Miracle-dz/UniFAR-FTUs huggingface dataset:
Perspectives in affective disorders: Clocks and sleep

Mood disorders are often characterised by alterations in circadian rhythms, sleep disturbances and seasonal exacerbation. Conversely, chronobiological treatments utilise zeitgebers for circadian rhythms such as light to improve mood and stabilise sleep, and manipulations of sleep timing and duration as rapid antidepressant modalities. Although sleep deprivation (“wake therapy”) can act within hours, and its mood‐elevating effects be maintained by regular morning light administration/medication/earlier sleep, it has not entered the regular guidelines for treating affective disorders as a first‐line treatment. The hindrances to using chronotherapeutics may lie in their lack of patentability, few sponsors to carry out large multi‐centre trials, non‐reimbursement by medical insurance and their perceived difficulty or exotic “alternative” nature. Future use can be promoted by new technology (single‐sample phase measurements, phone apps, movement and sleep trackers) that provides ambulatory documentation over long periods and feedback to therapist and patient. Light combinations with cognitive behavioural therapy and sleep hygiene practice may speed up and also maintain response. The urgent need for new antidepressants should hopefully lead to reconsideration and implementation of these non‐pharmacological methods, as well as further clinical trials. We review the putative neurochemical mechanisms underlying the antidepressant effect of sleep deprivation and light therapy, and current knowledge linking clocks and sleep with affective disorders: neurotransmitter switching, stress and cortico‐limbic reactivity, clock genes, cortical neuroplasticity, connectomics and neuroinflammation. Despite the complexity of multi‐system mechanisms, more insight will lead to fine tuning and better application of circadian and sleep‐related treatments of depression.
Knockdown of PSMB7 Induces Autophagy in Cardiomyocyte Cultures: Possible Role in Endoplasmic Reticulum Stress

Proteasomal and autophagic pathways of protein degradation are two essential, endoplasmic reticulum (ER)-associated proteolytic systems involved in the ER stress response. The functional interaction between them has been shown by proteasome pharmacological inhibition. However, little data have been found concerning autophagy induction using an RNA interference approach due to the multisubunit composition of proteolytic systems. We suggested that silencing of single proteasome subunits can induce massive autophagy. Psmb7-specific small interference RNA added to isolated cardiomyocytes significantly affected mRNA expression of essential ER stress marker proteins, including DDIT3/CHOP and HSPA5/GRP78. mRNA expression of the key autophagy regulator MTOR was also increased. These findings were confirmed by single-cell reverse transcription real-time PCR on individual monodansylcadaverine (MDC)-labeled cardiomyocytes. RNA interference that decreased the levels of non-catalytic PSMB7 subunits of the proteasome had no influence on chymotrypsin- and trypsin-like activities, but significantly decreased peptidyl-glutamyl peptide-hydrolyzing activity. Immunohistochemical analysis showed increased levels of LC3-marked vacuoles in the cytoplasm of Psmb7-knockdown cells, and MDC staining showed significantly increased numbers of neonatal cardiomyocytes with autophagic vacuoles. After anoxia-reoxygenation, the number of cells with signs of autophagy after Psmb7 gene silencing was higher. Our results indicate that Psmb7 knockdown induces ER stress and autophagy in cardiomyocytes, which may be a useful approach to activate specific autophagy.
The influence of cerebrospinal fluid on blood coagulation and the implications for ventriculovenous shunting.

OBJECTIVEThe effect of CSF on blood coagulation is not known. Enhanced coagulation by CSF may be an issue in thrombotic complications of ventriculoatrial and ventriculosinus shunts. This study aimed to assess the effect of CSF on coagulation and its potential effect on thrombotic events affecting ventriculovenous shunts.METHODSTwo complementary experiments were performed. In a static experiment, the effect on coagulation of different CSF mixtures was evaluated using a viscoelastic coagulation monitor. A dynamic experiment confirmed the amount of clot formation on the shunt surface in a roller pump model.RESULTSCSF concentrations of 9% and higher significantly decreased the activated clotting time (ACT; 164.9 seconds at 0% CSF, 155.6 seconds at 9% CSF, and 145.1 seconds at 32% CSF). Increased clot rates (CRs) were observed starting at a concentration of 5% (29.3 U/min at 0% CSF, 31.6 U/min at 5% CSF, and 35.3 U/min at 32% CSF). The roller pump model showed a significantly greater percentage of shunt surface covered with deposits when the shunts were infused with CSF rather than Ringer's lactate solution (90% vs 63%). The amount of clot formation at the side facing the blood flow (impact side) tended to be lower than that at the side facing away from the blood flow (wake side; 71% vs 86%). CONCLUSIONSAddition of CSF to blood accelerates coagulation. The CSF-blood-foreign material interaction promotes clot formation, which might result in thrombotic shunt complications. Further development of the ventriculovenous shunt technique should focus on preventing CSF-blood-foreign material interaction and stagnation of CSF in wake zones.
GRK2 and GRK5 as therapeutic targets and their role in maladaptive and pathological cardiac hypertrophy

ABSTRACT Introduction: One in every four deaths in the United States is attributed to cardiovascular disease, hence the development and employment of novel and effective therapeutics are necessary to improve the quality of life and survival of affected patient. Pathological hypertrophy is a maladaptive response by the heart to relieve wall stress that could result from cardiovascular disease. Maladaptive hypertrophy can lead to further disease progression and complications such as heart failure; hence, efforts to target hypertrophy to prevent and treat further morbidity and mortality are necessary. Areas covered: This review summarizes the compelling literature that describes the mechanistic role of GRK2 and GRK5 in maladaptive cardiac hypertrophy; it examines the approaches to inhibit these kinases in hypertrophic animal models and furthermore, it assesses the potential of GRK2 and GRK5 as therapeutic targets for hypertrophy. Expert opinion: GRK2 and GRK5 are novel therapeutic targets for pathological hypertrophy and may have added benefits of ameliorating morbidity and mortality. Despite the lesser researched role of GRK2 in cardiac hypertrophy, it may be the advantageous strategy for treating cardiac hypertrophy because of its role in other maladaptive pathways. Anti-GRK2 therapy optimization and the discovery and development of specific GRK2 and GRK5 small-molecule inhibitors is necessary for the eventual application of successful, effective therapeutics.
Design and implementation of a 35 d.o.f. full-body humanoid that can sit, stand up and grasp an object

We present a 35 d.o. f. humanoid which can perform a reach-and-grasp motion through coordinating legs and arms. The humanoid robot is designed to be a research testbed to integrate research tools. Each leg and arm has 6 d.o. f. The neck has 3 d.o. f. Each hand has 4 d.o. f. The key idea of the system architecture is a remote-brained approach. In this paper we describe the design concept and the details of the system, and introduce an experiment in which the robot reaches and grasps an object on a table through coordinating legs and arms.
LncIRS1 controls muscle atrophy via sponging miR‐15 family to activate IGF1‐PI3K/AKT pathway

Recent studies indicate important roles for long noncoding RNAs (lncRNAs) in the regulation of gene expression by acting as competing endogenous RNAs (ceRNAs). However, the specific role of lncRNAs in skeletal muscle atrophy is still unclear. Our study aimed to identify the function of lncRNAs that control skeletal muscle myogenesis and atrophy.
A comparison of characteristics and outcomes of patients admitted to the ICU with asthma in Australia and New Zealand and United states

Abstract Objective: To compare the characteristics, use of invasive ventilation and outcomes of patients admitted with critical asthma syndrome (CAS) to ICUs in Australia and New Zealand (ANZ), and a large cohort of ICUs in the United States (US). Methods: We examined two large databases of ICU for patients admitted with CAS in 2014 and 2015. We obtained, analyzed, and compared information on demographic and physiological characteristics, use of invasive mechanical ventilation, and clinical outcome and derived predictive models. Results: Overall, 2202 and 762 patients were admitted with a primary diagnosis of CAS in the ANZ and US databases respectively (0.73% vs. 0.46% of all ICU admissions, P < 0.001). A similar percentage of patients received invasive mechanical ventilation in the first 24 h (24.7% vs. 24.4%, P = 0.87) but ANZ patients had lower respiratory rates and higher PaCO2 levels. Overall mortality was low (1.23 for ANZ and 1.71 for USA; P = 0.36) and even among invasively ventilated patients (2.4% for ANZ vs. 1.1% for USA; P = 0.38). However, ANZ patients also had longer length of stay in ICU (43 vs. 37 h, P = 0.001) and hospital (105 vs. 78 h, P = 0.003). Conclusions: Patients admitted to ANZ and USA ICU with CAS are broadly similar and have a low and similar rate of invasive ventilation and mortality. However, ANZ patients made up a greater proportion of ICU patients and had longer ICU and hospital stays. These findings provide a modern invasive ventilation and mortality rates benchmark for future studies of CAS.
A surrogate mechanostatistical microstructural model to inform whole hip cortical bone remodelling

Multiscale models of bone remodelling which incorporate clinically important features at a wide range of spatial scales are computationally intractable. In addition, there is a large gap in existing bone remodelling literature which deals with Haversian‐level cortical bone remodelling behaviour and its effect on whole organ bone strength. In this study, we present an integration between continuum mechanics and surrogate modelling as an efficient circumvention to the problem of intractability, linked with an intricate 3D cortical bone remodelling algorithm which captures realistic microanatomical features at the Haversian level. The surrogate model predicted clear differentiation in long‐term bone strength changes in clinically significant cases with extremely high computational efficiency.
Making "Waves" With a Murine Model of Aortic Insufficiency.

Considering the current emphasis on valvular heart disease in clinical practice, a mouse model of valvular regurgitation is important and timely.1,2 Hajj et al revisit a previously reported mouse homozygous for a single nucleotide mutation in the gene encoding the epidermal growth factor receptor (EGFR), resulting in a 90% global reduction in EGFR-tyrosine kinase activity.3 Egfr Wa2/Wa2 , or waved-2 (Wave) mice, had been previously reported to develop abnormalities of the semilunar valves.3 In one report, the aortic valve of Wave mice was thickened and enlarged with mixed aortic stenosis (AS)/aortic regurgitation (AR) and a mean gradient ranging from 15 to 40 mm Hg.3 In a second, Barrick et al found that Egfr Wa2/Wa2 mice on the c57bl/6j background, in comparison to 129s1/svimj, had an increased aortic valve gradient, left ventricular hypertrophy, heart failure, and decreased survival.4 Aortic cusp separation was not measured, but these results were again interpreted to be caused by predominantly calcific AS.4 Both papers showed that reduced EGFR signaling was associated with the development of aortic valve disease, reflected by increased peak systolic pressure, left ventricular hypertrophy, and heart failure.3,4 Fortuitously, and in contrast to most models of murine congenital heart disease, animals were viable postnatally.5 However, it remained unclear whether AS or AR was the predominant disorder. See accompanying article on page 1653 Enter the present study by Hajj et al, who unequivocally demonstrate that Wave mice do not have AS, but are almost exclusively a model of noncalcific, myxomatous AR.2 At 1.5 months of age, 70% of mice had moderate to severe AR …
MicroRNA‐128 confers protection against cardiac microvascular endothelial cell injury in coronary heart disease via negative regulation of IRS1

Cardiac microvascular endothelial cells (CMECs) play a critical role in the physiological regulation of coronary blood flow and its dysfunction is associated with myocardium ischemic injury. This study was performed to clarify the effect of microRNA‐128 (miR‐128) on the CMEC injury in coronary heart disease (CHD) by binding to insulin receptor substrate 1 (IRS1).
Influence of visceral obesity on the secretion of adipokines with epicardial adipocytes in patients with coronary heart disease.

AIM To study adipokine-cytokine profile of epicardial adipocytes (EAT) and subcutaneous adipose tissue (SAT) in conjunction with the area of visceral adipose tissue (VAT), biochemical and clinical characteristics of patients with coronary heart disease. MATERIALS AND METHODS Examined 84 patients (70 men and 14 women) with coronary artery disease. In fact the presence of visceral obesity (VO) the patients were divided into two groups. Patients VO the sampling of adipocytes of EAT and SAT, with subsequent cultivation and evaluation of adipokine and provospalitelna activity. Carried out the determination of carbohydrate and lipid metabolism, adipokine and pro-inflammatory status in the blood serum. RESULTS It was found that adipokine-cytokine profile of adipocytes of EAT and SAT differ. Adipocytes art of the disease on the background characterized by an increase IL-1, TNF-α, leptin-adiponectin relationships and a decrease in the content of protective factors: adiponectin and anti-inflammatory cytokine IL-10. While the SAT adipocytes was characterized by a decrease in the concentration of soluble receptor for leptin and the more pronounced leptinresistance, and the increase in proinflammatory cytokines was offset by the increase in the concentration of IL-10. The presence associated with multi-vessel coronary bed lesion, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, an imbalance of adipokines and markers of inflammation. So the value of the square VAT determined higher concentrations of leptin, TNF-α in adipocytes and serum, lipid and carbohydrate metabolism and a lower content of soluble receptor for leptin. CONCLUSION Thus, the disease on the background of the status of the adipocytes of EAT characterized as a "metabolic inflammation", and may indicate the direct involvement of adipocytes in the pathogenesis of coronary artery disease, due to the formation of adipokine imbalance and the activation of proinflammatory reactions.
THE NEUROPHENOMENOLOGY OF OUT-OF-BODY EXPERIENCES INDUCED BY HYPNOTIC SUGGESTIONS

Abstract Inducing out-of-body experiences in hypnosis (H-OBEs) offers an almost unique opportunity to investigate them under controlled conditions. OBEs were induced as an imaginative task in a resting condition (I-OBE) or in hypnosis (H-OBE) in a group of 15 high hypnotizable subjects. A 32-channel EEG was recorded, and the spectral power and imaginary coherence of each frequency band and each couple of electrodes were calculated. At the end of each session, the Phenomenology of Consciousness Inventory (PCI) was administered to assess the phenomenological aspects of the subjects’ experience. Significantly higher scores in the altered state, positive affect altered experience, and attention subdimensions of the PCI were reported in H-OBE than in I-OBE, which were associated with a significant decrease of power in beta and gamma band activity in right parieto-temporal derivations. These results suggest that the H-OBE may offer a useful experimental model of spontaneous OBEs.
Lower extremity biomechanics and muscle activity differ between ‘new’ and ‘dead’ pointe shoes in professional ballet dancers

ABSTRACT The purpose of this study was to compare lower extremity (LE) biomechanics and muscle activity between ‘new’ and ‘dead’ pointe shoes in professional female ballet dancers performing relevé and arabesque. We compared sway area, peak ankle moments, and tibialis anterior and medial gastrocnemius muscle activation amplitudes. Nine ballet dancers participated (age = 22.2 ± 2.2 years, height = 163.2 ± 6.3 cm, body mass = 50.8 ± 6.5 kg) executed three trials of relevé and arabesque on pointe shoes under two conditions: ‘dead’ (108–144 training hours) and ‘new’ (3–36 training hours). While wearing ‘dead’ pointe shoes, dancers had significantly higher sway area during both relevé and arabesque (p = 0.017 and 0.028, respectively). Dancers exhibit significantly higher tibialis anterior activation (root mean square, %maximum voluntary contraction) during arabesque while wearing ‘dead’ pointe shoes (p = 0.043). No significant differences were identified in other dependent variables. The increased sway area and tibialis anterior muscle activity when wearing ‘dead’ pointe shoes during relevé and arabesque movements demonstrates that using ‘dead’ shoes is more demanding. Our findings provide quantitative evidence of possible deleterious biomechanical changes when wearing dead pointe shoes that may increase LE injury risk in dancers.
Furanocoumarin Content, Antioxidant Activity, and Inhibitory Potential of Heracleum verticillatum, Heracleum sibiricum, Heracleum angustisectum, and Heracleum ternatum Extracts against Enzymes Involved in Alzheimer's Disease and Type II Diabetes

Hexane extracts of Heracleum verticillatum, H. sibiricum, H. angustisectum, and H. ternatum were studied for their furanocoumarin content antioxidant potential and acetylcholinesterase and α‐amylase inhibitory activities. Quantification of the furanocoumarins was performed by 1H‐NMR. Pimpinellin was found to be the main component in the roots of all studied species. Bergapten and imperatorin were the major compounds in the fruits of H. sibiricum and H. verticillatum, respectively, while byakangelicol dominated in H. angustisectum and H. ternatum fruits. The leaf and fruit extracts of H. angustisectum demonstrated the highest DPPH radical scavenging activity and TEAC (IC50 0.58 mg/mL and 1.83 mm, respectively). The root extracts of H. verticillatum and H. angustisectum were found to be the most effective against acetylcholinesterase (IC50 0.30 and 0.34 mg/mL, respectively). The studied extracts were not active or demonstrated a weak inhibitory effect (%Inh. up to 29.7) towards α‐amylase.
The Role of Transcranial Doppler Monitoring in Patients with Multi‐Territory Acute Embolic Strokes: A Review

Acute multi‐territory, embolic cerebral infarctions are often associated with serious underlying clinical conditions including the presence of highly “active” emboligenic sources causing that in turn may result in high early recurrence rates. Prompt diagnosis, risk stratification, and treatment are substantial for the prevention of subsequent embolization that would result in further clinical deterioration. Among other clinical investigations, transcranial Doppler (TCD) monitoring is highly efficacious for the detection of microembolic signals (MES) that correspond to microthrombi entering the intracranial circulation. The presence and burden of MES, especially in multiple intracranial arteries, is clearly associated with an increased risk of symptomatic, recurrent embolization, and thus can justify a more aggressive treatment approach (clopidogrel load followed by dual antiplatelet therapy or alternatively therapeutic dose of low‐molecular‐weight heparin). In this narrative review, we discuss the most important causes of multi‐territory embolic ischemic strokes and also underscore the utility of TCD as a noninvasive tool for the diagnosis, risk stratification, and treatment.
Performance of Safety-Net Hospitals in Year 1 of the Comprehensive Care for Joint Replacement Model

The Comprehensive Care for Joint Replacement (CJR) model of 2016 aims to improve the quality and costs of care for Medicare beneficiaries undergoing hip and knee replacements. However, there are concerns that the safety-net hospitals that care for the greatest number of vulnerable patients may perform poorly in CJR. In this study, we used Medicare’s CJR data to evaluate the performance of 792 hospitals mandated to participate in the first year of CJR. We found that in comparison to non-safety-net hospitals, 42 percent fewer safety-net hospitals qualified for rewards based on their quality and spending performance (33 percent of safety-net hospitals qualified, compared to 57 percent of non-safety-net hospitals), and safety-net hospitals’ rewards per episode were 39 percent smaller ($456 compared to $743). Continuation of this performance trend might place safety-net hospitals at increased risk of penalties in future years. Medicare and hospital strategies such as those that reward high-quality care for vulnerable patients might enable safety-net hospitals to compete effectively in CJR.
Contralateral segmental transcutaneous electrical nerve stimulation inhibits nociceptive flexion reflex in healthy participants

Transcutaneous electrical nerve stimulation (TENS) is a non‐invasive treatment to relieve pain. Contralateral TENS (i.e. TENS administered to the contralateral side of a painful body part) is beneficial when TENS cannot be directly applied to pain site, such as in cases of trauma. Although TENS produces segmental analgesia in an ipsilateral limb, it has been unclear whether TENS produces higher analgesic effects in the contralateral segmental area. The aim of the present study was to investigate the analgesic effects of TENS in contralateral segmental or extra‐segmental areas on physiological and subjective pain outcomes, using a nociceptive flexion reflex (NFR) method.
Atypical Chemokine Receptors in Cardiovascular Disease

Abstract Inflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.