Miracle-dz/UniFAR-FTUs huggingface dataset:
The association between serotonin transporter availability and the neural correlates of fear bradycardia

Significance Reduced expression of the serotonin transporter (5-HTT) is associated with susceptibility to stress-related psychopathology, but the underlying mechanisms remain elusive. We investigated whether an aberrant physiological and neural response to threat underlies this increased vulnerability. In a cross-species approach, we investigated the association between genetically encoded differences in 5-HTT expression and the neural correlates of fear bradycardia, a defensive response linked to vigilance. In both humans and rats, reduced 5-HTT expression was associated with exaggerated bradycardia or bradycardia-associated freezing, reduced activity of the medial prefrontal cortex, and increased threat-induced amygdala-periaqueductal grey connectivity and central amygdala somatostatin neuron activity. We have delineated a previously unknown neurogenetic mechanism underlying individual differences in the expression of anticipatory threat responses, contributing to stress sensitivity. Susceptibility to stress-related psychopathology is associated with reduced expression of the serotonin transporter (5-HTT), particularly in combination with stress exposure. Aberrant physiological and neuronal responses to threat may underlie this increased vulnerability. Here, implementing a cross-species approach, we investigated the association between 5-HTT expression and the neural correlates of fear bradycardia, a defensive response linked to vigilance and action preparation. We tested this during threat anticipation induced by a well-established fear conditioning paradigm applied in both humans and rodents. In humans, we studied the effect of the common 5-HTT-linked polymorphic region (5-HTTLPR) on bradycardia and neural responses to anticipatory threat during functional magnetic resonance imaging scanning in healthy volunteers (n = 104). Compared with homozygous long-allele carriers, the 5-HTTLPR short-allele carriers displayed an exaggerated bradycardic response to threat, overall reduced activation of the medial prefrontal cortex (mPFC), and increased threat-induced connectivity between the amygdala and periaqueductal gray (PAG), which statistically mediated the effect of the 5-HTTLPR genotype on bradycardia. In parallel, 5-HTT knockout (KO) rats also showed exaggerated threat-related bradycardia and behavioral freezing. Immunohistochemistry indicated overall reduced activity of glutamatergic neurons in the mPFC of KO rats and increased activity of central amygdala somatostatin-positive neurons, putatively projecting to the PAG, which—similarly to the human population—mediated the 5-HTT genotype’s effect on freezing. Moreover, the ventrolateral PAG of KO rats displayed elevated overall activity and increased relative activation of CaMKII-expressing projection neurons. Our results provide a mechanistic explanation for previously reported associations between 5-HTT gene variance and a stress-sensitive phenotype.
CaMKIV limits metabolic damage through induction of hepatic autophagy by CREB in obese mice.

High-fat diet (HFD) not only induces insulin resistance in liver, but also causes autophagic imbalance, metabolic disorders, increases chronic inflammatory response and induces mitochondrial dysfunction. Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has recently emerged as an important regulator of glucose metabolism and skeletal muscle insulin action. Its activation has been involved in the improvement of hepatic and adipose insulin action. But the underlying mechanism are not fully understood. In the present study, we aimed to address the direct effects of CaMKIV in vivo and to evaluate the potential interaction of impaired insulin sensitivity and autophagic disorders in hepatic insulin resistance. Our results indicated obese mice receiving CaMKIV showed a decreased blood glucose and serum insulin, and improved insulin sensitivity as well as increased glucose tolerance compared with vehicle injection. Meanwhile, defective hepatic autophagy activity, impaired insulin signaling, increased inflammatory response and mitochondrial dysfunction in liver tissues which induced by high-fat diet were also effectively alleviated by injection of CaMKIV. Consistent with these results, the additional of CaMKIV to the culture medium of BNL cl.2 hepatocytes markedly restored palmitate induced hepatic insulin resistance and autophagic imbalance. These effects were nullified by blockade of cyclic AMP response element binding protein (CREB), indicating the causative role of CREB in action of CaMKIV. Our findings suggested that CaMKIV restores hepatic autophagic imbalance and improves impaired insulin sensitivity via phosphorylated CREB signaling pathway. Which may offer novel opportunities for treatment of obesity and diabetes.
Cardiac considerations in the treatment of the metabolic

To treat insulin resistance and avoid type 2 diabetes the condition must first be diagnosed. When diagnosed it can be assumed that with or without type 2 diabetes the insulin resistant subject has significant cardiovascular disease. Once diagnosed, aggressive therapy of insulin resistance and its associated risk factors has the potential to avoid cardiac events in both the diabetic and non-diabetic insulin resistant subjects. Treating insulin resistance can also avoid the development of diabetes and improve glycemic control and long-term complications in the established type 2 diabetic patient. Heart Metab. 2009;45:20–25.
Effect of the Geriatric Emergency Department Intervention on outcomes of care for residents of aged care facilities: A non‐randomised trial

As the population of Australia ages, EDs will experience an increasing frequency of presentations of older adults from residential aged care facilities (RACFs). These presentations are often complex and time consuming in the chaotic and potentially hazardous ED environment. The Geriatric Emergency Department Intervention (GEDI) model was developed to optimise the care of frail older adults, especially RACF residents, in the ED. The aim of the present study was to evaluate the effectiveness of the GEDI model on the primary outcomes of disposition (admission, discharge or death) and ED length of stay for residents of RACFs, presenting to an ED in regional Queensland, Australia.
Effect of Body Position on Measurement of Q Angle in Trained Individuals with and without Patellofemoral Pain

Purpose: To explore the difference between measuring the Q-angle from standing and supine position in trained subjects suffering from patellofemoral pain. Methods: The patellofemoral pain group (study group) consisted of 30 male participants (age = 26.8 ± 4.5 years, height = 172.9 ± 7.2 cm, mass = 73.3 ± 16.7 kg), the control group consisted of 30 male participants (age = 25.6 ± 2.8 years, height = 170.7 ± 8.4 cm, mass = 71.5 ± 15.9 kg) who were matched on age, height, and mass to the patellofemoral pain volunteers. The Q angle was measured from standing and supine position. Results: There was a significant difference between study group and control group at standing (p = 0.000) and supine position (p = 0.002). There was no effect of body position; either standing or supine on the values of Q angle for control group (p = 0.062). However, the Q angle value of study group in standing was significantly higher than its value in supine lying position (p = 0.000). Conclusions: Q angle measured from standing position is higher than that measured from supine lying for subjects suffering from patellofemoral pain. Therefore; it is recommended to perform Q angle measurements in the standing position for subjects suffering from patellofemoral pain.
Prevalence of Microembolic Signals in Embolic Stroke of Undetermined Source and Other Subtypes of Ischemic Stroke

Supplemental Digital Content is available in the text. Background and Purpose— Embolic stroke of undetermined source (ESUS) has been proposed to cause thromboembolic infarction from unknown but potential embolic sources. However, an embolus remains undetected in ESUS. The goal of this study was to characterize the prevalence and risk factors of microembolic signals (MESs) in ESUS. Methods— We examined 108 patients with acute ischemic stroke in the internal carotid artery territory or transient ischemic attack within 14 days of symptom onset and who were admitted to our hospital between April 2017 and March 2019. MESs were monitored in the middle cerebral artery on transcranial Doppler for 60 minutes. We examined the prevalence and number of MES in ESUS and other stroke subtypes, such as cardioembolism, large artery atherosclerosis, cerebral small vessel disease, and transient ischemic attack. The present study was registered in University Hospital Medical Information Network Clinical Trials Registry (UMIN000031913). Results— MESs were detected in 33 (31%) of 108 patients. ESUS showed the highest proportion (12/24 [50%]), followed by large artery atherosclerosis (8/20 [40%]), cardioembolism (6/18 [33%]), transient ischemic attack (4/24 [17%]), and cerebral small vessel disease (3/21 [14%]). Univariate analysis showed that higher systolic blood pressure, body mass index, hemoglobin A1c, and ESUS were significantly associated with MES. In multiple logistic regression analysis, ESUS remained significantly associated with MES after adjustment for described covariates from univariate analysis (odds ratio, 2.86 [95% CI, 1.01–8.08]). Conclusions— This study demonstrated significant association of ESUS with MES, supporting the embolic nature of this stroke subtype. Registration— URL: https://upload.umin. ac.jp. Unique identifier: UMIN000031913.
High - Sensitivity C - Reactive Protein: An Independent Proinflammatory Cardiac Marker in Healthy Overweight and Obese Individuals

In Asian countries, Indians are at high risk of premature CVD and T2DM due to abdominal obesity. Adipose tissue over the abdomen is a major source of inflammatory mediators. Numerous studies have demonstrated role of serum high sensitivity C reactive protein (hsCRP) as independent predictor of metabolic syndrome, T2DM and atherosclerotic diseases among healthy individuals. We postulated that in spite of normal glucose tolerance and normal lipid profile, obese persons are at high cardiac risk due to chronic low grade systemic inflammation. In present cross sectional study we enrolled 50 metabolically healthy overweight and obese individuals and 50 age and sex matched lean controls. We recorded history, anthropometric measures of adiposity BMI, waist and hip circumference, in study group. After overnight fast blood samples were assayed for blood glucose, lipid profile and hsCRP levels. Serum hsCRP levels were raised significantly in cases compared to control (mean 3.8+/-1.8 Vs 1.2+/-0.7 p< 0.001). We found significant positive association of hsCRP with anthropometric indices BMI and waist: hip ratio. In obese group there was evidence of significant family history of obesity, T2DM and CVD in first degree relatives compared to control.
The Prevalence Of Internet Addiction Among The Students Of Rafsanjan University Of Medical Sciences

Objective: Internet addiction is defined as mismanagement of internet use that causes mental, social and occupational problems. Thus, the assessment of prevalence of this disorder can lead to preventive measures and appropriate treatment to prevent its spread. Methods: In this cross-sectional study, prevalence of internet addiction disorder was assessed in Rafsanjan University of Medical Sciences, Rafsanjan, Iran in 2012. Stratified random sample was used to select 224 students. Demographic data were recorded and Internet Addiction test Test (IAT) questionnaire was administrated. Results: Out off 224 students participating in the study, 86 (38.4%) were males and 138 (61.6%) were female with a mean age of 21.05± 0.1 years. Most of the students (42.4%) were using the internet "under one hour" and the lowest (4%) "More than six hours". Mean test score of IAT was 24.81 ± 1.08 (mild addiction). In terms of internet addiction, 95 (42.4%) cases were normal users, 115 (51.3%) had mild addiction, 12 (5.4%) showed moderate addiction and 2 (0.9%) were cases of severe addiction which are lower compared to previous studies. Conclusion: The rate of internet addiction among students of Rafsanjan University of Medical Sciences in Iran is lower than the previous reports. It is still necessary to curb the spread of this problem due to its complications. Download ASEAN Journal of Psychiatry, Vol. 14 (2): July - December 2013 here .
Wearable-Sensor-Based Detection and Prediction of Freezing of Gait in Parkinson’s Disease: A Review

Freezing of gait (FOG) is a serious gait disturbance, common in mid- and late-stage Parkinson’s disease, that affects mobility and increases fall risk. Wearable sensors have been used to detect and predict FOG with the ultimate aim of preventing freezes or reducing their effect using gait monitoring and assistive devices. This review presents and assesses the state of the art of FOG detection and prediction using wearable sensors, with the intention of providing guidance on current knowledge, and identifying knowledge gaps that need to be filled and challenges to be considered in future studies. This review searched the Scopus, PubMed, and Web of Science databases to identify studies that used wearable sensors to detect or predict FOG episodes in Parkinson’s disease. Following screening, 74 publications were included, comprising 68 publications detecting FOG, seven predicting FOG, and one in both categories. Details were extracted regarding participants, walking task, sensor type and body location, detection or prediction approach, feature extraction and selection, classification method, and detection and prediction performance. The results showed that increasingly complex machine-learning algorithms combined with diverse feature sets improved FOG detection. The lack of large FOG datasets and highly person-specific FOG manifestation were common challenges. Transfer learning and semi-supervised learning were promising for FOG detection and prediction since they provided person-specific tuning while preserving model generalization.
In-Vivo Gene Therapy with Foamy Virus Vectors

Foamy viruses (FVs) are nonpathogenic retroviruses that infect various animals including bovines, felines, nonhuman primates (NHPs), and can be transmitted to humans through zoonotic infection. Due to their non-pathogenic nature, broad tissue tropism and relatively safe integration profile, FVs have been engineered as novel vectors (foamy virus vector, FVV) for stable gene transfer into different cells and tissues. FVVs have emerged as an alternative platform to contemporary viral vectors (e.g., adeno associated and lentiviral vectors) for experimental and therapeutic gene therapy of a variety of monogenetic diseases. Some of the important features of FVVs include the ability to efficiently transduce hematopoietic stem and progenitor cells (HSPCs) from humans, NHPs, canines and rodents. We have successfully used FVV for proof of concept studies to demonstrate safety and efficacy following in-vivo delivery in large animal models. In this review, we will comprehensively discuss FVV based in-vivo gene therapy approaches established in the X-linked severe combined immunodeficiency (SCID-X1) canine model.
Differential phosphorylation determines the repressor and activator potencies of GLI1 proteins and their efficiency in modulating the HPV life cycle

The Sonic Hedgehog (Shh) signalling pathway plays multiple roles during embryonic development and under pathological conditions. Although the core components of the Shh pathway are conserved, the regulation of signal transduction varies significantly among species and cell types. Protein kinases Ulk3 and Pka are involved in the Shh pathway as modulators of the activities of Gli transcription factors, which are the nuclear mediators of the signal. Here, we investigate the regulation and activities of two GLI1 isoforms, full-length GLI1 (GLI1FL) and GLI1ΔN. The latter protein lacks the first 128 amino acids including the conserved phosphorylation cluster and the binding motif for SUFU, the key regulator of GLI activity. Both GLI1 isoforms are co-expressed in all human cell lines analysed and possess similar DNA binding activity. ULK3 potentiates the transcriptional activity of both GLI1 proteins, whereas PKA inhibits the activity of GLI1ΔN, but not GLI1FL. In addition to its well-established role as a transcriptional activator, GLI1FL acts as a repressor by inhibiting transcription from the early promoters of human papillomavirus type 18 (HPV18). Additionally, compared to GLI1ΔN, GLI1FL is a more potent suppressor of replication of several HPV types. Altogether, our data show that the N-terminal part of GLI1FL is crucial for the realization of its full potential as a transcriptional regulator.
Cutaneous lupus erythematosus induced by drugs - novel insights

ABSTRACT Introduction: There is a growing list of drugs implicated in inducing both subacute and chronic forms of cutaneous lupus erythematosus. It is important to recognize these drugs in order to quickly treat patients with drug induced disease. Areas covered: This paper reviews the current literature describing drugs implicated in causing cutaneous lupus erythematosus. A Pubmed search was used to compile a list of medications implicated up to August 2019. It reviews new classes of drugs identified as causing cutaneous lupus erythematosus, the pathophysiology of the disease process, and current recommendations for treatment of the disease. Expert opinion: Many drugs have been identified as inducing lupus, and many more continue to be described in new reports. Further research is needed to understand this phenomenon, which will aid in the diagnosis and treatment of affected patients.
Intragastric administration of the bitter tastant, quinine, lowers the glycemic response to a nutrient drink without slowing gastric emptying, in healthy men.

Gastric emptying and the release of gastrointestinal (GI) hormones are major determinants of postprandial blood glucose concentrations and energy intake. Preclinical studies suggest that activation of GI bitter taste receptors potently stimulates GI hormones, including glucagon-like peptide-1 (GLP-1), thus, may reduce postprandial glucose and energy intake. We evaluated the effects of intragastric quinine on the glycemic response to, and gastric emptying of, a mixed-nutrient drink, and on subsequent energy intake, in healthy men. The study consisted of two parts; part A included 15, and part B 12, lean men (aged 26±2 years). In each part, participants received, on 3 separate occasions, in double-blind, randomized fashion, intragastric quinine (275 mg or 600 mg), or control, 30 min before a mixed-nutrient drink (part A), or before a buffet-meal (part B). In part A, plasma glucose, insulin, glucagon and GLP-1 concentrations were measured at baseline, after quinine alone, and for 2 h following the drink. Gastric emptying of the drink was also measured. In part B, energy intake at the buffet-meal was quantified. Q600 and Q275 alone stimulated insulin modestly (P<0.05). After the drink, Q600 and Q275 reduced plasma glucose and stimulated insulin (P<0.05), Q275 stimulated GLP-1 (P<0.05), and Q600 tended to stimulate GLP-1 (P=0.066) and glucagon (P=0.073), compared with control. Quinine did not affect gastric emptying of the drink or energy intake. In conclusion, in healthy men, intragastric quinine reduces postprandial blood glucose and stimulates insulin and GLP-1, but does not slow gastric emptying, or reduce energy intake, under our experimental conditions.
The effects of long‐term muscle disuse on neuromuscular function in unilateral transtibial amputees

What is the central question of this study? The effects of long‐term muscle disuse on neuromuscular function are unclear because disuse studies are typically short term. In this study, we used a new model (unilateral transtibial amputees) to investigate the effects of long‐term disuse on quadriceps neuromuscular function. What is the main finding and its importance? Kinetic analysis (knee‐extension moments during gait) indicated habitual disuse of the amputated limb quadriceps, accompanied by lower quadriceps muscle strength (60–76%) and neural activation (32–44%), slower contractile properties and altered muscle architecture in the amputated limb, which could not be predicted from short‐term disuse studies.
Complementary and Alternative Medicine in Patients With Breast Cancer: Exploratory Study of Social Network Forum Data

Background Patients and health care professionals are becoming increasingly preoccupied in complementary and alternative medicine (CAM) that can also be called nonpharmacological interventions (NPIs). In just a few years, this supportive care has gone from solutions aimed at improving the quality of life to solutions intended to reduce symptoms, supplement oncological treatments, and prevent recurrences. Digital social networks are a major vector for disseminating these practices that are not always disclosed to doctors by patients. An exploration of the content of exchanges on social networks by patients suffering from breast cancer can help to better identify the extent and diversity of these practices. Objective This study aimed to explore the interest of patients with breast cancer in CAM from posts published in health forums and French-language social media groups. Methods The retrospective study was based on a French database of 2 forums and 4 Facebook groups between June 3, 2006, and November 17, 2015. The extracted, anonymized, and compiled data (264,249 posts) were analyzed according to the occurrences associated with the NPI categories and NPI subcategories, their synonyms, and their related terms. Results The results showed that patients with breast cancer use mainly physical (37.6%) and nutritional (31.3%) interventions. Herbal medicine is a subcategory that was cited frequently. However, the patients did not mention digital interventions. Conclusions This exploratory study of the main French forums and discussion groups indicates a significant interest in CAM during and after treatments for breast cancer, with primarily physical and nutritional interventions complementing approved treatments. This study highlights the importance of accurate information (vs fake medicine), prescription and monitoring of these interventions, and the mediating role that health professionals must play in this regard.