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To solve the problem of spacecraft attitude manoeuvre planning under dynamic multiple mandatory pointing constraints and prohibited pointing constraints, a systematic attitude manoeuvre planning approach is proposed that is based on improved policy gradient reinforcement learning. This paper presents a succinct model of dynamic multiple constraints that is similar to a real situation faced by an in-orbit spacecraft. By introducing return baseline and adaptive policy exploration methods, the proposed method overcomes issues such as large variances and slow convergence rates. Concurrently, the required computation time of the proposed method is markedly reduced. Using the proposed method, the near optimal path of the attitude manoeuvre can be determined, making the method suitable for the control of micro spacecraft. Simulation results demonstrate that the planning results fully satisfy all constraints, including six prohibited pointing constraints and two mandatory pointing constraints. The spacecraft also maintains high orientation accuracy to the Earth and Sun during all attitude manoeuvres. [ABSTRACT FROM AUTHOR]

Objective. To explore the efficacy and safety of pramipexole sustained release (SR) versus pramipexole immediate release (IR) in treating nocturnal symptoms in levodopa-treated Chinese patients with advanced Parkinson's disease (PD) and sleep disturbances. Method. SUSTAIN was an open-label, randomised, active-controlled parallel group exploratory pilot study (NCT03521635). A total of 98 patients were randomly allocated (1 : 1) to either pramipexole SR (n = 49) or pramipexole IR (n = 49) groups. The primary endpoint was a change from baseline in PD Sleep Scale 2nd version (PDSS-2) total score at 18 weeks. A reduction in score represents improvement. Secondary endpoints included Nocturnal Hypokinesia Questionnaire, Scales for Outcomes in PD Sleep Scale, Early Morning Off (EMO), Epworth Sleepiness Scale, PD Questionnaire-8, and responder rates as measured by PDSS-2 total score (<18), EMO scores (≥1 point change), Clinical Global Impression Improvement scale, and Patient Global Impression-Improvement scale. Other endpoints included motor complications (MDS-UPDRS part IV) score. Adverse events were evaluated for each group. Results. The mean pramipexole dose for both groups was 1.5 mg/day at week 18, and the mean changes in PDSS-2 total score for pramipexole SR and IR were –13.7 (95% CI –16.0 to –11.4) and –14.4 (–16.8 to –12.0) (difference of 0.7; p = 0.688). Change from baseline for both groups achieved the minimal clinical important difference threshold (MCID = –3.44). No significant difference was observed in change from baseline for other measures of sleep-related disturbances or responder rates. For motor complications, a greater improvement in MDS-UPDRS part IV score was observed in pramipexole SR over IR (–3.4 vs –2.3; treatment group difference: –1.1; p = 0.036). Both groups had comparable safety profiles. Conclusion. In Chinese patients with advanced PD and sleep disturbances, pramipexole SR and IR have similar benefits in the treatment of nocturnal symptoms and safety, and an improvement from baseline in nocturnal symptoms was observed regardless of pramipexole formulation. [ABSTRACT FROM AUTHOR]

Background: Depression is a common non-motor symptom in patients with Parkinson's disease (PD). There are many kinds of antidepressants being used, such as tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and Dopamine agonists which are suggested as alternative antidepressants for the treatment of depression in PD. Which one should we choose first? Literatures have shown inconsistent results. Methods: We conducted a network meta-analysis of randomized controlled trials to compare the efficacy and acceptability of therapeutic methods for the treatment of depression in Parkinson's disease. Results: We used the odds ratios (OR) as effect size firstly and the results indicated no statistical significance between each compared intervention. Then we used the logarithm of the individual odds ratios as effect size. With efficacy of TCAs as the standard of comparison, the degree of incoherence (a measure of how closely the entire network fits together) was small (ω =  4.824827e-05). The logor were: SSRIs −0.69 (95% CI −1.28– −0.10); Pramipexole −0.73 (−1.71– −0.26); Pergolide −1.97 (−3.67– 0.27); SNRIs −0.86 (−1.86– 0.15); Placebo −1.24 (−1.99– −0.50). With Placebo as the standard of comparison, the logor were: TCAs 1.24 (0.50– 1.99); SSRIs 0.55 (−0.03– 1.13); Pramipexole 0.51 (−0.12– 1.15); Pergolide −0.73 (−2.25– 0.80); SNRIs 0.38 (−0.42– 1.19); TCAs, pramipexole, pergolide and SNRIs showed better profile of acceptability, leading to significant fewer discontinuations than that of SSRIs. Conclusions: There is insufficient evidence to support antidepressant efficacy for SSRIs, pramipexole, pergolide and SNRIs. TCAs might be the best choice when starting antidepressant treatment in patients of Parkinson's disease because it has the most favorable balance between benefits and acceptability, followed by pramipexole and SNRIs, SSRIs might be the last choice. [ABSTRACT FROM AUTHOR]

Ciliary neurotrophic factor (CNTF) is a pleiotropic cytokine that has been fully studied for its structure, receptor, and signaling pathways and its multiplex effects on neural system, skeletal muscle, and weight control. Recent research demonstrates that CNTF also plays an important role in neurogenesis and the differentiation of neural stem cells. In this article, we summarize the general characteristics of CNTF and its function on neural stem cells, which could be a valuable therapeutic strategy in treating neurological disorders. [ABSTRACT FROM AUTHOR]

Abstract: The 3′-untranslated regions (3′-UTRs) of growth-associated protein 43 (GAP-43), which is crucial for neural development and axonal regeneration, are highly conserved among vertebrates. Previous studies in mammals have identified one U-rich cis element within GAP-43 3′-UTR and several trans factors that regulate its mRNA stability. However, much less is known in lower vertebrates. The Xenopus GAP-43 3′-UTR, despite its high similarity with those in higher vertebrates, contains unique CU-rich sequences, suggesting the existence of novel cis elements and trans factors. In current study, we isolated four proteins bound to GAP-43 3′-UTR from juvenile frog brain using affinity purification. Mass spectrometry identified Hu antigen D (HuD) and poly(C) binding protein 2 (αCP2) as the proteins forming 48- and 44-kDa ribonucleoprotein complexes, respectively. We validated the association between αCP2 and GAP-43 3′-UTR in vivo. After confirming the post-transcriptional effects of αCP2 on GAP-43 expression, we demonstrated that αCP2 directly inhibited the translation of GAP-43 gene, without affecting its mRNA stability. αCP2 overexpression led to decreased level of GAP-43 protein and significantly inhibited axonal outgrowth in primarily cultured neurons. Our study therefore provided insights on novel functions of αCP2 in vertebrate nervous system during development and new mechanisms of post-transcriptional regulation for GAP-43 gene. [Copyright &y& Elsevier]

Context. Tetramine is an illegal rat poison that has resulted in a number of accidental mass poisonings in China. Objective. To investigate the long term outcome of tetramine poisoning. Materials and methods. A survey of epileptic attacks in 370 patients in the Hubei province of P. R. China who had survived tetramine poisoning in the last decade was undertaken by means of telephone calls, letters, and interviews. Data describing the initial acute episode was gathered from medical and public health records. Results. Among the 370 patients surveyed (188 males, 182 females, age range 10 to 71 y), 352 experienced seizures during the initial poisoning. One hundred fifty-eight individuals are currently seizure-free, after an average medication period of 2.93 years. The other patients have recurrent epilepsy, including 156 with tonic-clonic seizures and 39 with partial seizures. Six patients have other neurological problems. Discussion and conclusion. Tetramine, a rat poison sometimes ingested by mistake, blocks GABA receptors and causes seizures. These seizures can persist for years after the initial poisoning, even when no seizures are present initially. Sodium valproate, which has the ability to increase the amount of GABA in the CNS, would be a reasonable choice for the treatment of epilepsy caused by tetramine poisoning. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of mild brain hypothermia beginning at different time intervals on cerebral ischemic injury. Methods: Male Sprague–Dawley rats were divided into sham-operated group, normothermia (37–38°C) and mild hypothermia (31–32°C) ischemia groups. The last group was subdivided into four groups: 240 minute hypothermia, 30 minute normothermia plus 210 minute hypothermia, 60 minute normothermia plus 180 minute hypothermia, and 90 minute normothermia plus 150 minute hypothermia (n=8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model for 20 minutes and mild hypothermia was applied after 20 minutes of ischemia. Brain tissue was collected following 20 minute cerebral ischemia and 240 minute reperfusion, and used to measure the levels of malondialdehyde (MDA), lactate, water content and the amounts of electrolytes, such as sodium (Na+), potassium (K+) and calcium (Ca++). Results: Mild hypothermia beginning at 0–60 minutes decreased the levels of malondialdehyde and lactate (p<0.05 or p<0.01), decreased water content, Na+ and Ca++, and increased the amount of K+ (p<0.05 or p<0.01) in ischemic tissue, except the amounts of Na+, K+ and Ca++ in mild hypothermia beginning at 60 minute ischemia group (p>0.05). Mild hypothermia beginning at 90 minutes had little effect on the levels of targeted molecules, water content and amounts of electrolytes of Na+, K+ and Ca++ in ischemic tissue (p>0.05). Discussion: Post-ischemic mild brain hypothermia can decrease the accumulation of lactate and lipid peroxidation in ischemic tissue, and delay the development of brain edema following ischemic reperfusion. The best neuroprotection of mild hypothermia to attenuate ischemic injury was begun within 60 minutes. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy of post-ischemic mild brain hypothermia lasting for different time intervals on cerebral ischemic reperfusion injury. Method: Male Sprague–Dawley rats were divided into a sham-operated group, normothermia (37–38° C) ischemia group and mild hypothermia (31–32° C) group. The last group was subdivided into four groups: 30 minute hypothermia plus 210 minute normothermia, 60 minute hypothermia plus 180 minute nomothermia,120 minute hypothermia plus 120 minute normothermia, and 240 minute hypothermia (n=8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model. Brain tissue was collected following a 20 minute cerebral ischemia and 240 minute reperfusion, and was used to measure the levels of glutamate (Glu), aspartate (Asp), glycine (Gly), gamma-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin(5-HT) and hydroxyindoleacetic acid (5-HIAA), nitrite (NO2), endothelin-1 (ET1), tumor necrosis factor alpha(TNFα) and interleukin-1beta (IL-1β). Serum was collected to measure the levels of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), creatine kinase (CK) and its brain band isoenzyme (CK-BB). Results: Hypothermia lasting for 60–240 minutes delayed the decrease in these amino acids, postponed the decrease in DA, NE and 5-HT and increase in hydroxyindoleacetic acid (5-HIAA), and decreased the levels of IL-1β, TNFα, ET1 and NO2 in brain tissue. Hypothermia also decreased the levels of LDH, AST, CK and CK-BB in serum as compared to normothermia group (p<0.05 or p<0.01). Hypothermia lasting for 30 minutes delayed the decreases in these amino acids and 5-HT and increase in 5-HIAA in brain tissue (p<0.05), but failed to influence the levels of IL-1β, TNFα, ET1 and NO2 in brain tissue and the amounts of LDH, AST, CK and CK-BB in serum as compared to normothermia ischemia group (p>0.05). Conclusions: Post-ischemic mild brain hypothermia can significantly suppress the excessive release of amino acids, monoamine neurotransmitters and inflammation response in ischemic tissue. It can also stabilize the function of the cell membrane, which is associated with the mechanism of cerebral protection by mild hypothermia. These results suggest that mild hypothermia should be applied immediately after ischemia and last for more than 60 minutes in order to obtain neuroprotective effects. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To study the effects and mechanism of homocysteine(Hcy) on Parkinson''sdisease(PD) induced by 6-hydroxydopamine (6-OHDA) in vivo. Methods: Forty rats were divided into 4 groups. 6-OHDA or the solvent of 6-OHDA was focally administrated to induce PD, 2 h later Hcy or 0.9% sodium chloride was administrated in the ipsolateral substantial nigra(SN). We used behavioral testing, Immolunohistochemical techniques, biochemistry techniques to detect the injury of SN. Results: The rotary turns of PD rats induced by 6-OHDA showed significant increase after treatment with Hcy compared with the controls(P < 0.05). Also the numbers of tyrosine hydroxylase(TH)-stained neurons were decreased, and dendrites were fragmented and truncated. Free radicals were increased and antioxidant enzymes decreased. Conclusion: Focal infusion of Hcy into the SN increased the vulnerability of the dopaminergic neurons to 6-OHDA-induced degeneration, it seems that the endangering effect of Hcy is due to exacerbating oxidative stress. [Copyright &y& Elsevier]