Rejected

Osteoarthritis (OA) is the most common orthopedic condition in dogs, characterized as the chronic, painful end-point of a synovial joint with limited therapeutic options other than palliative pain control or surgical salvage. Since the 1970s, radiography has been the standard-of-care for the imaging diagnosis of OA, despite its known limitations. As newer technologies have been developed, the limits of detection have lowered, allowing for the identification of earlier stages of OA. Identification of OA at a stage where it is potentially reversible still remains elusive, however, yet there is hope that newer technologies may be able to close this gap. In this article, we review the changes in the imaging of canine OA over the past 50 years and give a speculative view on future innovations which may provide for earlier identification, with the ultimate goal of repositioning the limit of detection to cross the threshold of this potentially reversible disease.

Participation in American-style football (ASF), one of the most popular sports worldwide, has been associated with adverse health outcomes. However, prior clinical studies of former ASF players have been limited by reliance on subjective self-reported data, inadequate sample size, or focus on a single disease process in isolation.

: Intervertebral disc degeneration (IDD), the main cause of low back pain, is closely related to the inflammatory microenvironment in the nucleus pulposus (NP). Tumor necrosis factor-α (TNF-α) plays an important role in inflammation-related metabolic disturbance of NP cells. Melatonin has been proven to regulate the metabolism of NP cells, but whether it can protect NP cells from TNF-α-induced damage is still unclear. Therefore, this study aims to investigate the role and specific mechanism of melatonin on regulating the metabolism of NP cells in the inflammatory microenvironment. Western blotting, RT-qPCR and immunohistochemistry were used to detect the expression of melatonin membrane receptors (MTNR1A/B) and TNF-α in human NP tissues. , human primary NP cells were treated with or without vehicle, TNF-α and melatonin. And the metabolic markers were also detected by western blotting and RT-qPCR. The activity of NF-κB signaling and Hippo/YAP signaling were assessed by western blotting and immunofluorescence. Membrane receptors inhibitors, pathway inhibitors, lentiviral infection, plasmids transfection and immunoprecipitation were used to explore the specific mechanism of melatonin. , the rat IDD model was constructed and melatonin was injected intraperitoneally to evaluate its therapeutical effect on IDD. The upregulation of TNF-α and downregulation of melatonin membrane receptors (MTNR1A/B) were observed in degenerative NP tissues. Then we demonstrated that melatonin could alleviate the development of IDD in a rat model and reverse TNF-α-impaired metabolism of NP cells . Further investigation revealed that the protective effects of melatonin on NP cells mainly rely on MTNR1B, which subsequently activates Gαi2 protein. The activation of Gαi2 could upregulate the yes-associated protein (YAP) level, resulting in anabolic enhancement of NP cells. In addition, melatonin-mediated YAP upregulation increased the expression of IκBα and suppressed the TNF-α-induced activation of the NF-κB pathway, thereby inhibiting the catabolism of NP cells. Our results revealed that melatonin can reverse TNF-α-impaired metabolism of NP cells via the MTNR1B/Gαi2/YAP axis and suggested that melatonin can be used as a potential therapeutic drug in the treatment of IDD.

We describe a case of a 52 year-old woman who was hospitalized with rhombencephalitis caused by sensu lato. The patient presented with intermittent fever, dry cough, fatigue, global headache, night sweats, unintentional weight loss, and neurological symptoms like diplopia, tremor, paresthesia and ataxia. Examination of serum and cerebrospinal fluid (CSF) revealed positive -specific antibody index and presence of CSF oligoclonal IgG bands, indicating intrathecal synthesis of specific antibodies. The clinical and biochemical picture thus suggested neuroborreliosis. Unexpectedly a magnetic resonance imaging (MRI) scan demonstrated inflammation in rhombencephalon that are extremely rare in patients with neuroborreliosis. The patient was treated with intravenous ceftriaxone with rapid improvement of her symptoms. The MRI findings were in regress six weeks after onset of antibiotic treatment, and normalized after about seven months.

Renal fibrosis is the pathological repair reaction of the kidney to chronic injury, which is an important process of chronic kidney disease (CKD) progressing to end-stage renal failure. Nephrolithiasis is one of the most common renal diseases, with waist and abdomen pain, hematuria, urinary tract infection, and other clinical symptoms, which can increase the risk of renal fibrosis. Oxalate crystal-induced kidney injury is an early stage of nephrolithiasis; it is of great significance to explore the mechanism for the prevention and treatment of nephrolithiasis. A rodent model of calcium oxalate (CaOx) crystal-induced kidney injury was used in the present study, and a network analysis method combining proteomics and metabolomics was conducted to reveal the mechanism of crystal kidney injury and to provide potential targets for the intervention of nephrolithiasis. Using the metabolomics method based on the UHPLC-Q/TOF-MS platform and the iTRAQ quantitative proteomics method, we screened a total of 244 metabolites and 886 proteins from the kidney tissues that had significant changes in the Crystal group compared with that in the Control group. Then, the ingenuity pathway analysis (IPA) was applied to construct a protein-to-metabolic regulatory network by correlating and integrating differential metabolites and proteins. The results showed that CaOx crystals could induce inflammatory reactions and oxidative stress through Akt, ERK1/2, and P38 MAPK pathways and affect amino acid metabolism and fatty acid β-oxidation to result in kidney injury, thus providing an important direction for the early prevention and treatment of nephrolithiasis.

Tumor necrosis factor antagonists (anti-TNF-) are an established therapeutic option for several autoimmune and inflammatory bowel diseases. Despite their clinical effectiveness, neurological adverse events have been reported, and literature data suggest a potential role of anti-TNF- in the induction of demyelination. . In this series, we present three cases of demyelination after the use of anti-TNF- agents. The first case involved a 21-year-old man with HLA-B27 negative peripheral spondylarthritis who had been taking adalimumab for 2 years. He developed headache, urinary incontinence, and bilateral lower extremity numbness that progressed to the middle of the trunk for 2 days. Magnetic resonance imaging (MRI) showed multiple hyperintense enhancement lesions in the left paramedian anterior pons consistent with multiple sclerosis (MS). The second case included a 17-year-old woman who was on 2 years of adalimumab treatment for juvenile idiopathic arthritis and chronic anterior uveitis and developed new-onset dizziness and tremors. The clinical examination showed signs of cerebellar dysfunction. MRI findings were consistent with multiple sclerosis. The third case was a 34-year-old male who was on 5 years of infliximab treatment for ankylosing spondylitis when he developed left hand numbness and weakness. Cerebrospinal fluid (CSF) analysis and MRI findings were consistent with demyelination. Discontinuation of tumor necrosis factor antagonists (anti-TNF-) resulted in resolution of the symptoms with no recurrence in the first case, but there was evidence of recurrence in the other 2 cases, where one was managed with rituximab and the second one improved with pulse steroid therapy.

Whereas, many debilitating chronic pain disorders are dominantly bilateral (e.g., fibromyalgia, chronic migraine), non-invasive and invasive cortical neuromodulation therapies predominantly apply unilateral stimulation. The development of excitatory stimulation targeting bilateral primary motor (M1) cortices could potentially expand its therapeutic effect to more global pain relief. However, this is hampered by increased procedural and technical complexity. For example, repetitive transcranial magnetic stimulation (rTMS) and 4 × 1/2 × 2 high-definition transcranial direct current stimulation (4 × 1/2 × 2 HD-tDCS) are largely center-based, with unilateral-target focus-bilateral excitation would require two rTMS/4 × 1 HD-tDCS systems. We developed a system that allows for focal, non-invasive, self-applied, and simultaneous bilateral excitatory M1 stimulation, supporting long-term home-based treatment with a well-tolerated wearable battery-powered device. Here, we overviewed the most employed M1 neuromodulation methods, from invasive techniques to non-invasive TMS and tDCS. The evaluation extended from non-invasive diffuse asymmetric bilateral (M1-supraorbital [SO] tDCS), non-invasive and invasive unilateral focal (4 × 1/2 × 2 HD-tDCS, rTMS, MCS), to non-invasive and invasive bilateral bipolar (M1-M1 tDCS, MCS), before outlining our proposal for a neuromodulatory system with unique features. Computational models were applied to compare brain current flow for current laboratory-based unilateral M1 and bilateral M1 HD-tDCS models with a functional home-based M1 HD-tDCS prototype. We concluded the study by discussing the promising concept of bilateral excitatory M1 stimulation for more global pain relief, which is also non-invasive, focal, and home-based.

Performing a careful but effective mobilisation of the hemiplegic shoulder is essential for optimal muscle activation and to preserve the passive range of motion (PROM) needed to perform functional tasks. Studies concerning passive mobilisation of the post-stroke shoulder are scarce.

A 41-year-old gravida 4 para 3 (G4P3) and 38 weeks pregnant woman presented to labor and delivery with dizziness, headache, and decreased fetal movement after 12 hours of exposure to carbon monoxide (CO) from a grill that was used inside for heat. The mother was hemodynamically stable, and her neurologic examination was intact. Her carboxyhemoglobin level, which was obtained 12 hours after removal from the CO exposure, was 7.4%. The fetus's heart rate was 173 beats per minute with moderate variability and one late appearing deceleration, not associated with contractions. The biophysical profile score was 2 of 8. The obstetrics team performed a routine cesarean section. The 1- and 5-minute Apgar's scores were 7 and 8, respectively. The arterial cord gas result was as follows: pH = 7.05, PCO  = 71 mm Hg, pO  = 19 mm Hg, bicarbonate = 14 mmol/L, and carboxyhemoglobin = 11.9%. The mother and infant were treated with hyperbaric oxygen therapy consisting of 100% oxygen at 2.4 atmosphere absolutes (ATA) for 90 minutes at 2.5 hours after delivery. Following one hyperbaric oxygen treatment, the infant was transitioned to room air and routine postpartum treatment and was discharged 3 days later in good condition. Hyperbaric oxygen treatment was well tolerated in this neonate.

Scrub typhus, an acute febrile infectious disease prevalent in the "Tsutsugamushi Triangle", is a mite-born rickettsial zoonosis, caused by . Although the clinical presentation is protean, it rarely causes abducens nerve palsy. We report a 14-year-old previously healthy Indian girl who presented with a recent onset right abducens nerve palsy and headache, but without fever and without the classic dermatological manifestation ("eschar") of the disease. After exclusion of common infectious, autoimmune, and neoplastic causes, she was finally diagnosed with scrub typhus associated with an abducens nerve palsy, which responded to doxycycline therapy.