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Antibodies against neuronal surface antigens (NSA-Abs), particularly against the NMDA receptor (NMDAR-Ab), have been reported in acute stroke patients (ASP). However, their role in stroke is far from being understood. We conducted a systematic review and meta-analysis to investigate: 1) the frequency of NSA-Abs in patients with acute stroke compared to controls; 2) the appearance of NSA-Abs after stroke; and 3) their effects on the clinical outcome. We included nine studies in the qualitative analysis and seven in the quantitative analysis. Analyses were restricted to NMDAR-Abs due to the lack of data about other NSA-Abs. Considering only studies that adopted a cell-based assay, IgA-IgM NMDAR-Abs isotypes (but not the IgG) were found more frequently in patients with acute stroke (OR 2.69, 95% CI 2.00-3.62, I = 4%). There was no NMDAR-Abs formation after stroke. There was no statistical difference in mean discharge/day-7 NIHSS (SMD 0.21, 95% CI -1.10-1.52, I2 = 84%) and 3-12-month mRS (SMD 0.38, 95% CI -0.56-1.32, I2 = 78%) between patients with stroke with and without NMDAR-Abs seropositivity. Serum IgA/IgM NMDAR-Abs are more frequent in patients with stroke than controls. Due to several methodological issues, these findings should be interpreted cautiously. Additional, methodologically robust studies are needed to clarify the prevalence and significance of NMDAR-Abs in patients with stroke. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022241278#:~:text=https%3A//www.crd.york.ac.uk/prospero/display_record.php%3FID%3DCRD42022241278, identifier CRD42022241278.

Autoimmune encephalitis and neurodegenerative disorders share several clinical features, including behavioural and psychiatric manifestations, cognitive impairment, sleep and movement disorders. Therefore, it is not surprising that autoimmune encephalitis is one of the main differential diagnoses of rapidly progressive dementia. However, more chronic presentations of autoimmune disorders have been reported and can lead to the misdiagnosis of a neurodegenerative disease. On the other hand, antibodies against neuronal proteins, such as those directed against NMDAR, can occur during established neurogenerative disorders, and their role in this context is still unclear. They might be simple bystanders or modify the disease course and phenotype. Indeed, autoimmune encephalitis can leave long-term cognitive sequelae and specific antibodies to neuronal surface antigens are associated with clinical and pathological neurodegenerative features. Here we review the link between these antibodies and neurodegeneration. In particular we discuss: (a) the possibility that autoimmune encephalitis presents as a neurodegenerative disease, identifying the red flags that can help in the differential diagnosis between antibody-mediated and neurodegenerative disorders; (b) the occurrence of antibodies against neuronal surface antigens in patients with neurodegenerative disorders and their possible role in the disease course; and (c) the long-term cognitive and neuroradiological changes associated with autoimmune encephalitis, as well as the biomarkers that can help to predict the cognitive outcome. Finally, we review the clinical and pathological features of IgLON5 antibodies-related encephalitis, a unique model of the relationship between antibodies and neurodegeneration.

The design of personal protective equipment (PPE) may affect well-being and clinical work. PPE as an integrated item may improve usability and increase adherence by healthcare professionals. Human factors design and safety may reduce occupational-acquired diseases. As an integrated PPE, a lightweight protective air-purifying respirator (L-PAPR) could be used during health procedures where healthcare professionals are exposed to airborne pathogens. The human factors affecting the implementation of alternative PPE such as L-PAPR have not been thoroughly studied. The population of interest is health care professionals, the intervention is the performance by PPE during tasks across the three PPE types 1.) N95 respirators and face shields, 2.)traditional powered air-purifying respirator(PAPR), and 3.) L-PAPR. The outcomes are user error, communications, safety, and end-user preferences. This study will assess whether the L-PAPR improves health care professionals' comfort in terms of perceived workload and physical and psychological burden during direct patient care when compared with the traditional PAPR or N95 and face shield. This study also aims to evaluate human factors during the comparison of the use of L-PAPR with a combination of N95 respirators plus face shields or the traditional PAPRs. This is an interventional randomized crossover quality improvement feasibility study consisting of a 3-site simulation phase with 10 participants per site and subsequent field testing in 2 sites with 30 participants at each site. The 3 types of respiratory PPE will be compared across medical tasks and while donning and doffing. We will evaluate the user's perceived workload, usability, usage errors, and heart rate. We will conduct semistructured interviews to identify barriers and enablers to implementation across each PPE type over a single continuous wear episode and observe interpersonal communications across conditions and PPE types. We expect the research may highlight communication challenges and differences in usability and convenience across PPE types along with error frequency during PPE use across PPE types, tasks, and time. The design of PPE may affect overall well-being and hinder or facilitate clinical work. Combining 2 pieces of PPE into a single integrated item may improve usability and reduce occupational-acquired diseases. The human factors affecting the implementation of an alternative PPE such as L-PAPR or PAPR have not been thoroughly studied. PRR1-10.2196/36549.

Small fiber neuropathy (SFN) is a peripheral nerve condition affecting thin myelinated Aδ and unmyelinated C-fibers, characterized by severe neuropathic pain and other sensory and autonomic symptoms. A variety of medical disorders can cause SFN; however, more than 50% of cases are idiopathic (iSFN). Some investigations suggest an autoimmune etiology, backed by evidence of the efficacy of IVIG and plasma exchange. Several studies suggest that autoantibodies directed against nervous system antigens may play a role in the development of neuropathic pain. For instance, patients with CASPR2 and LGI1 antibodies often complain of pain, and and studies support their pathogenicity. Other antibodies have been associated with SFN, including those against TS-HDS, FGFR3, and Plexin-D1, and new potential targets have been proposed. Finally, a few studies reported the onset of SFN after COVID-19 infection and vaccination, investigating the presence of potential antibody targets. Despite these overall findings, the pathogenic role has been demonstrated only for some autoantibodies, and the association with specific clinical phenotypes or response to immunotherapy remains to be clarified. The purpose of this review is to summarise known autoantibody targets involved in neuropathic pain, putative attractive autoantibody targets in iSFN patients, their potential as biomarkers of response to immunotherapy and their role in the development of iSFN.

Background Small fiber neuropathy (SFN) after both COVID‐19 infection or vaccination has been reported in sporadic cases, but a detailed description and comparison are missing. We aimed to screen a large cohort of patients complaining of pain and autonomic symptoms after COVID‐19 natural infection or vaccination to ascertain the presence of SFN and its correlation with autoimmune diseases. Methods We prospectively recruited for this case–control study 66 patients: 33 developing sensory and autonomic symptoms after a natural COVID‐19 infection (P‐COVID) and 33 after a mRNA vaccination against COVID‐19 (P‐VAC). We also used 33 matched healthy controls (HC) collected before 2019 when the COVID‐19 virus appeared. Patients underwent neurological examination and clinical scales, an extensive serum screening, and skin biopsy to detect small nerve fiber involvement. Results Clinical scales showed higher scores for autonomic symptoms in P‐COVID patients than in P‐VAC patients, but the other scales did not differ. P‐COVID and P‐VAC patients showed a significant decrease in somatic small nerve fibers compared with HC, whereas autonomic innervation did not differ. SFN was more frequent in P‐COVID patients (94%) than in P‐VAC patients (79%). Epidermal innervation was correlated with clinical scales for pain and autonomic dysfunctions. Autoimmune abnormalities were frequent in both groups but importantly they were not correlated with SFN. Conclusions Somatic SFN was frequently found in both P‐COVID and P‐VAC patients, with a higher incidence in the former group. Spared skin autonomic innervation was spared in both groups although a subtle autonomic involvement in P‐COVID patients was suggested by a high COMPASS‐31 scale score. SFN was not correlated with autoimmune dysfunctions, although autoimmune diseases were frequent in both groups.

Leber's hereditary optic neuropathy (LHON) is a mitochondrial disease characterized by visual loss, and rarely associated with extraocular manifestations including multiple sclerosis‐like lesions. The association of LHON and neuromyelitis optica spectrum disorders has rarely been reported. Here is reported a case of glial fibrillary acidic protein astrocytopathy presenting with area postrema syndrome in a patient with previously diagnosed recessive LHON due to mutations in the nuclear gene DNAJC30. This case emphasizes the necessity of extensive investigations for other treatable conditions in patients with LHON and otherwise unexplained extraocular involvement and the possibility that also visual symptoms can respond to immune therapy.

BackgroundCerebrospinal fluid myelin oligodendrocyte glycoprotein IgG (CSF MOG-IgG) are found in a proportion of patients with MOG antibody-associated disorder (MOGAD) and have been associated with severe disease presentations. However, most studies did not systematically investigate the role of MOG-IgG intrathecal synthesis (ITS).MethodsWe retrospectively studied 960 consecutive patients with paired serum and CSF samples screened for MOG-IgG using a live cell-based assays. MOG-IgG-specific antibody index (AIMOG) was systematically calculated using serum and CSF titres to assess MOG-IgG ITS, and clinical features were compared between MOG-IgG CSF+/CSF− and ITS+/ITS− patients.ResultsMOG-IgG were found in 55/960 patients (5.7%; serum+/CSF−: 58.2%, serum+/CSF+: 34.5%; serum−/CSF+: 7.3%). Serum/CSF MOG-IgG titres showed a moderate correlation in patients without ITS (ρ=0.47 (CI 0.18 to 0.68), p<0.001), but not in those with ITS (ρ=0.14 (CI −0.46 to –0.65), p=0.65). There were no clinical–paraclinical differences between MOG-IgG CSF+ vs CSF− patients. Conversely, patients with MOG-IgG ITS showed pyramidal symptoms (73% vs 32%, p=0.03), spinal cord involvement (82% vs 39%, p=0.02) and severe outcome at follow-up (36% vs 5%, p=0.02) more frequently than those without MOG-IgG ITS. A multivariate logistic regression model indicated that MOG-IgG ITS was an independent predictor of a poor outcome (OR: 14.93 (CI 1.40 to 19.1); p=0.03). AIMOG correlated with Expanded Disability Status Scale (EDSS) scores at disease nadir and at last follow-up (p=0.02 and p=0.01).ConclusionsConsistently with physiopathology, MOG-IgG ITS is a promising prognostic factor in MOGAD, and its calculation could enhance the clinical relevance of CSF MOG-IgG testing, making a case for its introduction in clinical practice.

Symmetry establishment is a critical process in the development of multicellular organs and requires careful coordination of polarity axes while cells actively divide within tissues. Formation of the apical style in the Arabidopsis gynoecium involves a bilateral-to-radial symmetry transition, a stepwise process underpinned by the dynamic distribution of the plant morphogen auxin. Here we show that SPATULA (SPT) and the HECATE (HEC) bHLH proteins mediate the final step in the style radialisation process and synergistically control the expression of adaxial-identity genes, HOMEOBOX ARABIDOPSIS THALIANA 3 ( HAT3 ) and ARABIDOPSIS THALIANA HOMEOBOX 4 ( ATHB4 ). HAT3/ATHB4 module drives radialisation of the apical style by promoting basal-to-apical auxin flow and via a negative feedback mechanism that finetune auxin distribution through repression of SPT expression and cytokinin sensitivity. Thus, this work reveals the molecular basis of axes-coordination and hormonal cross-talk during the sequential steps of symmetry transition in the Arabidopsis style. The apical style in Arabidopsis is formed following a bilateral-to-radial symmetry transition in the gynoecium. Here the authors show that the final step in style radialization is coordinated by the adaxial regulators HAT3 and ATHB4, which are induced by the SPT and HEC transcription factors.

Resembling the development of cancer by multistep carcinogenesis, the evolution towards metastasis involves several passages, from local invasion and intravasation, encompassing surviving anoikis into the circulation, landing at distant sites and therein establishing colonization, possibly followed by the outgrowth of macroscopic lesions. Within this cascade, epithelial to mesenchymal transition (EMT) works as a pleiotropic program enabling cancer cells to overcome local, systemic, and distant barriers against diffusion by replacing traits and functions of the epithelial signature with mesenchymal-like ones. Along the transition, a full-blown mesenchymal phenotype may not be accomplished. Rather, the plasticity of the program and its dependency on heterotopic signals implies a pendulum with oscillations towards its reversal, that is mesenchymal to epithelial transition. Cells in intermixed E⇔M states can also display stemness, enabling their replication together with the epithelial reversion next to successful distant colonization. If we aim to include the EMT among the hallmarks of cancer that could modify clinical practice, the gap between the results pursued in basic research by animal models and those achieved in translational research by surrogate biomarkers needs to be filled. We review the knowledge on EMT, derived from models and mechanistic studies as well as from translational studies, with an emphasis on gastrointestinal cancers (GI).

The peptide derived from E. contortisiliquum trypsin inhibitor (Pep-3-EcTI), peptide derived from kallikrein inhibitor isolated from B. bauhinioides (Pep-BbKI), and B. rufa peptide modified from B. bauhinioides (Pep-BrTI) peptides exhibit anti-inflammatory and antioxidant activities, suggesting their potential for treating asthma–chronic obstructive pulmonary disease (COPD) overlap (ACO). We compared the effects of these peptides with dexamethasone (DX) treatment in an ACO model. In this study, 11 groups of male BALB/c mice were pre-treated under different conditions, including sensitization with intraperitoneal injection and inhalation of ovalbumin (OVA), intratracheal instillation of porcine pancreatic elastase (ELA), sensitization with intraperitoneal injection, and various combinations of peptide treatments with Pep-3-EcTI, Pep-BbKI, Pep-BrTI, dexamethasone, and non-treated controls (SAL-saline). Respiratory system resistance, airway resistance, lung tissue resistance, exhaled nitric oxide, linear mean intercept, immune cell counts in the bronchoalveolar lavage fluid, cytokine expression, extracellular matrix remodeling, and oxidative stress in the airways and alveolar septa were evaluated on day 28. Results showed increased respiratory parameters, inflammatory markers, and tissue remodeling in the ACO group compared to controls. Treatment with the peptides or DX attenuated or reversed these responses, with the peptides showing effectiveness in controlling hyperresponsiveness, inflammation, remodeling, and oxidative stress markers. These peptides demonstrated an efficacy comparable to that of corticosteroids in the ACO model. However, this study highlights the need for further research to assess their safety, mechanisms of action, and potential translation to clinical studies before considering these peptides for human use.