Burchburks7765

BACKGROUND The association between sarcoidosis and pulmonary embolism (PE) has been described in the literature, but little is known about the origin of hypercoagulability and hypofibrinolysis in sarcoidosis. PE is a multifactorial disease that is rarely caused by a single risk factor, and might be expected in disabling sarcoidosis. No data are available, however, about sarcoidosis being a risk factor for venous thromboembolism in factor V Leiden thrombophilia. CASE REPORT We describe a case of a 40-year-old man with asymptomatic sarcoidosis. Diagnosis was based on abnormal chest radiology (enlargement of hilar and mediastinal lymph nodes), confirmed by histopathological examination (noncaseating granulomas involving the mediastinal lymph nodes). No therapy was proposed due to good exercise tolerance, normal pulmonary function test, and absence of extrapulmonary involvement. The patient was followed up for 5 years until he developed progressive exertional dyspnea and chest pain. Plasma D-dimers, serum NT-proBNP, and troponin were increased. A computed tomography angiogram confirmed PE. Factor V Leiden thrombophilia was diagnosed following a search for risk factors for thromboembolism. Spontaneous remission of the chest lymphadenopathy was observed on anticoagulation therapy. Different potential mechanisms that relate sarcoidosis to venous thromboembolism are discussed. CONCLUSIONS PE is a potentially fatal condition and may complicate sarcoidosis, a clinically insignificant condition. Sarcoidosis patients with new symptomatology and PE with a high concentration of plasma D-dimers merit extra consideration. In certain clinical situations, sarcoidosis may be considered as a risk factor for deep vein thrombosis/PE. The anti-inflammatory and anti-fibrotic properties of anticoagulation warrant further study.BACKGROUND The purpose of this study was to investigate the immediate effect of transcranial direct current stimulation (tDCS) on walking speed, functional strength of lower limbs, and balance in healthy older adults. Through this study, we intend to introduce a new method to improve the physical function of older adults. MATERIAL AND METHODS This was a randomized, controlled, double-blind study in which participants and evaluators were blinded. Among 57 healthy adults (aged 65 years or older), 31 underwent tDCS, while 26 received sham stimulation. For the pre-test, participants performed a 10-meter walk test, functional strength test of lower limbs, and static and dynamic balance tests. Next, the primary motor cortex area was subjected to tDCS for 20 min. Tests were repeated as post-tests. RESULTS There were significant differences in group-by-time interaction for 10-meter walk speed, functional strength of lower limbs, and static balance on the left side (P0.05). There were significant differences in the main effect of time for 10-meter walk speed, functional strength of lower limbs, static balance on the right side, and dynamic balance (P less then 0.05). CONCLUSIONS Results showed tDCS was effective in improving gait and functional strength of the lower limbs in older adults. We recommend tDCS as a safe and effective way to improve motor performance and increase physical function, including walking and functional strength of lower limbs, in older adults.

Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs (iPVINs) play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported, and that both ePVIN and iPVIN populations form synaptic connections amongst (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits, and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity.

Parvalbumin-expressing interneurons (PVINs) in the spinal dorsal horn are found primarily in laminae II inner and III. Inhibitory PVINs (iPVINs) play an important role in segregating innocuous tactile input from pain-processing circuits through presynaptic inhibition of myelinated low-threshold mechanoreceptors and postsynaptic inhibition of distinct spinal circuits. Harmine order By comparison, relatively little is known of the role of excitatory PVINs (ePVINs) in sensory processing. Here we use neuroanatomical and optogenetic approaches to show that ePVINs comprise a larger proportion of the PVIN population than previously reported, and that both ePVIN and iPVIN populations form synaptic connections amongst (and between) themselves. We find that these cells contribute to neuronal networks that influence activity within several functionally distinct circuits, and that aberrant activity of ePVINs under pathological conditions is well placed to contribute to the development of mechanical hypersensitivity.

Human NaV1.9 (hNaV1.9), encoded by SCN11A, is preferentially expressed in nociceptors, and its mutations have been linked to pain disorders. NaV1.9 could be a promising drug target for pain relief. However, the modulation of NaV1.9 activity has remained elusive. Here, we identified a new candidate NaV1.9-interacting partner, protein arginine methyltransferase 7 (PRMT7). Whole-cell voltage clamp recordings showed that coelectroporation of human SCN11A and PRMT7 in dorsal root ganglia (DRG) neurons of Scn11a-/- mice increased the hNaV1.9 current density. In contrast, a Prmt7 inhibitor (DS-437) reduced mNaV1.9 currents in Scn11a+/+ mice. Using the reporter molecule CD4, we observed an increased distribution of hLoop1 on the cell surface of PRMT7-overexpressing HKE293T cells. Furthermore, we found that PRMT7 mainly binds to residues 563-566 within the first intracellular loop of hNaV1.9 (hLoop1) and methylates hLoop1 at arginine residue 519. Moreover, overexpression of Prmt7 increased the number of action potence. Using the reporter molecule CD4, we observed an increased distribution of hLoop1 on the cell surface of PRMT7-overexpressing HKE293T cells. Furthermore, we found that PRMT7 mainly binds to residues 563-566 within the first intracellular loop of hNaV1.9 (hLoop1) and methylates hLoop1 at arginine residue 519. Moreover, overexpression of Prmt7 increased the number of action potential fired in DRG neurons of Scn11a+/+ mice but not Scn11a-/- mice. However, DS-437 significantly inhibited the action potential frequency of DRG neurons and relieved pain hypersensitivity in Scn11aA796G/A796G mice. In summary, our observations revealed that PRMT7 modulates neuronal excitability by regulating NaV1.9 currents, which may provide a potential method for pain treatment.

Yoga is frequently used for back pain relief. However, evidence was judged to be of only low- or moderate. To assess the efficacy and safety of yoga in patients with low back pain a meta-analysis was performed. Therefore Medline/PubMed, Scopus, and the Cochrane Library was searched to May 26 2020. Only randomized controlled trials (RCTs) comparing Yoga with passive control (usual care or waitlist), or an active comparator, for patients with low back pain, that assessed pain intensity or pain-related disability as a primary outcome were considered to be eligible. Two reviewers independently extracted data on study characteristics, outcome measures, and results at short-term and long-term follow-up. Risk of bias was assessed using the Cochrane Risk of Bias Tool. 30 articles on 27 individual studies (2702 participants in total) proved eligible for review. Compared to passive control, yoga was associated with short-term improvements in pain intensity (15 RCTs; Mean Difference (MD)=-0.74 points on a numeric ratictioning (9 RCTs; MD=2.80; 95%CI=1.00,4.70; SMD=0.28 95%CI=0.10,0.47). Except for mental health all effects sustained long-term. Compared to an active comparator, yoga was not associated with any significant differences in short- or long-term outcomes.In conclusion, yoga revealed robust short- and long-term effects for pain, disability, physical function and mental health, when compared to non-exercise controls. However these effects were mainly not clinically significant.

Efforts to reduce opioid-related harms have decreased opioid prescription but have provoked concerns about unintended consequences, particularly for long-term opioid therapy (LtOT) recipients. Research is needed to address the knowledge gap regarding how risk of substance-related morbidity changes across LtOT and its discontinuation. The present study used nationwide commercial insurance claims data and a within-individual design to examine associations of LtOT dose and discontinuation with substance-related morbidity. We identified 194 839 adolescents and adults who initiated opioid prescription in 2010-2018 and subsequently received LtOT. The cohort was followed for a median of 965 days (interquartile range, 525-1550), of which a median of 176 days (119-332) were covered by opioid prescription. During follow-up, there were 17 582 acute substance-related morbidity events, defined as claims for emergency visits, inpatient hospitalizations, and ambulance transportation with substance use disorder or overdose05-1.35). However, it was no greater than during the 30 days before discontinuations, indicating that the risk may not be wholly attributable to discontinuation itself. Results were supported by a negative control pharmacotherapy analysis and additional sensitivity analyses. They suggest that LtOT recipients may experience increased substance-related morbidity risk during treatment subsequent to initial opioid prescription, particularly in periods involving higher doses.

The existence of a trigeminocervical complex has been suggested based on animal data, but only indirect evidence exists in humans. We investigated the functional relationship between the trigeminal and the occipital region by stimulating one region and measuring electrical pain thresholds (EPTs) of the corresponding opposite region. This study consists of 2 single-blinded, randomised protocols. Forty healthy participants were recruited in the propaedeutic protocol I. Electrical pain thresholds were measured on the V1 and the greater occipital nerve (GON) dermatome bilaterally as well as on the left forearm longitudinally before and after application of topical capsaicin. Protocol II was then online preregistered, and, additionally, the ipsilateral trigeminal dermatomes V2 and V3 were tested. Greater occipital nerve stimulation increased the EPT ipsilateral at V1 after 20 minutes (P = 0.006) compared with baseline, whereas trigeminal stimulation increased the EPT at the ipsilateral (P = 0.023) as well as then of one of these dermatomes increases the EPT of the respective other nerve could be explained by segmental inhibition on the brainstem level.