Laustsendougherty4847

one.

Chronic feelings of emptiness are significant in the lives of people with Borderline Personality Disorder (BPD). Feelings of emptiness have been linked to impulsivity, self-harm, suicidal behaviour and impaired psychosocial function. This study aimed to understand the experience of chronic emptiness, the cognitions, emotions and behaviours linked to emptiness, and clarify the differences between chronic emptiness and hopelessness, loneliness and depression.

This study interviewed people (n = 15) with BPD and used a template analysis qualitative approach to understand their experiences of chronic feelings of emptiness.

Chronic feelings of emptiness were experienced as a feeling of disconnection from both self and others, and a sense of numbness and nothingness which was frequent and reduced functional capacity. Feelings of purposelessness and unfulfillment were closely associated with emptiness, and most participants experienced emptiness as distressing. Responses to feelings of emptiness varied, with participants largely engaging in either impulsive strategies to tolerate feelings of emptiness or distracting by using adaptive behaviours. Most participants distinguished chronic feelings of emptiness from loneliness, hopelessness, dissociation, and depression.

Feelings of chronic emptiness are an important and challenging symptom of BPD which require clinical intervention. Strengthening identity, sense of purpose and vocational and relationship functioning may reduce the intensity of emptiness.

Feelings of chronic emptiness are an important and challenging symptom of BPD which require clinical intervention. Strengthening identity, sense of purpose and vocational and relationship functioning may reduce the intensity of emptiness.

Various circular RNAs (circRNAs) are dysregulated in the placenta of fetal growth restriction (FGR) fetuses, but their roles and regulatory mechanisms have not been fully elucidated. Herein, we aimed to elucidate the role of hsa_circ_0081343 in regulating the migration, invasion, and apoptosis of human extravillous trophoblast HTR-8 cells.

CircRNA and miRNA levels were examined by quantitative reverse transcription PCR (qRT-PCR). Overexpression plasmid constructs and siRNAs were used to overexpress and knockdown hsa_circ_0081343, respectively. Transwell assays and flow cytometry analyses were performed to evaluate the effects of hsa_circ_0081343 or miR-210-5p on migration, invasion, and apoptosis. Protein levels were analyzed by western blotting. Dual luciferase activity and anti-AGO2 RNA immunoprecipitation (RIP) assays were performed to identify the relationship between miR-210-5p and hsa_circ_0081343.

Hsa_circ_0081343 expression was significantly downregulated in 37 FGR placental tissues compared to healthy placental control tissues. Hsa_circ_0081343 overexpression may inhibit apoptosis by downregulating the expression of cleaved caspase 3 and caspase 9 and alleviating the migration and invasion of HTR-8 cells by inducing the expression of MMP2 and MMP9. The dual luciferase activity and anti-AGO2 RIP assay results showed that hsa_circ_0081343 binds to miR-210-5p. miR-210-5p overexpression eliminated the effect of hsa_circ_0081343 overexpression in HTR-8 cells. Finally, DLX3 was identified as a direct target of miR-210-5p.

hsa_circ_0081343 expression levels are significantly downregulated in FGR placental tissues. Hsa_circ_0081343 regulates the migration, invasion, and apoptosis of HTR-8 cells via the hsa-miR-210-5p/DLX3 axis.

hsa_circ_0081343 expression levels are significantly downregulated in FGR placental tissues. Hsa_circ_0081343 regulates the migration, invasion, and apoptosis of HTR-8 cells via the hsa-miR-210-5p/DLX3 axis.Skeletal muscles are considered the largest reservoirs of the protein pool in the body and are critical for the maintenances of body homeostasis. Skeletal muscle atrophy is supported by various physiopathological conditions that lead to loss of muscle mass and contractile capacity of the skeletal muscle. Lysosomal mediated autophagy and ubiquitin-proteasomal system (UPS) concede the major intracellular systems of muscle protein degradation that result in the loss of mass and strength. Both systems recognize ubiquitination as a signal of degradation through different mechanisms, a sign of dynamic interplay between systems. Hence, growing shreds of evidence suggest the interdependency of autophagy and UPS in the progression of skeletal muscle atrophy under various pathological conditions. Therefore, understanding the molecular dynamics as well associated factors responsible for their interdependency is a necessity for the new therapeutic insights to counteract the muscle loss. Based on current literature, the present review summarizes the factors interplay in between the autophagy and UPS in favor of enhanced proteolysis of skeletal muscle and how they affect the anabolic signaling pathways under various conditions of skeletal muscle atrophy.Alzheimer's disease is a neurodegenerative disease characterized by a progressive decline in memory and cognitive functions. It is a multifactorial disease involving a wide range of pathological factors that are not fully understood. As supported by a growing amount of evidence in recent years, the gut microbiota plays an important role in the pathogenesis of Alzheimer's disease through the brain-gut-microbiota axis. This suggests that direct modulation of the gut microbiota can be a potential therapeutic target for Alzheimer's disease. This review summarizes recent research findings on the modulation of the gut microbiota by probiotic therapies and faecal microbiota transplantation for controlling the pathologies of Alzheimer's disease. Current limitations and future research directions of this field are also discussed.Autism Spectrum Disorder (ASD) is a composite disorder of brain development with uncertain etiology and pathophysiology. Genetic factors are important in ASD causation, although environmental factors are also involved in ASD pathophysiology. Environmental factors might affect the genetic processes of brain development through the modulation of molecular pathways that might be involved with ASD. Valproic acid and Propionic acid are the major environmental factors that serve as medicine and food preservative. VPA is used as an anti-epileptic medicine, but it has adverse effects on pregnant women and alters the developmental patterns of the embryo. It is a multi-targeting agent and affects through the 5-HT, GABA, etc. PPA is a secondary metabolite of gut microbiota that is commonly used as a food preservative. PPA plays a significant role in ASD causation by altering the several developmental molecular pathways like PTEN/Akt, mTOR/Gskβ, Cytokines activated pathways, etc., at the prenatal and neonatal stage. Moreover, ASD complexity might be increased by some other important factors like vitamin A deficiency and Vitamin A is important for cortical brain development and neuronal cell differentiation. Additionally, several important genes such as RELN, Lhx2, CREB, IL-6, NMDA, BDNF, etc. also altered in ASD that involved in brain development, Central Nervous System, Enteric Nervous System. These genes affect the neuronal differentiation, hyperactivity, oxidative stress, oxytocin, and GABA imbalance that lead the improper behavior in autistic individuals. These genes are also studied in VPA and PPA ASD-like animal models. In this review, we explored the mechanical pathways that might be altered with VPA and PPA exposures at the embryonic developmental stage or neonatal developmental stage.

Laryngopharyngeal Reflux (LPR) may be part of Gastroesophageal Reflux Disease (GERD). However, sometimes suspected LPR seems refractory to proton pump inhibitors (PPI), questioning therefore the GERD diagnosis. Our aim was to evaluate the real-life prevalence of GERD in patients with a recent laryngoscopic diagnosis of LPR, and unresponsive to PPI. We assessed also whether other causes than GERD could explain the laryngoscopic findings in those patients.

We retrospectively analyzed patients with diagnosis of LPR, and unresponsive to PPI. Those patients must have been investigated by upper gastrointestinal endoscopy with biopsies; multichannel intraluminal impedance and pH monitoring (MII-pH); X-ray of the chest and/or of the paranasal sinuses; hormonal thyroid assessment; prick tests to assess food and/or inhalants and pollen allergy.

We enrolled 28 patients (18, 64.3%, males and 10, 35.7%, females; median, IQR age 39.4, 21-75 yrs). Endoscopic hiatal hernia was found in 9/28 (32.1%) patients; the MII-pH analysis showed abnormality in 2/28 (7.14%) patients (both having also GERD symptoms); Chest X-ray found chest diseases in 2/28 (7.14%) patients and X-rays of the paranasal sinuses found sinusitis in 1/28 (3.6%); 2/28 (7.14%) patients had hyperthyroidism; food and/or inhalants and pollen allergy was found in 9 (32.1%) patients. In 12/28 (42.9%) patients, any of the investigated diseases was found.

This study found that the real prevalence of GERD in patients with a recent laryngoscopic diagnosis of LPR, and unresponsive to PPI, is low. Moreover, more than 40% of them did not show any of the investigated diseases in real-life.

This study found that the real prevalence of GERD in patients with a recent laryngoscopic diagnosis of LPR, and unresponsive to PPI, is low. Moreover, more than 40% of them did not show any of the investigated diseases in real-life.

Alcohol dependence is a significant public health problem, contributing to the global health burden. Due to its immense socio-economic burden, various psychosocial, psychological, and pharmacological approaches have attempted to alter the behaviour of the patient misusing or abusing alcohol, but their efficacy is modest at best. Therefore, there is a search for newer treatment approaches, including noninvasive brain stimulation in the management of alcohol dependence. We plan to study the efficacy of Prefrontal Cortex Transcranial direct current stimulation Treatment in Alcohol dependence syndrome (PreCoTTA).

Two hundred twenty-five male patients with alcohol dependence syndrome will be randomized into the three study arms (2 active, left dorsolateral prefrontal cortex and left orbitofrontal cortex, and 1 sham) to receive a total of 14 tDCS sessions (10 continuous and 4 booster sessions). Data will be collected from them at five different time points on clinical, neuropsychological and biochemical parametderstanding of the neuropsychological and biochemical effects of non-invasive brain stimulation techniques which are of interest in the comprehensive treatment of addiction disorders.

The study has been registered with the Clinical Trials Registry-India (CTRI/2020/09/027582) on September 03rd 2020.

The study has been registered with the Clinical Trials Registry-India (CTRI/2020/09/027582) on September 03rd 2020.

Cycle-regulating and transcriptional cyclin-dependent kinases (CDKs) are attractive targets in cancer drug development. Several CDK inhibitors have already been obtained or are close to regulatory approval for clinical applications.

Phenylazopyrazole CAN508 has been described as the first selective CDK9 inhibitor with an IC50 of 350 nM. Since the azo-moiety is not a suitable functionality for drugs due to pharmacological reasons, the preparation of carbo-analogues of CAN508 with similar biological activities is desirable. The present work is focused on the synthesis of carbo-analogues similar to CAN508 and their CDK inhibition activity.

Herein, the synthesis of 21 novel carbo analogues of CAN508 and their intermediates is reported. CX-5461 nmr Subsequently, target compounds 8a - 8u were evaluated for protein kinase inhibition (CDK2/cyclin E, CDK4/cyclin D, CDK9/cyclin T) and antiproliferative activities in cell lines (K562, MCF-7, MV4-11). Moreover, the binding mode of derivative 8s in the active site of CDK9 was revealed by molecular docking.