VCAM1, HMOX1 and NOS3 differential endothelial expression may impact sickle cell anemia vasculopathy.

Endothelial dysfunction plays a major role in sickle cell anemia (SCA) systemic vasculopathy, with upregulation of adhesion molecules (e.g., VCAM-1), decreased nitric oxide bioavailability, and oxidative stress. We aimed to assess the modulation role of pro-inflammatory and pro-oxidative stimuli on endothelial VCAM1, NOS3, and HMOX1 expression. We also evaluated the effect of the main SCA therapeutic agent, hydroxyurea, on that modulation. Our results showed that two VCAM1 promoter haplotypes, we previously associated with pediatric cerebral vasculopathy and severe hemolysis in SCA, increased promoter activity in TNF-α-stimulated transfected EA.hy926 and HBEC cell lines, consistent with a higher VCAM1 expression in macro and microvascular settings. In non-transfected cells, we also observed TNF-α-induced VCAM1 overexpression as well as heme-induced overexpression of HMOX1 in both cell models. Heme did not affect VCAM1 nor NOS3 expression and the latter was also not affected by TNF-α stimulus. Hydroxyurea treatment lowered TNF-induced VCAM1 and NOS3 expression but did not affect heme-induced HMOX1 expression. These data further indicate that VCAM1 haplotypes we studied lead to higher VCAM1 expression affecting not only cerebral but also systemic vasculopathy risk. The differential endothelial expression of VCAM1, NOS3, and HMOX1 also confirms their genetic modulation role in SCA systemic vasculopathy.

Emerging Marine Biotoxins in European Waters: Potential Risks and Analytical Challenges.

Harmful algal blooms pose a challenge regarding food safety due to their erratic nature and forming circumstances which are yet to be disclosed. The best strategy to protect human consumers is through legislation and monitoring strategies. Global warming and anthropological intervention aided the migration and establishment of emerging toxin producers into Europe's temperate waters, creating a new threat to human public health. The lack of information, standards, and reference materials delay effective solutions, being a matter of urgent resolution. In this work, the recent findings of the presence of emerging azaspiracids, spirolildes, pinnatoxins, gymnodimines, palitoxins, ciguatoxins, brevetoxins, and tetrodotoxins on European Coasts are addressed. The information concerning emerging toxins such as new matrices, locations, and toxicity assays is paramount to set the risk assessment guidelines, regulatory levels, and analytical methodology that would protect the consumers.

Elemental Chemometrics as Tools to Depict Stalked Barnacle (Pollicipes pollicipes) Harvest Locations and Food Safety.

The stalked barnacle Pollicipes pollicipes is an abundant species on the very exposed rocky shore habitats of the Spanish and Portuguese coasts, constituting also an important economical resource, as a seafood item with high commercial value. Twenty-four elements were measured by untargeted total reflection X-ray fluorescence spectroscopy (TXRF) in the edible peduncle of stalked barnacles sampled in six sites along the Portuguese western coast, comprising a total of 90 individuals. The elemental profile of 90 individuals originated from several geographical sites (N = 15 per site), were analysed using several chemometric multivariate approaches (variable in importance partial least square discriminant analysis (VIP-PLS-DA), stepwise linear discriminant analysis (S-LDA), linear discriminant analysis (LDA), random forests (RF) and canonical analysis of principal components (CAP)), to evaluate the ability of each approach to trace the geographical origin of the animals collected. As a suspension feeder, this species introduces a high degree of background noise, leading to a comparatively lower classification of the chemometric approaches based on the complete elemental profile of the peduncle (canonical analysis of principal components and linear discriminant analysis). The application of variable selection approaches such as the VIP-PLS-DA and S-LDA significantly increased the classification accuracy (77.8% and 84.4%, respectively) of the samples according to their harvesting area, while reducing the number of elements needed for this classification, and thus the background noise. Moreover, the selected elements are similar to those selected by other random and non-random approaches, reinforcing the reliability of this selection. This untargeted analytical procedure also allowed to depict the degree of risk, in terms of human consumption of these animals, highlighting the geographical areas where these delicacies presented lower values for critical elements compared to the standard thresholds for human consumption.

(De)Politicizing Polyamory: Social Media Comments on Media Representations of Consensual Non-Monogamies.

Our research sits at the intersection of communication studies, sociology, cyberculture, and political philosophy and theory. In 2014, a 10+-min segment on polyamory aired on Portuguese open-access national television, during the prime-time newscast, and was viewed by several million people, according to official reports. The news piece was also advertised and shared online, especially via Facebook, by the network's official page. Moreover, the piece was aired within the context of a segment that celebrated the 40-year anniversary of the 1974 liberal revolution that overthrew the right-wing dictatorial regime that ruled Portugal for more than half of the twentieth century. This context served to frame polyamory (alongside other topics) as explicitly political by presenting them as freedoms seized by that liberal revolution. This study used a mixed-method approach to the analysis of online comments on Facebook made with respect to the referred news piece, by deploying both content analysis and critical discourse analysis to try to understand how the political nature of polyamory is negotiated (affirmed or disavowed), and what ideal of the "political" is mobilized in that negotiation, in connection with other elements of intimate citizenship and modes of systemic discrimination. Through this analysis, we will deepen our understanding of how lay people construe the "political" and the (non-)politicalness of polyamory. It also helps advance contemporary understandings of how polyamory is represented in mainstream media, understood by audiences, and how media-and debates on online social networks-can both amplify and help fight against harmful stereotypes of minorities. Through this research, we contribute to political theory by opening up new ways of conceptualizing the realm of the political as an open-ended definition that must encompass changes in modes of sociality, including a politics of relating as a sub-field, likewise to the study of social movements, and their strategies, around consensual non-monogamies. Overall, results show that the recognition of the validity of polyamory is not the same as the realization that relationship orientation is a political issue in itself and that a privatized mode of understanding politics seems prevalent as well as the default framework used in the comments we analyzed. In addition to that, and as other research has already noted, incivility and hate speech was prevalent in online comments and discussions, further dampening the political potential of dissident modes of existence, especially given that incivility is also deployed by those speaking in favor of Othered identities and experiences.

Exploitation of Marine Molecules to Manage Alzheimer's Disease.

Neurodegenerative diseases are sociosanitary challenges of today, as a result of increased average life expectancy, with Alzheimer's disease being one of the most prevalent. This pathology is characterized by brain impairment linked to a neurodegenerative process culminating in cognitive decline and behavioral disorders. Though the etiology of this pathology is still unknown, it is usually associated with the appearance of senile plaques and neurofibrillary tangles. The most used prophylaxis relies on anticholinesterase drugs and NMDA receptor antagonists, whose main action is to relieve symptoms and not to treat or prevent the disease. Currently, the scientific community is gathering efforts to disclose new natural compounds effective against Alzheimer's disease and other neurodegenerative pathologies. Marine natural products have been shown to be promising candidates, and some have been proven to exert a high neuroprotection effect, constituting a large reservoir of potential drugs and nutraceutical agents. The present article attempts to describe the processes of extraction and isolation of bioactive compounds derived from sponges, algae, marine bacteria, invertebrates, crustaceans, and tunicates as drug candidates against AD, with a focus on the success of pharmacological activity in the process of finding new and effective drug compounds.

Biomarkers and genetic modulators of cerebral vasculopathy in sub-Saharan ancestry children with sickle cell anemia.

We investigated biomarkers and genetic modulators of the cerebral vasculopathy (CV) subphenotype in pediatric sickle cell anemia (SCA) patients of sub-Saharan African ancestry. We found that one VCAM1 promoter haplotype (haplotype 7) and VCAM1 single nucleotide variant rs1409419_T were associated with stroke events, stroke risk, as measured by time-averaged mean of maximum velocity in the middle cerebral artery, and with high serum levels of the hemolysis biomarker lactate dehydrogenase. Furthermore, VCAM-1 ligand coding gene ITGA4 variants rs113276800_A and rs3770138_T showed a positive association with stroke events. An additional positive relationship between a genetic variant and stroke risk was observed for ENPP1 rs1044498_A. Conversely, NOS3 variants were negatively associated with silent cerebral infarct events (VNTR 4b_allele and haplotype V) and CV globally (haplotype VII). The -alpha3.7kb-thal deletion did not show association with CV. However, it was associated with higher red blood cell and neutrophil counts, and lower mean corpuscular volume, mean corpuscular hemoglobin and red cell distribution width. Our results underline the importance of genetic modulators of the CV sub-phenotype and their potential as SCA therapeutic targets. We also propose that a biomarker panel comprising biochemical, hematological, imaging and genetic data would be instrumental for CV prediction, and prevention.

Genetic modulators of fetal hemoglobin expression and ischemic stroke occurrence in African descendant children with sickle cell anemia.

Sickle cell anemia (SCA) is an autosomal recessive monogenic disease with significant clinical variability. Cerebrovascular disease, particularly ischemic stroke, is one of the most severe complications of SCA in children. This study aimed to investigate the influence of genetic variants on the levels of fetal hemoglobin (Hb F) and biochemical parameters related with chronic hemolysis, as well as on ischemic stroke risk, in ninety-one unrelated SCA patients, children of sub-Saharan progenitors. Our results show that a higher Hb F level has an inverse relationship with the occurrence of stroke, since the group of patients who suffered stroke presents a significantly lower mean Hb F level (5.34 ± 4.57% versus 9.36 ± 6.48%; p = 0.024). Furthermore, the co-inheritance of alpha-thalassemia improves the chronic hemolytic pattern, evidenced by a decreased reticulocyte count (8.61 ± 3.58% versus 12.85 ± 4.71%; p < 0.001). In addition, our findings have confirmed the importance of HBG2 and BCL11A loci in the regulation of Hb F expression in sub-Saharan African SCA patients, as rs7482144_A, rs11886868_C, and rs4671393_A alleles are significantly associated with a considerable increase in Hb F levels (p = 0.019, p = 0.026, and p = 0.028, respectively). Concerning KLF1, twelve different variants were identified, two of them novel. Seventy-three patients (80.2%) presented at least one variant in this gene. However, no correlation was observed between the presence of these variants and Hb F level, severity of hemolysis, or stroke occurrence, which is consistent with their in silico-predicted minor functional consequences. Thus, we conclude that the prevalence of functional KLF1 variants in a sub-Saharan African background does not seem to be relevant to SCA clinical modulation.

The Incidence of Tetrodotoxin and Its Analogs in the Indian Ocean and the Red Sea.

Tetrodotoxin (TTX) is a potent marine neurotoxin with bacterial origin. To date, around 28 analogs of TTX are known, but only 12 were detected in marine organisms, namely TTX, 11-oxoTTX, 11-deoxyTTX, 11-norTTX-6(R)-ol, 11-norTTX-6(S)-ol, 4-epiTTX, 4,9-anhydroTTX, 5,6,11-trideoxyTTX, 4-CysTTX, 5-deoxyTTX, 5,11-dideoxyTTX, and 6,11-dideoxyTTX. TTX and its derivatives are involved in many cases of seafood poisoning in many parts of the world due to their occurrence in different marine species of human consumption such as fish, gastropods, and bivalves. Currently, this neurotoxin group is not monitored in many parts of the world including in the Indian Ocean area, even with reported outbreaks of seafood poisoning involving puffer fish, which is one of the principal TTX vectors know since Egyptian times. Thus, the main objective of this review was to assess the incidence of TTXs in seafood and associated seafood poisonings in the Indian Ocean and the Red Sea. Most reported data in this geographical area are associated with seafood poisoning caused by different species of puffer fish through the recognition of TTX poisoning symptoms and not by TTX detection techniques. This scenario shows the need of data regarding TTX prevalence, geographical distribution, and its vectors in this area to better assess human health risk and build effective monitoring programs to protect the health of consumers in Indian Ocean area.

Acute Prosthetic Aortic Valve Obstruction Leading to Free Aortic Insufficiency Veno-Arterial Extracorporeal Membrane Oxygenation as a bridge to surgery.

INTRODUCTION: Mechanical prosthetic valve thrombosis (PVT) and obstruction is a lifethreatening event. The significant morbidity and mortality associated with this condition warrants rapid diagnostic evaluation and treatment. CASE REPORT: A 66-year-old female patient with a history of aortic valve replacement 13 years before, was admitted to our intensive cardiac care unit with symptoms and signs of prosthetic aortic valve dysfunction. During cardiac angiography, she collapsed and fluoroscopy showed an immobile disc, stopped in an open position and causing free aortic regurgitation. Cardio-pulmonary resuscitation (CPR) was initiated and a VA-ECMO was inserted as a bridge to emergent cardiac surgery. Surgery was then performed and the patient was successfully discharged with no neurological impairment. DISCUSSION: We present a case where Veno-Arterial Extracorporeal Membrane Oxygenation (VA- ECMO) was successfully used as a bridge to emergent surgery in a cardiac arrest patient due to prosthetic valve thrombosis. CONCLUSIONS: This case illustrates how a relative contraindication (severe aortic insufficiency) to VA-ECMO may, in the end, be an indication in a very particular scenario.

Arterial Vascular Complications in Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) has evolved as a life-saving measure for patients requiring emergent support of respiratory and cardiac function. The femoral artery is the standard site for vascular access when initiating adult venoarterial (VA) ECMO. Cannulation-related complications are a known source of morbidity and it has been speculated that patients undergoing ECMO via femoral arterial cannulation are more likely to develop peripheral vascular complications (up to 70%). METHODS: Retrospective institutional review of patients requiring ECMO (January 2011-August 2017). The primary outcome of this study was to investigate the prevalence of cannulation-related complications on VA ECMO and to determine its effect on patient morbimortality. RESULTS: Eighty-two patients underwent ECMO during the period of study, 56,1% were male with a mean age of 55,8 years. The VA mode was used in 61 patients, 56 with peripheral cannulation. Femoral arterial access was established in 52 patients (73% percutaneously). Vascular complications were observed in 28,6% of the VA femoral ECMOs: 12 acute limb ischemias and 3 major hemorrhages. At the time of femoral cannulation, distal peripheral catheter (DPC) was placed in 5 patients and none developed limb ischemia. For those who developed limb ischemia, several interventions were performed: DPC placement in 9 cases, fasciotomy in 4 and 2 major amputations. Thirty patients underwent arterial cannulas open surgical removal: 8 underwent balloon catheter trombectomy and 5 needed femoral reconstruction. There was an association between PAD (p=0,03) and ischemic cardiopathy (p=0,02;OR 4,5) with the present of vascular complications after ECMO implantation. CONCLUSIONS: Cannulation of femoral vessels remains associated with considerable rates of vascular events (28.6%). PAD and ischemic cardiopathy are associated with vascular complications in this form of cannulation.

Excess body weight, weight gain and obesity-related cancer risk in women in Norway: the Norwegian Women and Cancer study.

BACKGROUND: Excess body weight and weight gain have been reported to independently increase the risk of several cancers. There are few published studies in nationally representative populations of women on specific, 'obesity-related' cancers in relation to prior weight change and relevant confounders. METHODS: Based on self-reported anthropometry, we prospectively assessed body mass index (BMI), weight change over 6 years and subsequent obesity-related cancer risk in the Norwegian Women and Cancer study. We used Cox proportional hazard models to calculate hazard ratios and restricted cubic splines to model potential non-linear dose-response relationships. RESULTS: Excess body weight increased the risk of overall obesity-related cancer, postmenopausal breast, colorectal, colon, endometrial and kidney cancer, with endometrial cancer showing a threefold elevated risk. High weight gain ( ≥ 10 kg) increased the risk of overall obesity-related cancer, postmenopausal breast, endometrial and pancreatic cancer. The association between high weight gain and pancreatic cancer was strong, with 91% increased risk. CONCLUSIONS: Maintaining stable weight in middle adulthood, irrespective of BMI category at baseline, and avoiding excess body weight are both important in the prevention of several obesity-related cancers in women. Our finding of increased risk of pancreatic cancer in women with moderate and high weight gain is novel.

Widening the spectrum of deletions and molecular mechanisms underlying alpha-thalassemia.

Inherited deletions of α-globin genes and/or their upstream regulatory elements (MCSs) give rise to α-thalassemia, an autosomal recessive microcytic hypochromic anemia. In this study, multiplex ligation-dependent probe amplification performed with commercial and synthetic engineered probes, Gap-PCR, and DNA sequencing were used to characterize lesions in the sub-telomeric region of the short arm of chromosome 16, possibly explaining the α-thalassemia/HbH disease phenotype in ten patients. We have found six different deletions, in heterozygosity, ranging from approximately 3.3 to 323 kb, two of them not previously described. The deletions fall into two categories: one includes deletions which totally remove the α-globin gene cluster, whereas the other includes deletions removing only the distal regulatory elements and keeping the α-globin genes structurally intact. An indel was observed in one patient involving the loss of the MCS-R2 and the insertion of 39 bp originated from a complex rearrangement spanning the deletion breakpoints. Finally, in another case, no α-globin gene cluster deletion was found and the patient revealed to be a very unusual case of acquired α-thalassemia-myelodysplastic syndrome. This study further illustrates the diversity of genomic lesions and underlying molecular mechanisms leading to α-thalassemia.

Reversal of Acute Spinal Cord Injury in the Immediate Post-Operative Period After Thoracoabdominal Aneurysm Repair with CSF Drainage.

INTRODUCTION: Spinal cord injury after thoracoabdominal aortic aneurysm surgery is a devastating and unpredictable complication (1). With surgical manipulation, particularly with aortic clamping, cerebrospinal fluid (CSF) pressure may rise, and its pressure exceeds the spinal arterial pressure, spinal perfusion may be reduced, leading to neurological dysfunction. METHODS AND RESULTS: This clinical case reports to a 70-year-old male patient with an early onset of post-operative paraesthesia of the lower limbs in the immediate post-operative period of thoracoabdominal aortic aneurysm repair. Reversal of the neurological deficit was achieved after emergency CSF drainage. CONCLUSION: CSF drainage has a therapeutic potential value of reducing its pressure, allowing an improvement of spinal perfusion pressure, therefore diminishing the risk of an ischemic and permanent lesion(2), thus it may have a role in preventing and/or treating acute paraplegia.

Lumbar Cerebrospinal Fluid Drainage in Endovascular Aortic Repair - Reference Centre Experience.

INTRODUCTION: Spinal cord ischemia (SCI) and the resulting paraplegia are one of the most feared postoperative complications after thoraco-abdominal aortic surgery, with an incidence 4,3-8,0% after thoracic endovascular aortic repair (TEVAR), increasing patients morbi-mortality. Lumbar cerebrospinal fluid (CSF) drainage catheter is recommended as preventive measure in high risk patients. OBJECTIVE: To evaluate the efficiency and safety of CSF drainage catheter as preventive or therapeutic measure in endovascular aortic repair (EAR). METHODS: Retrospective study in 19 patients submitted to TEVAR or fEVAR (fenestrated endovascular aneurism repair), in whom CSF drainage catheter was used, between January 2010 and March 2017. Collected data regarding demographic, perioperative patients characteristics, neurologic symptoms (NS) and other complications. All patients were submitted to general anesthesia (GA) as result of complexity and length of surgery. Known risk factors (RF) for SCI were taken into account. RESULTS: 19 patients, 89,5% (n=17) male, mean age of 66±9 years. 63,2% were classified as ASA III and 36,8% as ASA IV. 9 patients submitted to TEVAR (47,4%); the remaining were submitted to fEVAR. 73,7 % were programed procedures. There were intraoperative complications in 3 patients: iliac artery (IA) rupture in 2 patients, laceration of the axillary artery in 1 patient, all required surgical repair. All catheters were placed in awake patients, before GA induction, and were left in place 2,5 days. 7 patients needed drainage because of CSF pressure>10mmHg intra- or postoperatively. 3 patients developed early symptoms of SCI (decreased mobility and strength of legs). Complete recovery occurred in all patients, except one who recovered just partially. 1 patient developed late NS: paraparesia on 40th postoperative day (POD) as result of spinal stroke. 30 days mortality was 10,5% (n=2), due to cardiorespiratory arrest- 1 by hypovolemic shock (on 3rd POD), 1 by unknown cause (14th POD). CONCLUSION: This study was limited by the small sample size. CSF drainage catheter was an efficient measure in prevention and treatment of SCI in this sample, since there was no case of complications due to SCI. CSF drainage seems to be an effective technique in preventing SCI. Further studies are required to determine the effectiveness and compare the different methods available for the prevention of SCI complications.

Arterial Vascular Complications in Peripheral Venoarterial Extracorporeal Membrane Oxygenation Support.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) has been evolved as a life-saving measure for patients requiring emergent support of respiratory and cardiac function.The femoral artery is the standard site for vascular access when initiating adult venoarterial (VA) ECMO.Cannulation-related complications are a known source of morbidity and it has been speculated that patients undergoing ECMO via femoral arterial cannulation are more likely to develop peripheral vascular complications (up to 70%). In patients with severe peripheral arterial disease (PAD) these risks are even higher and its presence may be considered a relative contraindication for femoral artery cannulation. METHODS: Retrospective institutional review of patients requiring ECMO (January 2011-August 2017).The primary outcome of this study was to investigate the prevalence of cannulation- -related complications on VA ECMO and to determine its effect on patient morbimortality.We evaluated demographics and co-morbidities data.Patients were divided into two groups (complications present VS not present) and statistic analysis was performed to determine the impact of different variables such as co-morbidities,cannulation strategy and time on ECMO in each group.Operative reports were reviewed to analyze the surgical procedures implied for treating vascular complications. RESULTS: Eighty-two patients underwent ECMO therapy during the period of study, 56,1% were male with a mean age of 55,8 years.The median time on the ECMO device was 5,5 days.The VA mode was used in 61 patients, 56 with peripheral cannulation.Femoral arterial access was established in 52 patients (73% percutaneously).Vascular complications were observed in 28,6% of the VA femoral ECMOs:12 acute limb ischemias and 3 major hemorrhages. At the time of femoral cannulation, distal peripheral catheter (DPC) was placed in 5 patients and none developed subsequent limb ischemia.For those who developed limb ischemia, several interventions were performed: DPC placement in 9 cases, fasciotomy in 4 and 2 major amputations. Thirty patients underwent arterial cannulas open surgical removal:8 underwent balloon catheter trombectomy and 5 needed femoral reconstruction.There was an association between PAD (p=0,03) and ischemic cardiopathy (p=0,02;OR 4,5) with the present of vascular complications after ECMO implantation.VA femoral ECMO mortality was 69,2% (n=36).Vascular complications after ECMO support are not associated with higher mortality rates (p>0,05). CONCLUSION: Cannulation of femoral vessels remains associated with considerable rates of vascular events (28.6%).PAD and ischemic cardiopathy are associated with vascular complications in this form of cannulation.Physical examination and the assessment of ankle-brachial índex before ECMO implantation is therefore recommended.Improved efforts at preventing these complications need to be developed to avoid additional morbidity in an already critical patient population.

Viscera-associated bacterial diversity among intertidal gastropods from Northern-Atlantic coast of Portugal.

Culture-dependent evaluation of the bacteria was carried out on gastropods, such as Monodonta lineata, Gibbula umbilicalis, Nucella lapillus and Patella intermedia, and the environmental samples (biofilm and surrounding sea water) collected from six different locations of Northern Portugal coastal area to investigate the interactions between the microbes in the viscera of gastropods and in the environment. A total of 141 isolates and 39 operational taxonomic units were identified. Phylogenetic analysis based on the 16S rRNA gene showed that bacterial isolates are highly diverse and most of them were found in other marine environment. The observed bacterial diversity was distributed over five different classes (Gammaproteobacteria, Alphaproteobacteria, Flavobacteria, Bacilli and Actinobacteria) with the greatest number of 16S rRNA gene sequence derived from the Gammaproteobacteria (77 %). Vibrio is found to be the dominant one among the different bacterial species isolated. The results suggest that the microorganisms in the environment are maintained in the viscera of the gastropods which may have a key role in the metabolic functions.

Dorsal Lytic Lesions: Cancer or Infection?

Infectious spondylodiscitis is a rare disease and typically presents with an insidious progression characterized by spinal pain that usually starts gradually and progressively worsens over several weeks to months. It occurs through three main mechanisms: direct contamination in cases of trauma or surgery, hematogenous dissemination, or through contiguity. We report the case of a 63-year-old male, admitted due to a history of dorsolumbar pain after falling from a height of 1.5 meters, with four months of evolution, without other accompanying symptoms, and refractory to anti-inflammatory and analgesic therapy. Initial laboratory evaluation revealed normocytic and normochromic anemia and a slight elevation in C-reactive protein. Computed tomography of the spine showed pathological fractures of T7-T9. A percutaneous biopsy was performed, positive for methicillin-sensitive Staphylococcus aureus, and the patient underwent 12 weeks of targeted antibiotic therapy. A surgical procedure with percutaneous posterior arthrodesis from T4 to T12 was performed. With this case, the authors aim to emphasize the importance of biopsy as a complementary diagnostic method to imaging studies in the diagnosis of spondylodiscitis, with the possibility of identifying the causative agent.

Twelve-year trends in unprotected left main coronary artery occlusion: insights from a real-world multicentre study.

AIMS: Acute myocardial infarction (AMI) resulting from unprotected left main coronary artery (LMCA) occlusion and subtotal occlusion is a life-threatening condition. Although AMI management has improved in the past two decades, there is limited information on recent trends in patient characteristics, management, and outcomes for acute unprotected LMCA-related AMI. This study aims to assess such trends over a 12 year period. METHODS AND RESULTS: This retrospective multicentre study includes patients with unprotected LMCA occlusion/subtotal occlusion admitted to three tertiary hospitals between 2008 and 2020. The patients were divided into two groups based on the chronology of presentation: a 'past group' (January 2008 to December 2014) and a 'contemporary group' (January 2015 to December 2020). The study compares clinical characteristics, management approaches, and outcomes between the two groups. The study includes 128 patients, with 51 (40%) in the 'past group' and 77 (60%) in the 'contemporary group'. Baseline risk factors did not show statistically significant differences between the two groups, except for hypertension (49% vs. 74%; P = 0.005). Chest pain was more frequent in the 'past group' (98% vs. 89%; P = 0.014), and a trend towards more cardiac arrests was observed in the 'contemporary group' (18% vs. 31%; P = 0.087). Revascularization type did not differ significantly (P = 0.419), but manual thrombectomy was less frequently used (41% vs. 23%; P = 0.032) and stent implantation showed a trend towards higher rates (66% vs. 78%; P = 0.150) in the 'contemporary cohort'. There was a gradual shift from bare-metal to drug-eluting stents, with a significantly higher percentage of ticagrelor/prasugrel loading in the 'contemporary cohort' (5% vs. 79%; P < 0.001). The use of mechanical circulatory support (MCS), although not statistically significant, was higher among patients in the 'past group' (67% vs. 51%; P = 0.073). The type of MCS differed significantly between groups, with a decrease in intra-aortic balloon pump use (67% vs. 42%; P = 0.005) and an increase in veno-arterial extracorporeal membrane oxygenation (4% vs. 22%; P = 0.005) and Impella system (0% vs. 3%) over time. Survival analysis showed no significant differences (P = 0.599; log-rank test) in all-cause mortality between the different time groups, with the long-term survival rate being approximately 30%. CONCLUSIONS: In our real-world population, despite the progressive use of newer drugs and more advanced devices over time, patients with unprotected LMCA occlusion/subtotal occlusion remain a subpopulation with poor prognosis.

New invertebrate vectors for PST, spirolides and okadaic acid in the North Atlantic.

The prevalence of poisoning events due to harmful algal blooms (HABs) has declined during the last two decades through monitoring programs and legislation, implemented mainly for bivalves. However, new toxin vectors and emergent toxins pose a challenge to public health. Several locations on the Portuguese coast were surveyed between 2009 and 2010 for three distinct biotoxin groups [saxitoxin (PST), spirolide (SPX) and okadaic acid (OA)], in 14 benthic species of mollusks and echinoderms. Our main goals were to detect new vectors and unravel the seasonal and geographical patterns of these toxins. PSTs were analyzed by the Lawrence method, SPXs by LC-MS/MS, and OA by LC-MS/MS and UPLC-MS/MS. We report 16 new vectors for these toxins in the North Atlantic. There were differences in toxin contents among species, but no significant geographical or seasonal patterns were found. Our results suggest that legislation should be adjusted to extend the monitoring of marine toxins to a wider range of species besides edible bivalves.

From Stress to Sick(le) and Back Again-Oxidative/Antioxidant Mechanisms, Genetic Modulation, and Cerebrovascular Disease in Children with Sickle Cell Anemia.

Sickle cell anemia (SCA) is a genetic disease caused by the homozygosity of the HBB:c.20A>T mutation, which results in the production of hemoglobin S (HbS). In hypoxic conditions, HbS suffers autoxidation and polymerizes inside red blood cells, altering their morphology into a sickle shape, with increased rigidity and fragility. This triggers complex pathophysiological mechanisms, including inflammation, cell adhesion, oxidative stress, and vaso-occlusion, along with metabolic alterations and endocrine complications. SCA is phenotypically heterogeneous due to the modulation of both environmental and genetic factors. Pediatric cerebrovascular disease (CVD), namely ischemic stroke and silent cerebral infarctions, is one of the most impactful manifestations. In this review, we highlight the role of oxidative stress in the pathophysiology of pediatric CVD. Since oxidative stress is an interdependent mechanism in vasculopathy, occurring alongside (or as result of) endothelial dysfunction, cell adhesion, inflammation, chronic hemolysis, ischemia-reperfusion injury, and vaso-occlusion, a brief overview of the main mechanisms involved is included. Moreover, the genetic modulation of CVD in SCA is discussed. The knowledge of the intricate network of altered mechanisms in SCA, and how it is affected by different genetic factors, is fundamental for the identification of potential therapeutic targets, drug development, and patient-specific treatment alternatives.