Cue-induced cocaine craving enhances psychosocial stress and vice versa in chronic cocaine users

There is evidence that stress and craving contribute to the development, maintenance, and relapse in cocaine use disorder. Previous research has shown altered physiological responses to psychosocial stress as well as increased vegetative responding to substance-related cues in chronic cocaine users (CU). However, how psychosocial stress and cue-induced craving interact in relation to the physiological response of CU is largely unknown. Therefore, we investigated the interaction between acute psychosocial stress and cocaine-cue-related reactivity in 47 CU and 38 controls. Participants were randomly exposed first to a video-based cocaine-cue paradigm and second to the Trier Social Stress Test (TSST) or vice versa in a crossed and balanced design to investigate possible mutually augmenting effects of both stressors on the physiological stress response. Plasma cortisol, ACTH, and noradrenaline as well as subjective stress and craving were assessed repeatedly over the course of the experimental procedure. Growth models and discontinuous growth models were used to estimate the responses during the cocaine-cue paradigm and TSST. Overall, both groups did not differ in their endocrinological responses to the TSST but CU displayed lower ACTH levels at baseline. The TSST did not elevate craving in CU. However, if the cocaine-cue video was shown first, CU displayed an enhanced cortisol response to the subsequent TSST. Cocaine-cues robustly evoked craving in CU but no stress response, while cue-induced craving was intensified after the TSST. Taken together, CU did not show an altered acute stress response during the TSST but stress and craving together seem to have mutually augmenting effects on their stress response.

Experimental Study on the Evolution Mechanism of Landslide with Retaining Wall Locked Segment

The failure of locked segment-type slopes is often affected by rainfall, earthquake, and other external loads. Rainfall scours the slope and weakens the mechanical properties of rock-soil mass. At the same time, rainfall infiltrates into cracks of slope rock mass. Under the action of in situ stress, hydraulic fracturing leads to the development and expansion of rock cracks, which increases the risk of slope instability. Under seismic force, the slope will be subjected to large horizontal inertial force, resulting in slope instability. In this paper, a self-developed loading device was used to simulate the external loads such as rainfall and earthquake, and the model tests are carried out to study the evolution mechanism of landslide with retaining wall locked segment. Three-dimensional laser scanner, microearth pressure sensors, and high-definition camera are applied for the high-precision monitoring of slope shape, deformation, and stress. Test results show that the retaining wall locked segment has an important control effect on landslide stability. The characteristics of deformation evolution and stress response of landslide with retaining wall locked segment are analyzed and studied by changing the slope shape, earth pressure, and the displacement cloud map. The evolutionary process of landslide with retaining wall locked segment is summarized. Experimental results reveal that as the landslide with retaining wall locked segment is at failure, the upper part of the landslide thrusts and slides and the retaining wall produces a locking effect; the middle part extrudes and uplifts, which is accompanied with shallow sliding; and compression-shear fracture of the locked segment leads to the landslide failure.

Experimental-analytical approach to assessing mechanosensitive cartilage blood marker kinetics in healthy adults: dose-response relationship and interrelationship of nine candidate markers

Purpose: To determine the suitability of selected blood biomarkers of articular cartilage as mechanosensitive markers and to investigate the dose-response relationship between ambulatory load magnitude and marker kinetics in response to load. Methods: Serum samples were collected from 24 healthy volunteers before and at three time points after a 30-minute walking stress test performed on three test days. In each experimental session, one of three ambulatory loads was applied: 100% body weight (BW); 80%BW; 120%BW. Serum concentrations of COMP, MMP-3, MMP-9, ADAMTS-4, PRG-4, CPII, C2C and IL-6 were assessed using commercial enzyme-linked immunosorbent assays. A two-stage analytical approach was used to determine the suitability of a biomarker by testing the response to the stress test (criterion I) and the dose-response relationship between ambulatory load magnitude and biomarker kinetics (criterion II). Results. COMP, MMP-3 and IL-6 at all three time points after, MMP-9 at 30 and 60 minutes after, and ADAMTS-4 and CPII at immediately after the stress test showed an average response to load or an inter-individual variation in response to load of up to 25% of pre-test levels. The relation to load magnitude on average or an inter-individual variation in this relationship was up to 8% from load level to load level. There was a positive correlation for the slopes of the change-load relationship between COMP and MMP-3, and a negative correlation for the slopes between COMP, MMP-3 and IL-6 with MMP-9, and COMP with IL6. Conclusions: COMP, MMP-3, IL-6, MMP-9, and ADAMTS-4 warrant further investigation in the context of articular cartilage mechanosensitivity and its role in joint degeneration and OA. While COMP seems to be able to reflect a rapid response, MMP-3 seems to reflect a slightly longer lasting, but probably also more distinct response. MMP-3 showed also the strongest association with the magnitude of load.

Comparison of the Cardiovascular Effects of Extreme Psychological and Physical Stress Tests in Male Soccer Players

Background: The purpose of our study was to compare the physiological effects of extreme physical and psychological stress tests in male soccer players, since these two types of stress apply to athletes with high performance requirements. Methods: A total of 63 healthy male soccer players participated in this study, all of whom underwent both of the tests. A physical stress test was carried out in an exercise physiology laboratory, where subjects completed an incremental treadmill running test to full exhaustion, and a psychological test was performed in a military tactical room, where subjects met a street offence situation. Heart rate variability (HRV) and blood pressure (BP) were recorded directly before, immediately after, and 30 min after the stress tests. Results: The majority of HRV indices changed significantly in both stress protocols. Inverse, significant changes (positive for the physical test, negative for the psychological test, p < 0.001) were found when comparing the alterations of HRV indices between the tests. Significant differences were found in the changes in systolic (p = 0.003) and diastolic (p < 0.001) BP between the test protocols, and also between the baseline and post-test measurements (p < 0.001). Conclusion: Both HRV and BP are sensitive physiological parameters to measure the impact of extreme physical and/or psychological stress

Research on Co-Estimation Algorithm of SOC and SOH for Lithium-Ion Batteries in Electric Vehicles

The accurate estimation of the state of charge (SOC) and state of health (SOH) is of great significance to energy management and safety in electric vehicles. To achieve a good trade-off between real-time capability and estimation accuracy, a collaborative estimation algorithm for SOC and SOH is presented based on the Thevenin equivalent circuit model, which combines the recursive least squares method with a forgetting factor and the extended Kalman filter. First, the parameter identification accuracy is studied under a dynamic stress test (DST) and the federal urban driving schedule (FUDS) test at different ambient temperatures (0 °C, 25 °C, and 45 °C). Secondly, the FUDS test is used to verify the SOC estimation accuracy. Thirdly, two batteries with different aging degrees are used to validate the proposed SOH estimation algorithm. Subsequently, the accuracy of the SOC estimation algorithm is studied, considering the influence of updating the SOH. The proposed SOC estimation algorithm can achieve good performance at different ambient temperatures (0 °C, 25 °C, and 45 °C), with a maximum error of less than 2.3%. The maximum error for the SOH is less than 4.3% for two aged batteries at 25 °C, and it can be reduced to 1.4% after optimization. Furthermore, calibrating the capacity as the SOH changes can effectively improve the SOC estimation accuracy over the whole battery life.

Mitigating Initial Orthostatic Hypotension: Mechanistic Roles of Muscle Contraction Versus Sympathetic Activation

Background: Initial orthostatic hypotension (IOH) is defined by a large drop in blood pressure (BP) within 15 s of standing. IOH often presents during an active stand, but not with a passive tilt, suggesting that a muscle activation reflex involving lower body muscles plays an important role. To our knowledge, there is no literature exploring how sympathetic activation affects IOH. We hypothesized involuntary muscle contractions before standing would significantly reduce the drop in BP seen in IOH while increasing sympathetic activity would not. Methods: Study participants performed 4 sit-to-stand maneuvers including a mental stress test (serial 7 mental arithmetic stress test), cold pressor test, electrical stimulation, and no intervention. Continuous heart rate and beat-to-beat BP were measured. Cardiac output and systemic vascular resistance were estimated from these waveforms. Data are presented as mean±SD. Results: A total of 23 female IOH participants (31±8 years) completed the study. The drops in systolic BP following the serial 7 mental arithmetic stress test (−26±12 mm Hg; P =0.004), cold pressor test (−20±15 mm Hg; P <0.001), and electrical stimulation (−28±12 mm Hg; P =0.01) were significantly reduced compared with no intervention (−34±11 mm Hg). The drops in systemic vascular resistance following the serial 7 mental arithmetic stress test (−391±206 dyne×s/cm 5 ; P =0.006) and cold pressor test (−386±179 dyne×s/cm 5 ; P =0.011) were significantly reduced compared with no intervention (−488±173 dyne×s/cm 5 ). Cardiac output was significantly increased upon standing (7±2 L/min) compared with during the sit (6±1 L/min; P <0.001) for electrical stimulation. Conclusion: Sympathetic activation mitigates the BP response in IOH, while involuntary muscle contraction mitigates the BP response and reduces symptoms. Active muscle contractions may induce both of these mechanisms of action in their pretreatment of IOH. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03970551.

Effect of renin-angiotensin system blocker on COVID-19 in young patients with hypertension

Hypertension is found frequently in patients with COVID-19 and is often treated with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). SARS-CoV-2, the pathogen of COVID-19, binds to the receptors of ACE2 to enter the alveolar cells, raising questions on whether these drugs are salutary or harmful with respect to any propensity for COVID-19 or to disease prognosis. We investigated the impact of ACEI/ARB and the clinical prognosis of patients with hypertension with COVID-19. In this study, 250 patients with hypertension (<45 years old) with COVID-19 were recruited. None of these patients had any chronic disease except for hypertension. The study population was grouped according to antihypertensive medication: ACEI/ARB user and non-ACEI/ARB user. Patients were followed for clinical prognosis and biochemical and radiological findings during their hospital stay. Adverse cardiovascular event (myocardial infarction, all-cause death, stroke), transfer to the intensive care unit, severity of symptoms during the treatment course, length of hospital stay and effort capacity in the treadmill stress test were recorded. During hospital stay, there was no significant difference in terms of length of hospital stay, medication for COVID-19, left ventricular ejection fraction on echocardiography and metabolic equivalents in the treadmill stress test between patients treated with and without ACEI/ARB. During treatment of COVID-19, there was no significant difference in clinical adverse event, effort capacity and clinical course between patients with and without ACEI/ARB. It appears that patients with COVID-19 may continue to use ACEI/ARB or that ACEI/ARB may be added safely to their antihypertensive treatment.

A Novel Stability Study of Simvastatin Generic Tablet in Public Pharmacy Facilities of Purwakarta District, Indonesia

Drug stability is one of the most important criteria for producing safe, excellent and effective products. Some environmental factors that influence drug stability are light, temperature, and humidity. Simvastatin is a cholesterol-lowering drug that is known to be sensitive to high temperature and humidity. The purpose of this study is to analyze the effect of 6 months of real-time storage conditions on the stability of generic simvastatin tablets in public pharmacy facilities. This study used simulation method with 4 brands of simvastatin generic tablets with two different strengths (10 mg and 20 mg). In the process, the sample was conditioned in 6 different regions for 6 months. The results of temperature and humidity monitoring showed 2 locations at ≤ 25 ° C, 4 locations had a temperature of ≥ 25 °C and all locations had humidity > 65 %. The drug was evaluated for physical and chemical quality parameters at months 0, 3, and 6. After being stored for 6 months, the tablets showed a decrease in disintegration time and an increase in the friability, showing lack of durability. Similarly, there was a decrease in the content concentration in the tablets but fortunately the level was still within the accepted specification range (90 – 110 %). However, there was one tablet that did not meet the dissolution test requirements after the storage duration (Q ≤ 75 % at 30 minutes). The results of the stress test showed that simvastatin degraded in all conditions. This stress test confirmed the extreme instability of simvastatin. Poor storage conditions can reduce the quality of generic simvastatin tablets, thus a well-controlled environment is vital in pharmacy facilities.

Clinical Outcomes of Operative Repair for Patients Who Fail to Conserve the Complete Rupture of the Collateral Ligament in the Proximal Interphalangeal Joint

Objective: The purpose of this study was to compare the preoperative and postoperative outcomes of surgical treatment for patients who fail to conserve the complete rupture of the collateral ligament in the proximal interphalangeal (PIP) joint.Methods: A complete rupture of the collateral ligament was confirmed by a radiologist using ultrasound or magnetic resonance imaging for patients who had symptoms after 4 weeks of conservative treatment. Eleven patients underwent operative collateral ligament repair using an anchor. All patient was followed up for at least 6 months postoperatively. We evaluated clinical outcomes preoperatively and at 6 months follow-up: (1) range of motion of the PIP, (2) joint stability, (3) Visual Analog Scale score, (4) fusiform index of the PIP joint, and (5) functional & cosmetic satisfaction.Results: There was no instability in the lateral stress test at 6-month follow-up. The ranges of motion of the PIP were not statistically different between preoperative and at 6-month follow-up. Patients had less pain but the cosmetic appearance of the PIP joint did not improve. Functional satisfaction differed statistically, but there was no difference in cosmetic satisfaction.Conclusion: Surgical treatment for patients who fail to conserve the complete rupture of the collateral ligament in the PIP joint can provide good joint stability, functional recovery.