A feline model of spontaneously occurring autoimmune limbic encephalitis.

Autoimmune encephalitis (AE) is an important cause of encephalitis in humans and occurs at a similar rate to infectious encephalitis. It is frequently associated with antibodies against the extracellular domain of neuronal proteins. Among human AE, that with antibodies against leucine-rich glioma-inactivated 1 (LGI1) is one of the most prevalent forms, and was recently described in cats with limbic encephalitis (LE). In this study, we describe a large cohort (n = 32) of cats with AE, tested positive for voltage gated potassium channel (VGKC)-antibodies, of which 26 (81%) harboured LGI1-antibodies. We delineate their clinical and paraclinical features as well as long-term outcomes up to 5 years. Similar to human cases, most cats with LGI1-antibodies had a history of focal seizures (83%), clustering in the majority (88%), with interictal behavioural changes (73%). Among feline AE patients, there was no seizure type or other clinical characteristic that could distinguish LGI1-antibody positive from negative cats, unlike the pathognomic faciobrachial dystonic seizures seen in humans. Although six cats were euthanased in the first year for epilepsy-associated reasons, those attaining at least 1-year survival had good seizure control and quality of life with appropriate veterinary care and medication. Acute-phase immunotherapy (prednisolone) was given to the most severely unwell cases and its effect is retrospectively evaluated in 10 cats. Our data show LGI1-antibodies are an important cause of feline encephalitis, sharing many features with human AE. Further research should examine optimal therapeutic management strategies and the cause of LE in seronegative cats, building on paradigms established in the counterpart human disease.

Mir-106b Cluster Regulates Primordial Germ Cells Differentiation from Human Mesenchymal Stem Cells.

OBJECTIVE: Numerous evidence indicates that microRNAs (miRNAs) are critical regulators in the spermatogenesis process. The aim of this study was to investigate miR-106b cluster regulates primordial germ cells (PGCs) differentiation from human mesenchymal stem cells (MSCs). MATERIALS AND METHODS: In this experimental study, samples containing male adipose (n: 9 samples- age: 25-40 years) were obtained from cosmetic surgeries performed for the liposuction in Imam Khomeini Hospital. The differentiation of MSCs into PGCs was accomplished by transfection of a lentivector expressing miR-106b. The transfection of miR-106b was also confirmed by the detection of a clear green fluorescent protein (GFP) signal in MSCs. MSCs were treated with bone morphogenic factor 4 (BMP4) protein, as a putative inducer of PGCs differentiation, to induce the differentiation of MSCs into PGCs (positive control). After 4 days of transfection, the expression of miR-106b, STELLA, and FRAGILIS genes was evaluated by real-time polymerase chain reaction (PCR). Also, the levels of thymocyte differentiation antigen 1 (Thy1) protein was assessed by the western blot analysis. The cell surface expression of CD90 was also determined by immunocytochemistry method. The cytotoxicity of miR-106b was examined in MSCs after 24, 48, and 72 hours using the MTT assay. RESULTS: MSCs treated with BMP4 or transfected by miR-106b were successfully differentiated into PGCs. The results of this study also showed that the expression of miR-106b was significantly increased after 48 hours from transfection. Also, we showed STELLA, FARGILIS, as well as the protein expression of Thy1, was significantly higher in MSCs transfected by lentivector expressing miR-106b in comparison with MSCs treated with BMP4 (P≤0.05). MTT assay showed miR-106b was no toxic during 72 hours in 1 µg/ml dose, that this amount could elevated germ cells marker significantly higher than other experimental groups (P≤0.05). CONCLUSION: According to this findings, it appears that miR-106b plays an essential role in the differentiation of MSCs into PGCs.

Outcomes of peroral endoscopic myotomy in patients with achalasia and prior bariatric surgery: A multicenter experience.

Peroral endoscopic myotomy (POEM) in patients with achalasia who are status post bariatric surgery may be technically challenging due to postsurgical scarring and altered anatomy. The aim of the study was to assess the efficacy and safety of POEM for achalasia in patients with prior bariatric surgery. A review of prospectively maintained databases at three tertiary referral centers from January 2015 to January 2021 was performed. The primary outcome of interest was clinical success, defined as a post-treatment Eckardt score ≤ 3 or improvement in Eckardt score by ≥ 1 when the baseline score was <3, and improvement of symptoms. Secondary outcomes were adverse event rates and symptom recurrence. Sixteen patients status post Roux-en-Y gastric bypass (n = 14) and sleeve gastrectomy (n = 2) met inclusion criteria. Indications for POEM were achalasia type I (n = 2), type II (n = 9), and type III (n = 5). POEM was performed either by anterior or posterior approach. The pre-POEM mean integrated relaxation pressure was 26.2 ± 7.6 mm Hg. The mean total myotomy length was 10.2 ± 2.7 cm. The mean length of hospitalization was 1.4 ± 0.7 days. Pre- and postprocedure Eckardt scores were 6.1 ± 2.1 and 1.7 ± 1.8, respectively. The overall clinical success rate was 93.8% (15/16) with mean follow-up duration of 15.5 months. One patient had esophageal leak on postprocedure esophagram and managed endoscopically. Dysphagia recurred in two patients, which was successfully managed with pneumatic dilation with or without botulinum toxin injection. POEM appears to be safe and effective in the management of patients with achalasia who have undergone prior bariatric surgery.

A large multicenter cohort on the use of full-thickness resection device for difficult colonic lesions.

BACKGROUND: Introduction of the full-thickness resection device (FTRD) has allowed endoscopic resection of difficult lesions such as those with deep wall origin/infiltration or those located in difficult anatomic locations. The aim of this study is to assess the outcomes of the FTRD among its early users in the USA. METHODS: Patients who underwent endoscopic full-thickness resection (EFTR) for lower gastrointestinal tract lesions using the FTRD at 26 US tertiary care centers between 10/2017 and 12/2018 were included. Primary outcome was R0 resection rate. Secondary outcomes included rate of technical success (en bloc resection), achievement of histologic full-thickness resection (FTR), and adverse events (AE). RESULTS: A total of 95 patients (mean age 65.5 ± 12.6 year, 38.9% F) were included. The most common indication, for use of FTRD, was resection of difficult adenomas (non-lifting, recurrent, residual, or involving appendiceal orifice/diverticular opening) (66.3%), followed by adenocarcinomas (22.1%), and subepithelial tumors (SET) (11.6%). Lesions were located in the proximal colon (61.1%), distal colon (18.9%), or rectum (20%). Mean lesion diameter was 15.5 ± 6.4 mm and 61.1% had a prior resection attempt. The mean total procedure time was 59.7 ± 31.8 min. R0 resection was achieved in 82.7% while technical success was achieved in 84.2%. Histologically FTR was demonstrated in 88.1% of patients. There were five clinical AE (5.3%) with 2 (2.1%) requiring surgical intervention. CONCLUSIONS: Results from this first US multicenter study suggest that EFTR with the FTRD is a technically feasible, safe, and effective technique for resecting difficult colonic lesions.

Betanin effect on PPAR-α and SREBP-1c expression in NMRI mice model of steatohepatitis with fibrosis.

PURPOSE: Betanin is a betacyanin with antioxidant and anti-inflammatory activities whose effects were investigated in a nonalcoholic steatohepatitis (NASH) model. MAIN METHODS: Ninety-six male naval medical research institute (NMRI) mice were divided into eight groups (n = 12) including normal control, high fat diet (HFD), Sham, and positive control treated with trans-chalcone. Three experimental groups were treated with 5 mg/kg, 10 mg/kg or 20 mg/kg betanin, and a betanin protective group was also defined. RESULTS: Four weeks of HFD treatment resulted in steatohepatitis with associated fibrosis. Significant increase was observed in serum levels of triglycerides (TG), total cholesterol (TC), glucose, insulin, leptin, liver enzymes, malondialdehyde (MDA), furthermore insulin resistance and (sterol regulatory element-binding protein-1c) SREBP-1c were detected. Levels of high-density lipoprotein cholesterol (HDL-C), adiponectin, superoxide dismutase (SOD), catalase (CAT), and PPAR-α (peroxisome proliferator-activated receptor-α) considerably decreased. Treatment by betanin, particularly the 20 mg/kg dosage, attenuated these changes. CONCLUSION: Betanin is a potential treating agent of steatohepatitis and works through up-regulation of PPAR-α, down-regulation of SREBP-1c, modification of adipokine levels and modulation of lipid profile.

LGI1-antibody associated epilepsy successfully treated in the outpatient setting.

We report six patients with anti-LGI1 associated epilepsy. Two patients presented with new-onset generalized tonic-clonic seizures, four developed faciobrachial dystonic seizures and two piloerection. All patients had significant cognitive complaints at the time of diagnosis. All patients described seizure reduction during the first week of carbamazepine, and seizure freedom was obtained at a median of 13 days (range 7-22), sustained after the initiation of immunosuppression. Median time from symptom onset to carbamazepine initiation was 164 days (range 38-206 days). We discuss the particular seizure response to sodium channel blocking antiepileptic drugs, alone or associated with immunosuppression in this antibody mediated seizures.

Liquid Nitrogen Spray Cryotherapy in Treatment of Barrett's Esophagus, where do we stand? A Systematic Review and Meta-Analysis.

Radiofrequency ablation (RFA) is the preferred treatment option for Barrett's esophagus (BE) to achieve complete eradication (CE) of dysplasia (D), and intestinal metaplasia (IM). Cryotherapy, using liquid nitrogen (LNC), is a cold-induced tissue-injury technique option for the ablation of BE. We conducted a systematic review and meta-analysis to assess the overall efficacy and safety of LNC in the treatment of BE. We conducted a search of multiple electronic databases and conference proceedings from inception through June 2018. The primary outcome was to estimate the pooled rates of CE-IM, CE-D, and CE-HGD. The secondary outcome was to estimate the risk of adverse events and recurrence of disease after LNC. Nine studies reported 386 patients who were treated with LNC. The pooled rate of CE-IM was 56.5% (95% CI 48.5-64.2, I2 = 47), pooled rate of CE-D was 83.5% (95% CI 78.3-87.7, I2 = 22.8), and pooled rate of CE-HGD was 86.5% (95% CI 64.4-95.8, I2 = 88.1). Rate of adverse events was 4.7%, and the risk of BE recurrence was 12.7%. On subgroup analysis, the pooled rate of CE-IM with LNC in patients who failed RFA was 58.4% (95% CI 47.2-68.8, I2 = 32.5), and the pooled rate of CE-D in the same population was 81.9% (95% CI 72.5-88.6, I2 = 5.9). CE-D rates with LNC are comparable to RFA while CE-IM rates appear to be lower than the rates achievable with RFA. CE-IM rate in RFA failed patients is 58.4% and thus LNC is a rescue option to consider in this population.

Acquired neuromyotonia in thymoma-associated myasthenia gravis: a clinical and serological study.

BACKGROUND AND PURPOSE: Acquired neuromyotonia can occur in patients with thymoma, alone or in association with myasthenia gravis (MG), but the clinical prognostic significance of such comorbidity is largely unknown. The clinico-pathological features were investigated along with the occurrence of neuromyotonia as predictors of tumour recurrence in patients with thymoma-associated myasthenia. METHODS: A total number of 268 patients with thymomatous MG were studied retrospectively. Patients with symptoms of spontaneous muscle overactivity were selected for autoantibody testing using immunohistology for neuronal cell-surface proteins and cell-based assays for contactin-associated protein 2 (CASPR2), leucine-rich glioma inactivated 1 (LGI1), glycine receptor and Netrin-1 receptor antibodies. Neuromyotonia was diagnosed according to the presence of typical electromyography abnormalities and/or autoantibodies against LGI1/CASPR2. RESULTS: Overall, 33/268 (12%) MG patients had a thymoma recurrence. Five/268 (2%) had neuromyotonia, four with typical autoantibodies, including LGI1 (n = 1), CASPR2 (n = 1) or both (n = 2). Three patients had Netrin-1 receptor antibodies, two with neuromyotonia and concomitant CASPR2+LGI1 antibodies and one with spontaneous muscle overactivity without electromyography evidence of neuromyotonia. Thymoma recurrence was more frequent in those with (4/5, 80%) than in those without (28/263, 10%, P < 0.001) neuromyotonia. Neuromyotonia preceded the recurrence in 4/5 patients. In univariate analysis, predictors of thymoma recurrence were age at thymectomy [odds ratio (OR) 0.95, 95% confidence interval (CI) 0.93-0.97], Masaoka stage ≥IIb (OR 10.73, 95% CI 2.38-48.36) and neuromyotonia (OR 41.78, 95% CI 4.71-370.58). CONCLUSIONS: De novo occurrence of neuromyotonia in MG patients with previous thymomas is a rare event and may herald tumour recurrence. Neuronal autoantibodies can be helpful to assess the diagnosis. These observations provide pragmatic risk stratification for tumour vigilance in patients with thymomatous MG.

Induction Effects of Bacteroides fragilis Derived Outer Membrane Vesicles on Toll Like Receptor 2, Toll Like Receptor 4 Genes Expression and Cytokines Concentration in Human Intestinal Epithelial Cells.

OBJECTIVE: Gastrointestinal (GI) tract, like other mucosal surface, is colonized with a microbial population known as gut microbiota. Outer membrane vesicles (OMVs) which are produced by gram negative bacteria could be sensed by Toll like receptors (TLRs). The interaction between gut microbiota and TLRs affects homeostasis and immune responses. In this study, we evaluated TLR2, TLR4 genes expression and cytokines concentration in Caco-2 cell line treated with Bacteroides fragilis (B. fragilis) and its OMVs. MATERIALS AND METHODS: In this experimental study, OMVs were extracted using sequential centrifugation and their physicochemical properties were evaluated as part of quality control assessment. Caco-2 cells were treated with B. fragilis and its OMVs (180 and 350 µg/ml). Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to assess TLR2 and TLR4 mRNA expression levels. Pro-inflammatory (IFNᵧ) and anti-inflammatory (IL- 4 and IL-10) cytokines were evaluated by ELISA. RESULTS: B. fragilis significantly decreased TLR2 and slightly increased TLR4 mRNA levels in Caco-2 cell line. The TLR2 mRNA level was slightly increased at 180 and 350 µg/ml of OMVs. Conversely, the TLR4 mRNA level was decreased at 180 µg/ml of OMVs, while it was significantly increased at 350 µg/ml of OMVs. Furthermore, B. fragilis and its OMVs significantly increased and decreased IFNᵧ concentration, respectively. Anti-inflammatory cytokines were increased by B. fragilis and its OMVs. CONCLUSION: B. fragilis and its OMVs have pivotal role in the cross talk between gut microbiota and the host especially in the modulation of the immune system. Based on the last studies on immunomodulatory effect of B. fragilis derived OMVs on immune cells and our results, we postulate that B. fragilis derived OMVs could be possible candidates for the reduction of immune responses.

Use of intravenous immunoglobulin for the treatment of autoimmune encephalitis: audit of the NHS experience.

OBJECTIVES: The treatments of limbic and other autoimmune encephalitis include immunosuppression, symptomatic treatment, and in the case of paraneoplastic syndromes, appropriate therapy for underlying neoplasms. When immunotherapy is considered, intravenous immunoglobulin is one option for treatment, either alone or in combination with corticosteroids. To date, however, evidence for the use of intravenous immunoglobulin in this context comes from case series/expert reviews as no controlled trials have been performed. We aimed to analyse the NHS England Database of intravenous immunoglobulin usage, which was designed to log use and guide procurement, to explore usage and therapeutic effect of intravenous immunoglobulin in autoimmune encephalitis in England. DESIGN: We conducted a retrospective audit and review of the NHS England Database on intravenous immunoglobulin use. SETTING: NHS England Database of intravenous immunoglobulin use which covers secondary and tertiary care prescribing and use of intravenous immunoglobulin for all patients in hospitals in England. PARTICIPANTS: Hospital in-patients with confirmed or suspected autoimmune/limbic encephalitis between September 2010 and January 2017. RESULTS: A total of 625 patients who were 18 years of age or older were treated with intravenous immunoglobulin for autoimmune encephalitis, of whom 398 were determined as having 'highly likely' or 'definite' autoimmune/limbic encephalitis. Ninety-six percent were treated with a single course of intravenous immunoglobulin. The availability and accuracy of reporting of outcomes was very poor, with complete data only available in 27% of all cases. CONCLUSIONS: This is the first review of data from this unique national database. Whilst there was evidence for clinical improvement in many cases of patients treated with intravenous immunoglobulin, the quality of outcome data was generally inadequate. Methods to improve quality, accuracy and completeness of reporting are crucial to maximise the potential value of this resource as an auditing tool.

Antiglycine receptor antibody related disease: a case series and literature review.

BACKGROUND AND PURPOSE: Antibodies to glycine receptors (GlyR-Abs) were first defined in progressive encephalopathy with rigidity and myoclonus (PERM) but were subsequently identified in other clinical presentations. Our aim was to assess the clinical associations of all patients identified with GlyR-Abs in Queensland, Australia, between April 2014 and May 2017 and to compare these to cases reported in the literature. METHODS: A literature review identified the clinical features of all published GlyR-Ab-positive cases through online databases. A case series was undertaken via collection of clinical information from all patients diagnosed or known to immunology, pathology or neurological services in Queensland during the study period of 3 years. RESULTS: In all, 187 GlyR-Ab-positive cases were identified in the literature. The majority (47.6%) had PERM, 22.4% had epilepsy, but the remaining 30% included mixed phenotypes consisting of cerebellar ataxia, movement disorders, demyelination and encephalitis/cognitive dysfunction. By contrast, in our series of 14 cases, eight had clinical presentations consistent with seizures and epilepsy and only three cases had classical features of PERM. There was one case each of global fatiguable weakness with sustained clonus, laryngeal dystonia and movement disorder with hemiballismus and tics. The rate of response to immune therapy was similar in all groups. CONCLUSION: Antibodies to glycine receptors are linked to a spectrum of neurological disease. The results of the literature review and our case series suggest a greater relationship between GlyR-Abs and epilepsy than previously reported.

The effectiveness of gynaecology teaching associates in teaching pelvic examination to medical students: a randomised controlled trial.

OBJECTIVES: To assess whether teaching female pelvic examinations using gynaecological teaching associates (GTAs); women who are trained to give instruction and feedback on gynaecological examination technique, improves the competence, confidence and communication skills of medical students compared to conventional teaching. STUDY DESIGN: Randomised controlled trial. SETTING: Ten University of Birmingham (UoB) affiliated teaching hospitals in the UK. POPULATION: 492 final year medical students. METHODS: GTA teaching of gynaecological examination compared with conventional pelvic manikin based teaching at the start of a five week clinical placement in obstetrics and gynaecology (O&G). MAIN OUTCOME MEASURES: Student's perception of their confidence was measured on a 10cm visual analogue scale (VAS). Domains of competence were measured by a senior clinical examiner using a standardised assessment tool which utilised 10cm VAS and by a GTA using a four point Likert scale. Assessors were blinded to the allocated teaching intervention. RESULTS: 407/492 (83%) students completed both the intervention and outcome assessment. Self-reported confidence was higher in students taught by GTAs compared with those taught on manikins (median score GTA 6.3; vs. conventional 5.8; p=0.03). Competence was also higher in those taught by GTAs when assessed by an examiner (median global score GTA 7.1 vs. conventional 6.0; p<0.001) and by a GTA (p<0.001). CONCLUSIONS: GTA teaching of female pelvic examination at the start of undergraduate medical student O&G clinical placements improves their confidence and competence compared with conventional pelvic manikin based teaching. GTAs should be introduced into undergraduate medical curricula to teach pelvic examination.

Engineered electrospun poly(caprolactone)/polycaprolactone-g-hydroxyapatite nano-fibrous scaffold promotes human fibroblasts adhesion and proliferation.

Polycaprolactone (PCL)/hydroxyapatite nano-composites are among the best candidates for tissue engineering. However, interactions between nHAp and PCL are difficult to control leading to inhomogeneous dispersion of the bio-ceramic particles. Grafting of polymer chains at high density/chain length while promotes the phase compatibility may result in reduced HAp exposed surface area and therefore, bioactivity is compromised. This issue is addressed here by grafting PCL chains onto HAp nano-particles through ring opening polymerization of ε-caprolactone (PCL-g-HAp). FTIR and TGA analysis showed that PCL (6.9wt%), was successfully grafted on the HAp. PCL/PCL-g-HAp nano-fibrous scaffold showed up to 10 and 33% enhancement in tensile strength and modulus, respectively, compared to those of PCL/HAp. The effects of HAp on the in vitro HAp formation were investigated for both the PCL/HAp and PCL/PCL-g-HAp scaffolds. Precipitation of HAp on the nano-composite scaffolds observed after 15days incubation in simulated body fluid (SBF), as confirmed by scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). Human fibroblasts were seeded on PCL, PCL/HAp and PCL/PCL-g-HAp scaffolds. According to MTT assay, the highest cell proliferation was recorded for PCL/PCL-g-HAp nano-composite, at all time intervals (1-21days, P<0.001). Fluorescent microscopy (of DAPI stained samples) and electron microscopy images showed that all nano-fibrous scaffolds (PCL, PCL/HAp, and PCL/PCL-g-HAp), were non-toxic against cells, while more cell adhesion, and the most uniform cell distribution observed on the PCL/PCL-g-HAp. Overall, grafting of relatively short chains of PCL on the surface of HAp nano-particles stimulates fibroblasts adhesion and proliferation on the PCL/PCL-g-HAp nano-composite.

Generation of GFP Native Protein for Detection of Its Intracellular Uptake by Cell-Penetrating Peptides.

Different types of lipid- and polymer-based vectors have been developed to deliver proteins into cells, but these methods showed relatively poor efficiency. Recently, a group of short, highly basic peptides known as cell-penetrating peptides (CPPs) were used to carry polypeptides and proteins into cells. In this study, expression and purification of GFP protein was performed using the prokaryotic pET expression system. We used two amphipathic CPPs (Pep-1 and CADY-2) as a novel delivery system to transfer the GFP protein into cells. The morphological features of the CPP/GFP complexes were studied by scanning electron microscopy (SEM), Zetasizer, and SDS-PAGE. The efficiency of GFP transfection using Pep-1 and CADY-2 peptides and TurboFect reagent was compared with FITC-antibody protein control delivered by these transfection vehicles in the HEK-293T cell line. SEM data confirmed formation of discrete nanoparticles with a diameter of below 300 nm. Moreover, formation of the complexes was detected using SDS-PAGE as two individual bands, indicating non-covalent interaction. The size and homogeneity of Pep-1/GFP and CADY-2/GFP complexes were dependent on the ratio of peptide/cargo formulations, and responsible for their biological efficiency. The cells transfected by Pep-1/GFP and CADY-2/GFP complexes at a molar ratio of 20 : 1 demonstrated spreading green regions using fluorescent microscopy. Flow cytometry results showed that the transfection efficiency of Pep-based nanoparticles was similar to CADY-based nanoparticles and comparable with TurboFect-protein complexes. These data open an efficient way for future therapeutic purposes.

Obstetric complications on deployed operations: a guide for the military surgeon.

Modern military general surgeons tend to train and then practice in 'conventional' surgical specialties in their home nation; however, the reality of deployed surgical practice, either in a combat zone or on a humanitarian mission, is that they are likely to have to manage patients with a broad range of ages, conditions and pathologies. Obstetric complications of war injury include injury to the uterus and fetus as well as the mother and both placental abruption and uterine rupture are complications that military surgeons may have little experience of recognising and managing. On humanitarian deployments, fetomaternal complications are a common reason for surgical intervention. We report a recent patient's story to highlight the obstetric training needs of military surgeons.

Autoantibodies to central nervous system neuronal surface antigens: psychiatric symptoms and psychopharmacological implications.

RATIONALE: Autoantibodies to central nervous system (CNS) neuronal surface antigens have been described in association with autoimmune encephalopathies which prominently feature psychiatric symptoms in addition to neurological symptoms. The potential role of these autoantibodies in primary psychiatric diseases such as schizophrenia or bipolar affective disorder is of increasing interest. OBJECTIVES: We aimed to review the nature of psychiatric symptoms associated with neuronal surface autoantibodies, in the context of autoimmune encephalopathies as well as primary psychiatric disorders, and to review the mechanisms of action of these autoantibodies from a psychopharmacological perspective. RESULTS: The functional effects of the autoantibodies on their target antigens are described; their clinical expression is at least in part mediated by their effects on neuronal receptor function, primarily at the synapse, usually resulting in receptor hypofunction. The psychiatric effects of the antibodies are related to known functions of the receptor target or its complexed proteins, with reference to supportive genetic and pharmacological evidence where relevant. Evidence for a causal role of these autoantibodies in primary psychiatric disease is increasing but remains controversial; relevant methodological controversies are outlined. Non-receptor-based mechanisms of autoantibody action, including neuroinflammatory mechanisms, and therapeutic implications are discussed. CONCLUSIONS: An analysis of the autoantibodies from a psychopharmacological perspective, as endogenous, bioactive, highly specific, receptor-targeting molecules, provides a valuable opportunity to understand the neurobiological basis of associated psychiatric symptoms. Potentially, new treatment strategies will emerge from the improving understanding of antibody-antigen interaction within the CNS.

Physical activity and the frequency of acute exacerbations in patients with chronic obstructive pulmonary disease.

PURPOSE: Acute exacerbations (AE) in patients with COPD are associated with a decline in lung function, increased risk of hospitalization, and mortality. In this cross-sectional study we tested whether the level of objectively measured daily physical activity and exercise capacity are associated with the number of COPD exacerbations. METHODS: In 210 patients with COPD (67 % men; mean (SD) age: 63 (8) years) enrolled in The Obstructive Pulmonary Disease Outcomes Cohort of Switzerland (TOPDOCS) physical activity (PA) (steps per day, physical activity level, (PAL)), exercise capacity (6-min walking distance, (6MWD)), comorbidities, lung function, and medication were assessed. Differences between COPD patients with frequent (≥2 year) and infrequent (0-1 year) exacerbations were assessed. Univariate and multivariate analyses were performed to investigate whether the level of objectively measured daily physical activity and exercise capacity are associated with the number of COPD exacerbations. RESULTS: Patients with frequent AE had a significantly lower FEV1 and 6MWD compared to patients with infrequent AE. In univariate analysis, the number of exacerbations was inversely associated with FEV1, 6MWD, BMI, and smoking status while there was a positive association with RV/TLC and combined inhaled medication. However, there was no significant association with PAL and steps per day. In multivariate analysis, FEV1 and the use of combined inhaled medication were independently associated with the number of AE, after correction for covariates. CONCLUSIONS: The findings of this study imply that FEV1, independent of inhaled medication, is significantly associated with COPD exacerbations. Neither physical activity nor exercise capacity was independently associated with COPD exacerbations.