Feasibility of methotrexate discontinuation following tocilizumab and methotrexate combination therapy in patients with long-standing and advanced rheumatoid arthritis: a 3-year observational cohort study.

Objectives: Methotrexate (MTX) is associated with extensive side effects, including myelosuppression, interstitial pneumonia, and infection. It is, therefore, critical to establish whether its administration is required after achieving remission with tocilizumab (TCZ) and MTX combination therapy in patients with rheumatoid arthritis (RA). Therefore, the aim of this multicenter, observational, cohort study was to evaluate the feasibility of MTX discontinuation for the safety of these patients.

Antispasmodic Effect of Bergamot Essential Oil on Rat Isolated Gut Tissues.

Preclinical data indicate that bergamot essential oil (BEO) can modulate the synaptic functions within the central nervous system (CNS). Particularly, several data shows that essential oil is endowed with reproducible analgesic and anxiolytic effects that may derived from the ability to modulate the excitatory and inhibitory neurotransmission in the CNS. Although there are differences in the functional complexity of the enteric nervous system (ENS), it is likely that the phytocomplex has biological properties in gut superimposable to those showed in the CNS.

Core Fucosylation Regulates the Function of Pre-BCR, BCR and IgG in Humoral Immunity.

Most of the membrane molecules involved in immune response are glycosylated. N-glycans linked to asparagine (Asn) of immune molecules contribute to the protein conformation, surface expression, stability, and antigenicity. Core fucosylation catalyzed by core fucosyltransferase (FUT8) is the most common post-translational modification.

Autophagic dysfunction in the liver enhances the expression of insoluble nuclear proteins 14-3-3ζ and importin α4.

Aims: Autophagic dysfunction is associated with the progression of various liver diseases, including nonalcoholic fatty liver disease (NAFLD). However, serum markers for evaluating autophagic function have not been reported. Highly insoluble nuclear proteins participate in many cellular functions and are potential diagnostic markers for cancer.

Is there a rational basis for cannabinoids research and development in ocular pain therapy? A systematic review of preclinical evidence.

Background: Purpose of the present systematic review is to investigate preclinical evidence in favor of the working hypothesis of efficacy of cannabinoids in ocular pain treatment.

Methods: Literature search includes the most relevant repositories for medical scientific literature from inception until November, 24 2021. Data collection and selection of retrieved records adhere to PRISMA criteria.

Development and Translation of NanoBEO, a Nanotechnology-Based Delivery System of Bergamot Essential Oil Deprived of Furocumarins, in the Control of Agitation in Severe Dementia.

Dementia is one of the most common causes of disability worldwide characterized by memory loss, cognitive impairment, and behavioral and psychological symptoms (BPSD), including agitation. Treatment of the latter consists of the off-label use of harmful atypical antipsychotics, though a significant reduction is afforded by pain control. The use of an essential oil endowed with analgesic properties and devoid of toxicity would represent an important option for the management of agitation in dementia.

Effect of Gabapentin in a Neuropathic Pain Model in Mice Overexpressing Human Wild-Type or Human Mutated Torsin A.

Background: DYT1 dystonia is the most common form of early-onset inherited dystonia, which is caused by mutation of torsin A (TA) belonging to the "ATPases associated with a variety of cellular activities" (AAA + ATPase). Dystonia is often accompanied by pain, and neuropathic pain can be associated to peripherally induced movement disorder and dystonia. However, no evidence exists on the effect of gabapentin in mice subjected to neuropathic pain model overexpressing human normal or mutated TA.

Impact of nutraceuticals on glaucoma: A systematic review.

Background: glaucoma is a remarkable social issue being the leading cause of irreversible blindness worldwide. It is a progressive neuropathy characterized by the death of the retinal ganglion cells, of which the most important risk factor is represented by the increase of intraocular pressure (IOP). The role of nutraceutical supplementations with anti-oxidant activity has been extensively tested in preclinical models of glaucoma.

Pharmacokinetic Interactions between Herbal Medicines and Drugs: Their Mechanisms and Clinical Relevance.

The therapeutic efficacy of a drug or its unexpected unwanted side effects may depend on the concurrent use of a medicinal plant. In particular, constituents in the medicinal plant extracts may influence drug bioavailability, metabolism and half-life, leading to drug toxicity or failure to obtain a therapeutic response. This narrative review focuses on clinical studies improving knowledge on the ability of selected herbal medicines to influence the pharmacokinetics of co-administered drugs.

Strategy for Designing Selective Lysosomal Acid α-Glucosidase Inhibitors: Binding Orientation and Influence on Selectivity.

Deoxynojirimycin (DNJ) is the archetypal iminosugar, in which the configuration of the hydroxyl groups in the piperidine ring truly mimic those of d-glucopyranose; DNJ and derivatives have beneficial effects as therapeutic agents, such as anti-diabetic and antiviral agents, and pharmacological chaperones for genetic disorders, because they have been shown to inhibit α-glucosidases from various sources. However, attempts to design a better molecule based solely on structural similarity cannot produce selectivity between α-glucosidases that are localized in multiple organs and tissues, because the differences of each sugar-recognition site are very subtle. In this study, we provide the first example of a design strategy for selective lysosomal acid α-glucosidase (GAA) inhibitors focusing on the alkyl chain storage site.

Hyaluronidase inhibitory saponins and a trypanocidal isoflavonoid from the aerial parts of Oxytropis lanata.

A chemical examination of an extract from the aerial part of Oxytropis lanata led to the isolation and identification of 36 compounds, including saponins, isoflavonoids, oxazoles, and glycosides. The three among them were previously unreported oleanane-type saponins. In trypanocidal screening, 5,7,4'-trihydroxyisoflavone showed inhibitory activity against Trypanosoma congolense (IC = 10.

Convergent creative thinking performance is associated with white matter structures: Evidence from a large sample study.

In laboratory settings, creativity is measured using tasks of divergent as well as convergent thinking. It has been suggested that brain connectivity is important for creativity. In the present study, we investigated the associations of convergent thinking performance of compound Remote Associates Test (CRAT) with fractional anisotropy (FA) in diffusion tensor imaging and regional white matter (WM) volume (rWMV) in voxel-based morphometry in a large sample of healthy young adults (360 males and 280 females; mean age: 20.

Empathizing associates with mean diffusivity.

Empathizing is defined as "the drive to identify another's mental states and to respond to these with an appropriate emotion" and systemizing is defined as "the drive to the drive to analyze and construct rule-based systems". While mean diffusivity (MD) has been robustly associated with several cognitive traits and disorders related with empathizing and systemizing, its direct correlation with empathizing and systemizing remains to be investigated. We undertook voxel-by-voxel investigations of regional MD to discover microstructural correlates of empathizing, systemizing, and the discrepancy between them (D score: systemizing - empathizing).

Possible involvement of the peripheral Mu-opioid system in antinociception induced by bergamot essential oil to allodynia after peripheral nerve injury.

The essential oil of bergamot (BEO) is one of the most common essential oils and is most familiar to the general public. The aims of this study were to investigate the effect of intraplantar (i.pl.

Peripheral gabapentin regulates mosquito allergy-induced itch in mice.

The antipruritic activity of gabapentin, an anticonvulsant, was studied in a mouse model of allergic itch. In mice sensitized by an extract of the salivary glands of the mosquito (ESGM), an intradermal injection of ESGM elicited scratching and increased peripheral nerve firing. Oral or intradermal administration of gabapentin at the ESGM injection site inhibited ESGM-induced scratching and peripheral nerve firing.

Shorter sleep duration and better sleep quality are associated with greater tissue density in the brain.

Poor sleep quality is associated with unfavorable psychological measurements, whereas sleep duration has complex relationships with such measurements. The aim of this study was to identify the associations between microstructural properties of the brain and sleep duration/sleep quality in a young adult. The associations between mean diffusivity (MD), a measure of diffusion tensor imaging (DTI), and sleep duration/sleep quality were investigated in a study cohort of 1201 normal young adults.

Neuropharmacological Properties of the Essential Oil of Bergamot for the Clinical Management of Pain-Related BPSDs.

Background: Alzheimer's Disease (AD) accounts for approximately 50% of all cases of dementia and, in spite of the great effort for the development of disease-modifying drugs, a definitive treatment of cognitive impairment is not available yet. A perfect adherence to the current therapy of cognitive decline is needed for a better control of the disease and this is proven to reduce, though not completely abolish, the associated Behavioural and Psychological Symptoms of Dementia (BPSDs) from occurring. This cluster of symptoms, remarkably affecting patients' health-related quality of life (HRQL), is tightly associated with pain states.

National survey of de novo malignancy after solid organ transplantation in Japan.

Purpose: In Japan, there have been no national surveys on the incidence of de novo malignancy after solid organ transplantation, which is one of the leading causes of death in transplant recipients.

Methods: A questionnaire was distributed to institutions that perform solid organ transplantation in Japan, and clinical information was collected from patients who underwent transplantation between 2001 and 2010 and who exhibited de novo malignancies.

Results: Nine thousand two hundred ten solid organ transplants (kidney, 49.

Refractive error is associated with intracranial volume.

Myopia is part of the spectrum of refractive error. Myopia is associated with psychometric intelligence and, the link between brain anatomy and myopia has been hypothesized. Here we aimed to identify the associations between brain structures and refractive error in developed young adults.

Segmentation of the hippocampus by transferring algorithmic knowledge for large cohort processing.

The hippocampus is a particularly interesting target for neuroscience research studies due to its essential role within the human brain. In large human cohort studies, bilateral hippocampal structures are frequently identified and measured to gain insight into human behaviour or genomic variability in neuropsychiatric disorders of interest. Automatic segmentation is performed using various algorithms, with FreeSurfer being a popular option.

What factors determine the survival of patients with an acute exacerbation of interstitial lung disease after lung cancer resection?

Purposes: Acute exacerbation of interstitial pneumonia (AEIP) is a leading cause of death after lung cancer resection in patients with interstitial lung disease.

Methods: We retrospectively analyzed 1763 patients with non-small cell lung cancer with a clinical diagnosis of interstitial lung disease (ILD) who underwent lung cancer resection between 2000 and 2009 at 61 hospitals in Japan. AEIP occurred in 164 of 1763 (9.

Murine Sialidase Neu3 facilitates GM2 degradation and bypass in mouse model of Tay-Sachs disease.

Tay-Sachs disease is a severe lysosomal storage disorder caused by mutations in Hexa, the gene that encodes for the α subunit of lysosomal β-hexosaminidase A (HEXA), which converts GM2 to GM3 ganglioside. Unexpectedly, Hexa mice have a normal lifespan and show no obvious neurological impairment until at least one year of age. These mice catabolize stored GM2 ganglioside using sialidase(s) to remove sialic acid and form the glycolipid GA2, which is further processed by β-hexosaminidase B.

A randomized controlled trial of eicosapentaenoic acid in patients with coronary heart disease on statins.

Background: There is a residual risk of coronary heart disease (CHD) despite intensive statin therapy for secondary prevention. The aim of this study was to investigate whether coronary plaque regression and stabilization are reinforced by the addition of eicosapentaenoic acid (EPA) to high-dose pitavastatin (PTV).

Methods: We enrolled 193 CHD patients who underwent percutaneous coronary intervention (PCI) in six hospitals.