Chronic stressful occurrences are documented as a vital cause of both depression and anxiety disorders. However, the stress-induced molecular mechanisms underlying the common and distinct pathophysiology of these disorders remains largely unclear. We utilized a chronic mild stress (CMS) rat model to differentiate and subgroup depression-susceptible, anxiety-susceptible, and insusceptible rats. The hippocampus was analyzed for differential proteomes by combining mass spectrometry and the isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique. Out of 2593 quantified proteins, 367 were aberrantly expressed. These hippocampal protein candidates might be associated with susceptibility to stress-induced depression or anxiety and stress resilience. They provide the potential protein systems involved in various metabolic pathways as novel investigative protein targets. Further, independent immunoblot analysis identified changes in Por, Idh2 and Esd; Glo1, G6pdx, Aldh2, and Dld; Dlat, Ogdhl, Anxal, Tpp2, and Sdha that were specifically associated to depression-susceptible, anxiety-susceptible, or insusceptible groups respectively, suggesting that identical CMS differently impacted the mitochondrial and metabolic processes in the hippocampus. Collectively, the observed alterations to protein abundance profiles of the hippocampus provided significant and novel insights into the stress regulation mechanism in a CMS rat model. This might serve as the molecular basis for further studies that would contributed to a better understanding of the similarities and differences in pathophysiologic mechanisms underlying stress-induced depression or anxiety, and stress resiliency.

ObjectivesWe aimed to investigate which prevention strategies for low back pain (LBP) are most effective.DesignWe completed a Bayesian network meta-analysis to summarise the comparative effectiveness of LBP prevention strategies. The primary outcomes were an episode of LBP and LBP-associated work absenteeism represented as ORs with associated 95% credibility intervals (CrIs). We ranked all prevention strategies with surface under the cumulative ranking curve (SUCRA) analysis.Data sourcesPubMed, EMBASE and CENTRAL databases were searched along with manual searches of retrieved articles. We only included randomised controlled trials (RCTs) that reported an episode of LBP and/or LBP-associated work absenteeism evaluating LBP prevention strategies were included.Eligibility criteria for selecting studiesData were independently extracted by two investigators, and RCT quality was assessed using the Cochrane Risk of Bias tool.Results and summaryForty RCTs were included. Exercise combined with education (OR: 0.59, CrI: 0.41 to 0.82) and exercise alone (OR: 0.59, CrI: 0.36 to 0.92) both prevented LBP episodes; exercise combined with education and education alone both had large areas under the curve (SUCRA: 81.3 and 79.4, respectively). Additionally, exercise (OR: 0.04, CrI: 0.00 to 0.34) prevented LBP-associated work absenteeism, with exercise and the combination of exercise and education ranking highest (SUCRA: 99.0 and 60.2, respectively).ConclusionsExercise alone and exercise combined with education can prevent episodes of LBP and LBP-related absenteeism.Trial registration numberPROSPERO 42017056884.

Borna disease virus (BDV) is a neurotropic virus that produces neuropsychiatric dysfunction in a wide range of warm-blooded species. Several studies have associated BDV with human psychiatric illness, but the findings remain controversial. Although oligodendrocytes are a major glial component of brain white matter and play a pivotal role in neuronal cell function, BDV's effects on human oligodendrocytes have not been clarified. Here, the effects of two BDV strains, Hu-H1 (isolated from a bipolar patient) and Strain V (a laboratory strain), on the proliferation and apoptosis of human oligodendrocytes were investigated. Three experimental cell lines were constructed: Hu-H1-infected oligodendroglioma (Hu-H1) cells, Strain V-infected oligodendroglioma (Strain V) cells, and non-infected oligodendroglioma (control) cells. BDV infection was assayed by BDV nucleoprotein (p40) immunofluorescence, cell proliferation was assayed by Cell Counting Kit-8 (CCK8), and cell cycle phases and apoptosis were assayed by flow cytometry. Expressions of the apoptosis-related proteins Bax and Bcl-2 were measured by Western blotting. p40 expression was confirmed in Hu-H1 and Strain V on and after day three post-infection. Strain V cells showed significantly greater cellular proliferation than Hu-H1 cells on and after day three post-infection. In Hu-H1 cells, Bax and Bcl-2 expression were significantly increased and decreased, respectively, on and after day three post-infection. In contrast, in Strain V cells, Bax and Bcl-2 expression were significantly decreased and increased, respectively, on and after day three post-infection. In conclusion, Hu-H1 inhibits cellular proliferation and promotes apoptosis in human oligodendrocytes via Bax upregulation and Bcl-2 downregulation. In contrast, Strain V promotes cellular proliferation and inhibits apoptosis in human oligodendrocytes via Bax downregulation and Bcl-2 upregulation. The effects of the Hu-H1 strain (isolated from a bipolar patient) are opposite from those of Strain V (a laboratory strain), thereby providing a proof of authenticity for both.

Poly(lactide‐co‐glycolic acid) (PLGA) particles are biocompatible and bio­degradable, and can be used as a carrier for various chemotherapeutic drugs, imaging agents and targeting moieties. Micrometer‐sized PLGA particles were synthesized with gold nanoparticles and DiI dye within the PLGA shell, and perfluorohexane liquid (PFH) in the core. Upon laser irradiation, the PLGA shell absorbs the laser energy, activating the liquid core (liquid conversion to gas). The rapidly expanding gas is expelled from the particle, resulting in a microbubble; this violent process can cause damage to cells and tissue. Studies using cell cultures show that PLGA particles phagocytosed by single cells are consistently vaporized by laser energies of 90 mJ cm−2, resulting in cell destruction. Rabbits with metastasized squamous carcinoma in the lymph nodes are then used to evaluate the anti‐cancer effects of these particles in the lymph nodes. After percutaneous injection of the particles and upon laser irradiation, through the process of optical droplet vaporization, ultrasound imaging shows a significant increase in contrast in comparison to the control. Histology and electron microscopy confirm damage with disrupted cells throughout the lymph nodes, which slows the tumor growth rate. This study shows that PLGA particles containing PFC liquids can be used as theranostic agents in vivo.

The objective of this study was to compare outcomes in patients with rotator cuff tears undergoing all-arthroscopic versus mini-open rotator cuff repair. A systematic review and meta-analysis of outcomes of all-arthroscopic repair versus mini-open repair in patients with rotator cuff repair was conducted. Studies meeting the inclusion criteria were screened and included from systematic literature search for electronic databases including Medline, Embase, Cochrane CENTRAL, and CINAHL library was conducted from 1969 and 2015. A total of 18 comparative studies including 4 randomized clinical trials (RCTs) were included. Pooled results indicate that there was no difference in the functional outcomes, range of motion, visual analog scale (VAS) score, and short-form 36 (SF-36) subscales. However, Constant-Murley functional score was found to be significantly better in patients with mini-open repair. However, the results of the review should be interpreted with caution due to small size and small number of studies contributing to analysis in some of the outcomes. All-arthroscopic and mini-open repair surgical techniques for the management of rotator cuff repair are associated with similar outcomes and can be used interchangeably based on the patient and rotator tear characteristics.

Borna disease virus (BDV) is a non-cytolytic, neurotropic RNA virus that can infect a wide variety of vertebrate species from birds and primates to humans. Several studies have been carried out to investigate whether BDV is associated with neuropsychiatric diseases. However, this association is still inconclusive. Two panels of subjects consisting of 1,679 various neuropsychiatric patients and healthy people from three western China provinces were enrolled in this study. BDV p24 or p40 RNA in peripheral blood mononuclear cells (PBMCs) were detected in the first panel of 1,481 subjects using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and cerebrospinal fluid (CSF) samples from the BDV RNA-positive individuals were subjected to BDV p24 antibodies testing by enzyme-linked immunosorbent assay (ELISA). BDV p24 or p40 RNA in PBMCs and p24 antibodies in plasma were detected in the second panel of 198 subjects by RT-qPCR and Western blot. A higher prevalence for BDV RNA was demonstrated in patients with viral encephalitis (6.70%), Guillain-Barré syndrome (6.70%), schizophrenia (9.90%) and chronic fatigue syndrome (CFS) (12.70%) compared to healthy controls in the first panel. CSF p24 antibodies were demonstrated in three viral encephalitis patients, two schizophrenia patients and two major depressive disorder (MDD) patients. The prevalences of p24 antibodies in plasma from patients with viral encephalitis (13.24%), multiple sclerosis (25.00%) and Parkinson's disease (22.73%) were significantly higher than healthy controls. This study demonstrates that BDV infection also exists in humans from three western China provinces, and suggests the involvement of the contribution of BDV in the aetiology of Chinese patients with some neuropsychiatric disorders, including viral encephalitis, schizophrenia, CFS, multiple sclerosis and Parkinson's disease.

BackgroundBorna disease virus is a neurotropic, non-cytolytic virus that has been widely employed in neuroscientific research. Previous studies have revealed that metabolic perturbations are associated with Borna disease viral infection. However, the pathophysiological mechanism underlying its mode of action remains unclear.MethodologyHuman oligodendroglia cells infected with the human strain Borna disease virus Hu-H1 and non-infected matched control cells were cultured in vitro. At day 14 post-infection, a proton nuclear magnetic resonance-based metabonomic approach was used to differentiate the metabonomic profiles of 28 independent intracellular samples from Borna disease virus-infected cells (n = 14) and matched control cells (n = 14). Partial least squares discriminant analysis was performed to demonstrate that the whole metabonomic patterns enabled discrimination between the two groups, and further statistical testing was applied to determine which individual metabolites displayed significant differences between the two groups.FindingsMetabonomic profiling revealed perturbations in 23 metabolites, 19 of which were deemed individually significant: nine energy metabolites (α-glucose, acetate, choline, creatine, formate, myo-inositol, nicotinamide adenine dinucleotide, pyruvate, succinate) and ten amino acids (aspartate, glutamate, glutamine, glycine, histidine, isoleucine, phenylalanine, threonine, tyrosine, valine). Partial least squares discriminant analysis demonstrated that the whole metabolic patterns enabled statistical discrimination between the two groups.ConclusionBorna disease viral infection perturbs the metabonomic profiles of several metabolites in human oligodendroglia cells cultured in vitro. The findings suggest that Borna disease virus manipulates the host cell’s metabolic network to support viral replication and proliferation.

PURPOSE Opioids are the primary choice for managing chronic cancer pain. However, many nonopioid therapies are currently prescribed for chronic cancer pain with little published evidence comparing their efficacy. METHODS Electronic databases were searched for randomized controlled trials (RCTs) comparing any systemic pharmaceutical intervention and/or combination thereof in treating chronic cancer pain. The primary outcome was global efficacy reported as an odds ratio (OR). The secondary outcome was change in pain intensity reported as a standardized mean difference (SMD). RESULTS We included 81 RCTs consisting of 10,003 patients investigating 11 medication classes. Most RCTs (80%) displayed low risk of bias. The top-ranking classes for global efficacy were nonopioid analgesics (network OR, 0.30; 95% credibility interval [CrI], 0.13 to 0.67), nonsteroidal anti-inflammatory drugs (network OR, 0.44; 95% CrI, 0.22 to 0.90), and opioids (network OR, 0.49; 95% CrI, 0.27 to 0.86), whereas the top-ranked interventions were lidocaine (network OR, 0.04; 95% CrI, 0.01 to 0.18; surface under the cumulative ranking curve analysis [SUCRA] score, 98.1), codeine plus aspirin (network OR, 0.22; 95% CrI, 0.08 to 0.63; SUCRA score, 81.1), and pregabalin (network OR, 0.29; 95% CrI, 0.08 to 0.92; SUCRA score, 73.8). In terms of reducing pain intensity, we found that no class was superior to placebo, whereas the following top-ranked interventions were superior to placebo: ziconotide (network SMD, −24.98; 95% CrI, −32.62 to −17.35; SUCRA score, 99.8), dezocine (network SMD, −13.56; 95% CrI, −23.37 to −3.69; SUCRA score, 93.5), and diclofenac (network SMD, −11.22; 95% CrI, −15.91 to −5.80; SUCRA score, 92.9). CONCLUSION There are significant differences in efficacy among current regimens for chronic cancer pain. Our evidence suggests that certain nonopioid analgesics and nonsteroidal anti-inflammatory drugs can serve as effectively as opioids in managing chronic cancer pain.