Higginsemery0750

Comparisons between BPD patients with childhood trauma and patients and controls without revealed significant differences in four genes (POU5F1, GGT6, TNFRSF13C and FAM113B), none of them in the X chromosome. Gene set enrichment analyses revealed that epigenetic alterations were more frequently found in genes controlling oestrogen regulation, neurogenesis and cell differentiation. These results suggest that epigenetic alterations in the X chromosome and oestrogen-regulation genes may contribute to the development of BPD and explain the differences in presentation between genders. Furthermore, childhood trauma events may modulate the magnitude of the epigenetic alterations contributing to BPD.

Starting March 2020 the Italian Government imposed a lockdown to limit the spread of SARS-CoV-2. During lockdown outpatient visits were limited and telemedicine (TM) was encouraged.

We retrospectively analyzed data from continuous or flash glucose monitoring systems shared through different cloud systems during the lockdown by subjects with type 1 diabetes and compared data obtained 4 weeks before and 4 weeks after structured telephonic visit. Variables considered were mean glucose, time spent in target (70-180 mg/dl), hypoglycemia (<70 mg/dl) and hyperglycemia (>180 mg/dl), coefficient of variation, and length of sensor use.

During the 4 weeks following the telephonic visit there was an improvement of glycemic control, with a significant reduction of mean glucose values (161.1 before vs 156.3 mg/dl after, p = 0.001), an increase of the time spent in target (63.6 vs 66.3, p = 0.0009) and a reduction of time spent in hyperglycemia (33.4 vs 30.5, p = 0.002). No changes were observed regarding glucose variability, time spent in hypoglycemia, and length of sensor use. Similar results were observed in subjects treated with multiple daily injections or continuous subcutaneous insulin infusion.

A structured telephonic visit appears to be an effective way to replace or integrate routine visits in particular conditions.

A structured telephonic visit appears to be an effective way to replace or integrate routine visits in particular conditions.Understanding the common dimension of mental disorders (such as anxiety, depression, and drug addiction) might contribute to the construction of biological frameworks (Research Domain Criteria, RDoC) for novel ways of treatment. One common dimension at the behavioral level observed across these disorders is a generalization. Testing generalization in serotonin transporter (5-HTT) knockout (KO) rats, an animal model showing depression/anxiety-like behaviors and drug addiction-like behaviors, could therefore provide more insights into this framework. We tested the outcome and stimulus generalization in wild-type (WT) and 5-HTT KO rats. Using a newly established touchscreen-based task, subjects directly responded to visual stimuli (Gabor patch images). We measured the response time and outcome in a precise manner. We found that 5-HTT KO rats processed visual information faster than WT rats during outcome generalization. Interestingly, during stimulus generalization, WT rats gradually responded faster to the stimuli as the sessions progressed, while 5-HTT KO rats responded faster than WT in the initial sessions and did not change significantly as the sessions progressed. This observation suggests that KO rats, compared to WT rats, may be less able to update changes in information. Taken together, KO 5-HTT modulates information processing when the environment changes.Antidepressants that target monoaminergic systems, such as selective serotonin reuptake inhibitors (SSRIs), are widely used to treat neuropsychiatric disorders including major depressive disorder, several anxiety disorders, and obsessive-compulsive disorder. However, these treatments are not ideal because only a subset of patients achieve remission. The reasons why some individuals remit to antidepressant treatments while others do not are unknown. Here, we developed a paradigm to assess antidepressant treatment resistance in mice. Exposure of male C57BL/6J mice to either chronic corticosterone administration or chronic social defeat stress induces maladaptive affective behaviors. Subsequent chronic treatment with the SSRI fluoxetine reverses these maladaptive affective behavioral changes in some, but not all, of the mice, permitting stratification into persistent responders and non-responders to fluoxetine. We found several differences in expression of Activin signaling-related genes between responders and non-responders in the dentate gyrus (DG), a region that is critical for the beneficial behavioral effects of fluoxetine. Enhancement of Activin signaling in the DG converted behavioral non-responders into responders to fluoxetine treatment more effectively than commonly used second-line antidepressant treatments, while inhibition of Activin signaling in the DG converted responders into non-responders. Taken together, these results demonstrate that the behavioral response to fluoxetine can be bidirectionally modified via targeted manipulations of the DG and suggest that molecular- and neural circuit-based modulations of DG may provide a new therapeutic avenue for more effective antidepressant treatments.Transforming growth factor-β (TGFβ) family members are structurally and functionally related cytokines that have diverse effects on the regulation of cell fate during embryonic development and in the maintenance of adult tissue homeostasis. Dysregulation of TGFβ family signaling can lead to a plethora of developmental disorders and diseases, including cancer, immune dysfunction, and fibrosis. In this review, we focus on TGFβ, a well-characterized family member that has a dichotomous role in cancer progression, acting in early stages as a tumor suppressor and in late stages as a tumor promoter. The functions of TGFβ are not limited to the regulation of proliferation, differentiation, apoptosis, epithelial-mesenchymal transition, and metastasis of cancer cells. Recent reports have related TGFβ to effects on cells that are present in the tumor microenvironment through the stimulation of extracellular matrix deposition, promotion of angiogenesis, and suppression of the anti-tumor immune reaction. The pro-oncogenic roles of TGFβ have attracted considerable attention because their intervention provides a therapeutic approach for cancer patients. However, the critical function of TGFβ in maintaining tissue homeostasis makes targeting TGFβ a challenge. Here, we review the pleiotropic functions of TGFβ in cancer initiation and progression, summarize the recent clinical advancements regarding TGFβ signaling interventions for cancer treatment, and discuss the remaining challenges and opportunities related to targeting this pathway. We provide a perspective on synergistic therapies that combine anti-TGFβ therapy with cytotoxic chemotherapy, targeted therapy, radiotherapy, or immunotherapy.As one of the most successful therapeutic target families, G protein-coupled receptors (GPCRs) have experienced a transformation from random ligand screening to knowledge-driven drug design. We are eye-witnessing tremendous progresses made recently in the understanding of their structure-function relationships that facilitated drug development at an unprecedented pace. This article intends to provide a comprehensive overview of this important field to a broader readership that shares some common interests in drug discovery.There is increasing awareness that oxidative stress may be implicated in the pathophysiology of autism spectrum disorder (ASD). Here we aimed to investigate blood oxidative stress marker profile in ASD children by a meta-analysis. Two independent investigators systematically searched Web of Science, PubMed, and Cochrane Library and extracted data from 87 studies with 4928 ASD children and 4181 healthy control (HC) children. check details The meta-analysis showed that blood concentrations of oxidative glutathione (GSSG), malondialdehyde, homocysteine, S-adenosylhomocysteine, nitric oxide, and copper were higher in children with ASD than that of HC children. In contrast, blood reduced glutathione (GSH), total glutathione (tGSH), GSH/GSSG, tGSH/GSSG, methionine, cysteine, vitamin B9, vitamin D, vitamin B12, vitamin E, S-adenosylmethionine/S-adenosylhomocysteine, and calcium concentrations were significantly reduced in children with ASD relative to HC children. However, there were no significance differences between ASD children and HC children for the other 17 potential markers. Heterogeneities among studies were found for most markers, and meta-regressions indicated that age and publication year may influence the meta-analysis results. These results therefore clarified blood oxidative stress profile in children with ASD, strengthening clinical evidence of increased oxidative stress implicating in pathogenesis of ASD. Additionally, given the consistent and large effective size, glutathione metabolism biomarkers have the potential to inform early diagnosis of ASD.Unusual behaviors and brain activity to socio-emotional stimuli have been reported in Autism Spectrum Disorder (ASD). Atypical reactivity to change and intolerance of uncertainty are also present, but little is known on their possible impact on facial expression processing in autism. The visual mismatch negativity (vMMN) is an electrophysiological response automatically elicited by changing events such as deviant emotional faces presented among regular neutral faces. While vMMN has been found altered in ASD in response to low-level changes in simple stimuli, no study has investigated this response to visual social stimuli. Here two deviant expressions were presented, neutral and angry, embedded in a sequence of repetitive neutral stimuli. vMMN peak analyses were performed for latency and amplitude in early and late time windows. The ASD group presented smaller amplitude of the late vMMN to both neutral and emotional deviants compared to the typically developed adults (TD) group, and only the TD group presented a sustained activity related to emotional change (i.e., angry deviant). Source reconstruction of the vMMNs further revealed that any change processing elicited a reduced activity in ASD group compared to TD in the saliency network, while the specific processing emotional change elicited activity in the temporal region and in the insula. This study confirms atypical change processing in ASD and points to a specific difficulty in the processing of emotional changes, potentially playing a crucial role in social interaction deficits. Nevertheless, these results require to be further replicated with a greater sample size and generalized to other emotional expressions.Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p  less then  0.0001) and other adhesion molecules involved in platelet activation and platelet-leukocyte interactions.