Systems genetics identifies miRNA-mediated regulation of host response in COVID-19.

BACKGROUND: Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes. The nature and magnitude of miRNA perturbations associated with blood phenotypes and intensive care unit (ICU) admission in COVID-19 are poorly understood. RESULTS: We combined multi-omics profiling-genotyping, miRNA and RNA expression, measured at the time of hospital admission soon after the onset of COVID-19 symptoms-with phenotypes from electronic health records to understand how miRNA expression contributes to variation in disease severity in a diverse cohort of 259 unvaccinated patients in Abu Dhabi, United Arab Emirates. We analyzed 62 clinical variables and expression levels of 632 miRNAs measured at admission and identified 97 miRNAs associated with 8 blood phenotypes significantly associated with later ICU admission. Integrative miRNA-mRNA cross-correlation analysis identified multiple miRNA-mRNA-blood endophenotype associations and revealed the effect of miR-143-3p on neutrophil count mediated by the expression of its target gene BCL2. We report 168 significant cis-miRNA expression quantitative trait loci, 57 of which implicate miRNAs associated with either ICU admission or a blood endophenotype. CONCLUSIONS: This systems genetics study has given rise to a genomic picture of the architecture of whole blood miRNAs in unvaccinated COVID-19 patients and pinpoints post-transcriptional regulation as a potential mechanism that impacts blood traits underlying COVID-19 severity. The results also highlight the impact of host genetic regulatory control of miRNA expression in early stages of COVID-19 disease.

Intravenous thrombolysis in ischemic stroke with unknown onset using CT perfusion.

BACKGROUND: Acute ischemic stroke patients with unclear onset time presenting >4.5 h from last-seen-normal (LSN) time are considered late patients and excluded from i.v. thrombolysis. We aimed to evaluate whether this subgroup of patients is different from patients presenting >4.5 h from a witnessed onset, in terms of eligibility and response to computed tomography perfusion (CTP)-guided i.v. thrombolysis. METHODS: We prospectively studied consecutive acute non-lacunar middle cerebral artery (MCA) ischemic stroke patients presenting >4.5 h from LSN. All patients underwent multimodal CT and were considered eligible for i.v. thrombolysis according to CTP criteria. Two patient groups were established based on the knowledge of the stroke onset time. We compared the proportion of candidates suitable for intravenous thrombolysis between both groups, and their outcome after thrombolytic therapy. RESULTS: Among 147 MCA ischemic stroke patients presenting >4.5 h from LSN, stroke onset was witnessed in 74 and unknown in 73. Thirty-seven (50%) patients in the first group and 32 (44%) in the second met CTP criteria for thrombolysis (P = 0.7). Baseline variables were comparable between both groups with the exception of age, which was higher in the unclear onset group. The rates of early neurological improvement (54.1% vs 46.9%), 2-h MCA recanalization (43.5% vs 37%), symptomatic hemorrhagic transformation (3% vs 0%) and good 3-month functional outcome (62.2% vs 56.3%) did not differ significantly between both groups. CONCLUSION: Delayed stroke patients with unknown onset time were no different than patients >4.5 h regarding eligibility and response to CTP-based i.v. thrombolysis.

Spatial characterization of landscapes through multifractal analysis of DEM.

Landscape evolution is driven by abiotic, biotic, and anthropic factors. The interactions among these factors and their influence at different scales create a complex dynamic. Landscapes have been shown to exhibit numerous scaling laws, from Horton's laws to more sophisticated scaling of heights in topography and river network topology. This scaling and multiscaling analysis has the potential to characterise the landscape in terms of the statistical signature of the measure selected. The study zone is a matrix obtained from a digital elevation model (DEM) (map 10 × 10 m, and height 1 m) that corresponds to homogeneous region with respect to soil characteristics and climatology known as "Monte El Pardo" although the water level of a reservoir and the topography play a main role on its organization and evolution. We have investigated whether the multifractal analysis of a DEM shows common features that can be used to reveal the underlying patterns and information associated with the landscape of the DEM mapping and studied the influence of the water level of the reservoir on the applied analysis. The results show that the use of the multifractal approach with mean absolute gradient data is a useful tool for analysing the topography represented by the DEM.

[The clinic of apathy in schizophrenia: a critical review of the issue]. / L'apathie dans la schizophrénie: une revue clinique et critique de la question.

INTRODUCTION: Today the concept of apathy is subject to many questions. This psychological state is present and predominant in different disorders such as neurodegenerative and psychiatric diseases or neurological acquired disorders. Apathy is a part of the clinical vocabulary, however, we can note that in the literature there remains confusion in its definition, and we can find an amalgam with other clinical symptoms. OBJECTIVES: The aim of this review is to provide a clarification of the concept of apathy in clinical practice in schizophrenia as well as to highlight the gaps that exist. LITERATURE FINDINGS: Apathy belongs to the negative symptoms of schizophrenia. For its understanding, it is necessary to define apathy as a multidimensional syndrome (cognitive, emotional, and behavioral) manifesting as a quantitative reduction of voluntary behaviors directed toward one or several goals. However, at present, we are witnessing a reductionist and simplistic conception of the syndrome of apathy and this especially in the Anglo-Saxon literature. Several authors reduce apathy to its behavioral component, so in other words, to avolition/amotivation. Avolition refers to a loss of self-initiated and spontaneous behaviors. In this definition only observable behavior is taken into account and not the underlying mechanisms (cognitive and emotional). In order to understand the syndrome of apathy, it is necessary to have a holistic and multidimensional outlook. Some authors have proposed diagnostic criteria for apathy by taking into account the different dimensions of apathy. Moreover not only is apathy confused with avolition, but it is also still difficult to distinguish it from depression. Apathy and depression share common clinical signs (i.e. loss of interest), but they also have distinct clinical signs (lack of motivation for apathy, and suicidal ideation for depression). Authors have shown that the presence of one symptom (apathy or depression) does not predict the presence of the other. An apathetic patient does not have to be necessarily in a depressive state and vice versa. However, to our knowledge, there is no data capable of distinguishing depression from apathy in schizophrenia, and knowing what is the part of one and the other when the patient has both symptoms. In addition, we can see that the confusion that persists between those two symptoms also stems from assessment tools. Indeed, some assessment tools such as the Montgomery and Asberg Depression Rating Scale (MARDS) have an apathy subscale. Therefore, this scale does not only evaluate depression. Regarding the assessment of apathy in schizophrenia, there are specific and nonspecific tools. Nonspecific tools define apathy differently. For this reason, authors have proposed to measure apathy by using analytic factors of negative symptoms. In this case, apathy is going to be assessed by the factor "motivation/pleasure" including anhedonia, asociality and avolition. This factor will provide the possibility of a better assessment of apathy. Concerning specific scales (like AES), there are gaps such as a lack of standardization in the execution and the quotation. Furthermore, no scale takes into account the factors causing apathy. CONCLUSION: Knowing the reasons for apathy is necessary because this syndrome is frequent in schizophrenia, and it is found in the different phases of this disease (prodromal, first episode psychosis, and chronic). In addition, apathy has significant functional consequences on the patient's quality of life, as well as on his or her global functioning. Indeed, apathy impacts on his or her social and professional life. Patients with schizophrenia have a loss of autonomy, less employment and social withdrawal. Consequently, interest in its drug or treatment it is obvious. However, drug and non-drug treatments are not specific to apathy and therefore little effective on this syndrome. Implications to stimulate future research are presented.

Collateral circulation on perfusion-computed tomography-source images predicts the response to stroke intravenous thrombolysis.

BACKGROUND AND PURPOSE: Perfusion-computed tomography-source images (PCT-SI) may allow a dynamic assessment of leptomeningeal collateral arteries (LMC) filling and emptying in middle cerebral artery (MCA) ischaemic stroke. We described a regional LMC scale on PCT-SI and hypothesized that a higher collateral score would predict a better response to intravenous (iv) thrombolysis. METHODS: We studied consecutive ischaemic stroke patients with an acute MCA occlusion documented by transcranial Doppler/transcranial color-coded duplex, treated with iv thrombolysis who underwent PCT prior to treatment. Readers evaluated PCT-SI in a blinded fashion to assess LMC within the hypoperfused MCA territory. LMC scored as follows: 0, absence of vessels; 1, collateral supply filling ≤ 50%; 2, between> 50% and < 100%; 3, equal or more prominent when compared with the unaffected hemisphere. The scale was divided into good (scores 2-3) vs. poor (scores 0-1) collaterals. The predetermined primary end-point was a good 3-month functional outcome, while early neurological recovery, transcranial duplex-assessed 24-h MCA recanalization, 24-h hypodensity volume and hemorrhagic transformation were considered secondary end-points. RESULTS: Fifty-four patients were included (55.5% women, median NIHSS 10), and 4-13-23-14 patients had LMC score (LMCs) of 0-1-2-3, respectively. The probability of a good long-term outcome augmented gradually with increasing LMCs: (0) 0%; (1) 15.4%; (2) 65.2%; (3) 64.3%, P = 0.004. Good-LMCs was independently associated with a good outcome [OR 21.02 (95% CI 2.23-197.75), P = 0.008]. Patients with good LMCs had better early neurological recovery (P = 0.001), smaller hypodensity volumes (P < 0.001) and a clear trend towards a higher recanalization rate. CONCLUSIONS: A higher degree of LMC assessed by PCT-SI predicts good response to iv thrombolysis in MCA ischaemic stroke patients.

[Evolution of the concept of apathy: the need for a multifactorial approach in schizophrenia]. / Évolution du concept d'apathie: nécessité d'une approche multifactorielle dans la schizophrénie.

BACKGROUND: Schizophrenia is a chronic and severe mental illness that affects over 1% of the population, characterized by multiple symptom dimensions. One of this class of symptoms, "negative symptoms", have received more attention over the last few years. Negative symptoms, including among others blunted affect, withdrawal or apathy, are particularly important for recovery and are associated with negative functional outcomes, such as inability to get an employment and conduct normal daily living activities. While positive symptoms are usually treated by antipsychotic drugs, negative symptoms are usually persistent, which indicates the need for better treatment. The aim of this article is to highlight recent scientific progress on apathy and to explore current multidimensional approaches of this concept in schizophrenia. Apathy is a symptom frequently encountered in schizophrenia and in many neurological disorders. Therefore, it can be regarded as a transnosographic symptom. LITERATURE FINDINGS: A long time considered as a loss of motivation (psychological concept hard to define), recent descriptive and etiological models have proposed to consider apathy as a multidimensional phenomenon. Marin et al., have proposed a model of apathy in reference to the motivation concept. Marin et al.'s apathy model is composed of three dimensions: firstly, cognitive dimension, secondly, sensory-motor dimension and thirdly, affective dimension. These authors propose to differentiate "apathy syndrome" from "apathy symptom". "Apathy syndrome" resulting from a lack of motivation whereas "apathy symptom" results from cognitive and/or emotional/affective disorders. In addition, Marin et al. propose that apathy syndrome corresponds to the "lack of motivation" not attributable to diminished level of consciousness, cognitive impairment or emotional distress. Following this proposal, Levy and Dubois propose to define apathy as a quantitative reduction of self-generated, voluntary and purposeful behaviors. It is therefore observable and can be quantified. Levy and Dubois have proposed an apathy model considering: firstly, apathy as a syndrome related to reduction in goal-directed behaviors; secondly, anatomically, apathy can be secondary to dysfunctions or lesions of the prefrontal cortex. Since the prefrontal cortex is functionally and anatomically heterogeneous, subtypes of apathy occur in diseases affecting the basal ganglia, because these diseases disrupt associative and limbic pathways from/to the prefrontal cortex; thirdly, from a pathophysiological point of view, apathy may be explained by the impact of lesions or dysfunctions of the basal ganglia, because these lesions or dysfunctions lead to a loss of temporal and spatial focalization, both of which result in a diminished extraction of the relevant signal within the frontal cortex, thereby inhibiting the capacity of the frontal cortex to select, initiate, maintain and shift programs of action.

Mantle cell lymphoma with involvement of the digestive tract. / Linfoma del manto con afección del tubo digestivo.

INTRODUCTION AND AIM: Mantle cell lymphoma is an aggressive subtype of B-cell non-Hodgkin lymphoma and its incidence is 0.5/100,000 inhabitants. Gastrointestinal involvement at diagnosis is 15-30%. The aim of our study was to analyze the clinical and endoscopic characteristics of mantle cell lymphoma affecting the digestive tract. MATERIAL AND METHODS: A retrospective study was conducted, based on a case series of patients with mantle cell lymphoma affecting the gastrointestinal tract that were diagnosed over a 10-year period. RESULTS: Ten patients (11.7%) had gastrointestinal tract involvement. The upper endoscopic findings were polypoid lesions (66%), thickened folds (44%), and nonspecific changes in the mucosa (33%). At colonoscopy, polypoid lesions were viewed in 100% of the patients and ulcerated lesions in 40%. CONCLUSION: Polypoid lesions are the most common endoscopic characteristics in patients with mantle cell lymphoma of the gastrointestinal tract. Upper endoscopy and colonoscopy should be carried out on patients with mantle cell lymphoma, even those with nonspecific symptoms, to check their gastrointestinal status. Gastrointestinal involvement has an impact on disease staging.

Fully covered stents versus partially covered stents for palliative treatment of esophageal cancer: Is there a difference? / Prótesis totalmente cubiertas versus parcialmente cubiertas para el tratamiento paliativo del cáncer de esófago: ¿hay alguna diferencia?

INTRODUCTION AND AIMS: Malignant dysphagia is difficulty swallowing resulting from esophageal obstruction due to cancer. The goal of palliative treatment is to reduce the dysphagia and improve oral dietary intake. Self-expandable metallic stents are the current treatment of choice, given that they enable the immediate restoration of oral intake. The aim of the present study was to describe the results of using totally covered and partially covered esophageal stents for palliating esophageal cancer. MATERIALS AND METHODS: A retrospective study was conducted on patients with inoperable esophageal cancer treated with self-expandable metallic stents. The 2 groups formed were: group A, which consisted of patients with a fully covered self-expandable stent (SX-ELLA®), and group B, which was made up of patients with a partially covered self-expandable stent (Ultraflex®). RESULTS: Of the 69-patient total, 50 were included in the study. Group A had 19 men and 2 women and their mean age was 63.6 years (range 41-84). Technical success was achieved in 100% (n=21) of the cases and clinical success in 90.4% (n=19). Group B had 24 men and 5 women and their mean age was 67.5 years (range 43-92). Technical success was achieved in 100% (n=29) of the cases and clinical success in 89.6% (n=26). Complications were similar in both groups (33.3 vs. 51.7%). CONCLUSION: There was no difference between the 2 types of stent for the palliative treatment of esophageal cancer with respect to technical success, clinical success, or complications.

[Lingual abscess]. / Absceso lingual.

The unilateral abscess of the anterior portion of the tongue is an extremely rare occurrence. We report a case in which we have used the ultrasonography in the diagnosis, and discuss, as etiologic hypothesis the participation of Blandin-Nühn glands in the genesis of these abscess.

[Perfusion computed tomography makes it possible to overcome important SITS-MOST exclusion criteria for the endovenous thrombolysis of cerebral infarction]. / La tomografia computarizada de perfusion permite superar importantes criterios de exclusion SITS-MOST para la trombolisis endovenosa del infarto cerebral.

AIM. To study the frequency, safety and efficacy of perfusion computed tomography (PCT), through identification of brain tissue-at-risk, to guide intravenous thrombolysis in stroke patients with regulatory exclusion criteria (SITS-MOST and ECASS-3). PATIENTS AND METHODS. We studied consecutive acute non-lacunar ischemic stroke patients. After conventional CT was considered eligible, PCT was performed in the following circumstances: 4.5 to 6 h window, wake-up stroke or unknown time of onset; extent early infarct signs on CT; minor or severe stroke; seizures or loss of consciousness. Intravenous 0.9 mg/kg alteplase was indicated if: cerebral blood volume lesion covered < 1/3 of middle cerebral artery territory; mismatch > 20% between mean transit time and cerebral blood volume maps existed; and informed consent. SITS-MOST safety-efficacy parameters were used as endpoint variables. RESULTS. Between May 2009-April 2010, 66 hyperacute ischemic stroke patients a priori not eligible for intravenous thrombolysis underwent PCT. Indications were: > 4.5 h in 18 patients, wake up stroke or unknown onset in 25, extent infarct signs in 6, seizures at onset in 11, and minor stroke (NIHSS < 4) in 6. Twenty-nine (44%) of them finally received intravenous thrombolysis. Symptomatic hemorrhagic transformation occurred in 2 (6.9%) patient and 18 (62.1%) achieved a modified Rankin scale score equal or less than 2 on day 90. CONCLUSION. A high proportion of acute stroke patients with SITS-MOST and ECASS-3 exclusion criteria can be safely and efficaciously treated with intravenous thrombolysis using a PCT selection protocol. However randomized control trials will be needed to confirm our results.