Notes

Metallic atom-guided conformational analysis of one polynuclear control molecules.
Disuse-induced bone loss is characterized by alterations in bone turnover. Accruing evidence suggests that osteocytes respond to inflammation and express and/or release pro-inflammatory cytokines; however, it remains largely unknown whether osteocyte inflammatory proteins are influenced by disuse. The goals of this project were (1) to assess osteocyte pro-inflammatory cytokines in the unloaded hindlimb and loaded forelimb of hindlimb unloaded rats, (2) to examine the impact of exogenous irisin during hindlimb unloading (HU). Male Sprague Dawley rats (8 weeks old, n = 6/group) were divided into ambulatory control, HU, and HU with irisin (HU + Ir, 3×/week). Lower cancellous bone volume, higher osteoclast surfaces (OcS), and lower bone formation rate (BFR) were present at the hindlimb and 4th lumbar vertebrae in the HU group while the proximal humerus of HU rats exhibited no differences in bone volume, but higher BFR and lower OcS vs. Con. Osteocyte tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), RANKL, and sclerostin were elevated in the cancellous bone of the distal femur of HU rats vs. Con, but lower at the proximal humerus in HU rats vs. Con. Exogenous irisin treatment increased BFR, and lowered OcS and osteocyte TNF-α, IL-17, RANKL, and sclerostin in the unloaded hindlimb of HU + Ir rats while having minimal changes in the humerus. In conclusion, there are site-specific and loading-specific alterations in osteocyte pro-inflammatory cytokines and bone turnover with the HU model of disuse bone loss, indicating a potential mechanosensory impact of osteocyte TNF-α and IL-17. Additionally, exogenous irisin significantly reduced the pro-inflammatory status of the unloaded hindlimb.Human spaceflight has been fascinating man for centuries, representing the intangible need to explore the unknown, challenge new frontiers, advance technology, and push scientific boundaries further. A key area of importance is cardiovascular deconditioning, that is, the collection of hemodynamic changes-from blood volume shift and reduction to altered cardiac function-induced by sustained presence in microgravity. A thorough grasp of the 0G adjustment point per se is important from a physiological viewpoint and fundamental for astronauts' safety and physical capability on long spaceflights. However, hemodynamic details of cardiovascular deconditioning are incomplete, inconsistent, and poorly measured to date; thus a computational approach can be quite valuable. We present a validated 1D-0D multiscale model to study the cardiovascular response to long-term 0G spaceflight in comparison to the 1G supine reference condition. Cardiac work, oxygen consumption, and contractility indexes, as well as central mean and pulse pressures were reduced, augmenting the cardiac deconditioning scenario. Exercise tolerance of a spaceflight traveler was found to be comparable to an untrained person with a sedentary lifestyle. At the capillary-venous level significant waveform alterations were observed which can modify the regular perfusion and average nutrient supply at the cellular level. The present study suggests special attention should be paid to future long spaceflights which demand prompt physical capacity at the time of restoration of partial gravity (e.g., Moon/Mars landing). Since spaceflight deconditioning has features similar to accelerated aging understanding deconditioning mechanisms in microgravity are also relevant to the understanding of aging physiology on the Earth.Parkinson's disease (PD) is a complex multisystem disorder with motor and non-motor symptoms (NMS). NMS may have an even greater impact on quality of life than motor symptoms. Subthalamic nucleus deep brain stimulation (STN-DBS) has been shown to improve motor fluctuations and quality of life, whereas the effects on different NMS have been less examined. Selleck Ro 20-1724 Sleep disturbances and autonomic dysfunction are among the most prevalent NMS. We here report the efficacy of STN-DBS on sleep disturbances and autonomic dysfunction. In the parent trial, 60 patients were included in a single-center randomized prospective study, with MDS-UPDRS III and PDQ-39 as primary endpoints at 12 months of STN-DBS. Preplanned assessments at baseline and postoperatively at 3 and 12 months also included Parkinson's Disease Sleep Scale (PDSS); Scopa-Aut; and MDS-UPDRS I, II, and IV. We found that STN-DBS had a significant and lasting positive effect on overall sleep quality, nocturnal motor symptoms and restlessness, and daytime dozing. Several aspects of autonomic dysfunction were also improved at 3 months postoperatively, although at 12 months only thermoregulation (sudomotor symptoms) remained significantly improved. We could not identify preoperative factors that predicted improvement in PDSS or Scopa-Aut. There was a close relationship between improved autonomic symptoms and improved quality of life after 1 year. NMS and especially sleep and autonomic dysfunction deserve more focus to improve patient outcomes further.Social isolation and its deleterious effects on health increases with age in the general population. People with Parkinson's Disease (PWP) are no exception. Social isolation is a risk factor for worsened health outcomes and increased mortality. Symptoms such as depression and sleep dysfunction are adversely affected by loneliness. There is a paucity of research on social isolation in Parkinson's disease (PD), which is all the more critical now in the setting of social distancing due to COVID-19. The goal of this study was to survey individuals with PD to evaluate whether social isolation is associated with PD symptom severity and quality of life. Only individuals reporting a diagnosis of idiopathic PD were included in this analysis. The primary outcome measures were the Patient-Reported Outcomes in PD (PRO-PD) and questions from PROMIS Global related to social health. PRO-PD scores increased as social performance and social satisfaction scores diminished. Individuals who reported being lonely experienced a 55% greater symptom severity than those who were not lonely (P  less then  0.01). Individuals who documented having a lot of friends had 21% fewer symptoms than those with few or no friends (P  less then  0.01). Social isolation was associated with greater patient-reported PD severity and lower quality of life, although it is unclear whether this is the cause and/or a consequence of the disease. In essence, the Parkinson pandemic and the pandemic of social isolation have been further compounded by the recent COVID-19 pandemic. The results emphasize the need to keep PWP socially connected and prevent loneliness in this time of social distancing. Proactive use of virtual modalities for support groups and social prescribing should be explored.To compare the differences between asleep and awake robot-assisted deep brain stimulation (DBS) surgery for Parkinson's Disease (PD), we conducted this retrospective cohort study included 153 PD patients undergoing bilateral robot-assisted DBS from June 2017 to August 2019, of which 58 cases were performed under general anesthesia (GA) and 95 cases under local anesthesia (LA). Procedure duration, stimulation parameters, electrode implantation accuracy, intracranial air, intraoperative electrophysiological signal length, complications, and Unified PD Rating Scale (UPDRS) measurements were recorded and compared. The clinical evaluation was conducted by two raters who were blinded to the choice of anesthesia. Procedure duration was significantly shorter in the GA group, while on stimulation off medication motor scores (UPDRS-III) were significantly improved in both the GA and LA group. ANCOVA covariated for the baseline UPDRS-III and levodopa challenge exhibited no significant differences. In terms of amplitude, frequency, and pulse width, the stimulation parameters used for DBS power-on were similar. There were no significant differences in electrode implantation accuracy, intraoperative electrophysiological signal length, or intracerebral hemorrhage (no occurrences in either group). The pneumocephalus volume was significantly smaller in the GA group. Six patients exhibited transient throat discomfort associated with tracheal intubation in the GA group. The occurrence of surgical incision infection was similar in both groups. Compared with the awake group, the asleep group exhibited a shorter procedure duration with a similar electrode implantation accuracy and short-term motor improvement. Robot-assisted asleep DBS surgery is a promising surgical method for PD.Electric Extradural Motor Cortex Stimulation (EMCS) is a neurosurgical procedure suggested for treatment of patients with advanced Parkinson's disease (PD). We report two PD patients treated by EMCS, who experienced worsening of motor symptoms and cognition 5 years after surgery, when EMCS batteries became discharged. One month after EMCS restoration, they experienced a subjective improvement of motor symptoms and cognition. Neuropsychological assessments were carried out before replacement of batteries (off-EMCS condition) and 6 months afterward (on-EMCS condition). As compared to off-EMCS condition, in on-EMCS condition both patients showed an improvement on tasks of verbal episodic memory and backward spatial short-term/working memory task, and a decline on tasks of selective visual attention and forward spatial short-term memory. These findings suggest that in PD patients EMCS may induce slight beneficial effects on motor symptoms and cognitive processes involved in verbal episodic memory and in active manipulation of information stored in working memory.The pandemic of the SARS CoV-2 virus, which causes COVID-19 sickness, constitutes a global challenge to well-being. Positive psychology constructs of grit and growth mindset may offer a solution to this challenge as both are associated with psychological resilience. A growth mindset describes the underlying beliefs people have about the malleability of intelligence, and grit refers to dedication to long-term goals. The present study explored whether such constructs could constitute protective factors against the academic stress associated with loneliness and perceived lack of control among international students (n = 170) during social isolation, induced by COVID-19 restrictions. The results of a hierarchical multiple regression model explained 36% of the variance in academic stress with a perceived lack of control (ß = .53, p  less then  .001) and growth mindset (ß = -.22, p  less then  .001) being significant direct predictors. Moderation analysis explained 17% of the variance and confirmed that a level of dispositional grit moderated the detrimental influence loneliness had on academic stress. Simple slopes analysis revealed a significant effect for moderate (β = .07, p = .01) and high (β = .16, p = .001) levels of grit. Our findings suggest that grit and growth mindset, as dynamic variables, could be taught to students as resilience-building prevention of academic stress during the COVID-19 pandemic. Lastly, our results have shown that parents (37%) and friends (32%) were most frequently identified by students as supporters during the COVID-19 pandemic with minimal reported support from universities (2.5%).
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