Outcomes of Decompressive Surgery for Patients With Severe Cerebral Venous Thrombosis: DECOMPRESS2 Observational Study.

BACKGROUND: Decompressive neurosurgery is recommended for patients with cerebral venous thrombosis (CVT) who have large parenchymal lesions and impending brain herniation. This recommendation is based on limited evidence. We report long-term outcomes of patients with CVT treated by decompressive neurosurgery in an international cohort. METHODS: DECOMPRESS2 (Decompressive Surgery for Patients With Cerebral Venous Thrombosis, Part 2) was a prospective, international cohort study. Consecutive patients with CVT treated by decompressive neurosurgery were evaluated at admission, discharge, 6 months, and 12 months. The primary outcome was death or severe disability (modified Rankin Scale scores, 5-6) at 12 months. The secondary outcomes included patient and caregiver opinions on the benefits of surgery. The association between baseline variables before surgery and the primary outcome was assessed by multivariable logistic regression. RESULTS: A total of 118 patients (80 women; median age, 38 years) were included from 15 centers in 10 countries from December 2011 to December 2019. Surgery (115 craniectomies and 37 hematoma evacuations) was performed within a median of 1 day after diagnosis. At last assessment before surgery, 68 (57.6%) patients were comatose, fixed dilated pupils were found unilaterally in 27 (22.9%) and bilaterally in 9 (7.6%). Twelve-month follow-up data were available for 113 (95.8%) patients. Forty-six (39%) patients were dead or severely disabled (modified Rankin Scale scores, 5-6), of whom 40 (33.9%) patients had died. Forty-two (35.6%) patients were independent (modified Rankin Scale scores, 0-2). Coma (odds ratio, 2.39 [95% CI, 1.03-5.56]) and fixed dilated pupil (odds ratio, 2.22 [95% CI, 0.90-4.92]) were predictors of death or severe disability. Of the survivors, 56 (78.9%) patients and 61 (87.1%) caregivers expressed a positive opinion on surgery. CONCLUSIONS: Two-thirds of patients with severe CVT were alive and more than one-third were independent 1 year after decompressive surgery. Among survivors, surgery was judged as worthwhile by 4 out of 5 patients and caregivers. These results support the recommendation to perform decompressive neurosurgery in patients with CVT with impending brain herniation.

Optimized operation of a controlled stirred tank reactor system for the production of mesenchymal stromal cells and their extracellular vesicles.

The therapeutic effects of human mesenchymal stromal cells (MSC) have been attributed mostly to their paracrine activity, exerted through small-secreted extracellular vesicles (EVs) rather than their engraftment into injured tissues. Currently, the production of MSC-derived EVs (MSC-EVs) is performed in laborious static culture systems with limited manufacturing capacity using serum-containing media. In this work, a serum-/xenogeneic-free microcarrier-based culture system was successfully established for bone marrow-derived MSC cultivation and MSC-EV production using a 2  l-scale controlled stirred tank reactor (STR) operated under fed-batch (FB) or fed-batch combined with continuous perfusion (FB/CP). Overall, maximal cell numbers of (3.0 ± 0.12) × 108 and (5.3 ± 0.32) × 108 were attained at Days 8 and 12 for FB and FB/CP cultures, respectively, and MSC(M) expanded under both conditions retained their immunophenotype. MSC-EVs were identified in the conditioned medium collected from all STR cultures by transmission electron microscopy, and EV protein markers were successfully identified by Western blot analysis. Overall, no significant differences were observed between EVs isolated from MSC expanded in STR operated under the two feeding approaches. EV mean sizes of 163 ± 5.27 nm and 162 ± 4.44 nm (p > 0.05) and concentrations of (2.4 ± 0.35) × 1011 EVs/mL and (3.0 ± 0.48) × 1011 EVs/mL (p > 0.05) were estimated by nanoparticle tracking analysis for FB and FB/CP cultures, respectively. The STR-based platform optimized herein represents a major contribution toward the development of human MSC- and MSC-EV-based products as promising therapeutic agents for Regenerative Medicine settings.

Hydroxyapatite-filled osteoinductive and piezoelectric nanofibers for bone tissue engineering.

Osteoporotic-related fractures are among the leading causes of chronic disease morbidity in Europe and in the US. While a significant percentage of fractures can be repaired naturally, in delayed-union and non-union fractures surgical intervention is necessary for proper bone regeneration. Given the current lack of optimized clinical techniques to adequately address this issue, bone tissue engineering (BTE) strategies focusing on the development of scaffolds for temporarily replacing damaged bone and supporting its regeneration process have been gaining interest. The piezoelectric properties of bone, which have an important role in tissue homeostasis and regeneration, have been frequently neglected in the design of BTE scaffolds. Therefore, in this study, we developed novel hydroxyapatite (HAp)-filled osteoinductive and piezoelectric poly(vinylidene fluoride-co-tetrafluoroethylene) (PVDF-TrFE) nanofibers via electrospinning capable of replicating the tissue's fibrous extracellular matrix (ECM) composition and native piezoelectric properties. The developed PVDF-TrFE/HAp nanofibers had biomimetic collagen fibril-like diameters, as well as enhanced piezoelectric and surface properties, which translated into a better capacity to assist the mineralization process and cell proliferation. The biological cues provided by the HAp nanoparticles enhanced the osteogenic differentiation of seeded human mesenchymal stem/stromal cells (MSCs) as observed by the increased ALP activity, cell-secreted calcium deposition and osteogenic gene expression levels observed for the HAp-containing fibers. Overall, our findings describe the potential of combining PVDF-TrFE and HAp for developing electroactive and osteoinductive nanofibers capable of supporting bone tissue regeneration.

Embedded Sensors for Structural Health Monitoring: Methodologies and Applications Review.

Sensing Technology (ST) plays a key role in Structural Health-Monitoring (SHM) systems. ST focuses on developing sensors, sensory systems, or smart materials that monitor a wide variety of materials' properties aiming to create smart structures and smart materials, using Embedded Sensors (ESs), and enabling continuous and permanent measurements of their structural integrity. The integration of ESs is limited to the processing technology used to embed the sensor due to its high-temperature sensitivity and the possibility of damage during its insertion into the structure. In addition, the technological process selection is dependent on the base material's composition, which comprises either metallic or composite parts. The selection of smart sensors or the technology underlying them is fundamental to the monitoring mode. This paper presents a critical review of the fundaments and applications of sensing technologies for SHM systems employing ESs, focusing on their actual developments and innovation, as well as analysing the challenges that these technologies present, in order to build a path that allows for a connected world through distributed measurement systems.

Recovery of SARS-CoV-2 from large volumes of raw wastewater is enhanced with the inuvai R180 system.

Wastewater-based epidemiology (WBE) for severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is a powerful tool to complement syndromic surveillance. Although detection of SARS-CoV-2 in raw wastewater may be prompted with good recoveries during periods of high community prevalence, in the early stages of population outbreaks concentration procedures are required to overcome low viral concentrations. Several methods have become available for the recovery of SARS-CoV-2 from raw wastewater, generally involving filtration. However, these methods are limited to small sample volumes, possibly missing the early stages of virus circulation, and restrained applicability across different water matrices. The aim of this study was thus to evaluate the performance of three methods enabling the concentration of SARS-CoV-2 from large volumes of wastewater: i) hollow fiber filtration using the inuvai R180, with an enhanced elution protocol and polyethylene glycol (PEG) precipitation; ii) PEG precipitation; and iii) skimmed milk flocculation. The performance of the three approaches was evaluated in wastewater from multiple wastewater treatment plants (WWTP) with distinct singularities, according to: i) effective volume; ii) percentage of recovery; iii) extraction efficiency; iv) inhibitory effect; and v) the limits of detection and quantification. The inuvai R180 system had the best performance, with detection of spiked control across all samples, with average recovery percentages of 68% for porcine epidemic diarrhea virus (PEDV), with low variability. Mean recoveries for PEG precipitation and skimmed milk flocculation were 9% and 14%, respectively. The inuvai R180 enables the scalability of volumes without negative impact on the costs, time for analysis, and recovery/inhibition. Moreover, hollow fiber ultrafilters favor the concentration of different microbial taxonomic groups. Such combined features make this technology attractive for usage in environmental waters monitoring.

Inflammatory Biomarkers Correlate with Time Evolution in Cerebral Venous Thrombosis.

OBJECTIVES: We aimed to analyse the relationship between specific inflammatory biomarkers' levels and the temporal pattern of cerebral venous thrombosis (CVT) symptoms. MATERIALS AND METHODS: We performed a retrospective study of adult CVT patients admitted between Jan 01 2006 and Dec 31 2019. We excluded patients with infection at admission, autoimmune, inflammatory or haematological disorders. We evaluated serum inflammatory biomarkers at admission: C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), absolute neutrophil count, absolute lymphocyte count, platelet count, monocyte count, neutrophile-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), bilirubin and monocyte-to-HDL ratio (M-HDLR). These were evaluated according to the time from symptom onset (acute, subacute or chronic). RESULTS: We included 78 patients with CVT (mean age 41 ± 13 years). Neutrophil count (p = 0.017), monocyte (p = 0.024), CRP (p = 0.004), NLR (p<0.001) and LMR (p = 0.004) showed significant variation with CVT duration. Acute onset CVT exhibited higher absolute neutrophil count and NLR but lower LMR. The subacute group had higher monocyte values, and the chronic phase patients displayed higher LMR, but lower CRP. ESR, PLR and M-HDLR showed a tendency to decrease in the chronic phase. We did not observe any statistical difference between the duration of symptoms and levels of bilirubin. CONCLUSIONS: CVT patients present a differential inflammatory pattern along the time course of the disease: higher NLR and lower LMR in acute phase, and higher LMR and lower CRP level during the chronic phase. These differences may help to ascertain the onset of poorly defined symptoms and provide input regarding anticoagulation management.

Cerebral Venous Thrombosis after BNT162b2 mRNA SARS-CoV-2 vaccine.

The development of SARS-CoV-2 vaccines has raised several concerns regarding venous thromboembolism, namely cerebral venous thrombosis. Although cerebral venous thrombosis has been reported after administration of a viral vector vaccine, due to a possible auto-immune mechanism inducing thrombocytopenia, the same has not happened in mRNA vaccines. We report two cases of cerebral venous thrombosis, shortly after administration of mRNA vaccine. In both patients, there was no evidence of thrombocytopenia or antiplatelet antibodies, and alternative causes for cerebral venous thrombosis were found. As such, despite the temporal relation of both cases to vaccine administration, these types of cerebral venous thrombosis do not seem to be pathophysiological different from cerebral venous thrombosis not associated to SARS-CoV-2 vaccination. Continuous pharmacovigilance is necessary to monitor possible new events and clarify this association.

Loss and rescue of osteocalcin and osteopontin modulate osteogenic and angiogenic features of mesenchymal stem/stromal cells.

Noncollagenous proteins in the bone extracellular matrix, such as osteocalcin (OC) and osteopontin (OPN), inherent to evolution of bone as a skeletal tissue, are known to regulate bone formation and mineralization. However, the fundamental basis of this regulatory role remains unknown. Here, for the first time, we use mouse mesenchymal stem/stromal cells (MSC) lacking both OC and OPN to investigate the mechanistic roles of OC and OPN on the proliferation capacity and differentiation ability of MSC. We found that the loss of OC and OPN reduces stem cells self-renewal potential and multipotency, affects their differentiation into an osteogenic lineage, and impairs their angiogenic potential while maintaining chondrogenic and adipogenic lineages. Moreover, loss of OC and OPN compromises the extracellular matrix integrity and maturation, observed by an unexpected enhancement of glycosaminoglycans content that are associated with a more primitive skeletal connective tissue, and by a delay on the maturation of mineral species produced. Interestingly, exogenously supplemented OC and OPN were able to rescue MSC proliferative and osteogenic potential along with matrix integrity and mineral quality. Taken together, these results highlight the key contributions of OC and OPN in enhancing osteogenesis and angiogenesis over primitive connective tissue, and support a potential therapeutic approach based on their exogenous supplementation.

Early Recanalization in Patients With Cerebral Venous Thrombosis Treated With Anticoagulation.

Background and Purpose- The hypothesis that venous recanalization prevents progression of venous infarction is not established in patients with cerebral venous thrombosis (CVT). Evidence is also scarce on the association between residual symptoms, particularly headache, and the recanalization grade. We aimed to assess, in patients with CVT treated with standard anticoagulation, (1) the rate of early venous recanalization, (2) whether lack of early recanalization was predictor of parenchymal brain lesion progression, and (3) the prevalence and features of persistent headache according to the recanalization grade achieved. Methods- PRIORITy-CVT (Pathophysiology of Venous Infarction - Prediction of Infarction and Recanalization in CVT) was a multicenter, prospective, cohort study including patients with newly diagnosed CVT. Standardized magnetic resonance imaging was performed at inclusion (≤24 hours of therapeutic anticoagulation), days 8 and 90. Potential imaging predictors of recanalization were predefined and analyzed at each anatomical segment. Primary outcomes were rate of early recanalization and brain lesion progression at day 8. Secondary outcomes were headache (days 8 and 90) and functional outcome (modified Rankin Scale at days 8 and 90). Results- Sixty eight patients with CVT were included, of whom 30 (44%) had parenchymal lesions. At the early follow-up (n=63; 8±2 days), 68% (n=43) of patients had partial recanalization and 6% (n=4) full recanalization. Early recanalization was associated both with early regression (P=0.03) and lower risk of enlargement of nonhemorrhagic lesions (P=0.02). Lesions showing diffusion restriction (n=12) were fully reversible in 66% of cases, particularly in patients showing early venous recanalization. Evidence of new or enlarged hemorrhagic lesions, headache at days 8 and 90, and unfavorable functional outcome at days 8 and 90 were not significantly different in patients achieving recanalization. Conclusions- Venous recanalization started within the first 8 days of therapeutic anticoagulation in most patients with CVT and was associated with early regression of nonhemorrhagic lesions, including venous infarction. There was an association between persistent venous occlusion at day 8 and enlargement of nonhemorrhagic lesions.

Cerebral Venous Thrombosis in Hematological Malignancy: Balancing the Risks.

BACKGROUND AND AIM: The coexistence of cerebral venous thrombosis (CVT) and hematological neoplasms is rare. Currently available therapeutic options raise problems concerning the balance of thrombotic and hemorrhagic risks. Our purpose is to characterize a series of cases of CVT and concomitant hematological malignancy, focusing on predisposing factors and treatment strategies. METHODS: We performed a descriptive retrospective analysis of the cases of CVT and hematological neoplasms diagnosed in a tertiary center from 2006 to 2015. RESULTS: From the 111 CVT cases diagnosed, only 7 coexisted with hematological malignancy (lymphoma, leukemia, multiple myeloma, and myelodysplastic syndromes). These included 4 women; median age was 44 years old. Median follow-up time was 72 days. The hematological condition was already known in 5 cases. Besides malignancy, we identified other prothrombotic conditions in all cases. Several anticoagulant strategies were used during the acute phase, after which 5 patients remained on warfarin indefinitely. One patient died due to cerebral hemorrhage during the acute phase. In the remaining 6 patients, there was no recurrence of CVT or other complications of anticoagulation. CONCLUSIONS: Although these results reiterate the role of hematological malignancy as predisposing factor to CVT, in all cases other factors contributed to CVT etiology, potentiating the risk. We report 1 death directly attributable to a fatal hemorrhagic complication of anticoagulation, evidencing the delicate balance of thrombotic and hemorrhagic risk. Nevertheless, most patients benefited of long-term anticoagulation, which proved a reasonable option. A multidisciplinary approach is paramount in making decisions regarding the time and type of anticoagulation.

Synergistic effect of extracellularly supplemented osteopontin and osteocalcin on stem cell proliferation, osteogenic differentiation, and angiogenic properties.

A high demand for functional bone grafts is being observed worldwide, especially due to the increased life expectancy. Osteoinductive components should be incorporated into functional bone grafts, accelerating cell recruitment, cell proliferation, angiogenesis, and new bone formation at a defect site. Noncollagenous bone matrix proteins, especially osteopontin (OPN) and osteocalcin (OC), have been reported to regulate some physiological process, such as cell migration and bone mineralization. However, the effects of OPN and OC on cell proliferation, osteogenic differentiation, mineralization, and angiogenesis are still undefined. Therefore, we assessed the exogenous effect of OPN and OC supplementation on human bone marrow mesenchymal stem/stromal cells (hBM MSC) proliferation and osteogenic differentiation. OPN dose-dependently increased the proliferation of hBM MSC, as well as improved the angiogenic properties of human umbilical vein endothelial cells (HUVEC) by increasing the capillary-like tube formation in vitro. On the other hand, OC enhanced the differentiation of hBM MSC into osteoblasts and demonstrated an increase in extracellular calcium levels and alkaline phosphatase activity, as well as higher messenger RNA levels of mature osteogenic markers osteopontin and osteocalcin. In vivo assessment of OC/OPN-enhanced scaffolds in a critical-sized defect rabbit long-bone model revealed no infection, while new bone was being formed. Taken together, these results suggest that OC and OPN stimulate bone regeneration by inducing stem cell proliferation, osteogenesis and by enhancing angiogenic properties. The synergistic effect of OC and OPN observed in this study can be applied as an attractive strategy for bone regeneration therapeutics by targeting different vital cellular processes.

Compositional and structural analysis of glycosaminoglycans in cell-derived extracellular matrices.

The extracellular matrix (ECM) is a highly dynamic and complex meshwork of proteins and glycosaminoglycans (GAGs) with a crucial role in tissue homeostasis and organization not only by defining tissue architecture and mechanical properties, but also by providing chemical cues that regulate major biological processes. GAGs are associated with important physiological functions, acting as modulators of signaling pathways regulating several cellular processes such as cell growth and differentiation. Recently, in vitro fabricated cell-derived ECM have emerged as promising materials for regenerative medicine due to their ability of better recapitulate the native ECM-like composition and structure, without the limitations of availability and pathogen transfer risks of tissue-derived ECM scaffolds. However, little is known about the molecular and more specifically, GAG composition of these cell-derived ECM. In this study, three different cell-derived ECM were produced in vitro and characterized in terms of their GAG content, composition and sulfation patterns using a highly sensitive liquid chromatography-tandem mass spectrometry technique. Distinct GAG compositions and disaccharide sulfation patterns were verified for the different cell-derived ECM. Additionally, the effect of decellularization method on the GAG and disaccharide relative composition was also assessed. In summary, the method presented here offers a novel approach to determine the GAG composition of cell-derived ECM, which we believe is critical for a better understanding of ECM role in directing cellular responses and has the potential for generating important knowledge to use in the development of novel ECM-like biomaterials for tissue engineering applications.

The patient's safety and access to experimental drugs after the termination of clinical trials: regulations and trends.

PURPOSE: Participants' rights and safety must be guaranteed not only while a clinical trial is being conducted but also when a clinical trial finishes. The criteria for post-trial access to experimental drugs, however, are unclear in various countries. The objectives of this study were (i) to ascertain if there were regulations or guidelines related to patients' access to drugs after the end of clinical trials in the countries selected in the study and (ii) to analyze trends in post-trial access in countries classified by their level of economic development. METHODS: This study is a retrospective review. The data are from the records of clinical trials from 2014 registered in the World Health Organization's International Clinical Trials Registry Platform (ICTRP) database. RESULTS: Among the countries selected, provision of drugs post-trial is mandatory only in Argentina, Brazil, Chile, Finland, and Peru. The plans for post-trial access tend to be more present in low- and middle-income and upper middle-income countries, in comparison with high-income countries. Studies involving vulnerable populations are 2.53 times more likely to have plans for post-trial access than studies which do not. CONCLUSIONS: The guaranteeing of post-trial access remains mandatory in few countries. Considering that individuals seen as vulnerable have been included in clinical trials without plans for post-trial access, stakeholders must discuss the need to develop regulations mandating the guaranteeing of post-trial access in specified situations.

Cerebral vasoconstriction after carotid endarterectomy.

Carotid endarterectomy carries the risk of several complications. We report a 55-year-old woman with recurrent cerebral vasoconstriction postoperatively. She had bilateral high-grade internal carotid artery stenosis and underwent right endarterectomy because of transient left-sided sensory symptoms. She developed a reperfusion syndrome with severe right-sided headache, right frontotemporal oedema and increased velocities in transcranial Doppler ultrasound. Given her gradual increase of velocities and Lindegaard index, together with fixed left sensory and motor deficits, we performed CT angiography, which suggested cerebral vasoconstriction syndrome. A subsequent left carotid endarterectomy triggered a similar cerebrovascular response. We highlight the need for continuous monitoring of cerebral haemodynamics following carotid endarterectomy.

Intracranial arterial stenosis.

Intracranial arterial stenosis (IAS) is usually attributable to atherosclerosis and corresponds to the most common cause of stroke worldwide. It is very prevalent among African, Asian, and Hispanic populations. Advancing age, systolic hypertension, diabetes mellitus, high levels of low-density lipoprotein cholesterol, and metabolic syndrome are some of its major risk factors. IAS may be associated with transient or definite neurological symptoms or can be clinically asymptomatic. Transcranial Doppler and magnetic resonance angiography are the most frequently used ancillary examinations for screening and follow-up. Computed tomography angiography can either serve as a screening tool for the detection of IAS or increasingly as a confirmatory test approaching the diagnostic accuracy of catheter digital subtraction angiography, which is still considered the gold (confirmation) standard. The risk of stroke in patients with asymptomatic atherosclerotic IAS is low (up to 6% over a mean follow-up period of approximately 2 years), but the annual risk of stroke recurrence in the presence of a symptomatic stenosis may exceed 20% when the degree of luminal narrowing is 70% or more, recently after an ischemic event, and in women. It is a matter of controversy whether there is a specific type of treatment other than medical management (including aggressive control of vascular risk factors and antiplatelet therapy) that may alter the high risk of stroke recurrence among patients with symptomatic IAS. Endovascular treatment has been thought to be helpful in patients who fail to respond to medical treatment alone, but recent data contradict such expectation.

Efficient 2D Neck Model for Simulation of the Whiplash Injury Mechanism.

Whiplash injuries, mainly located in the neck, are one of the most common injuries resulting from road collisions. These injuries can be particularly challenging to detect, compromising the ability to monitor patients adequately. This work presents the development and validation of a computationally efficient model, called Efficient Neck Model-2D (ENM-2D), capable of simulating the whiplash injury mechanism. ENM-2D is a planar multibody model consisting of several bodies that model the head and neck with the same mass and inertia properties of a male occupant model in the 50th percentile. The damping and non-linear spring parameters of the kinematic joints were identified through a multiobjective optimization process, solved sequentially. The TNO-Human Body Model (TNO-HBM), a validated occupant model for rear impact, was simulated, and its responses were used as a reference for validation purposes. The root mean square (RMS) of the deviations of angular positions of the bodies were used as objective functions, starting from the bottom vertebra to the top, and ending in the head. The sequence was repeated until it converged, ending the optimization process. The identified ENM-2D model could simulate the whiplash injury mechanism kinematics and accurately determine the injury criteria associated with head and neck injuries. It had a relative deviation of 8.3% for the head injury criteria and was 12.5 times faster than the reference model.

Post cerebral venous thrombosis headache - Prevalence, mechanisms and risk factors.

INTRODUCTION: Headache after cerebral venous thrombosis (post-CVT headache [PCH]) is a common complaint during follow-up. Risk factors and their pathophysiology are not well known. We studied PCH prevalence in CVT patients, its pathophysiology, and possible risk factors. MATERIALS AND METHODS: We performed a retrospective observational study of patients admitted to a tertiary hospital between 2006 and 2019 with CVT and at least one follow-up appointment. We diagnosed PCH when patients reported headaches during the follow-up visit. Recanalization was retrospectively assessed by two neuroradiologists using the first available follow-up MRI/ MRV, and the PRIORITy-CVT study classification. RESULTS: Of 131 patients, sixty (60/131, 45.8 %) reported PCH at the 3-month follow-up. Of these PCH, 9 had previous migraine (9/60, 5.0 %) and 13 previous tension-type headaches (13/60, 21.6 %), before CVT. Forty-four (44/60, 73.3 %) PCH patients had de novo headache: 21 (21/60, 35.0 %) de novo tension-type headaches; 6 (6/60, 10.0 %) de novo migraine; 6 [(6/60, 10.0 %) secondary headache disorders: 3 due to dural arteriovenous fistula, 2 due to intracranial hypertension, and 1 recurrent CVT], and 11 other headache types. Most patients had at least partial recanalization, with no difference in PCH frequency amongst recanalization subgroups (p = 0.598). Premorbid depression (p = 0.009, OR 7.9, 95 % CI 1.6-31.4) increased the odds ratio of PCH, while superior sagittal sinus thrombosis (p = 0.005, OR 0.15, 95 % CI 0.03-0.56) decreased it. DISCUSSION: Our study shows that PCH is a common finding after CVT and elucidates potential risk factors. PCH is common in patients with previous or de novo primary headache. In PCH patients without previous headache, secondary causes of headache, namely related to CVT complications, should be excluded. PCH is also increased in patients with premorbid depression. There was no statistically significant difference in PCH amongst the PRIORITy-CVT recanalization subgroups, but most patients had at least partial recanalization.

Discovery of new heterocycles with activity against human neutrophile elastase based on a boron promoted one-pot assembly reaction.

Herein we demonstrate for the first time that a boron promoted one-pot assembly reaction may be used to discover novel enzyme inhibitors. Inhibitors for HNE were simply assembled in excellent yields, high diastereoselectivities and IC50 up to 1.10 µM, based on components like salicylaldehyde, aryl boronic acids and amino acids. The combination of synthetic, biochemical, analytical and theoretical studies allowed the identification of the 4-methoxy or the 4-diethyl amino substituent of the salicylaldehyde as the most important recognition moiety and the imine alkylation, lactone ring opening as key events in the mechanism of inhibition.

Seizures in cerebral venous thrombosis - A retrospective analysis of a tertiary centre cohort.

BACKGROUND: Seizures are common in cerebral venous thrombosis (CVT). The occurrence of acute symptomatic seizures (ASS) has implications for patients' management, with some patients developing unprovoked late seizures (ULS). We aimed to determine risk factors for the development of ASS, ULS, and seizure recurrence (SR) in patients with CVT. METHODS: We performed an observational retrospective analysis of 141 patients with CVT. We recorded the occurrence of seizures, their time relation to the first-symptom onset, and their relation with demographic, clinical, CVT risk factors, and radiological findings. Seizure recurrence (total recurrency, recurrent ASS, and recurrent LS), potential risk factors, and the use of antiepileptic drugs (AED) were also analysed. RESULTS: Thirty-two (22.7%) patients developed seizures: 23 (16.3%) were ASS and 9 (6.3%) ULS. After multivariable logistic regression, seizure patients had more focal deficits (p = 0.033), parenchymal lesion (p < 0.001), sagittal sinus thrombosis (p = 0.007). In ASS, more frequent focal deficits (p = 0.001), encephalopathy (p = 0.001), mutation in V Leiden factor (p = 0.029), and parenchymal brain lesions (p < 0.001) were observed. ULS patients were younger (p = 0.049) and took more hormonal contraceptives (p = 0.047). Thirteen (9.2%) patients suffered SR (2 recurrent ASS only, 2 recurrent LS only, 2 both acute and recurrent LS), which was more frequent in patients with focal deficits (p = 0.013), infarct with haemorrhagic transformation (p = 0.002), or previous ASS (p = 0.001). CONCLUSION: The occurrence of seizures in patients with CVT is related to focal deficits, structural parenchymal lesions, and superior sagittal sinus thrombosis. SR is frequent, even in patients under AED. This shows the important impact that seizures have on CVT and its long-term management.

Characterization of the Toxigenic Potential of Bacillus cereus sensu lato Isolated from Raw Berries and Their Products.

Bacillus cereus is estimated to be responsible for 1.4-12% of all food poisoning outbreaks worldwide. The objective of this study was to investigate the toxigenic potential of 181 isolates of B. cereus previously recovered from different types of berries and berry products (strawberries, raspberries, blackberries, and blueberries) by assessing the presence of enterotoxin genes (hblA, hblC, hblD, nheA, nheB, nheC, and cytK) and an emetic toxin cereulide synthetase gene (ces). The cytotoxic activity on Caco-2 cells was also evaluated for the two isolates containing the gene cytK. Twenty-three toxigenic profiles were found. The nheABC (91.7%) and hblACD (89.0%) complexes were the most prevalent among the isolates, while the cytK and ces genes were detected in low percentages, 1.1% and 3.3%, respectively. In addition, the nheABC/hblACD complex and ces genes were detected in isolates recovered throughout the production process of blackberries and strawberries. The cytotoxic activity on Caco-2 cells was also observed to be greater than 60% for isolates containing the cytK gene.