In health and illness: does taste remain consistent? Exploring the influence of inflammation on taste perception through a systematic review and meta-analysis.

OBJECTIVE: Dysgeusia is characterized by a loss of taste perception, leading to malnutrition. This situation affects inflammatory conditions such as respiratory and neurological conditions, obesity, cancer, chemotherapy, aging, and many others. To date, there is not much information on the prevalence and risk of dysgeusia in an inflammatory condition; also, it is unclear which flavor is altered. MATERIALS AND METHODS: We systematically searched three databases from January 2018 to January 2023. Participants were children, adults, or elderly persons with an inflammatory condition and evaluated taste loss. A random effects model was used for statistical analysis to calculate the pooled odds ratio with its corresponding 95.0% confidence interval to estimate the probability of taste alteration (dysgeusia) in an inflammatory condition. RESULTS: The data allowed us to conduct a systematic review, including 63 original articles and 15 studies to perform the meta-analysis. The meta-analysis indicated a heterogenicity of 84.7% with an odds ratio of 3.25 (2.66-3.96), indicating a significant risk of Alzheimer's disease, SARS-CoV-2, chemotherapy, and rhinosinusitis. CONCLUSIONS: Inflammatory conditions and taste alterations are linked. Dysgeusia is associated with a higher risk of malnutrition and poorer general health status, especially in vulnerable populations.

IBD-PODCAST Spain: A Close Look at Current Daily Clinical Practice in IBD Management.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) that contributes in part to irreversible bowel damage and long-term complications, reduced quality of life, invalidity, and economic burden. Suboptimal control of IBD is associated with higher healthcare resource utilization (HCRU), impaired quality of life (QoL), and reduced work productivity. AIMS: The IBD-PODCAST study aimed to assess the proportion of IBD patients with suboptimal control and its associated impact. METHODS: IBD-PODCAST is a cross-sectional, multicenter study that aimed to characterize the CD and UC population with optimal or suboptimal control according to the STRIDE-II criteria and patient- and physician-reported measures. Here we present the results of the Spanish cohort (n = 396). RESULTS: A total of 104/196 (53.1%) CD and 83/200 (41.5%) UC patients were found to have suboptimal disease control. Long-term treatment targets according to STRIDE-II were applied in 172 (87.8%) CD and 181 (90.5%) UC patients. 125 of 172 (72.7%) CD and 74 of 181 (40.9%) UC patients were currently treated with targeted immunomodulators. Patients with CD and UC and suboptimal disease control showed impaired QoL, higher HCRU and direct costs, and also loss of work productivity compared to those with optimal control. CONCLUSION: Despite a high rate of targeted immunomodulator therapy, a substantial proportion of IBD patients show suboptimal disease control according to the STRIDE II criteria. Those patients with suboptimal disease control exhibit impaired QoL, less work productivity, and higher HCRU, suggesting that there is considerable need for better treatment approaches in IBD.

Shift Current with Gaussian Basis Sets and General Prescription for Maximally Symmetric Summations in the Irreducible Brillouin Zone.

The bulk photovoltaic effect is an experimentally verified phenomenon by which a direct charge current is induced within a non-centrosymmetric material by light illumination. Calculations of its intrinsic contribution, the shift current, are nowadays amenable from first-principles employing plane-wave bases. In this work, we present a general method for evaluating the shift conductivity in the framework of localized Gaussian basis sets that can be employed in both the length and velocity gauges, carrying the idiosyncrasies of the quantum-chemistry approach. The (possibly magnetic) symmetry of the system is exploited in order to fold the reciprocal space summations to the representation domain, allowing us to reduce computation time and unveiling the complete symmetry properties of the conductivity tensor under general light polarization.

Endovascular therapy outcome in isolated posterior cerebral artery occlusion strokes: A multicenter analysis of the Swiss Stroke Registry.

PURPOSE: There is little data on the safety and efficacy of endovascular treatment (EVT) in comparison with intravenous thrombolysis (IVT) in acute ischemic stroke due to isolated posterior cerebral artery occlusion (IPCAO). We aimed to investigate the functional and safety outcomes of stroke patients with acute IPCAO treated with EVT (with or without prior bridging IVT) compared to IVT alone. METHODS: We did a multicenter retrospective analysis of data from the Swiss Stroke Registry. The primary endpoint was overall functional outcome at 3 months in patients undergoing EVT alone or as part of bridging, compared with IVT alone (shift analysis). Safety endpoints were mortality and symptomatic intracranial hemorrhage. EVT and IVT patients were matched 1:1 using propensity scores. Differences in outcomes were examined using ordinal and logistic regression models. FINDINGS: Out of 17,968 patients, 268 met the inclusion criteria and 136 were matched by propensity scores. The overall functional outcome at 3 months was comparable between the two groups (EVT vs IVT as reference category: OR = 1.42 for higher mRS, 95% CI = 0.78-2.57, p = 0.254). The proportion of patients independent at 3 months was 63.2% in EVT and 72.1% in IVT (OR = 0.67, 95% CI = 0.32-1.37, p = 0.272). Symptomatic intracranial hemorrhages were overall rare and present only in the IVT group (IVT = 5.9% vs EVT = 0%). Mortality at 3 months was also similar between the two groups (IVT = 0% vs EVT = 1.5%). CONCLUSION: In this multicenter nested analysis, EVT and IVT in patients with acute ischemic stroke due to IPCAO were associated with similar overall good functional outcome and safety. Randomized studies are warranted.

[What do medical students think about functional neurological disorders?] / ¿Qué piensan los estudiantes de Medicina sobre los trastornos neurológicos funcionales?

INTRODUCTION: Functional neurological disorders (FND) are a frequent reason for visits in neurology. However, specific training on these disorders during undergraduate and residency training is limited. This study assesses the knowledge, attitude and exposure of medical students to FNDs before completing their medical degree. PATIENTS AND METHODS: We conducted a 15-item survey to explore understanding, exposure and attitudes towards FNDs among sixth-year medical students at four Spanish universities. RESULTS: A total of 118 students (mean age 23.6 ± 1.2 years; 71.2% female) returned the survey. Of these, 88 (74.6%) were aware of the concept of FNDs and 78 (66.1%) had studied them in psychiatry classes. The term 'psychosomatic' was chosen by 54.1% of the students as the most appropriate term to refer to these disorders, and 111 (94.1%) believed that a history of sexual or physical abuse was common among FND patients. Fifty-seven students (48.3%) assumed that the diagnosis of FND was mostly a clinical diagnosis of exclusion and 63 (53.4%) indicated that it is managed only by psychiatry. One hundred and one students (85.6%) considered that adequate training on FNDs is an important aspect of their medical training. CONCLUSIONS: Medical students are aware of the existence of FNDs, but their preferred terminology, as well as the perceived aetiological factors, reflect that the historical view of these disorders is still deeply rooted. Medical students feel that they should receive adequate education on FNDs from specialists in neurology and psychiatry as part of their training.

TITLE: ¿Qué piensan los estudiantes de Medicina sobre los trastornos neurológicos funcionales?Introducción. Los trastornos neurológicos funcionales (TNF) son un motivo de consulta frecuente en neurología. Sin embargo, la formación específica sobre estos trastornos durante la formación universitaria y el período de residencia es limitada. En este estudio se evalúan los conocimientos, la actitud y la exposición de los estudiantes de Medicina a los TNF antes de terminar el grado de Medicina. Sujetos y métodos. Realizamos una encuesta de 15 ítems para explorar la comprensión, la exposición y las actitudes hacia los TNF entre los estudiantes de Medicina de sexto año en cuatro universidades españolas. Resultados. Devolvieron la encuesta 118 estudiantes (edad media 23,6 ± 1,2 años; 71,2%, mujeres). De ellos, 88 (74,6%) conocían el concepto de TNF y 78 (66,1%) los habían estudiado en las clases de psiquiatría. El 54,1% de los estudiantes eligió el término 'psicosomático' como el más adecuado para referirse a estos trastornos, y 111 (94,1%) creían que una historia de abuso sexual o físico era común entre los pacientes con TNF. Cincuenta y siete estudiantes (48,3%) asumieron que el diagnóstico de TNF era mayoritariamente un diagnóstico clínico de exclusión y 63 (53,4%) señalaron que el manejo se realiza únicamente desde psiquiatría. Ciento un estudiantes (85,6%) consideraron que una formación adecuada sobre los TNF es un aspecto importante de su formación médica. Conclusiones. Los estudiantes de Medicina son conscientes de la existencia de los TNF, pero la terminología preferida por ellos, así como los factores etiológicos percibidos, reflejan que la visión histórica acerca de estos trastornos está aún arraigada. Los estudiantes de Medicina consideran que deberían recibir una educación adecuada sobre los TNF como parte de su formación por parte de los especialistas en neurología y psiquiatría.

¿Qué piensan los estudiantes de Medicina sobre los trastornos neurológicos funcionales? / What do medical students think about functional neurological disorders?

Introducción: Los trastornos neurológicos funcionales (TNF) son un motivo de consulta frecuente en neurología. Sin embargo, la formación específica sobre estos trastornos durante la formación universitaria y el período de residencia es limitada. En este estudio se evalúan los conocimientos, la actitud y la exposición de los estudiantes de Medicina a los TNF antes de terminar el grado de Medicina. Sujetos y métodos: Realizamos una encuesta de 15 ítems para explorar la comprensión, la exposición y las actitudes hacia los TNF entre los estudiantes de Medicina de sexto año en cuatro universidades españolas. Resultados: Devolvieron la encuesta 118 estudiantes (edad media 23,6 ± 1,2 años; 71,2%, mujeres). De ellos, 88 (74,6%) conocían el concepto de TNF y 78 (66,1%) los habían estudiado en las clases de psiquiatría. El 54,1% de los estudiantes eligió el término ‘psicosomático’ como el más adecuado para referirse a estos trastornos, y 111 (94,1%) creían que una historia de abuso sexual o físico era común entre los pacientes con TNF. Cincuenta y siete estudiantes (48,3%) asumieron que el diagnóstico de TNF era mayoritariamente un diagnóstico clínico de exclusión y 63 (53,4%) señalaron que el manejo se realiza únicamente desde psiquiatría. Ciento un estudiantes (85,6%) consideraron que una formación adecuada sobre los TNF es un aspecto importante de su formación médica. Conclusiones: Los estudiantes de Medicina son conscientes de la existencia de los TNF, pero la terminología preferida por ellos, así como los factores etiológicos percibidos, reflejan que la visión histórica acerca de estos trastornos está aún arraigada. Los estudiantes de Medicina consideran que deberían recibir una educación adecuada sobre los TNF como parte de su formación por parte de los especialistas en neurología y psiquiatría.(AU)

Introduction: Functional neurological disorders (FND) are a frequent reason for visits in neurology. However, specific training on these disorders during undergraduate and residency training is limited. This study assesses the knowledge, attitude and exposure of medical students to FNDs before completing their medical degree. Patients and methods: We conducted a 15-item survey to explore understanding, exposure and attitudes towards FNDs among sixth-year medical students at four Spanish universities. Results: A total of 118 students (mean age 23.6 ± 1.2 years; 71.2% female) returned the survey. Of these, 88 (74.6%) were aware of the concept of FNDs and 78 (66.1%) had studied them in psychiatry classes. The term ‘psychosomatic’ was chosen by 54.1% of the students as the most appropriate term to refer to these disorders, and 111 (94.1%) believed that a history of sexual or physical abuse was common among FND patients. Fifty-seven students (48.3%) assumed that the diagnosis of FND was mostly a clinical diagnosis of exclusion and 63 (53.4%) indicated that it is managed only by psychiatry. One hundred and one students (85.6%) considered that adequate training on FNDs is an important aspect of their medical training. Conclusions: Medical students are aware of the existence of FNDs, but their preferred terminology, as well as the perceived aetiological factors, reflect that the historical view of these disorders is still deeply rooted. Medical students feel that they should receive adequate education on FNDs from specialists in neurology and psychiatry as part of their training.(AU)

Mechanical thrombectomy beyond 6 hours in acute ischaemic stroke with large vessel occlusion in the carotid artery territory: experience at a tertiary hospital.

INTRODUCTION: Thrombectomy in the carotid artery territory was recently shown to be effective up to 24 hours after symptoms onset. METHODS: We conducted a retrospective review of a prospective registry of patients treated at our stroke reference centre between November 2016 and April 2019 in order to assess the safety and effectiveness of mechanical thrombectomy performed beyond 6 hours after symptoms onset in patients with acute ischaemic stroke and large vessel occlusion in the carotid artery territory. RESULTS: Data were gathered from 59 patients (55.9% women; median age, 71 years). In 33 cases, stroke was detected upon awakening; 57.6% of patients were transferred from another hospital. Median baseline NIHSS score was 16, and median ASPECTS score was 8, with 94.9% of patients presenting > 50% of salvageable tissue. Satisfactory recanalisation was achieved in 88.1% of patients, beyond 24 hours after onset in 5 cases. At 90 days of follow-up, 67.8% were functionally independent; those who were not were older and presented higher prevalence of atrial fibrillation, greater puncture-to-recanalisation time, and higher NIHSS scores, both at baseline and at discharge. CONCLUSION: In our experience, mechanical thrombectomy beyond 6 hours was associated with good 90-day functional outcomes. Age, NIHSS score, puncture-to-recanalisation time, and presence of atrial fibrillation affected functional prognosis. The efficacy of the treatment beyond 24 hours after onset merits study.

Comorbidity, poverty and social vulnerability as risk factors for mortality in pregnant women with confirmed SARS-CoV-2 infection: analysis of 13 062 positive pregnancies including 176 maternal deaths in Mexico.

OBJECTIVE: Mortality in pregnancy due to coronavirus disease 2019 (COVID-19) is a current health priority in developing countries. Identification of clinical and sociodemographic risk factors related to mortality in pregnant women with COVID-19 could guide public policy and encourage such women to accept vaccination. We aimed to evaluate the association of comorbidities and socioeconomic determinants with COVID-19-related mortality and severe disease in pregnant women in Mexico. METHODS: This is an ongoing nationwide prospective cohort study that includes all pregnant women with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Mexican National Registry of Coronavirus. The primary outcome was maternal death due to COVID-19. The association of comorbidities and socioeconomic characteristics with maternal death was explored using a log-binomial regression model adjusted for possible confounders. RESULTS: There were 176 (1.35%) maternal deaths due to COVID-19 among 13 062 consecutive SARS-CoV-2-positive pregnant women. Maternal age, as a continuous (adjusted relative risk (aRR), 1.08 (95% CI, 1.05-1.10)) or categorical variable, was associated with maternal death due to COVID-19; women aged 35-39 years (aRR, 3.16 (95% CI, 2.34-4.26)) or 40 years or older (aRR, 4.07 (95% CI, 2.65-6.25)) had a higher risk for mortality, as compared with those aged < 35 years. Other clinical risk factors associated with maternal mortality were pre-existing diabetes (aRR, 2.66 (95% CI, 1.65-4.27)), chronic hypertension (aRR, 1.75 (95% CI, 1.02-3.00)) and obesity (aRR, 2.15 (95% CI, 1.46-3.17)). Very high social vulnerability (aRR, 1.88 (95% CI, 1.26-2.80)) and high social vulnerability (aRR, 1.49 (95% CI, 1.04-2.13)) were associated with an increased risk of maternal mortality, while very low social vulnerability was associated with a reduced risk (aRR, 0.47 (95% CI, 0.30-0.73)). Being poor or extremely poor were also risk factors for maternal mortality (aRR, 1.53 (95% CI, 1.09-2.15) and aRR, 1.83 (95% CI, 1.32-2.53), respectively). CONCLUSION: This study, which comprises the largest prospective consecutive cohort of pregnant women with COVID-19 to date, has confirmed that advanced maternal age, pre-existing diabetes, chronic hypertension, obesity, high social vulnerability and low socioeconomic status are risk factors for COVID-19-related maternal mortality. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Increased levels of soluble fms-like tyrosine kinase-1 are associated with adverse outcome in pregnant women with COVID-19.

OBJECTIVE: In addition to the lungs, the placenta and the endothelium can be affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are markers of endothelial dysfunction and could potentially serve as predictors of severe coronavirus disease 2019 (COVID-19). We aimed to investigate the association of serum concentrations of sFlt-1 and PlGF with the severity of COVID-19 in pregnancy. METHODS: This was a prospective cohort study carried out in a tertiary care hospital in Mexico City, Mexico. Symptomatic pregnant women with a positive reverse-transcription quantitative polymerase chain reaction test for SARS-CoV-2 infection who fulfilled the criteria for hospitalization were included. The primary outcome was severe pneumonia due to COVID-19. Secondary outcomes were intensive care unit (ICU) admission, viral sepsis and maternal death. sFlt-1 levels were expressed as multiples of the median (MoM). The association between sFlt-1 and each adverse outcome was explored by logistic regression analysis, adjusted for gestational age for outcomes occurring in more than five patients, and the predictive performance was assessed by receiver-operating-characteristics-curve analysis. RESULTS: Among 113 pregnant women with COVID-19, higher sFlt-1 MoM was associated with an increased probability of severe pneumonia (adjusted odds ratio (aOR), 1.817 (95% CI, 1.365-2.418)), ICU admission (aOR, 2.195 (95% CI, 1.582-3.047)), viral sepsis (aOR, 2.318 (95% CI, 1.407-3.820)) and maternal death (unadjusted OR, 5.504 (95% CI, 1.079-28.076)). At a 10% false-positive rate, sFlt-1 MoM had detection rates of 45.2%, 66.7%, 83.3% and 100% for severe COVID-19 pneumonia, ICU admission, viral sepsis and maternal death, respectively. PlGF values were similar between women with severe and those with non-severe COVID-19 pneumonia. CONCLUSION: sFlt-1 MoM is higher in pregnant women with severe COVID-19 and has the capability to predict serious adverse pregnancy events, such as severe pneumonia, ICU admission, viral sepsis and maternal death. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Molecular Functionalization of 2H-Phase MoS2 Nanosheets via an Electrolytic Route for Enhanced Catalytic Performance.

The molecular functionalization of two-dimensional MoS2 is of practical relevance with a view to, for example, facilitating its liquid-phase processing or enhancing its performance in target applications. While derivatization of metallic 1T-phase MoS2 nanosheets has been relatively well studied, progress involving their thermodynamically stable, 2H-phase counterpart has been more limited due to the lower chemical reactivity of the latter. Here, we report a simple electrolytic strategy to functionalize 2H-phase MoS2 nanosheets with molecular groups derived from organoiodides. Upon cathodic treatment of a pre-expanded MoS2 crystal in an electrolyte containing the organoiodide, water-dispersible nanosheets derivatized with acetic acid or aniline moieties (∼0.10 molecular groups inserted per surface sulfur atom) were obtained. Analysis of the functionalization process indicated it to be enabled by the external supply of electrons from the cathodic potential, although they could also be sourced from a proper reducing agent, as well as by the presence of intrinsic defects in the 2H-phase MoS2 lattice (e.g., sulfur vacancies), where the molecular groups can bind. The acetic acid-functionalized nanosheets were tested as a non-noble metal-based catalyst for nitroarene and organic dye reduction, which is of practical utility in environmental remediation and chemical synthesis, and exhibited a markedly enhanced activity, surpassing that of other (1T- or 2H-phase) MoS2 materials and most non-noble metal catalysts previously reported for this application. The reduction kinetics (reaction order) was seen to correlate with the net electric charge of the nitroarene/dye molecules, which was ascribed to the distinct abilities of the latter to diffuse to the catalyst surface. The functionalized MoS2 catalyst also worked efficiently at realistic (i.e., high) reactant concentrations, as well as with binary and ternary mixtures of the reactants, and could be immobilized on a polymeric scaffold to expedite its manipulation and reuse.

Hemorragia intraparenquimatosa relacionada con embolismo venoso secundario a isquemia mesentérica / Intraparenchymal hemorrhage related to cerebral venous air embolism secondary to mesenteric ischemia

Introducción: La presencia de aire en estructuras vasculares cerebrales puede condicionar una sintomatología neurológica y una importante morbilidad. Suele producirse como consecuencia de procedimientos terapéuticos invasivos y es muy infrecuente que el desencadenante sea otro. Caso clínico: Mujer de 76 años con antecedente de fibrilación auricular anticoagulada con acenocumarol. Acudió a urgencias por dolor abdominal de inicio brusco, vómitos y diarrea. Tras iniciar tratamiento sintomático y evidenciar analíticamente infradosificación del anticoagulante, presentó bruscamente focalidad neurológica. La tomografía computarizada craneal evidenció una hemorragia intraparenquimatosa aguda. Se trasladó a la paciente a la unidad de ictus del hospital de referencia. En cuestión de unas horas, presentó inestabilidad hemodinámica por shock séptico de causa abdominal. La tomografía computarizada abdominal evidenció extensa neumatosis intestinal y una interrupción al paso de contraste subsidiario de una isquemia mesentérica. Se intentó una trombectomía mecánica para embolizar el trombo a un nivel más distal, pero la paciente falleció. Conclusiones: La isquemia mesentérica puede causar una importante neumatosis intestinal, que, por un mecanismo retrógrado a través del sistema portal, consiga la llegada de burbujas de aire al sistema venoso cerebral, causando un ictus agudo.(AU)

Introduction: The presence of air in vascular structures of the brain can lead to neurological symptoms and significant morbidity. It usually occurs as a consequence of invasive therapeutic procedures and is very rarely triggered by any other cause. Case report: We report the case of a 76-year-old woman with a history of atrial fibrillation anticoagulated with acenocoumarol who visited the Emergency department because of sudden-onset abdominal pain, vomiting and diarrhoea. After starting symptomatic treatment and finding analytical evidence of underdosing of the anticoagulant, she suddenly presented with neurological focus. A cranial computed tomography scan revealed an acute intraparenchymal haemorrhage. The patient was transferred to the stroke unit of the referral hospital. Within a few hours, she developed haemodynamic instability due to a septic shock that had its origin in the abdomen. A computed tomography scan of the abdomen evidenced extensive pneumatosis intestinalis and an obstruction of contrast indicating mesenteric ischaemia. A mechanical thrombectomy was performed in an attempt to embolise the thrombus at a more distal level, but the patient died. Conclusions: Mesenteric ischaemia can cause significant pneumatosis intestinalis, which, by a retrograde mechanism through the portal system, can cause air bubbles to reach the cerebral venous system, leading to acute stroke.(AU)

Chronic Inhibition of FAAH Reduces Depressive-Like Behavior and Improves Dentate Gyrus Proliferation after Chronic Unpredictable Stress Exposure.

Symptoms of depressive disorders such as anhedonia and despair can be a product of an aberrant adaptation to stress conditions. Chronic unpredictable stress model (CUS) can generate an increase in the activity of the hypothalamic-pituitary-adrenal axis (HPA) and induce a reduction of neurotrophin signaling and the proliferation of neural progenitors in the adult dentate gyrus, together with increased oxidative stress. Levels of the endocannabinoid anandamide (AEA) seem to affect these depression-by-stress-related features and could be modulated by fatty acid amide hydrolase (FAAH). We aimed to evaluate the effects of FAAH inhibitor, URB597, on depressive-like behavior and neural proliferation of mice subjected to a model of CUS. URB597 was administered intraperitoneally at a dose of 0.2 mg/kg for 14 days after CUS. Depressive-like behaviors, anhedonia, and despair were evaluated in the splash and forced swimming tests, respectively. Alterations at the HPA axis level were analyzed using the relative weight of adrenal glands and serum corticosterone levels. Oxidative stress and brain-derived neurotrophic factor (BDNF) were also evaluated. Fluorescence immunohistochemistry tests were performed for the immunoreactivity of BrdU and Sox2 colabeling for comparison of neural precursors. The administration of URB597 was able to reverse the depressive-like behavior generated in mice after the model. Likewise, other physiological responses associated with CUS were reduced in the treated group, among them, increase in the relative weight of the adrenal glands, increased oxidative stress, and decreased BDNF and number of neural precursors. Most of these auspicious responses to enzyme inhibitor administration were blocked by employing a cannabinoid receptor antagonist. In conclusion, the chronic inhibition of FAAH generated an antidepressant effect, promoting neural progenitor proliferation and BDNF expression, while reducing adrenal gland weight and oxidative stress in mice under the CUS model.

Mechanical thrombectomy beyond 6hours in acute ischaemic stroke with large vessel occlusion in the carotid artery territory: Experience at a tertiary hospital. / Trombectomía mecánica más allá de 6horas en ictus isquémico agudo con oclusión de gran vaso en territorio carotídeo: experiencia en un hospital terciario.

INTRODUCTION: Thrombectomy in the carotid artery territory was recently shown to be effective up to 24hours after symptoms onset. METHODS: We conducted a retrospective review of a prospective registry of patients treated at our stroke reference centre between November 2016 and April 2019 in order to assess the safety and effectiveness of mechanical thrombectomy performed beyond 6hours after symptoms onset in patients with acute ischaemic stroke and large vessel occlusion in the carotid artery territory. RESULTS: Data were gathered from 59 patients (55.9% women; median age, 71 years). In 33 cases, stroke was detected upon awakening; 57.6% of patients were transferred from another hospital. Median baseline NIHSS score was 16, and median ASPECTS score was 8, with 94.9% of patients presenting>50% of salvageable tissue. Satisfactory recanalisation was achieved in 88.1% of patients, beyond 24hours after onset in 5 cases. At 90 days of follow-up, 67.8% were functionally independent; those who were not were older and presented higher prevalence of atrial fibrillation, greater puncture-to-recanalisation time, and higher NIHSS scores, both at baseline and at discharge. CONCLUSION: In our experience, mechanical thrombectomy beyond 6hours was associated with good 90-day functional outcomes. Age, NIHSS score, puncture-to-recanalisation time, and presence of atrial fibrillation affected functional prognosis. The efficacy of the treatment beyond 24hours after onset merits study.

Capsaicin attenuates immunosuppression induced by chronic stress in BALB/C mice.

Although acute stress generally exerts positive effects on the immune system, chronic stress typically causes immunosuppression via the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the effects of capsaicin (1.28 mg/kg intraperitoneally [i.p.] for 7 days) on immune parameters were evaluated under conditions of chronic stress. Capsaicin treatment significantly increased the immune response as evaluated by the delayed-type hypersensitivity (DTH) reaction to dinitrofluorobenzene (DNFB) and splenocyte proliferation assays- It also is able to rescue the splenocytes of the apoptosis induced by stress. The capsaicin treatment increased the production of Th1 cytokines and decreased the production of Th2 cytokines and TGF-ß1 in the plasma and culture supernatants of immunosuppressed mice, which is associated with the modulation of Th2 induced by stress cells. Moreover, the production of corticosterone significantly decreased in capsaicin-treated animals as compared to control groups. The capsaicin treatment further attenuated the immunosuppression induced by the corticosterone treatment (40 mg/kg i.p. for 7 days), albeit less potently, as exhibited in the DTH response. Intriguingly, the capsaicin treatment decreased the induction of IL-10, IL-4, and TGF-ß1 through high doses of corticosterone, indicating direct cellular immunomodulation. These results show, that capsaicin is able to modulate chronic stress-induced immunosuppression, mediating corticosterone released inhibition, but also, that capsaicin significantly modulates the pharmacological action of corticosterone in vivo.

Superior mechanical recovery in male and female MRL/MpJ tendons is associated with a unique genetic profile.

Tendon ruptures heal by forming a mechanically inferior scar. We have shown that male Murphy Roths large (MRL/MpJ) mice exhibit improved tendon healing, suggesting that they can inform biological mechanisms that lead to effective tendon healing. As sex impacts healing, we assessed the effect of sex on tendon healing in MRL/MpJ and normal healer C57BL/6 (B6) mice and compared the associated biological environment with identify genes that may be integral to the improved healing outcome. We hypothesized that (a) male MRL/MpJ mice will heal with improved mechanical properties compared to females; and (b) that regenerative tendon healing will be associated with decreased fibrotic pathways, decreased inflammation, and increased activity of matrix metalloproteinases (MMPs). A midsubstance punch was introduced, and tendons were harvested after (a) 1 or 7 days for profiling of 84 genes; (b) 7 or 14 days for the assessment of MMP-2 and MMP-9 activity; and (c) 6 weeks for mechanical assessment. MRL/MpJ tendons healed with the better restoration of mechanical properties than B6 tendons. Sex did not affect the mechanical properties of healing B6 or MRL/MpJ tendons. Comparison of the gene expression profiles in the context of the mechanical outcome revealed several differences between MRL/MpJ and B6 tendon healing, including, lower inflammation, an earlier higher expression of TGF-ß-related genes that diminish by 7 days, and genes associated with enhanced cell migration in MRL/MpJ in comparison to B6 tendons. We expect that the timecourse and expression levels of these genes in scarless MRL/MpJ tendon healing represent the balanced environment that leads to improved tendon healing.

ß-Caryophyllene exerts protective antioxidant effects through the activation of NQO1 in the MPTP model of Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder, caused by the selective death of dopaminergic neurons in the substantia nigra pars compacta. ß-caryophyllene (BCP) is a phytocannabinoid with several pharmacological properties, producing anti-inflammatory and antihypertensive effects. In addition, BCP protects dopaminergic neurons from neuronal death induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), yet it remains unclear if this effect is due to its antioxidant activity. To assess whether this is the case, the effect of BCP on the expression and activity of NAD(P)H quinone oxidoreductase (NQO1) was evaluated in mice after the administration of MPTP. Male C57BL/6 J mice were divided into four groups, the first of which received saline solution i.p. in equivalent volume and served as a control group. The second group received MPTP. The second group received MPTP hydrochloride (5 mg/kg, i.p.) daily for seven consecutive days. The third group received BCP (10 mg/kg) for seven days, administered orally and finally, the fourth group received MPTP as described above and BCP for 7 days from the fourth day of MPTP administration. The results showed that BCP inhibits oxidative stress-induced cell death of dopaminergic neurons exposed to MPTP at the same time as it enhances the expression and enzymatic activity of NQO1. Also, the BCP treatment ameliorated motor dysfunction and protected the dopaminergic cells of the SNpc from damage induced by MPTP. Hence, BCP appears to achieve at least some of its antioxidant effects by augmenting NQO1 activity, which protects cells from MPTP toxicity. Accordingly, this phytocannabinoid may represent a promising pharmacological option to safeguard dopaminergic neurons and prevent the progression of PD.

A commercial autogenous injection vaccine protects ballan wrasse (Labrus bergylta, Ascanius) against Aeromonas salmonicida vapA type V.

Atypical Aeromonas salmonicida (aAs) and Vibrionaceae related species are bacteria routinely recovered from diseased ballan wrasse used as cleaner fish in the Atlantic salmon farming industry. Autogenous (i.e. farm specific inactivated) multivalent vaccines formulated from these microorganisms are widely used to protect farmed wrasse despite limited experimental proof that they are primary pathogens. In this study, the components of a commercial multivalent injection vaccine containing four strains of Aeromonas salmonicida and one strain of Vibrio splendidus previously isolated from ballan wrasse in Scotland, were tested for infectivity, pathogenicity and virulence via intra peritoneal injection at pre-deployment size (25-50 g) and the efficacy of the vaccine for protection against aAs assessed. Injection with 3.5 × 109, 8 × 109 1.8 × 109 and 5 × 109 cfu/fish of Vibrio splendidus, V. ichthyoenteri, Aliivibrio logeii and A. salmonicida, respectively, did not cause significant mortalities, lesions or clinical signs after a period of 14 days. IP injection with both aAs and Photobacterium indicum successfully reproduced the clinical signs and internal lesions observed during natural outbreaks of the disease. Differences in virulence (LD50 at day 8-post infection of 3.6 × 106 cfu/fish and 1.6 × 107 cfu/fish) were observed for two aAs vapA type V isolates. In addition, the LD50 for Photobacterium indicum was 2.2 × 107 cfu/fish. The autogenous vaccine was highly protective against the two aAs vapA type V isolates after 700-degree days of immunisation. The RPSFINAL values for the first isolate were 95 and 91% at 1 × 106 cfu/fish and 1 × 107 cfu/fish, respectively, and 79% at 1 × 107 cfu/fish for the second isolate tested. In addition, significantly higher anti aAs seral antibodies (IgM), were detected by ELISA in vaccinated fish in contrast with control (mock vaccinated) fish. These results suggest wrasse can be effectively immunised and protected against aAs infection by injection with oil adjuvanted vaccines prepared with inactivated homologous isolates.

Atypical Aeromonas salmonicida vapA type V and Vibrio spp. are predominant bacteria recovered from ballan wrasse Labrus bergylta in Scotland.

Healthy and/or moribund farmed and wild ballan wrasse Labrus bergylta (>0.5 to 900 g) were sampled from hatcheries (n = 2) and Atlantic salmon Salmo salar cage sites (n = 8) in Scotland between February 2016 and October 2018. Less than half of the sampled individuals (n = 43; 32.3%) had been vaccinated (autogenous polyvalent vaccine; dip and/or injection) against atypical furunculosis (type V and VI), while 20 (15.0%) fish were not vaccinated, and the rest (70 individuals, 52.7%) were of unknown vaccination status. Swab samples from skin lesions, gill, liver, spleen and kidney were inoculated onto a variety of bacteriological agar plates, and bacteriology identification and sequencing analysis was performed on significant bacterial colonies. Atypical Aeromonas salmonicida (aAs) vapA type V was the predominant bacterial species (70/215 bacterial isolates, 32.5% of bacterial samples; 43/117 positive individual fish, 36.8%) isolated in this survey followed by Vibrio species, which were the most geographically prevalent bacteria. Photobacterium indicum/profundum was also isolated from L. bergylta for the first time during this study. The collection of these bacterial isolates provides useful information for disease management. Identifying the aAs isolates involved in disease in ballan wrasse could provide vital information for improving/updating existing autogenous vaccines.

Mitigation of greenhouse gases in dairy cattle via genetic selection: 2. Incorporating methane emissions into the breeding goal.

The objective of this study was to analyze the impact of incorporating enteric methane into the breeding objective of dairy cattle in Spain, and to evaluate both genetic and economic response of traits in the selection index under 4 scenarios: (1) the current ICO (Spanish total merit index), used as benchmark; (2) a hypothetical penalization of methane emissions through a carbon tax; (3) considering methane as a net energy loss for the animal; and (4) desired genetic response to reduce methane production by 20% in 10 yr. A bio-economic model was developed to derive the economic values for production and methane traits in each scenario. The estimated economic values for methane were estimated at -€1.21/kg and -€0.32/kg for scenarios 2 and 3, respectively. When merged with other traits in the selection index, methane had less economic importance (1-5%) than milk protein yield (39-42%) or milk fat yield (27-28%). Under these scenarios, selection resulted in an unfavorable response in methane emissions when it was included with an economic weight, with an increase in methane estimated from 0.52 to 0.60 kg/cow per year. Small differences in total profit per cow per year were observed between indices. The incorporation of methane production into the breeding objective had a negligible effect on production, with minor reductions in the expected genetic gain for fat and protein yields and in total economic benefits. However, total methane emissions in the dairy industry in Spain were estimated to decrease between 2 and 5% in the next 10 yr due to positive genetic trends for milk yield and an expected decrease in the total number of dairy cows. Additionally, methane intensity per 1 billion liters of milk would decrease in all scenarios. The uncertainty in the genetic parameters of methane and in carbon prices were tested in a sensitivity analysis, resulting in small deviations from the benchmark scenario. A major effect was observed only under the desired genetic response scenario. In this case, it was possible to achieve a 20% reduction of methane production in 10 yr via selective breeding but at the expense of a larger ad hoc weight (33%) of methane in the selection index and decelerating the genetic gain for production traits from 6 to 18%. This study shows the potential of including environmental traits in the selection indices while retaining populations profitable for producers.