OBJECTIVES: To evaluate fatigue, identify factors associated with fatigue and assess the effect of fatigue on health-related quality of life (HRQoL) in a multi-ethnic cohort of RA patients.
METHODS: A cross-sectional study was performed in patients who fulfilled European League Against Rheumatism/ American College of Rheumatology 2010 criteria for RA. Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) questionnaire was used to assess fatigue. Potential factors for fatigue were categorized into RA-related (gender, seropositivity [rheumatoid factor and/or anti-citrullinated protein antibody], disease duration, visual analog scale pain score, Disease Activity Score of 28 joints - erythrocyte sedimentation rate [DAS28-ESR], ESR, hemoglobin level, functional disability [Health Assessment Questionnaire - Disability Index, HAQ-DI score], EQ-5D-3L, concomitant prednisolone use and number of conventional synthetic disease-modifying anti-rheumatic drugs [csDMARDs] used) and non-RA-related (age, body mass index, ethnicity and number of co-morbidities).
RESULTS: A total of 214 patients (86.9% female) were included; the median age was 62 (25-91) years and 67.3% were seropositive. Seventy-six (33.5%) patients had moderate disease activity, 12 (5.6%) had high disease activity and 152 (71%) patients had mild difficulties to moderate disability HAQ-DI scores. Median of total FACIT-F score was 113.2 (36.3-160.0). Joint factors of younger age, longer disease duration, higher HAQ score (increased functional disability), and lower EQ-5D (poorer HRQoL) were significantly associated with higher levels of fatigue (all P
METHODS: Slitrk1-KD mice were induced by bilaterally injecting Slitrk1 siRNA into their dorsal striatum. Control mice received scrambled siRNA injection. Their TS-like tic behaviors, prepulse inhibition, sensory-motor function and dopamine-related behaviors were compared. We also compared dopamine and ACh levels in microdialysates, Slitrk protein and dopamine transporter levels, and numbers of Slitrk-positive ChIs and activated ChIs in the striatum between two mouse groups, and electrophysiological properties between Slitrk-positive and Slitrk-negative striatal ChIs.
RESULTS: Slitrk1-KD mice exhibit TS-like haloperidol-sensitive stereotypic tic behaviors, impaired prepulse inhibition, and delayed sensorimotor response compared with the control group. These TS-like characteristics correlate with lower striatal Slitrk1 protein levels, fewer Slitrk1-containing ChIs, and fewer activated ChIs in Slitrk1-KD mice. Based on their electrophysiological properties, Slitrk1-negative ChIs are less excitable than Slitrk1-positive ChIs. Slitrk1-KD mice have lower evoked acetylcholine and dopamine levels, higher tonic dopamine levels, and downregulated dopamine transporters in the striatum, increased apomorphine-induced climbing behaviors, and impaired methamphetamine-induced hyperlocomotion compared with controls.
INTERPRETATION: Slitrk1 is pivotal in maintaining striatal ChIs activity and subsequent dopaminergic transmission for normal motor functioning. Furthermore, conditional striatal Slitrk1-KD mice may serve as a translational modality with aspects of TS phenomenology. ANN NEUROL 2023.
METHODS: Male C57BL/6 mice of 8-12 week-old were subjected to intra-cerebroventricular (i.c.v.) and/or intra-vlPAG (i.pag.) microinjection of NPS, orexin-A or substance P alone or in combination with selective antagonists of NPS receptors (NPSRs), OX1 receptors (OX1Rs), NK1 receptors (NK1Rs), mGlu5 receptors (mGlu5Rs) and CB1 receptors (CB1Rs), respectively. Antinociceptive effects of these mediators were evaluated via the hot-plate test. SIA in mice was induced by a 30-min restraint stress. NPS levels in the LH and substance P levels in vlPAG homogenates were compared in restrained and unrestrained mice.
RESULTS: NPS (i.c.v., but not i.pag.) induced antinociception. This effect was prevented by i.c.v. blockade of NPSRs. Substance P (i.pag.) and orexin-A (i.pag.) also induced antinociception. Substance P (i.pag.)-induced antinociception was prevented by i.pag. Blockade of NK1Rs, mGlu5Rs or CB1Rs. Orexin-A (i.pag.)-induced antinociception has been shown previously to be prevented by i.pag. blockade of OX1Rs or CB1Rs, and here was prevented by NK1R or mGlu5R antagonist (i.pag.). NPS (i.c.v.)-induced antinociception was prevented by i.pag. blockade of OX1Rs, NK1Rs, mGlu5Rs or CB1Rs. SIA has been previously shown to be prevented by i.pag. blockade of OX1Rs or CB1Rs. Here, we found that SIA was also prevented by i.c.v. blockade of NPSRs or i.pag. blockade of NK1Rs or mGlu5Rs. Restrained mice had higher levels of NPS in the LH and substance P in the vlPAG than unrestrained mice.
CONCLUSIONS: These results suggest that, during stress, NPS is released and activates LH orexin neurons via NPSRs, releasing orexins in the vlPAG. Orexins then activate OX1Rs on substance P-containing neurons in the vlPAG to release substance P that subsequently. Activates NK1Rs on glutamatergic neurons to release glutamate. Glutamate then activates perisynaptic mGlu5Rs to initiate the endocannabinoid retrograde inhibition of GABAergic transmission in the vlPAG, leading to analgesia.
MATERIALS AND METHODS: Tristar Trubalance aligner sheets were used to fabricate the CAs. Thirty-four resin models were 3D printed and 17 each, were bonded with ellipsoidal or rectangular attachments on maxillary right central incisors. Fuji Prescale pressure film was used to measure the force generated by the attachment of CA. The images of colour density produced on the films were processed using a calibrated pressure mapping system utilising image processing techniques and topographical force mapping to quantify the force. The force measurement process was repeated after the flash was removed from the attachment using tungsten-carbide bur on a slow-speed handpiece.
RESULTS: The intraclass correlation coefficient showed excellent reliability (ICC = 0.96, 95% CI = 0.92-0.98). The average mean force exerted by ellipsoidal attachments with flash was 8.05 ± 0.16 N, while 8.11 ± 0.18 N was without flash. As for rectangular attachments, the average mean force with flash was 8.48 ± 0.27 N, while 8.53 ± 0.13 N was without flash. Paired t-test revealed no statistically significant difference in the mean force exerted by CA in the presence or absence of flash for both ellipsoidal (p = 0.07) and rectangular attachments (p = 0.41). Rectangular attachments generated statistically significantly (p 0.05).