Rejected

Chronic back pain (CBP) is a maladaptive health problem affecting the brain function and behavior of the patient. Accumulating evidence has shown that CBP may alter the organization of functional brain networks; however, whether the severity of CBP is associated with changes in dynamics of functional network topology remains unclear. Here, we generated dynamic functional networks based on resting-state functional magnetic resonance imaging (rs-fMRI) of 34 patients with CBP and 34 age-matched healthy controls (HC) in the OpenPain database a sliding window approach, and extracted nodal degree, clustering coefficient (CC), and participation coefficient (PC) of all windows as features to characterize changes of network topology at temporal scale. A novel feature, named temporal grading index (TGI), was proposed to quantify the temporal deviation of each network property of a patient with CBP to the normal oscillation of the HCs. The TGI of the three features achieved outstanding performance in predicting pain intensity on three commonly used regression models (i.e., SVR, Lasso, and elastic net) through a 5-fold cross-validation strategy, with the minimum mean square error of 0.25 ± 0.05; and the TGI was not related to depression symptoms of the patients. Furthermore, compared to the HCs, brain regions that contributed most to prediction showed significantly higher CC and lower PC across time windows in the CBP cohort. These results highlighted spatiotemporal changes in functional network topology in patients with CBP, which might serve as a valuable biomarker for assessing the sensation of pain in the brain and may facilitate the development of CBP management/therapy approaches.

Patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) show various clinical symptoms, including migraine, recurrent stroke, and cognitive impairment. We investigated the associations between magnetic resonance imaging (MRI) markers of small vessel disease and neuropsychological tests and identified the MRI characteristics for predicting cognitive impairment in patients with CADASIL.

Migraine is a common neurological disease, but its pathogenesis is still unclear. Previous studies suggested that migraine was related to immunoglobulin G (IgG). We intended to analyze the immune characteristics of migraine from the perspective of IgG glycosylation and provide theoretical assistance for exploring its pathogenesis.

This study aimed to investigate the risk factors of reversible posterior leukoencephalopathy syndrome (RPLS) in pregnant women with severe preeclampsia or eclampsia (SPE/E) based on a predicting model and to analyze the perinatal outcomes.

Multisystem inflammatory syndrome in children (MIS-C) is a pathologic condition that has emerged during the coronavirus disease 2019 (COVID-19) pandemic. Although the epidemiological evidence of association between MIS-C and SARS-CoV-2 infection has been demonstrated, its pathogenic mechanism is still undefined. We describe the case of a 17-year old female, previously vaccinated against SARS-CoV-2, presenting with a history of asthenia, fever, cough, anorexia, abdominal pain, and vomiting. During the hospitalization, the patient developed bilateral conjunctivitis, hand vasculitis, cutaneous rash, and multiple pulmonary nodules, following by hepatitis and pancreatitis. As she reported a high-risk contact with a SARS-CoV-2 positive patient 10 days before admission, the epidemiological link and the clinical picture characterized by multi-system organ disfunction and inflammatory biomarkers increase led us to the diagnosis of MIS-C. Therefore, the patient was treated with intravenous immunoglobulin and corticosteroids, resulting in a rapid resolution of fever, cutaneous, and pulmonary involvement, while the recovery of hepatitis and pancreatitis was observed in the following weeks. This case leads to the discussion on whether SARS-CoV-2 immunized children and adolescents should be considered at risk of developing MIS-C and on their possible presentation with non-classic clinical features. Additionally, due to the increasing number of vaccinated children and adolescents, the issues resulting either from the diagnostic suspect of MIS-C or from the consequent need of an early therapeutic approach are discussed.

Previous studies examined the association between chronic pain (CP) and serum 25-hydroxyvitamin D (25(OH)D) concentrations; however, the findings obtained were inconsistent. Single nucleotide polymorphisms (SNP) associated with the transcriptional activity of the vitamin D receptor () gene may influence the association of 25(OH)D levels with CP. We aimed to clarify the association between CP, serum 25(OH)D concentration, and SNPs.

is a medicinal plant used as an anti-inflammatory and for rheumatic pain in the traditional medicine of Peru. On the other hand, is the main vector of several tropical diseases and the transmitter of yellow fever, chikungunya, malaria, dengue, and Zika virus. In this study, the aim was to investigate the antioxidant activity in vitro and the insecticidal activity in silico, in the presence of the mosquito juvenile hormone-binding protein (mJHBP) from , of the essential oil from leaves. The volatile phytochemicals were analyzed by gas chromatography-mass spectrometry (GC-MS), and the profile antioxidants were examined by DPPH, ABTS, and FRAP assays. The evaluation in silico was carried out on mJHBP (PDB: 5V13) with an insecticidal approach. The results revealed that EO presented as the main volatile components to alpha-phellandrene (32.68%), D-limonene (12.59%), and beta-phellandrene (12.24%). The antioxidant activity showed values for DPPH = 11.42 ± 0.08 mol ET/g, ABTS = 134.88 ± 4.37 mol ET/g, and FRAP = 65.16 ± 1.46 mol ET/g. Regarding the insecticidal approach in silico, alpha-muurolene and gamma-cadinene had the best biding energy on mJHBP (Δ = -9.7 kcal/mol), followed by beta-cadinene (Δ = -9.5 kcal/mol). Additionally, the volatile components did not reveal antioxidant activity, and its potential insecticidal effect would be acting on mJHBP from

Mutations in the genes encoding calcium/calmodulin dependent protein kinase II (CAMK2) isoforms cause a newly recognized neurodevelopmental disorder (ND), for which the full clinical spectrum has yet to be described. Here we report the detailed description of a child with a gain of function (GoF) mutation in the gene Ca/Calmodulin dependent protein kinase 2 beta ( c.328G > A p.Glu110Lys) who presents with developmental delay and periodic neuropsychiatric episodes. The episodes manifest as encephalopathy with behavioral changes, headache, loss of language and loss of complex motor coordination. Additionally, we provide an overview of the effect of different medications used to try to alleviate the symptoms. We show that medications effective for mitigating the child's neuropsychiatric symptoms may have done so by decreasing CAMK2 activity and associated calcium signaling; whereas medications that appeared to worsen the symptoms may have done so by increasing CAMK2 activity and associated calcium signaling. We hypothesize that by classifying CAMK2 mutations as "gain of function" or "loss of function" based on CAMK2 catalytic activity, we may be able to guide personalized empiric treatment regimens tailored to specific mutations. In the absence of sufficient patients for traditional randomized controlled trials to establish therapeutic efficacy, this approach may provide a rational approach to empiric therapy for physicians treating patients with dysregulated CAMK2 and associated calcium signaling.

Chronic pain is common and debilitating in cancer survivors. Tibetan herbal pain-relieving plaster is used as an external analgesic to treat musculoskeletal pain in China; however, its safety and efficacy have not been evaluated via clinical trials in cancer survivors. We designed this Phase II randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov Identifier: NCT04916249) to assess the efficacy and safety of the pain-relieving plaster for temporary pain relief among cancer survivors with chronic musculoskeletal pain. Under ethical approval from the Institutional Review Board at the Memorial Sloan Kettering Cancer Center, we will enroll eligible cancer survivors who have a clinical diagnosis of moderate to severe chronic musculoskeletal pain in this study. We use a central randomization system to allocate the eligible participants to either the treatment or the control group in a 1:1 ratio, with stratification by baseline opioid use. We will instruct the participants to apply the herbal patch (Tibetree Pain-Relieving Plaster, Tibet Cheezheng Tibetan Medicine Co. Ltd., Tibet, China) or placebo patch daily at the focal area with worst pain for 14 consecutive days. Study physician, participant, outcome assessor, and biostatistician are blinded to the group allocation. The primary outcome is pain severity measured by the Brief Pain Inventory on Days 2-7. Secondary outcomes include changes in insomnia, anxiety, depression, fatigue, pressure pain threshold, pain medication use, and global impression of change. We will also monitor the adverse events throughout the study period. Statistical analysis will follow the intention-to-treat principle and linear mixed modeling will be used. With rigorous design and implementation, this randomized, placebo-controlled trial will provide the initial evidence on the efficacy and safety of the pain-relieving plaster for pain relief among cancer survivors with chronic musculoskeletal pain.

PMR is a common inflammatory condition in older adults, characterized by bilateral hip and shoulder pain and stiffness. Reducing oral glucocorticoids, classically used for ≤2 years, are the mainstay of treatment. This study considers the factors early in the disease course that might be associated with prolonged treatment.