Shotgun metagenomic analysis of saliva microbiome suggests Mogibacterium as a factor associated with chronic bacterial osteomyelitis.

Osteomyelitis of the jaw is a severe inflammatory disorder that affects bones, and it is categorized into two main types: chronic bacterial and nonbacterial osteomyelitis. Although previous studies have investigated the association between these diseases and the oral microbiome, the specific taxa associated with each disease remain unknown. In this study, we conducted shotgun metagenome sequencing (≥10 Gb from ≥66,395,670 reads per sample) of bulk DNA extracted from saliva obtained from patients with chronic bacterial osteomyelitis (N = 5) and chronic nonbacterial osteomyelitis (N = 10). We then compared the taxonomic composition of the metagenome in terms of both taxonomic and sequence abundances with that of healthy controls (N = 5). Taxonomic profiling revealed a statistically significant increase in both the taxonomic and sequence abundance of Mogibacterium in cases of chronic bacterial osteomyelitis; however, such enrichment was not observed in chronic nonbacterial osteomyelitis. We also compared a previously reported core saliva microbiome (59 genera) with our data and found that out of the 74 genera detected in this study, 47 (including Mogibacterium) were not included in the previous meta-analysis. Additionally, we analyzed a core-genome tree of Mogibacterium from chronic bacterial osteomyelitis and healthy control samples along with a reference complete genome and found that Mogibacterium from both groups was indistinguishable at the core-genome and pan-genome levels. Although limited by the small sample size, our study provides novel evidence of a significant increase in Mogibacterium abundance in the chronic bacterial osteomyelitis group. Moreover, our study presents a comparative analysis of the taxonomic and sequence abundances of all genera detected using deep salivary shotgun metagenome data. The distinct enrichment of Mogibacterium suggests its potential as a marker to distinguish between patients with chronic nonbacterial osteomyelitis and chronic bacterial osteomyelitis, particularly at the early stages when differences are unclear.

Golfers' Performance Is Improved More by Combining Foam Rolling and Dynamic Stretch to the Lead Hip Than Practice Golf Swinging.

ABSTRACT: Hamada, Y, Akasaka, K, Otsudo, T, Sawada, Y, Hattori, H, Kikuchi, Y, and Hall, T. Golfers' performance is improved more by combining foam rolling and dynamic stretch to the lead hip than practice golf swinging. J Strength Cond Res XX(X): 000-000, 2024-Warming up is considered effective in improving performance and preventing injury. Despite this, there have been few studies investigating warm-up programs in golf and whether specific factors contribute to improved performance. The purpose of this study was to examine the immediate effects of combined foam rolling and dynamic stretch (FR + DS) to the lead hip on golf swing performance, hip range of motion (ROM), and muscle strength in amateur golfers using a randomized crossover design. The study sample comprised 22 men (mean ± SD; age, 32.6 ± 8.5 years, body mass index (BMI), 23.4 ± 2.7 kg·m-2). Subjects were assigned to receive either FR + DS or repetitive golf swing practice (SW) before crossing over to the other intervention for another day. Measurements included golf swing performance (ball speed, club head speed, flight distance ["carry"], spin rate, and launch angle), hip internal rotation (IR), and external rotation (ER) ROM, as well as hip IR and ER muscle strength. Comparisons between groups were made before and after each intervention. For golf swing performance, FR + DS improved "carry" significantly more than SW (p < 0.05). No significant differences in golf swing performance other than "carry" were found. In addition, IR ROM and IR muscle strength of the lead hip were significantly increased in the FR + DS group (p < 0.05). FR + DS has effects on improving lead hip IR ROM and IR muscle strength, which may facilitate golfers' swing and "carry." FR + DS shows promise as a warm-up method for amateur golfers who want to improve golf performance.

Discovery of Novel NLRP3 Inflammasome Inhibitors Composed of an Oxazole Scaffold Bearing an Acylsulfamide.

The NLRP3 inflammasome plays an important role in the defense mechanism of the innate immune system and has recently attracted much attention as a drug target for various inflammatory disorders. Among the strategies for generating the novel chemotype in current drug discovery, scaffold hopping and bioisosteric replacement are known to be attractive approaches. As the results of our medicinal chemistry campaign, which involved exploration of core motifs using a ring closing approach, a five-membered oxazole-based scaffold was identified, and subsequent implementation of bioisosteric replacement led to discovery of a novel chemical class of NLRP3 inflammasome inhibitor bearing the acylsulfamide group. Further optimization of aniline and sulfamide moieties to improve potency in human whole blood assay led to the identification of the orally bioactive compound 32 in the LPS challenge model. Furthermore, compound 32 attenuated kidney injury in adriamycin-induced glomerulonephritis in mice. These investigations indicated that the NLRP3 inhibitor could be a potential therapeutic agent for glomerulonephritis.

Immediate Effects of Foam Roller and Stretching to the Lead Hip on Golfers Swing: A Randomized Crossover Trial.

Golfers with decreased range of motion (ROM) of their leading hip internal rotation (IR) have increased lumbar rotation ROM and load. This study investigated the effects of foam roller (FR) applied to their leading hip muscles combined with stretching to the leading hip together with lumbar rotation ROM during the golf swing. The study design was a crossover design. Subjects were allocated to one of two groups comprising FR and dynamic stretching (FR + DS) or practice swing. Motion analysis was used to evaluate hip and lumbar angles during the golf swing. Data were compared using analysis of variance with Bonferroni correction using paired t-test's post hoc. The association between lead hip IR angle and lumbar spine left rotation (Lrot) angle was investigated using correlation analysis. Lead hip IR ROM during the golf swing was significantly greater in the FR + DS group (p = 0.034). The FR + DS group showed a moderate negative correlation between lead hip IR ROM and lower lumbar spine Lrot ROM during the golf swing (r = -0.522). The application of FR + DS might be useful to increase lead hip IR angle during the golf swing. Moreover, the application of FR + DS improves lead hip IR angle and may decrease lumbar spine rotation.

Relationship between Isokinetic Trunk Muscle Strength and Return to Sports Competition after Conservative Therapy in Fresh Cases of Lumbar Spondylolysis: A Retrospective Observational Study.

This study aimed to clarify the relationship between isokinetic trunk muscle strength and return to sporting activities in fresh cases of lumbar spondylolysis treated with conservative therapy. Patients included a total of ten men (age: 13.5 ± 1.7) who were instructed by their attending physicians to stop exercising and who met the eligibility criteria. Isokinetic trunk muscle strength was measured immediately after exercising for the first time (First) and one month (1M). Flexion and extension and maximum torque/body weight ratio were significantly lower First compared to 1M at all angular velocities (p < 0.05). Maximum torque generation time was significantly lower for First at 120°/s and 180°/s than at 1M (p < 0.05). Correlations with the number of days to return to sports competition were detected at 60°/s for maximum torque generation time (p < 0.05, r = 0.65). Following conservative treatment for lumbar spondylolysis, it was considered necessary to focus on trunk flexion and extension muscle strength and contraction speed of trunk flexors at the beginning of the exercise period. It was suggested that trunk extension muscle strength in the extension range might be one of the critical factors for returning to sports.

Whole blood transcriptome profiling identifies gene expression subnetworks and a key gene characteristic of the rare type of osteomyelitis.

Chronic non-bacterial osteomyelitis (CNO) is a rare and severe inflammatory bone disorder that can occur in the jaw. It is often associated with systemic conditions including autoimmune deficiency. Medical management of patients and establishment of a correct diagnosis are difficult as the etiology of the disease remains unknown. Therefore, little is known about the disease characteristics at the gene expression level. Here, we explored aspects of CNO based on whole blood RNA sequencing (>6 Gb per sample) of 11 patients and 9 healthy controls in Japan and on a recently developed method that is applicable to small datasets, can estimate a directed gene network, and extract a subnetwork of genes underlying patient characteristics. We identified nine subnetworks, comprising 26 differentially regulated edges and 36 genes, with the gene encoding glycophorin C (GYPC) presenting the highest discrimination ability. The expression of the gene was mostly lower in patients with CNO than in the healthy controls, suggesting an abnormal status of red cells in patients with CNO. This study enhances our understanding of CNO at the transcriptome level and further provides a framework for whole blood RNA sequencing and analysis of data obtained for a better diagnosis of the disease.

A Case of Brain Abscess Caused by Actinomyces Cardiffensis and Parvimonas Micra.

Brain abscesses occur in 0.3-1.3 per 100,000 worldwide each year with 0.4-0.9 in Japan alone. Most of the causes are direct infection from a nearby infectious lesion and are rarely caused by an odontogenic infection. Here, we reported a case of brain abscess suspected to be associated with odontogenic infection. The patient was a 55-year-old woman. Blurred eyes and pain in the left eye noted, for which she consulted an ophthalmologist, but her eyes were normal. She was conscious and was able to converse clearly, but she could not read the letters and had difficulty in writing at the time of admission. A brain abscess was diagnosed based on the head magnetic resonance imaging (MRI) and clinical course, and a small craniotomy abscess drainage was performed. A. cardiffensis and P. micra were detected in the abscess, suggesting the involvement of periodontal disease bacteria. After the surgery, antimicrobial treatment was performed for about 2 months. At the same time, perioperative treatment was performed. On the 70th day after the surgery, tooth extraction, which was considered as the source of infection, was performed. The patient was discharged 74 days after surgery. A good turning point was obtained without relapse of symptoms.

Pyogenic Spondylitis with Rapid Bone Destruction After Chemoradiotherapy for Tongue Cancer: A Case Report and Literature Review.

Radiation therapy is a frequently used effective treatment for head and neck cancer. It has several adverse effects of which osteomyelitis is a late complication of radiotherapy. Although uncommon, when it occurs in the vertebral body, it results in pyogenic spondylitis, which can be fatal. We report a case of pyogenic spondylitis, observed 2 years and 5 months after chemoradiotherapy following surgery for the treatment of tongue cancer. The initial symptoms were fever and posterior cervical pain. Initial CT images showed no abnormality in the cervical spine. However, when CT and MRI were followed over time, bone destruction and abscess formation were observed at the C3 and C4 vertebral endplates. Hence, CT-guided puncture d rainage was performed from the anterior neck. The collected pus was d iagnosed as Class II pyogenic spondylitis by cytology and the culture test revealed the presence of Streptococcus agalactiae. The infection was successfully treated by drainage and antibacterial chemotherapy.

A Case of Long-standing Temporomandibular Joint Dislocation: Restoration of Oral Function Following Condylectomy.

BACKGROUND: Temporomandibular joint (TMJ) dislocation can be categorized into three groups: acute, habitual or recurrent, and long-standing. Long-standing TMJ dislocation refers to a condition that persists for more than one month without reduction. Long-standing dislocation of the TMJ is rare and the most challenging and difficult to treat of the three. CASE REPORT: The present case study relates to a 53-year-old woman with long-standing TMJ dislocation of a year's duration who presented for treatment. Due to this condition, she was unable to take food orally, and nutrition was managed by gastrostomy tube feeding. She also suffered from schizophrenia and had been admitted to a closed hospital. Bilateral mandibular condylectomy was performed, restoring oral function. However, post-reduction, an open bite remained, restricting the types of food that she could eat. Additional intermaxillary fixation and intermaxillary traction would have been required for an optimal outcome, but they were not possible for this patient. CONCLUSION: Despite an inability to provide comprehensive treatment, due to patient-related factors, occlusal and masticatory functions were restored to adequate levels following bilateral condylectomy alone. This enabled oral feeding and improved her quality of life.

Fatal Bleeding in Conjunction with Mandibular Medication-related Osteonecrosis of the Jaw (MRONJ).

Here, we report a case of fatal bleeding in conjunction with mandibular medicationrelated osteonecrosis of the jaw (MRONJ). A 75-year-old Japanese man was referred to our department with osteonecrosis of the jaw due to bisphosphonate (BP) for multiple bone metastases from prostate cancer. Aggressive surgical intervention was ruled out due to a poor prognosis in terms of life expectancy. Death occurred due to hemorrhagic shock resulting from massive oral bleeding caused by necrosis of the mandible. Numerous reports have suggested that jaw necrosis is induced not only by BP, but also RANKL antibody, steroids, and molecularly-targeted agents. This suggests that the number of cases of MRONJ is likely to increase among elderly patients in whom general health is already poor. The American Association of Oral and Maxillofacial Surgery recommends aggressive treatment only in cases of stage 3 disease. Therefore, such a therapeutic strategy may only be available for cases of jaw necrosis in which the general health status of the patient is otherwise good. To prevent a life-threatening outcome in cases of MRONJ, physicians, who are responsible for determining the drug strategy, should cooperate with oral surgeons in determining the best therapeutic strategy.

Orally administered selective TRPV1 antagonist, JTS-653, attenuates chronic pain refractory to non-steroidal anti-inflammatory drugs in rats and mice including post-herpetic pain.

Chronic pain refractory to non-steroidal anti-inflammatory drugs (NSAIDs) is a major problem and drugs for such pain are needed. Many studies suggest that transient receptor potential vanilloid type 1 (TRPV1) is associated with NSAID-refractory chronic pain. Therefore, we investigated the involvement of TRPV1 in NSAID-refractory chronic pain using experimental models for NSAID-refractory chronic pain reflecting severe arthritic and postherpetic pain. The selective TRPV1 antagonist JTS-653 {(3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide} reversed mechanical hyperalgesia on day 7 after injection of complete-Freund-adjuvant into the hindpaw in rats at 0.3 mg/kg, whereas indomethacin showed no effect. JTS-653 reduced chronic pain at 0.3 mg/kg in herpes simplex virus-1-inoculated mice that has been reported as NSAID-refractory pain. JTS-653 partially attenuated mechanical hyperalgesia in the L5 spinal nerve ligation model in rats at 0.3 mg/kg, whereas indomethacin showed no effect. Both JTS-653 and indomethacin reduced formalin-induced pain in the second phase, whereas they showed no effect in the first phase. JTS-653 did not affect the nociception of noxious thermal and mechanical stimuli and motor coordination in normal rats. These findings demonstrate the TRPV1 involvement in NSAID-refractory chronic pain reflecting severe arthritic and postherpetic pain. TRPV1 antagonists would be useful for the treatment of NSAID-refractory chronic pain.

Pharmacological characterization of (3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (JTS-653), a novel transient receptor potential vanilloid 1 antagonist.

Transient receptor potential vanilloid 1 (TRPV1) activation in peripheral sensory nerve is known to be associated with various pain-related diseases, thus TRPV1 has been the focus as a target for drug discovery. In this study, we characterized the pharmacological profiles of (3S)-3-(hydroxymethyl)-4-(5-methylpyridin-2-yl)-N-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-3,4-dihydro-2H-benzo[b][1,4]oxazine-8-carboxamide (JTS-653), a novel TRPV1 antagonist. JTS-653 displaced [(3)H]resiniferatoxin binding to human and rat TRPV1. JTS-653 competitively antagonized the capsaicin-induced activation of human TRPV1 with pA(2) values of 10.1. JTS-653 also inhibited proton-induced activation of human and rat TRPV1 with IC(50) values of 0.320 and 0.347 nM, respectively. Electrophysiological studies indicated that JTS-653 blocked heat-induced inward currents in rat TRPV1 with IC(50) values of 1.4 nM. JTS-653 showed weak or no inhibitory effects on other TRP channels, receptors, and enzymes. JTS-653 significantly prevented capsaicin-induced mechanical hyperalgesia at 1 mg/kg p.o. and attenuated carrageenan-induced mechanical hyperalgesia at 0.3 mg/kg p.o. JTS-653 significantly attenuated carrageenan-induced thermal hyperalgesia at 0.1 mg/kg p.o. and fully reversed at 0.3 mg/kg p.o. without affecting the volume of the carrageenan-treated paw. JTS-653 showed a transient increase of body temperature at 0.3 mg/kg p.o. These results indicated that JTS-653 is a highly potent and selective TRPV1 antagonist in vitro and in vivo and suggested that JTS-653 is one of the most potent TRPV1 antagonists. The profiles of JTS-653, high potency in vivo and transient hyperthermia, seem to be associated with polymodal inhibition of TRPV1 activation.