Rejected

After spinal cord injury (SCI), macrophages infiltrate into the lesion and can adopt a wide spectrum of activation states. However, the pro-inflammatory, pathological macrophage activation state predominates and contributes to progressive neurodegeneration. Azithromycin (AZM), an FDA approved macrolide antibiotic, has been demonstrated to have immunomodulatory properties in a variety of inflammatory conditions. Indeed, we previously observed that post-SCI AZM treatment reduces pro-inflammatory macrophage activation. Further, a combined pre- and post-injury treatment paradigm improved functional recovery from SCI. Therefore, for the current study, we hypothesize that post-injury AZM treatment will improve recovery from SCI. To test this hypothesis, we examined the therapeutic potential of delayed AZM treatment on locomotor, sensory, and anatomical recovery. We administered AZM beginning 30-min, 3-h, or 24-h following contusion SCI in female mice, and then daily for 7 days. AZM administration beginning 30-min and 3-h post-injury improved locomotor recovery with increased stepping function relative to vehicle controls. Further, delaying treatment for 30-min after SCI significantly reduced lesion pathology. Initiating AZM treatment 24-h post-injury was not therapeutically effective. Regardless of the timing of the initial treatment, AZM did not statistically reduce the development of neuropathic pain (mechanical allodynia) nor increase neuron survival. Collectively, these results add to a growing body of evidence supporting AZM's translational potential as a therapeutic agent for SCI and other neuroinflammatory conditions in which patients currently have very few options.

Chronic prostatitis / chronic pelvic pain syndrome (CP/CPPS) is commonly diagnosed in men younger than 50 years old. It is characterized by pelvic pain, voiding symptoms and sexual dysfunction. The considerable discomfort or pain experienced has a negative impact on the quality of life of patients and is a huge economic burden because of the high recurrence rate and the low cure rate. Appropriate animal models are essential for the development of new drugs for the treatment of CP/CPPS, and several rodent models induced by different methods and over different time frames have been established. This article reviews studies of three in vivo rodent models of prostatitis, namely, chemical-induced, autoimmune-induced and hormone-associated models reported by us and other investigators. Recent clinical investigation has suggested that tadalafil improves the International Prostatic Symptom Score and the total National Institutes of Health Chronic Prostatitis Symptom Index score of patients with benign prostatic hyperplasia with CP/CPPS, which enables us to investigate the effect of tadalafil on the pelvic-pain-related behavior and prostatic inflammation in two of these prostatitis model types, experimental autoimmune prostatitis (EAP) and hormone/castration-induced prostatitis (HCP). Both models showed the pelvic-pain-related behavior and prostatic inflammation that are characteristic of chronic prostatitis. In EAP, tadalafil suppressed both the pelvic-pain-related behavior and the prostatic inflammation. In HCP, tadalafil suppressed the pelvic-pain-related behavior. These results mimic the clinical findings. Therefore EAP and HCP are suitable for the evaluation of the potency of drugs for the treatment of CP/CPPS.

When mobile health (mHealth) applications (apps) are investigated, the question of the proper control condition arises. Normally, the randomized controlled trial (RCT) is seen as the gold standard when testing efficacy of clinical interventions. Yet, mHealth apps rarely comprise innovative treatments but rather provide established treatments digitally. The classical RCT utilizing a placebo or waiting group condition may not always be the suitable methodology, since non-treatment is not appropriate if a disease urges treatment and the development of chronic disease needs to be prevented. The present commentary discusses conceivable control conditions in mHealth trials and illustrates their limitations.

Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through anti-inflammatory mechanisms, but this has not been tested in clinical studies. With the essing the effect of nti–6 treatment in (ASSAIL-MI) trial, we aim to examine whether a single administration of the IL-6 receptor antagonist tocilizumab can increase myocardial salvage in patients with acute ST-elevation MI (STEMI).

Intravenous immunoglobulin (IVIG) is a pooled human plasma protein that has shown efficacy in treating a variety of disorders. IVIG is generally well tolerated and has a good safety profile. There are various IVIG products available on the market, which results in differences in efficacy and safety profile. The aim of this study was to assess the safety profile of IVIG use in pediatric patients and its association with other predicted factors.

Prioritization of animal welfare issues can help identify which areas most require research funding and raise awareness of best practices. A modified Delphi method was used to obtain expert opinion on the highest priority welfare issues for UK farmed livestock. Fifty-eight UK-based experts were recruited onto the study, with a minimum of 3 years experience of working with either cattle, pigs, poultry, or small ruminants (12-16 experts per group). Experts were chosen to represent a broad range of opinions. Two rounds of surveys were conducted online using Online Survey, and the final round was an in-person workshop with 21 experts. In the first survey, experts were provided with a comprehensive list of species-specific welfare issues derived from the literature. Participants were asked to score each welfare issue, for (i) severity, (ii) duration, and (iii) prevalence on a 6-point Likert scale. The results of the first survey were reviewed and the welfare issues which scored a neutral-to-high response (scores 3-6) were carried forward. In round 2, participants were asked whether they agreed or disagreed with the rankings that were made from the results of round 1. The final stage of the process was a workshop, which consisted of a combination of group exercises and discussions, to reach the final consensus. Welfare priority lists were divided into two categories: severity/duration, and prevalence, to identify the priority welfare issues affecting individual animals and the population, respectively. Across all farmed species common concerns were inadequate or inappropriate nutrition, inability of stockpeople to recognize or treat welfare issues (such as pain or behavioral problems), lameness, chronic or endemic health issues, euthanasia and mortality and morbidity of neonates. Specific concerns related to behavioral restriction and damaging or abnormal behavior in pigs, poultry and dairy animals, inadequate housing for pigs and poultry, consequences of breeding decisions in pigs and poultry, and lack of access to veterinary care in sheep and beef. This Delphi process resulted in consensus on the most significant welfare challenges faced by UK livestock species and can help to guide future research and education priority decisions.

Nephrotic syndrome is defined by three characteristic features including proteinuria of >3 g in 24 hours, hypoalbuminemia of less than 3 g/dL, and peripheral edema. Multiple nephropathies can result in nephrotic syndrome. Most commonly, minimal change disease is seen in children under the age of 10, while adults are more commonly found to have membranous nephropathy. Hypercoagulability and thrombotic sequela can be seen in nephrotic syndrome, regardless of underlying etiology, and thrombosis is most commonly seen in deep veins of the lower extremities and renal veins. Our case identifies an adult with previously diagnosed and treated for minimal change disease who presented with weight gain, peripheral edema, foamy urine, headache but no neurologic deficits. The patient was found to have near to complete occlusion of the entire superior sagittal sinus, near complete occlusion of the left transverse and sigmoid sinuses, and nonocclusive thrombus in the right sigmoid sinus. She was treated with heparin and IV steroids then transitioned to warfarin and PO steroids, respectively, with resolution of symptoms. This case report emphasizes on the importance of recognizing CVST as a potential complication of nephrotic syndrome at both initial presentation and relapse.

Extracellular electrophysiology has been widely applied in neural network studies. Local field potentials and single-unit activities can be recorded with high-density electrodes, which facilitate the decoding of neural codes. However, the chronic multi-regional recording is still a challenging task for achieving high placement accuracy and long-term stability. Here, we present a novel electrode design with low-cost 3D-printed parts and custom printed circuits boards. This new design could facilitate precise electrode placement in multiple brain regions simultaneously and reduce the working time for surgical procedures as well. In this paper, the design and fabrication of the 3D printed multi-channel microdrive are explained in detail. We also show the result of high-quality electrophysiological recordings in eight pain-related areas from rats and the electrode placement accuracy. This novel 3D-printed multi-drive system could achieve synchronous electrophysiological recording in multiple brain regions and facilitate future neural network research.

Esophagogastroduodenoscopy (EGD) is commonly performed for abdominal pain in children, and in the presence of alarm symptoms, the diagnostic yield of this procedure is high. The aim of this study was to investigate the utility of EGD when performed for uncomplicated abdominal pain in children in the absence of alarm symptoms. Charts of all children less than 18 years of age who underwent EGD at the University of Florida between January 2016 and October 2018 were reviewed. Of 1478 children who underwent EGD for any indication, 287 patients (male-to-female = 123:164) were discovered to have undergone EGD, in the absence of colonoscopy, for uncomplicated acute or chronic abdominal pain, nausea, vomiting, gastroesophageal reflux, and/or dyspepsia, with no alarm symptoms. A significant change in clinical management was noted in 20 (7.0%) children. The findings of this procedure changed clinical management in a minority of our study participants.

: Due to its unique pharmacologic properties, efficacy as an analgesic, and role as a first-line medication for the treatment of opioid use disorder, sublingual buprenorphine has emerged as a treatment for patients with concurrent chronic pain and opioid use disorders. One challenge to utilizing buprenorphine is that precipitated opioid withdrawal can result if this medication is initiated in the presence of other opiates with lesser binding affinities. Micro-dosing induction regimens utilize a slower titration to avoid the need for a period of abstinence from other opiates and decrease the risk of precipitated withdrawal. : The aim of this article is to present a case where a standardized micro-dosing induction regimen was used to transition a patient from other opiate analgesia to a sublingual formulation of buprenorphine/naloxone. : This case took place on an inpatient neurosurgical unit of a Canadian tertiary-care city hospital. Written informed consent was collected prior to a detailed chart review. : Here we present a case of a postoperative neurosurgical inpatient who was referred to our team for pain management in the context of chronic pain and a past history of opioid use disorder. She was successfully transitioned to buprenorphine/naloxone, replacing all other opioid analgesia, without a period of opioid withdrawal using a micro-dosing induction regimen. : Sublingual buprenorphine/naloxone can be safe and effective for treatment of chronic pain, particularly for those with past or current opioid use disorder. Micro-dosing provides a preferable induction strategy for patients who are not able to tolerate the requirement for moderate opioid withdrawal prior to initiation with existing regimens.