Seasonal changes in NRF2 antioxidant pathway regulates winter depression-like behavior.

Seasonal changes in the environment lead to depression-like behaviors in humans and animals. The underlying mechanisms, however, are unknown. We observed decreased sociability and increased anxiety-like behavior in medaka fish exposed to winter-like conditions. Whole brain metabolomic analysis revealed seasonal changes in 68 metabolites, including neurotransmitters and antioxidants associated with depression. Transcriptome analysis identified 3,306 differentially expressed transcripts, including inflammatory markers, melanopsins, and circadian clock genes. Further analyses revealed seasonal changes in multiple signaling pathways implicated in depression, including the nuclear factor erythroid-derived 2-like 2 (NRF2) antioxidant pathway. A broad-spectrum chemical screen revealed that celastrol (a traditional Chinese medicine) uniquely reversed winter behavior. NRF2 is a celastrol target expressed in the habenula (HB), known to play a critical role in the pathophysiology of depression. Another NRF2 chemical activator phenocopied these effects, and an NRF2 mutant showed decreased sociability. Our study provides important insights into winter depression and offers potential therapeutic targets involving NRF2.

Revisited relationships between probable sleep bruxism and clinical muscle symptoms.

OBJECTIVES: Sleep bruxism (SB), characterized by repetitive jaw-muscle activity during sleep, is often suggested as a cause of temporomandibular disorders (TMD), orofacial pain, and headache. This study aimed to challenge the relationship between jaw-muscle electromyographic (EMG) activity during sleep and jaw muscle symptoms including pain by modulation of the levels of EMG activity. Contingent electrical stimulation (CES) using a portable single-channel EMG device was applied at different stimulus intensities to inhibit jaw muscle activity. MATERIALS AND METHODS: Sixty probable sleep-bruxers, screened and confirmed by a 2-week use of a portable EMG device, were randomly allocated into one of 3 groups (High/Low/Placebo CES). At baseline and after 2 weeks CES intervention, the participants were asked to score pain intensity, as well as unpleasantness, fatigue, tension, soreness and stiffness in their jaw muscles, on 0-10 numerical rating scales (NRS). RESULTS: Only in the High CES group, the number of EMG events/hour was significantly decreased (P = 0.024). Although the NRS scores of pain did not change, interestingly the NRS scores of unpleasantness (P = 0.037), tension (P < 0.001) and soreness (P = 0.004) in the High CES group and tiredness (P = 0.002) and soreness (P = 0.006) in the Low CES group were significantly decreased after the CES intervention compared to baseline. CONCLUSION: High intensity CES demonstrated inhibitory effect on masticatory muscle EMG activity during sleep and was associated with significant decreases in jaw muscle symptoms (unpleasantness/tiredness/soreness) but not pain responses. These findings challenge the traditional concept that probable sleep bruxism is directly related to pain but appears related to more unspecific muscle symptoms.

Effects of exercise therapy on painful temporomandibular disorders.

Temporomandibular disorders (TMD) are common chronic musculoskeletal pain conditions among orofacial pain. Painful TMD condition such as myalgia and arthralgia can be managed by exercise therapy. However, as it is hard to access actual effect of each modality that is included in an exercise therapy programme due to multiple choice of the management modality, their efficacy remains controversial. Therefore, this review focused on the effects of exercise therapy for the management of painful TMD. The aims of this review were to summarise the effects of exercise therapy for major symptoms of painful TMD and to establish a guideline for the management of painful TMD, resulting in higher quality and reliability of dental treatment. In this review, exercise modalities are clearly defined as follows: mobilisation exercise, muscle strengthening exercise (resistance training), coordination exercise and postural exercise. Furthermore, pain intensity and range of movements were focused as outcome parameters in this review. Mobilisation exercise including manual therapy, passive jaw mobilisation with oral appliances and voluntary jaw exercise appeared to be a promising option for painful TMD conditions such as myalgia and arthralgia. This review addressed not only the effects of exercise therapy on various clinical conditions of painful TMD shown in the past, but also an urgent need for consensus among dentists and clinicians in terms of the management of each condition, as well as terminology.

[Comparison of ciprofloxacin with biapenem in patients with moderate or severe pneumonia].

We conducted the comparative study to clarify the clinical efficacy and features of ciprofloxacin (CPFX) and biapenem (BIPM) in the treatment of moderate or severe pneumonia. Among 209 patients enrolled, 173 patients (CPFX; 87, BIPM; 86) complying with the protocol were evaluated for safety and 171 (CPFX; 85, BIPM; 86) for efficacy. No significant difference was noted between groups in patient profiles. Both groups were similar in efficacy, as evaluated by the following variables: fever, WBC, CRP, and chest X ray score. The incidence of adverse drug reactions was 16.1% (14/87 patients) in the CPFX group and 16.3% (14/86 patients) in the BIPM group. Phlebitis occasionally occurred in the CPFX group and drug eruption and liver function disorder occasionally in the BIPM group. In conclusion, both CPFX and BIPM were useful in treating moderate or severe pneumonia and no difference was seen between groups in efficacy. Some differences were noted in adverse reactions, however.