Rejected

Emerging evidence suggests that access to chiropractic care may reduce the likelihood of initiating an opioid prescription for spinal pain; however, the impact of chiropractic care for patients already prescribed opioids is uncertain. We undertook a sequential explanatory mixed methods study to evaluate the association between initiating chiropractic care and continued opioid use among adult patients attending an Ontario community health centre (CHC) and receiving opioid therapy for chronic non-cancer spinal pain.

Topiramate (TOP) is a psychotropic drug prescribed for the treatment of epilepsy in children older than 2 years of age and for migraine prophylaxis in adolescents. There is evidence that TOP promotes negative effects on the reproductive system of male rats. This study aimed to evaluate the immediate and late treatment effects of TOP during childhood and adolescence on the male rat reproductive system. Two experimental groups received 41 mg/kg of TOP daily, by gavage, from postnatal day (PND) 16 to 28 (TOPc group) or from PND 28 to 50 (TOPa group). Control groups (CTRc group or CTRa group) received water daily. Half of the anim-als were evaluated 24 h after the end of treatment (PND 29 and PND 51, respectively) and the remainder were evaluated in adulthood (PND120). The following parameters were determined: anogenital distance, sperm evaluation, testis' histomorphometry and plasma testosterone concentration. At PND 120, the volume (CTRc:62.58 ± 2.13; TOPc: 54.54 ± 2.10*%, = 0.018) and total length (CTRc: 25.48 ± 1.61; TOPc: 18.94 ± 2.41*, = 0.035) of seminiferous tubules were decreased and the volume of interstitial tissue (CTRc:37.41 ± 2.13; TOPc: 45.45 ± 2.09*%, = 0.018) and number of Leydig cells/testis (CTRc: 277.00 ± 36.70; TOPc: 400.20 ± 13.23*, = 0.013) were increased in the TOPc group. The other parameters remained similar between the groups. Therefore, the present study contributes to our understanding that childhood treatment with TOP has an impact on the rat reproductive system in adulthood, suggesting that this period is more sensitive to TOP exposure than adolescence.

To evaluate the relationship between measures of neuromuscular impairment and limb accelerations (LA) collected during sleep among individuals with chronic spinal cord injury (SCI) to provide evidence of construct and concurrent validity for LA as a clinically meaningful measure.

In the United States, approximately 18-25 percent of carotid duplex ultrasound (CUS) studies are ordered to assess patients with non-lateralizing neurological complaints such as syncope, blurry vision, lightheadedness, headache, and altered mental status. The purpose of this study is to evaluate the benefit of CUS in the evaluation of patients presenting with non-lateralizing signs or symptoms.

Spreading depolarization (SD) occurs in a plethora of clinical conditions including migraine aura, delayed ischemia after subarachnoid hemorrhage and malignant hemispheric stroke. It describes waves of near-breakdown of ion homeostasis, particularly Na homeostasis in brain gray matter. SD induces tone alterations in resistance vessels, causing either hyperperfusion in healthy tissue; or hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk. Observations from mice with genetic dysfunction of the ATP1A2-encoded α-isoform of Na/K-ATPase (αNaKA) suggest a mechanistic link between (1) SD, (2) vascular dysfunction, and (3) salt-sensitive hypertension via αNaKA. Thus, αNaKA-dysfunctional mice are more susceptible to SD and show a shift toward more inverse hemodynamic responses. αNaKA-dysfunctional patients suffer from familial hemiplegic migraine type 2, a Mendelian model disease of SD. αNaKA-dysfunctional mice are also a genetic model of salt-sensitive hypertension. To determine whether SD thresholds and hemodynamic responses are also altered in other genetic models of salt-sensitive hypertension, we examined these variables in stroke-prone spontaneously hypertensive rats (SHRsp). Compared with Wistar Kyoto control rats, we found in SHRsp that electrical SD threshold was significantly reduced, propagation speed was increased, and inverse hemodynamic responses were prolonged. These results may have relevance to both migraine with aura and stroke.

Cranial autonomic dysregulation is a common symptom of patients suffering from cluster headache or migraine. The peripheral vascular dysfunction may increase the risk for ischemic or hemorrhagic strokes, myocardial infarction, retinal vasculopathy, cardiovascular mortality, and peripheral artery diseases. Furthermore, it may also manifest with ocular symptoms, e.g., increased lacrimation, conjunctival injection, and facial swelling.

Old age and spinal surgery significantly increase the risk of postoperative hyponatremia. However, detailed analyses of postoperative hyponatremia after spinal surgery in elderly patients are lacking. Therefore, we retrospectively reviewed the records of 582 consecutive patients aged > 60 years who underwent spinal surgery to evaluate the frequency, risk factors, and symptoms of postoperative hyponatremia after spinal surgery in the elderly population. Postoperative hyponatremia was defined as a postoperative blood sodium level < 135 meq/L at postoperative day (POD)1, POD3, and/or after POD6. A total of 92 (15.8%) patients showed postoperative hyponatremia. On a multivariate analysis, a diagnosis of a spinal tumor/infection, decompression and fusion surgery, and lower preoperative sodium levels were significant independent factors of postoperative hyponatremia (p = 0.014, 0.009, and < 0.001, respectively). In total, 47/92 (51%) cases could have been symptomatic; vomiting was noted in 34 cases (37%), nausea in 19 cases (21%), headache in 14 cases (15%), and disturbances in consciousness, including delirium, in ten cases (21%); all incidences of these symptoms were significantly higher in elderly patients with postoperative hyponatremia than in the matched control group without postoperative hyponatremia (p < 0.05, respectively). Additionally, the length of stay was 2 days longer in patients than in the matched controls (p = 0.002).

Cardiomyocyte reprogramming plays a pivotal role in sepsis-induced cardiomyopathy through the induction or overexpression of several factors and enzymes, ultimately leading to the characteristic decrease in cardiac contractility. The initial trigger is the binding of LPS to TLR-2, -3, -4, and -9 and of pro-inflammatory cytokines, such as TNF, IL-1, and IL-6, to their respective receptors. This induces the nuclear translocation of nuclear factors such as NFkB, via activation of MyD88, TRIF, IRAK and MAPKs. Among the latter, ROS- and estrogen -dependent p38 and ERK 1 / 2 are pro-inflammatory, whereas JNK may play antagonistic, anti-inflammatory roles. Nuclear factors induce the synthesis of cytokines, which can amplify the inflammatory signal in a paracrine fashion, and of several effector enzymes, such as NOS-2, NOX-1, and others, which are ultimately responsible for the degradation of cardiomyocyte contractility. In parallel, the downregulation of enzymes involved in oxidative phosphorylation causes metabolic reprogramming, followed by a decrease in ATP production and the release of fragmented mitochondrial DNA, which may augment the process in a positive feedback loop. Other mediators, such as NO, ROS, the enzymes PI3K and Akt, and adrenergic stimulation may play regulatory roles, but not all signaling pathways that mediate cardiac dysfunction of sepsis do that by regulating reprogramming. Transcription may be globally modulated by miRs, which exert protective or amplifying effects. For all these mechanisms, differentiating between modulation of cardiomyocyte reprogramming versus systemic inflammation has been an an ongoing but worthwhile experimental challenge.

Pediatric neoplastic diseases account for about 10% of cases of fever of unknown origin (FUO), and most neoplastic disease cases are leukemia, lymphoma, and neuroblastoma. Brain tumors are rarely reported as the cause of FUO, although craniopharyngioma, metastatic brain tumor, and Castleman's disease have been reported. We report a case of intracranial mesenchymal tumor (IMT) with a FET:CREB fusion gene, which had inflammatory phenotype without neurological signs. A 10-year-old girl was admitted with a 2-month history of intermittent fever and headache, whereas her past history as well as her family history lacked special events. Sepsis work-up showed no pathological organism, and empirical antibiotic therapy was not effective. Bone marrow examination showed a negative result. Cerebrospinal fluid examination showed elevated protein as well as cell counts, and head magnaetic resonance imaging showed a hypervascular mass lesion with contrast enhancement in the left cerebellar hemisphere. The patient underwent tumor excision, which made the intermittent fever disappear. Pathological examinations resembled those of classic angiomatoid fibrous histiocytoma (AFH), but the morphological features were distinct from the AFH myxoid variant; then we performed break-apart fluorescence in situ hybridization and confirmed the tumor harbored the rare EWSR1::CREM fusion gene (Ewing sarcoma breakpoint region 1 gene (EWSR1) and cAMP response element binding (CREB) family gene). Consequently, we diagnosed the condition as IMT with EWSR1::CREM fusion. Elevated serum concentration of interleukin 6 (IL-6) was normalized after tumor resection, which suggested the fever could be caused by tumor-derived IL-6. This is the first case of IMT with EWSR1::CREM fusion that showed paraneoplastic symptoms associated with the IL-6/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Although brain tumors are rarely diagnosed as a responsible disease for FUO, they should be considered as a cause of unknown fever even in the absence of abnormal neurological findings.

Placebo-controlled surgical designs are recommended to ascertain treatment effects for elective surgeries when there is genuine doubt about the effectiveness of the surgery. Some elective surgeries for pain have been unable to show an effect beyond sham surgery, suggesting contributions from contextual factors. However, the nature of contextual factors in elective surgery is largely unexplored. Further, methodological difficulties in placebo-controlled surgical trials impact the ability to estimate the effectiveness of a surgical procedure. These include an overall lack of testing the success of blinding, absence of comparison to a no-surgery control group and dearth of test for neuropathic pain.For women with peritoneal endometriosis, there is uncertainty regarding the pain-relieving effect of surgery. Surgery may put patients at risk of complications such as postsurgical neuropathic pain, without guarantees of sufficient pelvic pain relief. The planned placebo-controlled trial aims to examine the effect of surgery on pelvic pain, widespread pain and neuropathic pain symptoms in women with peritoneal endometriosis, and to test the contribution of contextual factors to pain relief.