate morphological fingerprints that are NLRP3 trigger-specific but it can also identify cellular fingerprints associated with NLRP3 inflammasome activation.

OBJECTIVE The endonasal transsphenoidal approach (ETA) developed over the years has become the standard of care for sellar and parasellar lesions. However, because it necessitates the removal of the skull base bone, it is often accompanied by CSF leakage. The authors aimed to provide technical nuances and analyze the results of their routine fat grafting technique after ETA. METHODS A consecutive patient cohort (2004-2024) of 168 patients who underwent ETA for sellar and parasellar lesions and the modified fat grafting technique for skull base repair were retrospectively reviewed. RESULTS Overall, combined ETA and transcranial approach (TCA) was performed in 7 (4.2%) patients, and 4 (2.4%) patients had prior transsphenoidal surgery. The size of the lesion was < 10 mm in 24 (14.3%) patients, 10-30 mm in 93 (55.4%), and > 30 mm in 51 (30.4%). Histopathological diagnoses were as follows: 154 (91.7%) pituitary adenomas, of which 45 (26.8%) were secreting; 8 (4.8%) Rathke's cleft cysts; 2 (1.2%) inflammatory/autoimmune lesions; 2 (1.2%) craniopharyngiomas; 1 (0.6%) renal cell carcinoma metastasis; and 1 (0.6%) chordoma. Gross-total resection was achieved in 127 (75.6%) patients, near-total resection in 22 (13.1%), and subtotal resection/partial resection/biopsy in 19 (11.3%). Overall, 122 (72.6%) procedures had intraoperative CSF leakage. Postoperative CSF leakage was observed in 1 (0.6%) patient treated with a revision operation and regrafting with a slightly larger graft and lumbar drainage. CONCLUSIONS Even slight modifications in contemporary surgical techniques and the addition of an innovative approach may improve the treatment of sellar and parasellar lesions via ETA and reduce the risk of CSF leakage. The authors have developed and described a modified fat grafting technique with gradual crafting and preprocessing of the abdominal fat tissue for skull base repair, and they have demonstrated its effectiveness in significantly reducing the CSF leak rate. This technique enables adequate reconstruction of skull base defects with low donor-site complication rates and obviates the need for external lumbar drainage.

Continuous exploration of innovative and sustainable solutions within green chemistry is imperative to tackle challenges inherent in traditional production processes. This study examined three novel methods for obtaining polyphenolic extracts from dill seeds: nonthermal high voltage electric discharge (HVED), subcritical water extraction (SWE), and microwave-assisted extraction (MAE). SWE was conducted at temperatures ranging from 100 to 200°C under 30 bar pressure, while MAE utilized a hydroethanolic solvent at temperatures from 40 to 120°C. HVED extraction was performed at varying frequencies (40-100 Hz) and durations (5-15 min) in water. The total phenolic and flavonoid content of the extracts was quantified, and antioxidant activity was evaluated via 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Polyphenol content and DPPH radical scavenging capacity varied across techniques, with MAE at 40°C yielding the highest values. Increasing MAE temperature caused a steep decline in total phenol and flavonoid contents and a rise in DPPH IC50 values. Conversely, SWE significantly increased phenolic recovery at temperatures between 150-200°C. HVED extraction revealed frequency as the most critical parameter for phenolic recovery. Catechin (224.88 µg/mL), epicatechin (120.62 µg/mL), epigallocatechin (107.56 µg/mL), and procyanidin B1 (116.36 µg/mL) emerged as the primary phenolics. SWE demonstrated superior suitability for individual phenolic recovery compared with the other two techniques. Multivariate data analysis reveals relationships between extraction parameters and polyphenol recovery, underscoring the potential for eco-friendly and efficient extraction processes. This study highlights the transition toward sustainable extraction methods in modern industrial processing. PRACTICAL APPLICATION: This study provides insights into innovative extraction techniques for obtaining polyphenols from dill seeds, which could be applied in the food, cosmetic, and pharmaceutical industries. The findings suggest that these eco-friendly methods can improve the efficiency of extracting antioxidants, offering manufacturers a greener and more effective approach to producing health-promoting ingredients.