Intravenous Tenecteplase for Acute Ischemic Stroke During Active Menstruation.

We report a case of a 51-year-old female who presented to the emergency department with stroke symptoms within the time window for intravenous (IV) thrombolytic therapy. Her initial CT head imaging showed no evidence of acute changes and her CT perfusion demonstrated an area of ischemia in the left parieto-occipital region. While she had no absolute contraindications for IV tenecteplase (TNK), she was actively menstruating at the time, which could represent a relative contraindication due to increased bleeding risk from a site that would not be easily compressible. She elected to receive TNK and did not experience any adverse events after treatment was administered. At her follow-up clinic visit, her neurological deficits were completely resolved. In the context of increasingly widespread usage of TNK, this case report highlights an uncommon but important consideration when treating acute ischemic strokes with IV thrombolytic in the female population. While no definitive conclusions should be drawn from this case, it would hopefully encourage the continued usage of TNK in menstruating females who present with stroke symptoms within the therapeutic window and with no other contraindications.

Personality interferences in the pathology of breast cancer: a cross-sectional single-center study.

Individual personality refers to the Ego and the interpersonal sector. The Ego corresponds to consciousness and self-esteem, including the capacities for emotional self-regulation, self-control, self-evaluation, and self-direction in relation to personal goals. When neoplastic and psychiatric diseases coexist, a patient's quality of life is significantly impacted. While there are somatic differences in disease progression, how the illness is perceived and mainly experienced depends on personality traits. In this study, we administered the DECAS Personality Inventory (a Romanian-validated instrument based on the Five-Factor model of personality) to a group of 121 patients diagnosed with breast cancer to explore the relationships among their personality traits. Descriptive statistics revealed that the mean T scores for openness, extroversion, and emotional stability were low, while the scores for conscientiousness and agreeableness were at an average level. Our findings suggest that, in the studied group, low levels of emotional stability, extroversion, and openness were unfavorable personality dimensions that should be a primary focus of therapeutic strategies, as they significantly affect the quality of life in patients with breast cancer.

Small leucine zipper protein negatively regulates liver fibrosis by suppressing the expression of plasminogen activator inhibitor-1.

Liver fibrosis, which is caused by viral infection, toxic exposure, and autoimmune diseases, is a chronic liver disease. Plasminogen activator inhibitor-1 (PAI-1) is a serine protease inhibitor of tissue-type plasminogen activator (tPA) and urokinase plasminogen activator, which convert plasminogen into plasmin. Therefore, PAI-1 suppresses fibrinolysis by blocking plasmin synthesis and is involved in liver fibrosis via extracellular matrix deposition. Small leucine zipper protein (sLZIP) acts as a transcription factor and plays critical roles in many cellular processes. However, the role of sLZIP in liver fibrosis remains unclear. In this study, we investigated the role of sLZIP in regulating PAI-1 transcription and liver fibrosis. sLZIP knockdown enhanced the expression of PAI-1 at the mRNA and protein levels. sLZIP knockdown also increased PAI-1 secretion and suppressed blood clot lysis by blocking tPA activity. Moreover, conditioned medium derived from sLZIP knockdown cells downregulated the expression of matrix metalloprotease (MMP)-2 and MMP-9 in the presence of tPA in hepatic stellate cells (HSCs). Liver-specific sLZIP knockout mice showed deteriorated liver fibrosis compared to control mice in a bile duct ligation-induced fibrosis model. These findings demonstrate that sLZIP functions as a negative regulator of liver fibrosis by suppressing PAI-1 transcription and HSC activation.

Berberine Targets PKM2 to Activate the t-PA-Induced Fibrinolytic System and Improves Thrombosis.

BACKGROUND: Arterial thrombosis, a condition in which thrombi form in arteries, can lead to various acute cardiovascular diseases and impact the quality of life and survival of patients. Berberine (BBR), a quaternary ammonium alkaloid, has been shown to treat these diseases. However, further exploration is needed to understand underlying mechanisms of BBR. METHODS AND RESULTS: Rats were administered BBR via intramuscular injection. Then, an FeCl3-coated filter paper was applied to a carotid artery to induce thrombosis. The size of the thrombus and the blood flow velocity were evaluated by carotid ultrasound. The shape of the thrombus was observed using staining and microscopy. The expression levels of mRNA and proteins were verified. Additionally, mass spectrometry and single-cell RNA sequencing analysis were conducted. The administration of BBR resulted in a significant reduction in the thrombus area and an extension of the thrombus-clogging time. Furthermore, BBR administration effectively reversed the decreasing tissue-plasminogen activator (t-PA) expression and alterations in fibrinolysis system of model group. Additionally, the expression of PKM2 was suppressed following BBR administration, and the overexpression of PKM2 inhibited t-PA expression. CONCLUSIONS: BBR ameliorates thrombosis by modulating expression of PKM2, subsequently impacting the expression of t-PA within fibrinolytic system. These preliminary findings suggest that BBR could be a potential preventive and therapeutic strategy for arterial thromboembolic diseases.

Alcohol use disorder disrupts BDNF maturation via the PAI-1 pathway which could be reversible with abstinence.

The plasminogen activator inhibitor-1 (PAI-1)→mature brain-derived neurotrophic factor (mBDNF) pathway plays a pivotal role in the conversion of probrain-BDNF (ProBDNF) to mBDNF, but its clinical relevance in patients with alcohol use disorder (AUD) remains unknown. Enzyme-linked immunosorbent assays were used to examine the relevant protein levels of components of the PAI-1→mBDNF pathway in plasma samples from three groups of subjects, and statistical analysis was performed using analysis of variance (ANOVA) and one-way repeated-measures ANOVA. Our findings revealed significant alterations induced by alcohol. (1) AUD was associated with significant decreases in tissue plasminogen activator (tPA), mBDNF, and tropomyosin receptor kinase B (TrkB); significant increases in PAI-1, ProBDNF, and P75 neurotrophin receptor (P75NTR); and inhibited conversion of ProBDNF to mBDNF. (2) Following abstinence, the levels of tPA, mBDNF, and TrkB in the AUD group significantly increased, whereas the levels of PAI-1, ProBDNF, and P75NTR significantly decreased, promoting the conversion of ProBDNF to mBDNF. These clinical outcomes collectively suggest that AUD inhibits the conversion of ProBDNF to mBDNF and that abstinence reverses this process. The PAI-1→mBDNF cleavage pathway is hypothesized to be associated with AUD and abstinence treatment.

Successful Treatment of Central Retinal Artery Occlusion With Tissue Plasminogen Activator Followed by Recurrent Retinal Ischemia.

Purpose: To describe the use of intra-arterial tissue plasminogen activator (tPA) to treat central retinal artery occlusion (CRAO). Methods: A case and its findings were analyzed. Results: A 45-year-old man diagnosed with a CRAO and had cerebral angiography and treatment with intra-arterial tPA. After treatment, follow-up included optical coherence tomography (OCT), fundus photography, fluorescein angiography, and OCT angiography. The visual acuity (VA) improved from hand motions to 20/30 immediately after fibrinolysis. A vascular occlusion event the next day resulted in a decrease in VA to 20/400. After initiation of dual antiplatelet therapy, the patient's VA improved to 20/20. As the retina recovered, the evolution of retinal ischemic changes to a finding similar to paracentral acute middle maculopathy was seen on imaging. Conclusions: This is the first report describing a patient safely started on dual antiplatelet therapy that led to vision improvement after initial treatment with intra-arterial tPA for a CRAO resulted in recurrent vision loss.

Intraoperative OCT-Guided Volumetric Measurements of Subretinal Therapy Delivery in Humans.

Purpose: To evaluate a recently developed technique using intraoperative optical coherence tomography (OCT) to measure subretinal tissue plasminogen activator (tPA) volumes in patients with submacular hemorrhage secondary to exudative age-related macular degeneration (AMD). Methods: Three patients (72 to 83 years old) had 25-gauge pars plana vitrectomy, subretinal tPA, and a partial gas fill. An investigational intraoperative OCT system with a modified widefield noncontact indirect viewing apparatus was used to image subretinal tPA blebs. Using the recently developed technique, the volume and surface area in the segmented region of interest were determined. Results: In each case, the delivered tPA volume measured from the syringe differed from the intraoperative OCT-measured subretinal tPA volume: Patient 1, 130 µL from syringe, 118 µL based on intraoperative OCT, 9% difference; Patient 2, 140 µL, 50 µL, 64%; Patient 3, 110 µL, 122 µL, 11%. The total bleb surface area was 129 mm2 in Patient 1, 55 mm2 in Patient 2, and 106 mm2 in Patient 3. Conclusions: This was the first human study to implement and evaluate intraoperative OCT image-based methods to obtain volumetric bleb measurements in patients receiving subretinal tPA for exudative AMD. This proof-of-concept study showed that intraoperative OCT-obtained bleb volume differed from intraoperative recordings, which could be explained by tPA delivery into the vitreous, efflux through the retinotomy, or human error. Intraoperative OCT can provide visualization and quantification of subretinal tPA bleb volume and surface area, which has implications for improved safety, efficacy, and analysis of the effects of subretinal drug delivery.

Behavioral mirroring in Wistar rats investigated through temporal pattern analysis.

The study of social interactions lies at the core of several disciplines such as psychiatry, psychology and ethology, just to name a few. In this context, understanding the temporal patterns underlying interactive behaviors is of crucial importance. Here, we employed T-pattern detection and analysis to study social interactions in ten pairs of Wistar rats tested in an Open-Field environment. We found four different categories of interactive behaviors. One of them was of particular interest to us because it consisted of behavioral events that, taken individually, should not underlie an interaction of any kind; however, they were included in T-patterns, which is suggestive of a dyadic temporal coordination in the behavioral expression of two individuals. Within this category, we described for the first time a new subcategory of apparent interaction patterns characterized by events that one of the two rats repeats only if previously produced by the partner (i.e., behavioral mirroring). These findings are discussed in functional terms for rodents and in light of our current understanding of social interactions in humans.

Lung Entrapment Secondary to Loculated Rheumatoid Effusions Treated With Alteplase and Dornase.

Rheumatoid arthritis is a multisystemic inflammatory disease that can involve the respiratory system, including the pleural space. Most rheumatoid pleural effusions (PE) are incidentally found and do not require any treatment. Very rarely, however, they can become symptomatic and loculated, leading to lung entrapment or trapped lung. Surgical decortication remains the mainstay of management in such circumstances, although recent studies showed comparable efficacy of intrapleural fibrinolytics (alteplase and dornase alfa) in non-rheumatoid complicated effusions. We present a case of rheumatoid PE leading to lung entrapment successfully treated with intrapleural fibrinolytics without complications and good clinical status at six-month follow-up.

Comparison of Telemedicine-Administered Thrombolytic Therapy for Acute Ischemic Stroke by Neurology Subspecialty: A Cross-Sectional Study.

Background and Purpose: To determine if any difference exists in safety and outcomes of thrombolytic therapy for acute ischemic stroke administered via telemedicine, based on the subspeciality of the treating neurologist. Methods: We performed a retrospective cross-sectional study using data from our local stroke registry of thrombolytic therapy administered via telemedicine at our rural stroke network over 5 years. The cohort was divided in 2 groups based on the subspecialty of the treating neurologist: vascular neurology (VN) and neurocritical care (NCC). Demographics, clinical characteristics, stroke metrics, thrombolytic complications, and final diagnosis were reviewed. In-hospital mortality and mRS and 30 days were noted. Results: Among 142 patients who received thrombolytic therapy via telemedicine, 44 (31%) were treated by VN specialists; 98 (69%) by NCC specialist. There was no difference in baseline characteristics and stroke metrics between the 2 groups. Compared to NCC, VN had a trend toward higher, but non-significant, sICH (6% vs 1%, P = 0.05). In a logistic regression analysis, correcting for NIHSS, SBP, door-to-needle time, and use of antiplatelet therapy, the type of neurology subspecialty was not independently associated with development of sICH (OR: 0.141, SE: 0.188, P = 0.141). The rate of in-hospital mortality was also similar between VN and NCC (7% vs 5%, P = 0.8). In a model that accounted for stroke severity, no association was established between the type of neurology subspecialty and mRS at 30 days (OR: 1.589, SE: 0.662, P = 0.266). Conclusions: Safety and outcome of thrombolytic therapy via telemedicine was not influenced by the subspecialty of treating neurologist. Our study supports the expansion of telemedicine for acute stroke patients in rural and underserved areas.

Influence of furcellaran and safflower oil concentration on the properties of model emulgel systems.

The aim of this study was to investigate the effect of varying concentrations of furcellaran (FUR) and safflower (Carthamus Tinctorius) oil on the functional properties of emulgels as potential carriers of bioactive substances. The textural, mechanical, thermal and structural properties of twenty different formulations were characterised. The pH stability and zeta-potential of the emulgels was also examined. It was found clear correlation between gelling agent and oil fraction content and investigated properties. The hardness, strength, thermal stability expressed as melting point of the investigated systems increased with increasing concentration of the furcellaran and decreasing proportion of safflower oil, which indicated a significant weakening of the structure as a result of the addition of the oil fraction. Stored under refrigeration, emulgels appeared to be relatively stable showing a slight decrease in pH values after 7 days. Swelling ratio (SW) of emulgels increased with increasing both, polysaccharide and oil content, in emulgels. Based on the microstructure analyses, it can also be concluded that only part of the added safflower oil chemically bound to the functional groups of the polysaccharide, while the vast majority of it was only physically immobilized in the furcellaran matrix. Colour of furcellaran - safflower oil emulsion gels depended largely on the amount of oil fraction. The presented research demonstrating the wide spectrum of functional properties of polysaccharide-oil systems is a first step to developing a carrier composition for lipophilic compounds at further stages of research.

Histidine-rich glycoprotein modulates neutrophils and thrombolysis-associated hemorrhagic transformation.

Intravenous thrombolysis using recombinant tissue plasminogen activator (tPA) remains the primary treatment for patients with acute ischemic stroke (AIS). However, the mechanism of tPA-related hemorrhagic transformation (HT) remains poorly understood. Elevation of histidine-rich glycoprotein (HRG) expression was detected by nano-liquid chromatography tandem mass spectrometry at 1 h following tPA infusion as compared to baseline prior to tPA infusion (discovery cohort, n = 10), which was subsequently confirmed in a validation cohort (n = 157) by ELISA. Surprisingly, no elevation of HRG was detected in individuals who subsequently developed HT. During in vitro experiments, HRG reduced neutrophil NETosis, inflammatory cytokine production, and migration across the blood-brain barrier induced by tPA. In a photothrombotic murine AIS model, HRG administration ameliorated HT with delayed thrombolysis, by inhibiting neutrophil immune infiltration and downregulating pro-inflammatory signaling pathways. Neutrophil depletion or NETosis inhibition also alleviated HT, whereas HRG siRNA treatment exacerbated HT. In conclusion, fluctuations in HRG levels may reflect tPA therapy and its associated HT. The inhibitory effect of HRG on neutrophils may counteract tPA-induced immune abnormalities and HT in patients with AIS.

Cardiocerebral Infarction Presenting in a Neurosurgical Emergency: A Case Report and Literature Review.

Cardiocerebral infarction (CCI), the simultaneous occurrence of acute ischemic stroke and acute myocardial infarction (AMI), is a rare but critical condition. However, the optimal treatment strategy, particularly regarding the use of tissue plasminogen activator (t-PA), remains unclear. This case report describes a patient with CCI diagnosed during a neurosurgical emergency. A 67-year-old man with a history of hypertension presented with sudden right hemiparesis and sensory aphasia 30 minutes prior to hospital arrival. Diffusion-weighted magnetic resonance imaging revealed acute cerebral infarction in the left middle cerebral artery territory but without large-vessel occlusion. Routine electrocardiography (ECG) showed ST-T elevation in leads V1, V2, II, III, and aVF (augmented vector foot). Subsequent blood tests confirmed positive troponin T and elevated creatine kinase levels. Despite the absence of reported AMI symptoms, the patient received a diagnosis of CCI. Due to the uncertain time of AMI onset and to expedite transfer to the percutaneous coronary intervention (PCI) unit, t-PA administration was withheld. Upon transfer, dual antiplatelet therapy with aspirin (200 mg) and clopidogrel (300 mg) was initiated. Emergency coronary angioplasty successfully treated a 99% stenosis of the left anterior descending artery (#7). The patient's post-procedure course was uneventful. After 18 days, he was transferred to a rehabilitation hospital with a modified Rankin Scale score of 3. This case highlights the importance of routine 12-lead ECG in neurosurgical emergencies, regardless of presenting symptoms like chest pain. While guidelines support the use of t-PA in CCI, its administration requires careful consideration due to specific risks, including cardiac rupture and limitations on antithrombotic therapy within the first 24 hours.

Physiology, patterns and behavior.

This article endeavors to provide a useful perspective for Researchers and Authors within the realm of Behavioral Sciences, particularly those engaged in the study of Behavioral Physiology, namely the discipline focusing on the intricate interplay between physiological processes and the related behavioral manifestations. Alongside the prevailing conservatism that has characterized the progression of behavioral sciences in recent decades, it advocates for an additional approach in the study of Behavioral Physiology that revolves around a more inclusive perspective: beyond the analysis of isolated behavioral events as discrete components, akin to scattered pieces of a larger puzzle, emphasis also is placed on elucidating their interconnectedness. It is within these interrelationships that the governing constraints of behavior, whether exhibited by humans or any other species, manifest as a cohesive and functional structure.

A Potential Link between Myeloperoxidase Modified LDL, Atherosclerosis and Depression.

Atherosclerosis is a chronic inflammatory disease that involves modified low-density lipoproteins (LDL) which play a pivotal role in the initiation and progression of the disease. Myeloperoxidase oxidized LDL (Mox-LDL) is considered to be the most patho-physiologically relevant type of modified LDL and has been reported to be ubiquitously present in atheroma plaques of patients with atherosclerosis. Besides its involvement in the latter disease state, Mox-LDL has also been shown to be implicated in the pathogenesis of various illnesses including sleep disorders, which are in turn associated with heart disease and depression in many intricate ways. Meanwhile, we have recently shown that lox-1-mediated Mox-LDL signaling modulates neuroserpin activity in endothelial cells, which could have major implications that go beyond the pathophysiology of stroke and cerebrovascular disease (CD). Of note is that tissue plasminogen activator (tPA), which is the main target of neuroserpin in the brain, has a crucial function in the processing of brain-derived neurotrophic factor (BDNF) into its mature form. This factor is known to be involved in major depressive disorder (MDD) development and pathogenesis. Since tPA is more conventionally recognized as being involved in fibrinolytic mechanisms, and its effect on the BDNF system in the context of MDD is still not extensively studied, we speculate that any Mox-LDL-driven change in the activity of tPA in patients with atherosclerosis may lead to a decrease in the production of mature BDNF, resulting in impaired neural plasticity and depression. Deciphering the mechanisms of interaction between those factors could help in better understanding the potentially overlapping pathological mechanisms that regulate disease processes in CD and MDD, supporting the possibility of novel and common therapeutic opportunities for millions of patients worldwide.

YouTube as a source of recognizing acute stroke; progress in 2 years.

BACKGROUND: YouTube™ has a great role in providing information, which includes educational videos, to more than 2 billion users, making it the second most popular application in the world. BE-FAST is a modified version of the FAST mnemonic and is used to detect acute ischemic stroke by the patients or their relatives. The purpose of this study is to assess the overall usefulness of the information of YouTube in patients to realize an acute stroke attack. METHODS: YouTube was searched for the following five terms: "stroke", ''stroke diagnosis", "stroke signs", "brain attack" and "what is stroke" in November 2021 and May 2023, separately. Two independent neurology specialists scored each video by using Global Quality Scale (GQS). RESULTS: Among the total of 150 videos, the number that met inclusion criteria was 91 for the November 2021 search and 104 for the May 2023 search. For the 2021 search, in 30 videos (33%), the FAST mnemonic or its contents were noticed, whereas BE-FAST was mentioned in only four videos (4.4%). For the 2023 search, the FAST mnemonic or its contents were noticed in 36 videos (34.6%) and BE-FAST was mentioned in 11 videos (10.6%). Among the 2021 and 2023 searches, the mean GQS values were 3.09 and 2.96 points, 50 (54.8%) vs. 56 (53.8%) videos rated 3.5 points or higher (high quality), respectively. GQS scores of the videos mentioning balance, eyes, face, arms, speech, and time, the basic and advanced information about radiology and treatment, and mentioning FAST, BE-FAST, and TPA were significantly higher. CONCLUSION: We conclude that YouTube is not yet a very useful tool for patients to realize that they may have acute ischemic stroke, though over the years; information available on social media for healthcare information and education has improved.

Ultrasound and Intrapleural Enzymatic Therapy for Complicated Pleural Effusion: A Case Series with a Literature Review.

Pleural effusion is the most common manifestation of pleural disease, and chest ultrasound is crucial for diagnostic workup and post-treatment monitoring. Ultrasound helps distinguish the various types of pleural effusion and enables the detection of typical manifestations of empyema, which presents as a complicated, septated effusion. This may benefit from drainage and the use of intrapleural enzyme therapy or may require more invasive approaches, such as medical or surgical thoracoscopy. The mechanism of action of intrapleural enzymatic therapy (IPET) is the activation of plasminogen to plasmin, which breaks down fibrin clots that form septa or the loculation of effusions and promotes their removal. In addition, IPET has anti-inflammatory properties and can modulate the immune response in the pleural space, resulting in reduced pleural inflammation and improved fluid reabsorption. In this article, we briefly review the literature on the efficacy of IPET and describe a case series in which most practical applications of IPET are demonstrated, i.e., as a curative treatment but also as an alternative, propaedeutic, or subsequent treatment to surgery.

Management of Neonatal Aortic Thrombosis: Challenges and Outcomes With Systemic and Intra-arterial Thrombolysis.

Neonatal aortic thrombosis, though rare, is associated with high mortality and is frequently linked to umbilical vessel catheterization, especially in smaller and critically ill infants due to their low levels of natural anticoagulants and increased prothrombotic activity. We report a case of a term neonate with abdominal aortic thrombosis and severe lower limb ischemia, presenting with respiratory distress requiring intubation and subsequent development of thrombosis by day 7. Initial anticoagulation with heparin proved insufficient, necessitating the use of reteplase and intra-arterial thrombolysis, which resulted in clinical improvement despite limited immediate success in Doppler studies. The patient was discharged on low-molecular-weight heparin against medical advice, highlighting the complexities and need for individualized management strategies in neonatal thromboembolism.

Evaluation of thrombomodulin/thrombin activatable fibrinolysis inhibitor function in plasma using tissue-type plasminogen activator-induced plasma clot lysis time.

Background: Thrombin activatable fibrinolysis inhibitor (TAFI) is one of the most important physiological fibrinolysis inhibitors. Its inhibitory efficacy under physiological conditions remains uncertain. Objectives: Elucidate the role of soluble thrombomodulin (sTM)/TAFI axis in the regulation of fibrinlysis. Methods: Since thrombin is required to generate activated TAFI (TAFIa) that targets the C-terminal lysine of partially digested fibrin, a clot lysis assay is suitable for evaluating its function. Using tissue-type plasminogen activator-induced plasma clot lysis time (tPA-PCLT) together with TAFIa inhibitor and recombinant sTM (rsTM), we evaluated the specific function of TM/TAFI in the plasma milieu. Results: tPA-PCLT values were significantly shortened by the TAFIa inhibitor. rsTM supplementation prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor to a time similar to that obtained without rsTM and with the TAFIa inhibitor. Plasma obtained from patients treated with rsTM showed prolonged tPA-PCLT, which was shortened by the TAFIa inhibitor but not further prolonged by rsTM. However, no significant correlation was observed between tPA-PCLT and parameters of TM/TAFI system in the plasma. Conclusion: The role of the TM/TAFI system in regulating fibrinolysis was successfully evaluated using TAFIa inhibitor and rsTM. Trace amounts of soluble TM in normal plasma appeared sufficient to activate TAFI and inhibit fibrinolysis. Further, a therapeutic dose of rsTM appeared sufficient to activate TAFI and regulate fibrinolysis in the plasma milieu.