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Clinical and preclinical findings have suggested a role of the endocannabinoid system (ECS) in the etiopathology of autism spectrum disorder (ASD). Previous mouse studies have investigated the role of ECS in several behavioral domains; however, none of them has performed an extensive assessment of social and communication behaviors, that is, the main core features of ASD. This study employed a mouse line lacking the primary endocannabinoid receptor (CB1r) and characterized ultrasonic communication and social interaction in CB1-/- , CB1+/- , and CB1+/+ males and females. Quantitative and qualitative alterations in ultrasonic vocalizations (USVs) were observed in CB1 null mice both during early development (i.e., between postnatal days 4 and 10), and at adulthood (i.e., at 3 months of age). Adult mutants also showed marked deficits in social interest in the three-chamber test and social investigation in the direct social interaction test. These behavioral alterations were mostly observed in both sexes and appeaains.

Heart failure describes a large and heterogeneous spectrum of underlying cardiac diseases. MicroRNAs (miRs) are small non-coding RNAs that in recent years have been shown to play an important role in the pathogenesis of heart failure. Cardiac magnetic resonance imaging is a powerful imaging modality for the evaluation of cardiac characteristics in heart failure. In this study, we sought to compare heart failure patients with a diagnosis of either idiopathic dilated cardiomyopathy (DCM) or ischaemic heart disease (IHD), in the context of serum levels of certain miRs and also magnetic resonance imaging parameters of cardiac structure and function.

A total of 135 subjects were studied 53 patients with DCM (age 59±12years, mean±SD), 34 patients with IHD (66±9years), and 48 controls (64±5years). The participants underwent baseline medical examination, blood sampling, and a cardiac magnetic resonance imaging examination at 3 Tesla (Philips Ingenia). The serum levels of seven different miRs were analysed and assHD.Effusive-constrictive pericarditis (ECP) is an uncommon diagnosis, frequently missed due to its heterogeneous presentation, but a potentially reversible cause of heart failure. A 62-year-old Caucasian male presented with remittent right heart failure and mild-moderate pericardial effusion. Following an initial diagnosis of idiopathic pericarditis, indomethacin was started, but the patient shortly relapsed, presenting with severe pericardial effusion and signs of cardiac tamponade, requiring pericardiocentesis. ECP was diagnosed on cardiac catheterization. Cardiac computed tomography showed non-calcified, mildly thickened and inflamed parietal pericardium. Pericardiectomy was performed with symptoms remission. On histological examination of pericardium, chronic non-necrotizing granulomatous inflammation was noted. Polymerase chain reaction assay was positive for non-tuberculous mycobacteria. This case represents a rare finding of ECP with unusual presentation due to atypical mycobacteriosis in a non-immunocompromised patient and in a non-endemic area. Pericardiectomy can be an effective option in cases unresponsive to anti-inflammatory treatment, even in the absence of significant pericardial thickening or calcification.The emerging role of a microbiota-gut-brain axis in autism spectrum disorder (ASD) suggests that modulating gut microbial composition may offer a tractable approach to addressing the lifelong challenges of ASD. The aim of this systematic review was to provide an overview and critically evaluate the current evidence on the efficacy and safety of probiotic, prebiotic, synbiotic, and fecal microbiota transplantation therapies for core and co-occurring behavioral symptoms in individuals with ASD. Comprehensive searches of MEDLINE, EMBASE, Scopus, Web of Science Core Collection, Cochrane Library, and Google Scholar were performed from inception to March 5, 2020, and two update searches were completed on October 25, 2020, and April 22, 2021, respectively. A total of 4306 publications were identified, of which 14 articles met the inclusion criteria. Data were extracted independently by two reviewers using a preconstructed form. Results of probiotic studies do not confirm the supposed beneficial effect of probiotics modalities. Further clinical studies are needed.Calcifying fibrous tumor of the pleura (CFTP) is a rare benign tumor of the thoracic cavity. Due to the low incidence of CFPT, it is prone to be misdiagnosed because intraoperative analysis of frozen section is a challenge for pathologists. At present, it is difficult to distinguish this tumor from other benign thoracic tumors based on radiographic features. Therefore, surgical resection is the best method for definite diagnosis and treatment.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced or recurrent non-small cell lung cancer (NSCLC). They cause immune-related adverse events (irAEs), but the underlying mechanisms and predictors remain to be fully elucidated. In this retrospective study, we investigated the association between pretreatment neutrophil-to-lymphocyte ratio (NLR) and the occurrence of irAEs.

The study involved 115 patients with NSCLC who started ICI-only treatment in our hospital between January 2016 and April 2020.

Forty-five patients (39.1%) had irAEs, and pretreatment NLR was significantly lower in the irAEs group than in the non-irAEs group (2.8 vs. 4.1; p=0.036). The cutoff value of the NLR was 2.86 (area under curve, 0.62; sensitivity, 0.56; specificity, 0.71), and the incidence rate of irAEs was significantly higher in the NLR < 2.86 group than in the NLR ≥2.86 group (p=0.004; odds ratio [OR] 3.12; 95% confidence interval [CI] 1.43-6.84). The multivariate analysis showed that the NLR was significantly associated with the occurrence of irAEs (p=0.016; OR 2.69; 95% CI 1.21-6.01).

Low pretreatment NLR may be a predictive factor for the occurrence of irAEs. By focusing on the potential risk of irAEs in patients with a low pretreatment NLR, irAEs can be appropriately managed from an early period.

Low pretreatment NLR may be a predictive factor for the occurrence of irAEs. By focusing on the potential risk of irAEs in patients with a low pretreatment NLR, irAEs can be appropriately managed from an early period.

Venetoclax (VTX) is an anticancer drug. It is a selective Bcl-2 inhibitor that is clinically used for the treatment of patients with lymphomas and leukemias. Treatment with VTX, however, is accompanied by severe adverse events such as tumor lysis syndrome and neutropenia, because VTX readily binds to serum proteins, which results in poor pharmacokinetics and poor tumor tissue concentration. To avoid such adverse events, VTX is administered using a daily or weekly ramp-up schedule that is cumbersome in clinical situations.

To overcome these shortcomings, we prepared a novel polyethylene glycol (PEG)-drug conjugate of VTX (PEG-VTX) and evaluated its cytotoxic effects on acute myeloid leukemia (AML) both in vitro and in vivo.

VTX and 4-armed PEG derivatives were covalently attached through an amide bond linker. In a series of in vitro studies, PEG-VTX selectively induced potent growth inhibition of MV4-11 human AML cells via the inducement of Bcl-2-mediated apoptosis. PEG-VTX had the effect of free VTX, prThe results of this study suggest that PEG-VTX could be an alternative therapeutic option for the safe and effective treatment of patients with AML.Discovering new serological markers of Mycobacterium tuberculosis (MTB) infection and establishing a rapid and efficient detection technology is of great significance for the prevention and control of tuberculosis. In this study, we established an exponentially modified protein abundance index (emPAI) value-assisted strategy to investigate and improve the screening efficiency of serological biomarkers of tuberculosis. First, we used LC-MS/MS to analyse MTB culture filtrate proteins (MTB-CFPs), and 632 MTB proteins were identified. Then, the characteristic values of MTB-CFPs - including emPAI value, molecular weight (Mw), isoelectric point (pI), grand average of hydropathy (GRAVY), transmembrane domain (TMD) and functional groups were calculated. Next, we successfully prepared 10 MTB proteins with emPAI value > 1.0 and recombinantly expressed these proteins in Escherichia coli. At the same time, 3 MTB proteins with emPAI between 0.1 and 0.5 were randomly selected as the control groups, and the immunogenicity of the recombinant MTB proteins was detected using ELISA. The sensitivity and receiver operating characteristic (ROC) curves were calculated for each recombinant MTB protein. The results showed that the areas under the curve (AUC) value of Rv2031c, Rv0577, Rv0831c, Rv0934 and Rv3248c were all higher than those of Rv3875 (AUC, 0.6643). Further analysis of the relationship between emPAI value and antibody sensitivity, AUC value and antibody affinity in mice immunized with recombinant MTB protein showed that emPAI values were positively correlated with them, and R-squared value ranged from 0.64 to 0.79. The only exception was ESAT-6 (encoded by the Rv3875 gene), which AUC value was relatively low owing to its strong immunosuppressive properties. This study provides a rationale for the serological marker screening of emPAI-assisted tuberculosis clinical test. The results also provide new technical support for the screening of candidate serological markers of infectious diseases in the future.Beta rhythm modulation has been used as a biomarker to reflect the functional state of the sensorimotor cortex in both healthy subjects and patients. Here, the effect of reduced alertness and active attention to the stimulus on beta rhythm modulation was investigated. Beta rhythm modulation to tactile stimulation of the index finger was recorded simultaneously with MEG and EEG in 23 healthy subjects (mean 23, range 19-35 years). The temporal spectral evolution method was used to obtain the peak amplitudes of beta suppression and rebound in three different conditions (neutral, snooze, and attention). Neither snooze nor attention to the stimulus affected significantly the strength of beta suppression nor rebound, although a decrease in suppression and rebound strength was observed in some subjects with a more pronounced decrease of alertness. The reduction of alertness correlated with the decrease of suppression strength both in MEG (left hemisphere r = 0.49; right hemisphere r = 0.49, *p less then 0.05) and EEG (left hemisphere r = 0.43; right hemisphere r = 0.72, **p less then 0.01). The results indicate that primary sensorimotor cortex beta suppression and rebound are not sensitive to slightly reduced alertness nor active attention to the stimulus at a group level. Hence, tactile stimulus-induced beta modulation is a suitable tool for assessing the sensorimotor cortex function at a group level. However, subjects' alertness should be maintained high during recordings to minimize individual variability.The aetiology and epidemiology of vector borne apicomplexan Babesia and Hepatozoon and kinetoplastid Leishmania infantum infections in wildlife have not been explored in wide areas of southern Spain. We investigated these infections in 151 wild carnivores, including foxes, badgers, beech martens, hedgehogs, wild cats, Egyptian mongooses, otters, genets and racoons. Overall, Hepatozoon, Babesia and L. infantum infections were detected in 68%, 48% and 23% of the wild animals surveyed, respectively. L. infantum-infected wildlife were more likely to be also infected with the apicomplexan Hepatozoon and Babesia spp. compared to the non-infected counterparts (p less then .05). We report for the first time Hepatozoon martis in badgers and wild cats and H. canis in beech martens, and a Babesia sp. in wild cats from Spain. Our results also indicate the widespread distribution of H. canis in foxes (91%) and beech martens (13%), H. martis in beech martens (81%), wild cats (20%) and badgers (13%), H. felis in wild cats (60%), B.

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