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Background: Management of supracondylar humerus fractures (SCHF) with coexisting median nerve injury is controversial. Although many nerve injuries improve with the reduction and stabilization of the fracture, the speed and completeness of recovery are unclear. This study investigates median nerve recovery time using the serial examination., Methods: A prospectively maintained database of SCHF-related nerve injuries referred to a tertiary hand therapy unit between 2017 and 2021 was interrogated. Factors related to the injury (vascularity, Gartland grade, open vs. closed fracture) and treatment (fixation modality, adequacy, timing of reduction, vascular and nerve intervention, and secondary procedures) were assessed.Primary outcomes were the motor recovery of Medical Research Council (MRC) grade 4 or 5 in flexor pollicis longus or flexor digitorum profundus (index) and detection of the 2.83 Semmes Weinstein monofilament.A retrospective clinical note review of all SCHF presenting during the same period was also conducted., Results: Of 1096 SCHF, 74 (7%) had an associated median nerve palsy. Twenty-one patients [mean age 7 years (SD 1.6)] with SCHF-related median nerve injuries underwent serial examination. Nineteen (90%) were modified Gartland III or IV, and 10 (48%) were pulseless on presentation. The mean follow-up was 324 days.The mean motor recovery time was 120 days (SD 71). Four (27%) and 2 (13%) patients had not achieved MRC grade 4 by 6 months and 2 years, respectively. Only 50% attained MRC grade 5 at 2 years.When compared with closed reduction, those who underwent open reduction recovered motor function 80 days faster (mean 71 vs. 151 d, P =0.03) and sensory function 110 days faster (52 vs. 162, P =0.02). Fewer patients recovered after closed reduction (8 of 10) than open (5 of 5).Modified Gartland grade, vascular status, adequacy of reduction, and secondary surgery were not associated with recovery time., Conclusions: Median nerve recovery seems to occur slower than previously thought, is often incomplete, and is affected by treatment decisions (open vs. closed reduction). Retrospective reporting methods may overestimate median nerve recovery., Level of Evidence: Level III-therapeutic., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Patients with a prostatectomy are at high risk of developing erectile dysfunction (ED) that is refractory to phosphodiesterase type 5 inhibitors. The cavernous nerve (CN) is frequently damaged during prostatectomy, causing loss of innervation to the penis. This initiates corpora cavernosal remodeling (apoptosis and fibrosis) and results in ED., Aim: To aid in the development of novel ED therapies, the current aim was to obtain a global understanding of how signaling mechanisms alter in the corpora cavernosa with loss of CN innervation that results in ED., Methods: Microarray and pathway analysis were performed on the corpora cavernosal tissue of patients with a prostatectomy (n = 3) or Peyronie disease (control, n = 3). Results were compared with an analysis of a Sprague-Dawley rat CN injury model (n = 10). RNA was extracted by TRIzol, DNase treated, and purified by a Qiagen Mini Kit. Microarray was performed with the Human Gene 2.0 ST Array and the RU34 rat array. Differentially expressed genes were identified through several analytic tools (ShinyGO, Ingenuity, WebGestalt) and databases (GO, Reactome). A 2-fold change was used as the threshold for differential expression., Outcomes: Pathways that were altered (up- or downregulated) in response to CN injury in the prostatectomy patients and a rat CN injury model were determined., Results: Microarray identified 197 differentially expressed protein-coding genes in the corpora cavernosa from the prostatectomy cohort, with 100 genes upregulated and 97 genes downregulated. Altered signaling pathways that were identified that affect tissue morphology included the following: neurologic disease, cell death and survival, tissue and cellular development, skeletal and muscle development and disorders, connective tissue development and function, tissue morphology, embryonic development, growth and proliferation, cell-to-cell signaling, and cell function and maintenance. These human pathways have high similarity to those observed in the CN-injured rat ED model., Clinical Implications: Significant penile remodeling continues in patients long after the acute surgical injury to the CN takes place, offering the opportunity for clinical intervention to reverse penile remodeling and improve erectile function., Strengths and Limitations: Understanding how signaling pathways change in response to CN injury and how these changes translate to altered morphology of the corpora cavernosa and ensuing ED is critical to identify strategic targets for therapy development., Conclusion: Altered signaling in pathways that regulate tissue homeostasis, morphogenesis, and development was identified in penes of patients with a prostatectomy, and competitive forces of apoptosis and proliferation/regeneration were found to compete to establish dominance after CN injury. How these pathways interact to regulate penis tissue homeostasis is a complex process that requires further investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of The International Society of Sexual Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Neurogenic erectile dysfunction (ED) following radical prostatectomy (RP) is a frequent complication often leading to erectile tissue remodeling and permanent ED. Low-intensity electrostimulation (LIES) has been shown to enhance peripheral nerve regeneration, however, its application on cavernous nerves (CN) has never been investigated., Aims: To investigate whether LIES enhances CN regeneration, improves erectile function (EF) recovery, and prevents corpora cavernosal remodeling after CN injury, which is a principal factor for ED following RP., Methods: Adult male Sprague-Dawley rats were divided into Sham, Bilateral Cavernous Nerve Injury (BCNI), and BCNI + LIES (1V, 0.1ms, 12Hz, 1h/day). After 7days, EF was assessed (ICP measurement). Penes and CN were collected for molecular analyses of TGF-β1, Il-6, CRP, eNOS, ERK and AKT protein levels in corpus cavernosum (CC), and immunohistological analysis of DHE, total collagen and α-SMA in CC and S-100, Tub-III, DAPI, TUNEL, and nNOS in CN., Outcomes: Effects of LIES on EF, erectile tissue remodeling and CN structure., Results: EF was decreased (P < .05) 7 days after BCNI and increased (P < .05) by LIES. Intracavernosal reactive oxygen species (DHE) was increased (P < .05) after BCNI and normalized by LIES. Protein expressions of TGF-β1, IL-6, and CRP were increased in the penis (P < .05) after BCNI and normalized by LIES. The α-SMA and/or total collagen ratio was decreased (P < .05) after BCNI in the penis and normalized by LIES. Protein expression ratio of p-ERK/ERK and p-AKT/AKT did not change after BCNI but increased (P < .05) in LIES group. Myelination and number of nNOS positive cells in the CN were decreased (P < .05) after BCNI and normalized by LIES. The number of apoptotic nerve cells within the dorsal penile nerve was increased (P < .05) after BCNI and decreased (P < .05) by LIES compared to the BCNI group. There were no differences in eNOS expression in the penis between study groups., Clinical Translation: LIES may offer a potential new tool for penile rehabilitation and ED management following RP, potentially enhancing EF recovery and minimizing the side effects of this surgery., Strengths & Limitations: This study provides evidence of the protective effect of LIES on EF and tissue remodeling following CN injury; nevertheless, this study has been conducted on animals and the translation to humans remains to be demonstrated. Further research to identify the underlying mechanisms of action is required., Conclusion: This study demonstrates that LIES of the CN after CN injury protects CN structure, enhances EF recovery, and prevents corpora cavernosal remodeling. Sturny M, Karakus S, Fraga-Silva R, et al. Low-Intensity Electrostimulation Enhances Neuroregeneration and Improves Erectile Function in a Rat Model of Cavernous Nerve Injury. J Sex Med 2022;19:686-696., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Persistent postsurgical neuropathic pain (PPSNP) can occur after intraoperative damage to somatosensory nerves, with a prevalence of 29-57% in breast cancer surgery. Proteomics is an active research field in neuropathic pain and the first results support its utility for establishing diagnoses or finding therapy strategies., Methods: 57 women (30 non-PPSNP/27 PPSNP) who had experienced a surgeon-verified intercostobrachial nerve injury during breast cancer surgery, were examined for patterns in 74 serum proteomic markers that allowed discrimination between subgroups with or without PPSNP. Serum samples were obtained both before and after surgery., Results: Unsupervised data analyses, including principal component analysis and self-organizing maps of artificial neurons, revealed patterns that supported a data structure consistent with pain-related subgroup (non-PPSPN vs. PPSNP) separation. Subsequent supervised machine learning-based analyses revealed 19 proteins (CD244, SIRT2, CCL28, CXCL9, CCL20, CCL3, IL.10RA, MCP.1, TRAIL, CCL25, IL10, uPA, CCL4, DNER, STAMPB, CCL23, CST5, CCL11, FGF.23) that were informative for subgroup separation. In cross-validated training and testing of six different machine-learned algorithms, subgroup assignment was significantly better than chance, whereas this was not possible when training the algorithms with randomly permuted data or with the protein markers not selected. In particular, sirtuin 2 emerged as a key protein, presenting both before and after breast cancer treatments in the PPSNP compared with the non-PPSNP subgroup., Conclusions: The identified proteins play important roles in immune processes such as cell migration, chemotaxis, and cytokine-signaling. They also have considerable overlap with currently known targets of approved or investigational drugs. Taken together, several lines of unsupervised and supervised analyses pointed to structures in serum proteomics data, obtained before and after breast cancer surgery, that relate to neuroinflammatory processes associated with the development of neuropathic pain after an intraoperative nerve lesion.

Pain induced by inflammation and nerve injury arises from abnormal neural activity of primary afferent nociceptors in response to tissue damage, which causes long-term elevation of the sensitivity and responsiveness of spinal cord neurons. Inflammatory pain typically resolves following resolution of inflammation; however, nerve injury-either peripheral or central-may cause persistent neuropathic pain, which frequently manifests as hyperalgesia or allodynia. Neuralgias, malignant metastatic bone disease, and diabetic neuropathy are some of the conditions associated with severe, often unremitting chronic pain that is both physically and psychologically debilitating or disabling. Therefore, optimal pain management for patients with chronic neuropathic pain requires a multimodal approach that comprises pharmacological and psychological interventions. Non-opioid analgesics (e.g., paracetamol, aspirin, or other non-steroidal anti-inflammatory drugs) are first-line agents used in the treatment of mild-to-moderate acute pain, while opioids of increasing potency are indicated for the treatment of persistent, moderate-to-severe inflammatory pain. N-methyl D-aspartate receptor antagonists, antidepressants, anticonvulsants, or a combination of these should be considered for the treatment of chronic neuropathic pain. This review discusses the various neural signals that mediate acute and chronic pain, as well as the general principles of pain management.

Introduction: The human placenta provides a bountiful and noncontroversial source of stem cells which have the potential for regeneration of injured tissue. These cells may restore erectile function after neurovascular tissue injury such as that seen in radical pelvic surgeries and pelvic trauma., Aim: To determine the effect of human placenta-derived stem cells on erectile function recovery and histological changes at various time points in a cavernous nerve injury rat model and to study the fate of injected stem cells throughout the regenerative process., Methods: Human placental stem cells (PSCs) were dual labeled with monomeric Katushka far red fluorescent protein (mKATE)-renLUC using a lentivirus vector. A pelvic neurovascular injury-induced erectile dysfunction model was established in male, athymic rats by crushing the cavernous nerves and ligating the internal pudendal neurovascular bundles, bilaterally. At the time of defect creation, nonlabeled PSCs were injected into the corpus cavernosum at a concentration of 2.5 × 10 6  cells/0.2 mL. The phosphate-buffered saline-treated group served as the negative control group, and age-matched rats (age-matched controls) were used as the control group. Erectile function, histomorphological analyses, and Western blot were assessed at 1, 6, and 12 weeks after model creation. The distribution of implanted, dual-labeled PSCs was monitored using an in vivo imaging system (IVIS). Implanted cells were further tracked by detection of mKATE fluorescence in histological sections., Main Outcome Measure: The main outcome measure includes intracavernous pressure/mean arterial pressure ratio, neural, endothelial, smooth muscle cell regeneration, mKATE fluorescence, and IVIS imaging., Results: The ratio of intracavernous pressure to mean arterial pressure significantly increased in PSC-injected rats compared with phosphate-buffered saline controls (P < 0.05) at the 6- and 12-week time points, reaching 72% and 68% of the age-matched control group, respectively. Immunofluorescence staining and Western blot analysis showed significant increases in markers of neurons (84.3%), endothelial cells (70.2%), and smooth muscle cells (70.3%) by 6 weeks in treatment groups compared with negative controls. These results were maintained through 12 weeks. IVIS analysis showed luminescence of implanted PSCs in the injected corpora immediately after injection and migration of cells to the sites of injury, including the incision site and periprostatic vasculature by day 1. mKATE fluorescence data revealed the presence of PSCs in the penile corpora and major pelvic ganglion at 1 and 3 days postoperatively. At 7 days, immunofluorescence of penile PSCs had disappeared and was diminished in the major pelvic ganglion., Clinical Implications: Placenta-derived stem cells may represent a future "off-the-shelf" treatment to mitigate against development of erectile dysfunction after radical prostatectomy or other forms of pelvic injury., Strength & Limitations: Single dose injection of PSCs after injury resulted in maximal functional recovery and tissue regeneration at 6 weeks, and the results were maintained through 12 weeks. Strategies to optimize adult stem cell therapy might achieve more effective outcomes for human clinical trials., Conclusion: Human PSC therapy effectively restores the erectile tissue and function in this animal model. Thus, PSC therapy may provide an attractive modality to lessen the incidence of erectile dysfunction after pelvic neurovascular injury. Further improvement in tissue regeneration and functional recovery may be possible using multiple injections or systemic introduction of stem cells. Gu X, Thakker PU, Matz EL, et al. Dynamic Changes in Erectile Function and Histological Architecture After Intracorporal Injection of Human Placental Stem Cells in a Pelvic Neurovascular Injury Rat Model. J Sex Med 2020;17:400-411., (Copyright © 2019 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

It remains unclear whether electrical currents can affect biological factors that determine chronic wound healing in humans., Purpose: The aim of this study was to determine whether anodal and cathodal high-voltage monophasic pulsed currents (HVMPC) provided to the area of a pressure injury (PI) change the blood level of cytokines (interleukin [IL]-1β, IL-10, and tumor necrosis factor [TNF]-α) and growth factors (insulin-like growth factor [IGF]-1 and transforming growth factor [TGF]-β1) in patients with neurological injuries and whether the level of circulatory cytokines and growth factors correlates with PI healing progression., Methods: This study was part of a randomized clinical trial on the effects of HVMPC on PI healing. All patients with neurological injuries (spinal cord injury, ischemic stroke, and blunt trauma to the head) and a stage 2, stage 3, or stage 4 PI of at least 4 weeks' duration hospitalized in one rehabilitation center were eligible to participate if older than 18 years of age and willing to consent to donating blood samples. Exclusion criteria included local contraindications to electrical stimulation (cancer, electronic implants, osteomyelitis, tunneling, necrotic wounds), PIs requiring surgical intervention, patients with poorly controlled diabetes mellitus (HbA1C > 7%), critical wound infection, and/or allergies to standard wound treatment. Participants were randomly assigned to 1 of 3 groups: anodal (AG) or cathodal (CG) HVMPC treatment (154 μs; 100 Hz; 360 µC/sec; 1.08 C/day) or a placebo (PG, sham) applied for 50 minutes a day, 5 days per week, for 8 weeks. TNF-α, IL-1β, IL-10, TGF-β1, and IGF-1 levels in blood serum were assessed using the immunoenzyme method (ELISA) and by chemiluminescence, respectively, at baseline and week 4. Wound surface area measurements were obtained at baseline and week 4 and analyzed using a digitizer connected to a personal computer. Statistical analyses were performed using the maximum-likelihood chi-squared test, the analysis of variance Kruskal-Wallis test, the Kruskal-Wallis post-hoc test, and Spearman's rank order correlation; the level of significance was set at P ≤.05., Results: Among the 43 participants, 15 were randomized to AG (mean age 53.87 ± 13.30 years), 13 to CG (mean age 51.08 ± 20.43 years), and 15 to PG treatment (mean age 51.20 ± 14.47 years). Most PIs were located in the sacral region (12, 74.42%) and were stage 3 (11, 67.44%). Wound surface area baseline size ranged from 1.00 cm2 to 58.04 cm2. At baseline, none of the variables were significantly different. After 4 weeks, the concentration of IL-10 decreased in all groups (AG: 9.8%, CG: 38.54%, PG: 27.42%), but the decrease was smaller in the AG than CG group (P = .0046). The ratio of pro-inflammatory IL-10 to anti-inflammatory TNF-α increased 27.29% in the AG and decreased 26.79% in the CG and 18.56% in the PG groups. Differences between AG and CG and AG and PG were significant (AG compared to CG, P = .0009; AG compared to PG, P = .0054). Other percentage changes in cytokine and growth factor concentration were not statistically significant between groups. In the AG, the decrease of TNF-α and IL-1β concentrations correlated positively with the decrease of PI size (P <.05)., Conclusion: Anodal HVMPC elevates IL-10/TNF-α in blood serum. The decrease of TNF-α and IL-1β concentrations in blood serum correlates with a decrease of PI wound area. More research is needed to determine whether the changes induced by anodal HVMPC improve PI healing and to determine whether and how different electrical currents affect the activity of biological agents responsible for specific wound healing phases, both within wounds and in patients' blood. In clinical practice, anodal HVMPC should be used to increase the ratio of anti-inflammatory IL-10 to pro-inflammatory TNF-α , which may promote healing.

Stroke is the second-leading cause of death globally and the leading cause of disability in adults. Medical complications after stroke, especially infections such as pneumonia, are the leading cause of death in stroke survivors. Systemic immunodepression is considered to contribute to increased susceptibility to infections after stroke. Different experimental models have contributed significantly to the current knowledge of stroke pathophysiology and its consequences. Each model causes different changes in the cerebral microcirculation and local inflammatory responses after ischemia. The vast majority of studies which focused on the peripheral immune response to stroke employed the middle cerebral artery occlusion method. We review various experimental stroke models with regard to microcirculatory changes and discuss the impact on local and peripheral immune response for studies of CNS-injury (central nervous system injury) induced immunodepression.

This review summarizes studies that examined the effectiveness of cannabinoids in treating spasticity, with a focus on understanding the relevance of the existing evidence to paediatric populations. MEDLINE, Embase, PsycINFO, and the Cochrane Library were searched to identify studies that examined the use of cannabinoids in spasticity. We identified 32 studies in adult and paediatric populations. Results were summarized by condition, with adult and paediatric studies considered separately. There is evidence from randomized controlled clinical trials that cannabinoids are more effective than placebo in reducing symptoms of spasticity in adults with multiple sclerosis. Most positive effects were based on patient-rated rather than clinician-rated measures, were modest in size, and should be considered in the context of the narrow therapeutic index of cannabinoids for spasticity and adverse effects. There were comparatively few, and no large studies, of spasticity in conditions other than multiple sclerosis. Few studies have been conducted in paediatric populations. Paediatric studies of spasticity provide low quality evidence and are inadequate to inform clinical practice. Cannabinoids have modest efficacy in reducing muscle spasticity in adults with multiple sclerosis. There is limited evidence of efficacy for cannabinoid use in other conditions, particularly in paediatric populations. Studies in paediatric populations have been of low quality and are insufficient to inform clinical practice., (© 2019 Mac Keith Press.)

Background: Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated., Aim: To determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model., Methods: Male rats underwent 0 Gy or 22 Gy single fraction of prostate-confined, conformal RT. At 2 weeks or 10 weeks post-RT (n = 10/group), cavernous nerve stimulation was performed and erections were assessed. Tissue bath experiments were performed to assess both penile artery and internal pudendal artery (IPA) function. MPGs were dissociated and neurons grown in culture for 72 hours. Immunofluorescence staining was done to quantify neuron survival (terminal deoxynucleotidyl transferase nick-end labeling), outgrowth (beta-tubulin III), type (nitric oxide synthase [nNOS] and tyrosine hydroxylase [TH]), and nerve injury markers (small GTPase Rac1 and ninjurin-1 [Ninj-1]). Whole MPG real-time quantitative polymerase chain reaction (qPCR) was performed to measure expression of genes related to nerve type, neuron injury, repair, and myelination, such as Ninj-1, Rac1, ATF3, GAP43, GFAP, SOX10, and KROX20., Outcomes: Intracavernosal pressure (ICP) to mean arterial pressure (MAP) ratio, smooth muscle contractility and relaxation, gene expression, neuritogenesis, and apoptosis., Results: Following RT, ICP/MAP was unchanged at 2 weeks or 10 weeks. Nerve-mediated penile contraction was increased at 2 weeks, whereas adrenergic contraction was reduced at 10 weeks. Penile relaxation and IPA vasoreactivity were unchanged. Neuronal apoptosis was more than doubled both early and late post-RT. RT caused a progressive decrease in neurite branching but an early increase and then late decrease in neurite lengthening. RT reduced the numbers of nNOS-positive neurons both early and late and also decreased MPG nitrergic gene expression. TH neurons and gene expression were unchanged at 2 weeks; however, both were decreased after 10 weeks. Although most markers of gene injury and repair were unaffected early post-RT, MPG expression of Ninj1 and GFAP increased. After 10 weeks, Ninj1 and GFAP remained elevated while markers of neuron injury (ATF3), outgrowth (GAP43 and Rac1), and myelin regulation (SOX10) were decreased., Clinical Translation: RT-induced ED may result from damage to the ganglia controlling erections., Strengths & Limitations: This study used a clinically relevant, prostate-confined model to examine neurovascular structures not accessible in human studies. Unfortunately, rats did not exhibit ED at this time point., Conclusion: This is the first study to demonstrate impaired health and regeneration potential of dissociated MPG neurons following RT. Neuronal injury was apparent early post-RT and persisted or increased over time but was insufficient to cause ED at the time points examined. Powers SA, Odom MR, Pak ES, et al. Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth. J Sex Med 2019;16:27-41., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Erectile dysfunction (ED) caused by pelvic neurovascular injury (PNVI) is often refractory to treatment. In many cases, erectogenic therapy is administered in a delayed fashion., Aim: To evaluate penile hemodynamic effects and histologic changes associated with delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) after PNVI ED in a rat model. We visualized images using immunofluorescence and 3-dimensional imaging of solvent-cleared organs (3DISCO), a novel imaging technique., Methods: A total of 32 Sprague-Dawley male rats aged 12 weeks were divided equally into 4 groups: sham surgery as normal controls (NC), PNVI controls (PC), PNVI with very-low-energy Li-ESWT (PVL), and PNVI with low-energy Li-ESWT (PL). Bilateral cavernous nerve crush and internal pudendal bundle ligation were performed in the 3 PNVI groups. Li-ESWT was administered twice a week for 4 weeks in the PL and PVL groups starting at 4 weeks after PNVI., Outcomes: Intracavernous pressure (ICP) studies (normalized to mean arterial pressure [MAP]) were conducted in all subject animals. After testing, tissue was harvested for immunofluorescence staining and 3DISCO analysis., Results: Mean ICP/MAP was lower in PC animals compared with NC animals (0.37 ± 0.03 vs 0.91 ± 0.03, respectively; P = .001). The ICP/MAP ratio was significantly higher in PVL and PL animals (0.66 ± 0.07 and 0.82 ± 0.05, respectively) compared with PC animals (P = .002 and .001, respectively). Detailed microstructures and trajectories of nerves and vessels were identified with immunofluorescence and 3DISCO. The PC group had lower density of nerves, axons, neuronal nitric oxide synthase-positive nerves, and Schwann cells in the dorsal penis. Animals in the PL group had significantly higher expression of all of these markers compared with PC animals., Clinical Implications: Li-EWST may have utility in the management of severe ED related to PNVI from severe pelvic injury or radical pelvic surgeries, even when administered in a delayed fashion., Strength & Limitations: This study of a severe ED phenotype involved treatment administered in a delayed fashion, which is more consistent with how therapy likely would be delivered in a real-world clinical context. Moreover, because the treatment commenced at 4 weeks after injury, when nerve and tissue atrophy have already occurred, the results imply that Li-ESWT can be used for regenerative therapy. Additional studies on dose optimization and treatment interval are needed to inform the design of human clinical trials., Conclusion: Li-ESWT ameliorates the negative functional and histologic effects of severe pelvic neurovascular injury in a rat model system. 3DISCO provides high-resolution images of neuroanatomy and neural regeneration. Wang HS, Ruan Y, Banie L, et al. Delayed Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Impaired Penile Hemodynamics in Rats Subjected to Pelvic Neurovascular Injury. J Sex Med 2019;16:17-26., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Stress ulcer prophylaxis (SUP) with acid-suppressive drug therapy is widely utilized in critically ill patients following neurologic injury for the prevention of clinically important stress-related gastrointestinal bleeding (CIB). Data supporting SUP, however, largely originates from studies conducted during an era where practices were vastly different than what is considered routine by today's standard. This is particularly true in neurocritical care patients. In fact, the routine provision of SUP has been challenged due to an increasing prevalence of adverse drug events with acid-suppressive therapy and the perception that CIB rates are sparse. This narrative review will discuss current controversies with SUP as they apply to neurocritical care patients. Specifically, the pathophysiology, prevalence, and risk factors for CIB along with the comparative efficacy, safety, and cost-effectiveness of acid-suppressive therapy will be described.

Introduction: Many studies have shown that electrostimulation of the cavernosal nerve can induce and maintain penile erection. Based on these discoveries, neurostimulation to activate the erectile response has been considered a potential solution to treat erectile dysfunction (ED). However, despite recognized potential, this technology has not been further developed. The barrier is the complex anatomy of the human cavernous nerve, which challenges the intraoperative identification of the cavernosal nerves for electrode placement., Aim: To overcome this major barrier, we proposed a practical solution: a 2-dimensional flexible electrode array that can cover the entire plexus area, ensuring that at least 1 of the electrodes will be in optimal contact with the cavernosal nerve, without the need of intraoperative identification. The present study aims to evaluate this concept intraoperatively., Methods: 24 patients enrolled for open radical prostatectomy were recruited. During the surgical procedures, the electrode array was positioned on the pelvic plexus (on the prostatic apex or pelvic wall) and electrical stimulation was applied to induce penile erection. Penile erectile response was assessed by (i) visual change of penile tumescence and (ii) by a penile plethysmograph system., Main Outcome Measure: Ability and success rate of evoking penile response were measured by applying electrical stimulation using the developed electrode array., Results: Electrical stimulation produced immediate penile response in all cases when tested before (on prostatic apex) or after prostate removal (on pelvic wall). Clear visual penile engorgement was observed in 75% of the cases, whereas 25% showed minimal to moderate penile tumescence. As expected, patients with lower International Index of Erectile Function-5 score presented a reduced response, whereas stimulation before prostate removal showed greater response than following removal. Interestingly, erectile response was potentiated by bilateral stimulation (circumference increase [mm]: 2.7 ± 1.02 vs. 8.2 ± 1.9, P = .01)., Clinical Implications: These data bring sufficient proof of concept of a conceivable novel medical implant for the treatment of ED caused by mechanical nerve injury, such as prostatectomy and spinal cord injury., Strength & Limitations: This is the first approach that can ensure the optimal site stimulation of the erectogenic neuronal path within the lower pelvic area and overcome the major barrier of individual anatomic variability. However, because this study was performed intraoperatively in an acute scenario, further studies are needed to evaluate its chronic efficacy for clinical practice., Conclusion: The flexible electrode array concept can ensure the electrostimulation of erectogenic neuronal path when positioned on the prostate apex or pelvic floor. Skoufias S, Sturny M, Fraga-Silva R, et al. Novel concept enabling an old idea: A flexible electrode array to treat neurogenic erectile dysfunction. J Sex Med 2018;15:1558-1569., (Copyright © 2018. Published by Elsevier Inc.)

To investigate the incidence and pattern of child and adolescent (≤18 years old) traumatic fractures (TFs) as a result of collisions.We retrospectively reviewed 270 child and adolescent patients (228 males and 42 females aged 12.8 ± 5.1 years old) with TFs as a result of collisions admitted to our university-affiliated hospitals from 2001 to 2010. The incidence and patterns were summarized with respect to different age groups, sex, etiology, and whether the patient presented with nerve injury.The most common etiologies were struck by object (105, 38.9%) and wounded by person (74, 27.4%). The most common fracture sites were upper limb fractures (126, 46.7%) and craniofacial fractures (82, 30.4%). A total of 65 (24.1%) patients suffered a nerve injury. The frequency of early and late complications/associated injuries was 35.6% (n = 96) and 8.5% (n = 23), respectively. The mean age (P = .001) and frequency of wounded by person (P = .038) was significantly larger in male than in female patients. The frequency of earthquake injury (P < .001) and lower limb fractures (P = .002) was significantly larger in females than in male patients. The frequency of upper limb fracture was significantly higher in the wounded by machine group (83.3%) than in the other groups (all P < .05). The frequency of lower limb fractures was significantly higher in the earthquake injury group (64.7%) than in the other groups (all P < .05). The frequency of craniofacial fracture was significantly higher in the wounded by person group (54.1%) than in the other groups (all P < .05). The emergency admission rate (P = .047), frequency of wounded by person (P < .001), craniofacial fracture (P < .001), and early complications/associated injuries (P < .001) were significantly larger in patients with nerve injury than in other patients.Struck by object and upper limb fractures were the most common etiology and site, respectively. Wounded by person and craniofacial fractures were risk factors for nerve injury. Therefore, we should pay more attention to patients wounded by person, presenting with craniofacial fracture, to find whether there is nerve injury.

Background: Cavernous nerve injury (CNI) causes fibrosis and loss of smooth muscle cells (SMCs) in the corpus cavernosum and leads to erectile dysfunction, and lysyl oxidase (LOX) activation has been found to play an important role in fibrotic diseases., Aim: To evaluate the role of LOX in penile fibrosis after bilateral CNI (BCNI)., Methods: Rats underwent BCNI or a sham operation and were treated with vehicle or β-aminopropionitrile, a specific LOX activity inhibitor. 30 days after BCNI, rats were tested for erectile function before penile tissue harvest. LOX and extracellular matrix component expression levels in the corpus cavernosum, including matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), fibronectin (FN), collagen (COL) I, and COL IV, were evaluated by real-time quantitative polymerase chain reaction and western blot. Corporal fibrosis was evaluated by Masson trichrome staining. Localization of LOX and SMC content in the corpus cavernosum were assessed by immunohistochemistry., Outcomes: Ratio of intracavernous pressure to mean arterial blood pressure; LOX, MMPs, TIMPs, COL I, COL IV, and FN expression; penile fibrosis; penile SMC content., Results: After BCNI, there was an increase in penile LOX expression and activity, increased penile fibrosis, decreased SMC content, and impaired erectile function. TIMP1, TIMP2, COL I, COL IV, and FN expression was markedly upregulated, whereas the enzyme activity of MMPs was decreased after BCNI. β-Aminopropionitrile treatment, at least in part, prevented a decrease in the ratio of intracavernous pressure to mean arterial blood pressure, decreased penile expression of TIMP1, TIMP2, COL I, COL IV, and FN, increased MMP activity, prevented corporal fibrosis, and preserved SMC content., Clinical Translation: LOX over-activation contributes to penile fibrosis and LOX inhibition could be a promising strategy in preventing the progression of CNI-induced erectile dysfunction., Strengths and Limitations: This is the 1st study to demonstrate the role of LOX activation in penile fibrosis. However, the exact mechanism of how LOX influences extracellular matrix protein synthesis and SMC content preservation awaits further investigation., Conclusion: CNI induced LOX over-activation in cavernous tissue, and inhibition of LOX preserved penile morphology and improved erectile function in a rat model of BCNI. Wan Z-H, Li G-H, Guo Y-L, et al. Amelioration of Cavernosal Fibrosis and Erectile Function by Lysyl Oxidase Inhibition in a Rat Model of Cavernous Nerve Injury. J Sex Med 2018;15:304-313., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Whether combined transplantation of mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) is more effective than transplantation of a single cell type in the restoration of erectile function is unknown., Aim: To investigate the effect of combined transplantation of MSCs and EPCs on restoration of erectile function in rats with cavernous nerve injury (CNI)., Methods: MSCs were isolated from human bone marrow and EPCs were isolated from human umbilical cord blood. MSCs and EPCs were identified by flow cytometry and in vitro differentiation or immunofluorescence staining. 25 8-week-old male Sprague-Dawley rats were allocated to 1 of 5 groups: sham operation group, bilateral CNI group receiving periprostatic implantation of MSCs plus EPCs, MSCs, EPCs, or phosphate buffered saline (control group). 2 weeks after CNI and treatment, erectile function of rats was measured by electrically stimulating the CN. The penis and major pelvic ganglia were harvested for histologic examinations. RNA and protein levels of neurotrophin factors (vascular endothelial growth factor, nerve growth factor, and brain-derived neurotrophic factor) in mono- or coculture MSCs and EPCs were assessed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively., Outcomes: Intracavernous pressure and mean arterial pressure were measured to evaluate erectile function. Histologic examinations of the penis and major pelvic ganglia and RNA and protein levels of neurotrophin factors in MSCs and EPCs were performed., Results: MSCs and EPCs expressed the specified cell markers and exhibited the typical appearance and characteristics. Treatments using MSCs and/or EPCs could increase endothelial and smooth muscle contents of the corpus cavernosum, decrease caspase-3 expression and increase penile neuronal nitric oxide synthase expression, and restore the neural component of the major pelvic ganglia in rats with CNI. Combined transplantation of MSCs and EPCs had a better effect on improving erectile function than single transplantation of MSCs or EPCs. Expression levels of vascular endothelial growth factor and nerve growth factor in coculture MSCs and EPCs were significantly higher than those of primary MSCs or EPCs., Clinical Translation: Combined transplantation of MSCs and EPCs was more effective in restoring erectile function in CNI-related erectile dysfunction models., Strengths and Limitations: The study, for the 1st time, proved that combined transplantation of MSCs and EPCs was more effective in restoring erectile function in rats with CNI. The rat model might not represent the human condition., Conclusion: Combined periprostatic transplantation of MSCs and EPCs could restore erectile function in rats with CNI more effectively. MSCs might restore CN fibers by secreting neurotrophin factors such as vascular endothelial growth factor and nerve growth factor, and EPCs could enhance the paracrine activity of MSCs. Fang J-f, Huang X-n, Han X-y, et al. Combined Transplantation of Mesenchymal Stem Cells and Endothelial Progenitor Cells Restores Cavernous Nerve Injury-Related Erectile Dysfunction. J Sex Med 2018;15:284-295., (Copyright © 2018 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Although rarely reported in the literature, serious occipital and condylar fractures have been diagnosed more often with the widespread use of computed cranial tomography in traumas. In this paper, a 16-year-old female with a left occipital fracture extending from the left occipital condyle anterior of the hypoglossal canal to the inferior part of the clivus is presented. The fracture which had caused a neurological deficit was cured with conservative treatment. For delayed hypoglossal nerve paralysis due to swelling within the canal, methylprednisolone was started, and a complete cure was attained in about 10 days. Traumatic damage of bony structures of the condyle and clivus at the junction of many vital nerves, vessels, and ligaments may lead to traumatic deficit and death., (© 2018 S. Karger AG, Basel.)

Introduction: Cavernous nerve injury (CNI) in rats and radical prostatectomy (RP) in men result in loss of nitrergic function and increased adrenergic-neurogenic contractions of cavernosal tissue., Aim: To evaluate the modulation of the α-adrenergic system as a strategy to relieve erectile dysfunction (ED) and functional cavernosal alterations induced by CNI., Methods: A non-selective α-blocker (phentolamine 1 mg/kg daily), a selective α 1A -blocker (silodosin [SILOD] 0.1 mg/kg daily), or vehicle was orally administered for 4 weeks after bilateral crush CNI (BCNI). Erectile and neurogenic responses of the corpus cavernosum (CC) were evaluated. The acute effects of SILOD also were evaluated in vivo (0.03 mg/kg intravenously) and ex vivo (10 nmol/L). The effects of SILOD and tadalafil (TAD) on nitrergic relaxations were determined in human CC from patients with ED with a vascular etiology or ED secondary to RP., Main Outcome Measures: Erectile responses in vivo in rats and neurogenic contractions and relaxations of rat and human CC., Results: Long-term treatment with SILOD significantly improved erectile responses and allowed for the potentiation of erectile responses by acute treatment with TAD (0.3 mg/kg intravenously) in rats with BCNI. SILOD partly recovered nitrergic relaxations and normalized neurogenic contractions in CC from rats with BCNI. Long-term treatment with SILOD partly prevented BCNI-induced decreases in neuronal nitric oxide synthase expression. Acute administration of SILOD (0.03 mg/kg intravenously) improved erectile responses in vivo and potentiated nitrergic relaxation and decreased neurogenic contractions ex vivo in CC from rats with BCNI. In human CC from patients with ED with a vascular etiology, TAD (30 nmol/L), SILOD (10 nmol/L), or their combination increased nitrergic relaxations. Potentiation by TAD was lost in human CC from patients with ED after RP but was recovered after co-treatment with SILOD., Conclusion: α-Adrenergic modulation, especially selective α 1A -blockade, improves erectile and cavernosal functions after BCNI. Modulation of the adrenergic system, mainly in combination strategies, could have a role in the management of ED after RP., (Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

The present qualitative study was conducted in the second semester of 2014 via interviews with 12 doctors and 13 nurses working as managers at a large hospital that serves as a reference center for urgent and emergent care in the Zona da Mata region of Minas Gerais State, Brazil. The study sought to identify the criteria that doctors and nurses use to discharge individuals with disabling neurological injury with instructions related to accessing physical rehabilitation programs. Thematic content analysis was used to examine data. The results show that the participating hospital managers still have difficulties providing adequate referrals to specialized rehabilitation services and that their patients' autonomy and independence for self-care are impaired as a result. We concluded that in addition to involving relatives and other caregivers in the discharge of patients with a neurological injury that impairs their self-care abilities, managers should assess the accessibility of the patient's home and make adequate referrals to rehabilitation services in the community in light of the poor dispersal of information about what is available within the Care for People with Disability Network.

Myelin accelerates action potential conduction velocity and provides essential energy support for axons. Unfortunately, myelin and myelinating cells are often vulnerable to injury or disease, resulting in myelin damage, which in turn can lead to axon dysfunction, overt pathology and neurological impairment. Inflammation is a common component of trauma and disease in both the CNS and PNS and therefore an active inflammatory response is often considered deleterious to myelin health. While inflammation can certainly damage myelin, inflammatory processes also can positively affect oligodendrocyte lineage progression, myelin debris clearance, oligodendrocyte metabolism and myelin repair. In the periphery, inflammatory cascades can also augment myelin repair, including processes initiated by infiltrating immune cells as well as by local Schwann cells. In this review, various aspects of inflammation beneficial to myelin repair are discussed and should be considered when designing or implementing anti-inflammatory therapies for CNS and PNS injury involving myelinating cells., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The human T-Cell Lymphotropic Virus Type 1 (HTLV-1) is a retrovirus associated with neurological alterations; individuals with HTLV-1 infection may develop HTLV-1 associated myelopathy / tropical spastic paraparesis (HAM/TSP). Frequent neurological complaints include foot numbness and leg weakness. In this study, we compared the distribution of the body weight on different areas of the foot in HTLV-1 patients with HAM/TSP, asymptomatic HTLV-1 patients, and healthy individuals., Methodology: We studied 36 HTLV-1 infected patients, who were divided in two groups of 18 patients each based on whether or not they had been diagnosed with HAM/TSP, and 17 control subjects. The evaluation included an interview on the patient's clinical history and examinations of the patient's reflexes, foot skin tactile sensitivity, and risk of falling. The pressure distribution on different areas of the foot was measured with baropodometry, using a pressure platform, while the patients had their eyes open or closed., Main Findings: The prevalence of neurological disturbances-altered reflexes and skin tactile sensitivity and increased risk of falling-was higher in HTLV-1 HAM/TSP patients than in HTLV-1 asymptomatic patients. The medium and maximum pressure values were higher in the forefoot than in the midfoot and hindfoot in both HTLV-1 groups. In addition, the pressure on the hindfoot was lower in HAM/TSP patients compared to control subjects., Conclusions: The neurological disturbances associated with HTLV-1 infection gradually worsened from HTLV-1 asymptomatic patients to HAM/TSP patients. Baropodometry is a valuable tool to establish the extent of neurological damage in patients suffering from HTLV-1 infection.

Purpose: Recently intracavernous injection of stem cells has garnered great interest as a potential treatment of erectile dysfunction. However, most stem cells are washed out immediately after intracavernous injection. The goal of this study was to investigate using NanoShuttle™ magnetic nanoparticles to maintain stem cells in the corpus cavernosum after intracavernous injection, thereby improving stem cell therapy of erectile dysfunction in an animal model., Materials and Methods: Adipose derived stem cells were magnetized with NanoShuttle magnetic nanoparticles to create Nano-adipose derived stem cells. A total of 24 rats underwent bilateral cavernous nerve crush and were randomly assigned to 3 groups, including adipose derived stem cells, Nano-adipose derived stem cells and Nano-adipose derived stem cells plus magnet. Cells were tracked at days 1, 3, 5 and 9 after intracavernous injection. Another 40 rats with bilateral cavernous nerve crush were randomly assigned to 4 groups, including bilateral cavernous nerve crush, bilateral cavernous nerve crush plus adipose derived stem cell intracavernous injection, bilateral cavernous nerve crush plus Nano-adipose derived stem cell intracavernous injection and bilateral cavernous nerve crush plus Nano-adipose derived stem cell intracavernous injection plus magnet. Functional testing and histological analysis were performed 4 weeks after intracavernous injection., Results: In the in vitro study 1) NanoShuttle magnetic nanoparticles were successfully bound to adipose derived stem cells and 2) Nano-adipose derived stem cells migrated toward the magnet. In the in vivo study 1) cell tracking showed that Nano-adipose derived stem cells were successfully retained in the corpus cavernosum using the magnet for up to 3 days while most adipose derived stem cells were washed out in other groups by day 1 after intracavernous injection, and 2) intracavernous pressure/mean arterial pressure, and αSMA (α-smooth muscle actin) and PECAM-1 (platelet endothelial cell adhesion molecule 1) expression in the Nano-adipose derived stem cell group was significantly higher than in the other groups., Conclusions: Magnetization of adipose derived stem cells with NanoShuttle magnetic nanoparticles kept adipose derived stem cells in the corpus cavernosum and improved adipose derived stem cell therapy of erectile dysfunction in an animal model., (Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Because of the proximity of the oropharynx (a naturally contaminated region) to the spinal structures of the craniocervical junction, it is possible that small mucosal lacerations in the oropharynx caused by unstable traumatic craniocervical injuries may become contaminated and lead to secondary infection and osteomyelitis. In this report, the authors describe the case of a previously healthy and immunocompetent patient who developed a large retropharyngeal abscess with spinal osteomyelitis after a high-energy craniocervical injury. This unusual report of osteomyelitis with a delayed presentation after a high-energy traumatic injury of the craniocervical junction highlights the possibility of direct injury to a specific area in the oropharyngeal mucosa adjacent to the osteoligamentous structures of the craniocervical junction, an overall underrecognized complication of unstable craniocervical injuries.

Many researchers have attempted to pharmacologically modulate the adrenergic system to control locomotion, pain, and spasms after central nervous system (CNS) trauma, although such efforts have led to conflicting results. Despite this, multiple studies highlight that α-adrenoceptors (α-ARs) are promising therapeutic targets because in the CNS, they are involved in reactivity to stressors and regulation of locomotion, pain, and spasms. These functions can be activated by direct modulation of these receptors on neuronal networks in the brain and the spinal cord. In addition, these multifunctional receptors are also broadly expressed on immune cells. This suggests that they might play a key role in modulating immunological responses, which may be crucial in treating spinal cord injury and traumatic brain injury as both diseases are characterized by a strong inflammatory component. Reducing the proinflammatory response will create a more permissive environment for axon regeneration and may support neuromodulation in combination therapies. However, pharmacological interventions are hindered by adrenergic system complexity and the even more complicated anatomical and physiological changes in the CNS after trauma. This review is the first concise overview of the pros and cons of α-AR modulation in the context of CNS trauma., (© 2014 Wiley Periodicals, Inc.)

Study Design: Literature review., Purpose: The corticospinal system (CS) and peripheral nervous system (PNS) are common sites of damage during the early stages of life. The prenatal or immediately prenatal period is the most common time for damage to occur. Here we briefly review the basic features of the development of the CS and the PNS and the clinical consequences of injury to or improper development of these systems on upper extremity (UE) function., Results: The proper development of both the CS and PNS is necessary to achieve adequate function of the (UE). Injury or improper development of these systems can lead to upper extremity dysfunction and limit participation in activities of daily living., Conclusions: Both the PNS and CS play major roles in the proper functioning of the UE. A better understanding of their roles and common developmental disorders is needed to move rehabilitation of motor impairments forward., (Copyright © 2015 Hanley & Belfus. Published by Elsevier Inc. All rights reserved.)

Purpose: Craniocervical arterial dissections (CCADs) represent a preventable cause of acute ischemic stroke (AIS). Our objective was to describe clinical presentation, imaging features, treatment strategies, and report clinical and imaging outcomes of CCADs at a large pediatric tertiary referral center., Methods: Electronic medical records were queried using variations of the word dissection for patients under 25 years of age with neuroimaging over a 13-year period. Medical and imaging records were reviewed to identify carotid, vertebral, or intracranial dissections. Demographics, presenting symptoms, presence of AIS, mechanism of injury, dissection location, dissection treatment, and complications stemming from treatment were collected. Clinical outcome was classified according to modified Rankin Scale (mRS) score. Imaging follow-up was obtained until the dissection healed or stabilized., Results: A total 6,289 patients met initial search criteria. Of the 42 (0.7%) patients with CCADs, 23 (54.8%) had internal carotid artery (ICA) dissections, and 17 (40.5%) had vertebrobasilar (VB) dissections. More females had ICA dissections (p = 0.002), and more males had VB dissections (p = 0.01). CCADs associated with traumatic presentation occurred in 34 patients (81.0%), while 8 (19.0%) were spontaneous. Good outcomes (mRS 0-3) were noted for 36 patients, and 5 had poor outcomes (mRS 4-6). In the 17 patients with vessel occlusion, 50.0% had partial or complete recanalization at a mean follow-up of 23.9 months., Conclusions: CCAD is commonly related to trauma and presents with AIS. The majority of patients experience good clinical outcome. Recanalization of initial vessel occlusion occurs in half of cases at 2 years.

Background: Postoperative pain is an important adverse event following inguinal hernia repair. The aim of this trial was to compare postoperative pain within the first 3 months and 1 year after surgery in patients undergoing open mesh inguinal hernia repair using either a self-gripping lightweight polyester mesh or a polypropylene lightweight mesh fixed with sutures., Methods: Adult men undergoing Lichtenstein repair for primary inguinal hernia were randomized to ProGrip™ self-gripping mesh or standard sutured lightweight polypropylene mesh., Results: In total 557 men were included in the final analysis (self-gripping mesh 270, sutured mesh 287). Early postoperative pain scores were lower with self-gripping mesh than with sutured lightweight mesh: mean visual analogue pain score relative to baseline +1·3 and +8·6 respectively at discharge (P = 0·033), and mean surgical pain scale score relative to baseline +4·2 and +9·7 respectively on day 7 (P = 0·027). There was no significant difference in mid-term (1 month) and long-term (3 months and 1 year) pain scores between the groups. Surgery was significantly quicker with self-gripping mesh (mean difference 7·6 min; P < 0·001). There were no significant differences in reported mesh handling, analgesic consumption, other wound complications, patient satisfaction or hernia recurrence between the groups., Conclusion: Self-gripping mesh for open inguinal hernia repair was well tolerated and reduced early postoperative pain (within the first week), without increasing the risk of early recurrence. It did not reduce chronic pain., Registration Number: NCT00827944 (http://www.clinicaltrials.gov)., (© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.)

Cumulating evidence indicated that nerve injury-associated cellular and molecular changes play an essential role in contributing to the development of pathological pain, and more recent findings implicated the critical role of epigenetic mechanisms in pain-related sensitization in the DRG subsequent to nerve injury. In this part of the dyad review (Part II), we reviewed and paid special attention on the etiological contribution of DGR gene expression modulated by epigenetic mechanisms of CRPS. As essential effectors to different molecular activation, we first discussed the activation of various signaling pathways that subsequently from nerve injury, and in further illustrated the fundamental and functional underpinnings of nerve injury-induced pain, in which we argued for the potential epigenetic mechanisms in response to sensitizing stimuli or injury. Therefore, understanding the specific mediating factors that influence individual epigenetic differences contributing to pain sensitivity and responsiveness to analgesics possesses crucial clinical implications.

Introduction: Bilateral cavernous nerve injury (BCNI) causes profound penile changes such as apoptosis and fibrosis leading to erectile dysfunction (ED). Histone deacetylase (HDAC) has been implicated in chronic fibrotic diseases., Aims: This study will characterize the molecular changes in penile HDAC after BCNI and determine if HDAC inhibition can prevent BCNI-induced ED and penile fibrosis., Methods: Five groups of rats (8-10 weeks, n = 10/group) were utilized: (i) sham; (ii and iii) BCNI 14 and 30 days following injury; and (iv and v) BCNI treated with HDAC inhibitor valproic acid (VPA 250 mg/kg; 14 and 30 days). All groups underwent cavernous nerve stimulation (CNS) to determine intracavernosal pressure (ICP). Penile HDAC3, HDAC4, fibronectin, and transforming growth factor-β1 (TGF-β1) protein expression (Western blot) were assessed. Trichrome staining and the fractional area of fibrosis were determined in penes from each group. Cavernous smooth muscle content was assessed by immunofluorescence to alpha smooth muscle actin (α-SMA) antibodies., Main Outcome Measures: We measured ICP; HDAC3, HDAC4, fibronectin, and TGF-β1 protein expression; penile fibrosis; penile α-SMA content., Results: There was a voltage-dependent decline (P < 0.05) in ICP to CNS 14 and 30 days after BCNI. Penile HDAC3, HDAC4, and fibronectin were significantly increased (P < 0.05) 14 days after BCNI. There was a slight increase in TGF-β1 protein expression after BCNI. Histological analysis showed increased (P < 0.05) corporal fibrosis after BCNI at both time points. VPA treatment decreased (P < 0.05) penile HDAC3, HDAC4, and fibronectin protein expression as well as corporal fibrosis. There was no change in penile α-SMA between all groups. Furthermore, VPA-treated BCNI rats had improved erectile responses to CNS (P < 0.05)., Conclusion: HDAC-induced pathological signaling in response to BCNI contributes to penile vascular dysfunction. Pharmacological inhibition of HDAC prevents penile fibrosis, normalizes fibronectin expression, and preserves erectile function. The HDAC pathway may represent a suitable target in preventing the progression of ED occurring post-radical prostatectomy., (© 2014 International Society for Sexual Medicine.)

Perinatal asphyxia during delivery produces long-term disability and represents a major problem in neonatal and pediatric care. Numerous neuroprotective approaches have been described to decrease the effects of perinatal asphyxia. Enriched environment is a popular strategy to counteract nervous system injuries. The aim of the present study was to investigate whether enriched environment is able to decrease the asphyxia-induced neurobehavioral developmental delay in neonatal rats. Asphyxia was induced in ready-to-deliver mothers by removing the pups by caesarian section after 15 min of asphyxia. Somatic and neurobehavioral development was tested daily and motor coordination weekly. Our results show that rats undergoing perinatal asphyxia had a marked developmental delay and worse performance in motor coordination tests. However, pups kept in enriched environment showed a decrease in the developmental delay observed in control asphyctic pups. Rats growing up in enriched environment did not show decrease in weight gain after the first week and the delay in reflex appearance was not as marked as in control rats. In addition, the development of motor coordination was not as strikingly delayed as in the control group. Short-term neurofunctional outcome are known to correlate with long-term deficits. Our results thus show that enriched environment could be a powerful strategy to decrease the deleterious developmental effects of perinatal asphyxia.

Background: Craniocervical distraction injuries, including atlanto-axial dislocation (AAD) and atlanto-ocipital dislocation (AOD), are often associated with severe spinal cord involvement with high morbidity and mortality rates. Many patients with these injuries die at the accident scene, but advances in emergency resuscitation and transport permit that many patients arrive alive to hospitals., Discussion: Children with craniocervical distraction injuries usually present with a severe cranioencephalic traumatism that is the most relevant lesion at admission. After resuscitation and hemodynamic stabilization, the spinal cord damage appears as the main lesion. Apnea and quadriparesis, or quadriplegia, are usually present at the onset. Early diagnosis and management perhaps decrease life-threatening manifestations of the spinal lesion. But even so, the primary spinal cord insult is often irreversible and precludes obtaining a satisfactory functional outcome., Patients and Methods: We report the findings of four children with craniocervical distraction injuries (AOD and AAD) who presented with severe spinal cord damage. All patients were admitted with respiratory distress or apnea together with significant brain injuries. The medical records pertaining to these patients are summarized in regard to clinical features, management, and outcome., Conclusions: In spite of timely and aggressive management, craniocervical injuries with spinal cord involvement continue to have a dismal prognosis. Outcome is closely related to the severity of the initial brain and spinal cord damage and is nearly always fatal in cases of complete spinal cord transection. Priority should be given to life-threatening complications. Ethic issues on indications for surgery deserve a detailed discussion with the children's parents.

Following injury or disease, the central nervous system (CNS), to varying degrees, loses neurons, synaptic connections and conduction-promoting myelin insulation altering the neural circuitry assembled during development. This "New Anatomy" changes neural processing, bringing spasticity, paresis and paralysis to motor function and altered sensation, numbness and pain to sensory function. Focusing on the effects of CNS damage on the motor subsystems, this review offers a neurophysiological assessment perspective developed within the study of human spinal cord injury and extends it to other CNS disorders. It puts forward the concept that there are essential domains of CNS processing, altered by most neurological disorders, that are temporal, the speed of activation and deactivation, and spatial, the distribution across multiple muscles of motor units selected and activated. Measured through multiple-muscle recordings of selected motor-task performance, these domains can be useful in quantifying the severity of CNS damage and changes achieved through recovery or treatment., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Unlabelled: What's known on the subject? and What does the study add? With the present study, we aimed to provide a global picture of the molecular processes that are activated by CN injury. The present study used genomic expression profiling to identify candidate genes that might be useful targets in the CN recovery process and, thus, the ultimate preservation of penile erection. Regeneration of the CN and axonal outgrowth clearly involve changes in multiple biochemical pathways that have never been investigated by microarray analysis. We analyzed global gene expression in the major pelvic ganglion at early stages (48 h and 14 days) after CN injury and focused on the detection of changes in genes related to nervous tissue repair and proliferation. The findings of the present study provide important insight into the molecular systems affected by CN injury and identify candidate genes that may be utilized for novel molecular-based therapies for the preservation and protection of the CN during RP., Objectives: To to examine the complexity of the many molecular systems involved in supporting cavernous nerve (CN) repair and regeneration in a rat model of bilateral crush injury utilizing a microarray analysis approach. Erectile dysfunction (ED) is a common clinical complication after prostate cancer treatment by radical prostatectomy, and recovery of erectile function can take as long as 2 years. There are gaps in our understanding of the autonomic pelvic innervation of the penis that still need to be addressed for the development of an adequate treatment strategy for post-prostatectomy ED. The molecular mechanisms of the intrinsic ability of CN to regenerate after an injury have not been elucidated., Materials and Methods: We analyzed global gene expression in the major pelvic ganglion 48 h and 14 days after CN injury. Overall, a comparative analysis showed that 325 genes changed at the 48-h time point and 114 genes changed at 14 days. There were 60 changed genes in common with both time points. Using the Ingenuity Pathway Analysis® system (Ingenuity Systems, Inc., Redwood City, CA, USA), we were able to analyze the significantly changed genes that were unique and common to each time point by biological function. We focused on the detection of changes related to nervous tissue repair and proliferation, molecular networks of neurotrophic factors, stem cell regulation and synaptic transmission., Results: There was strong evidence of the early mobilization of genes involved in repair and neuroprotection mechanisms (SERPINF1, IGF1, PLAU/PLAUR, ARG1). Genes related to nervous system development (ATF3 GJA1, PLAU, SERPINE1), nerve regeneration (SERPINE2, IGF1, ATF3, ARG1) and synaptic transmission (GJC1, GAL) were changed. Several genes related to proliferation as well as apoptosis (A2M, ATF3, C3, EGR4, FN1, GJA1, GAL) were also changed, possibly as part of a protective mechanism or the initiation of remodelling., Conclusions: The results obtained show that multiple biological processes are associated with injury and repair of the CN and provide a systematic genome-wide screen for neurotrophic and/or inhibitory pathways of nerve regeneration. These data identify the candidate genes that may be utilized in novel molecular-based therapies for the preservation and protection of the CN during radical prostatectomy., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Although techniques for acute pain management have improved in recent years, a dramatic reduction in the incidence and severity of chronic pain following surgery has not occurred. Amputation and thoracotomy, although technically different, share the commonalities of unavoidable nerve injury and the frequent presence of persistent postsurgical neuropathic pain. The authors review the risk factors for the development of chronic pain following these surgeries and the current evidence that supports analgesic interventions. The inconclusive results from many preemptive analgesic studies may require us to reconceptualize the perioperative treatment period as a time of gradual neurologic remodeling., (Published by Elsevier Inc.)

In the article the questions of ways of development of the dissipated sclerosis, as nosologies, are affected from the group of autoimmune diseases. Examined etiology, epidedemiologiya, separate links of pathogeny of the dissipated sclerosis. The analysis of multifaktors of his origin is conducted, with the detailed study of internal and external factors, marked on the important role of inherited predisposition, infectious and klimato-geograficheskogo factors in genesis of the dissipated sclerosis.

Introduction: Clinical neurophysiological methods remain interesting research tools in urogynecology; their diagnostic role in the individual "pelvic floor" patient is, however, minor., Conclusion: The methods are diagnostically useful particularly in patients suspected to have a lesion involving the sphincters or the peripheral sacral nervous system, the diagnosis of which will influence management decisions or have prognostic or medicolegal relevance. Most helpful tests are the concentric needle EMG and bulbocavernosus reflex testing.

Objective: Animals with transected nerves may develop self-mutilating behavior (autotomy) directed at the denervated body part. Autotomy is often thought to be a response to deafferentation pain produced by pathological changes in the dorsal horn, and self-mutilation after dorsal rhizotomy has consequently been used as an outcome measure for the investigation of chronic pain in animal models. A less recognized hypothesis suggests that autotomy is simply an animal's efforts to remove the useless part. We report a case of self-mutilation of the thumb and fingers in a patient with loss of all sensory modalities in the arm after brachial plexus avulsion., Conclusion: Asking the patient about the reasons for his self-mutilation provides insights into the cause of autotomy which cannot be established from animal studies. We suggest that autotomy may not be a result of chronic pain, and discuss the human experience and alternative underlying pathological processes., (Wiley Periodicals, Inc.)

The incidence of the neurological damage of due to severe neonatal jaundice is increasing mainly due to early discharge from the hospital. However the molecular mechanisms at the basis of the neurological damage are still largely unknown. We here summarize what is known and what is not yet known on how bilirubin may cause cellular damage to selective regions of the brain. This may hopefully help to develop diagnostic and therapeutic strategies for a more effective handling of this invalidating condition.

Background: The purpose of this study was to evaluate the biomedical and psychosocial factors associated with disability at a minimum of six months following upper-extremity nerve injury., Methods: This cross-sectional study included patients who were assessed between six months and fifteen years following an upper-extremity nerve injury. Assessment measures included patient self-report questionnaires (the Disabilities of the Arm, Shoulder and Hand Questionnaire [DASH]; pain questionnaires; and general health and mental health questionnaires). DASH scores were compared by using unpaired t tests (sex, Workers' Compensation/litigation, affected limb, marital status, education, and geographic location), analysis of variance (nerve injured, work status, and income), or correlations (age and time since injury). Multivariable linear regression analysis was used to evaluate the predictors of the DASH scores., Results: The sample included 158 patients with a mean age (and standard deviation) of 41 ± 16 years. The median time from injury was fourteen months (range, six to 167 months). The DASH scores were significantly higher for patients receiving Workers' Compensation or involved in litigation (p = 0.02), had a brachial plexus injury (p = 0.001), or were unemployed (p < 0.001). There was a significant positive correlation between the DASH scores and pain intensity (r = 0.51, p < 0.001). In the multivariable regression analysis of the predictors of the DASH scores, the following predictors explained 52.7% of the variance in the final model: pain intensity (Beta = 0.230, p = 0.006), brachial plexus injury (Beta = -0.220, p = 0.000), time since injury (Beta = -0.198, p = 0.002), pain catastrophizing score (Beta = 0.192, p = 0.025), age (Beta = 0.187, p = 0.002), work status (Beta = 0.179, p = 0.008), cold sensitivity (Beta = 0.171, p = 0.015), depression score (Beta = 0.133, p = 0.066), Workers' Compensation/litigation (Beta = 0.116, p = 0.049), and female sex (Beta = -0.104, p = 0.090)., Conclusions: Patients with a peripheral nerve injury report substantial disability, pain, and cold sensitivity. Disability as measured with the DASH was predicted by brachial plexus injury, older age, pain intensity, work status, time since injury, cold sensitivity, and pain catastrophizing.

Objectives: The purpose of this study is to evaluate a consecutive series of proximally porous-coated hemiarthroplasty for the treatment of severe proximal humeral fractures with special emphasis on aseptic loosening and functional outcome., Design: Observational cohort of a consecutive series of a single prosthetic design., Setting: Orthopaedic clinic, nonacademic institutional hospital., Patients/participants: All patients (n = 30) treated with hemiarthroplasty for severe fractures of the proximal humerus with informed consent and at least 1 year follow-up were included. Follow-up averaged 37 months (range, 13-62 months)., Intervention: Uncemented proximally porous-coated hemiarthroplasty., Main Outcome Measurements: We evaluated clinical and radiologic aseptic loosening, Constant score, patient satisfaction and visual analog scale score, range of motion, radiologic parameters such as head-to-tuberosity distance, lateral projection, and lateral offset., Results: : The overall Constant score was 68 (standard deviation [SD] 18), the mean patient satisfaction 7.1 (SD 1.8), and the average visual analog scale score 3.7 (SD 2.5). We observed no cases of radiographic tilting or subsidence. In 17 cases (57%), radiolucent lines 1.0 mm or less were observed in less than three zones. None of the cases met the criteria for radiographic loosening. No revision was performed for aseptic loosening. The average head-to-tuberosity distance was 7.6 (SD 8.7 mm). We found that traumatic neurologic deficit and head-to-tuberosity distance significantly influenced Constant score. Lateral projection significantly correlated with Constant score, active forward flexion, and abduction., Conclusions: Proximally porous-coated hemiarthroplasty is a valuable alternative alongside cemented hemiarthroplasty for the treatment of severe fractures of the proximal humerus. The radiographic finding of increased lateral projection was associated with an improved range of motion.

Neurons have two types of processes: axons and dendrites. Axons have an active disassembly program activated by severing. It has not been tested whether dendrites have an analogous program. We sever Drosophila dendrites in vivo and find that they are cleared within 24 h. Morphologically, this clearance resembles developmental dendrite pruning and, to some extent, axon degeneration. Like axon degeneration, both injury-induced dendrite degeneration and pruning can be delayed by expression of Wld(s) or UBP2. We therefore hypothesized that they use common machinery. Surprisingly, comparison of dendrite pruning and degeneration in the same cell demonstrated that none of the specific machinery used to prune dendrites is required for injury-induced dendrite degeneration. In addition, we show that the rapid program of dendrite degeneration does not require mitochondria. Thus, dendrites do have a rapid program of degeneration, as do axons, but this program does not require the machinery used during developmental pruning.

Aims: The specific aims were to (1) define fever from the nurse's perspective; (2) describe fever management decision-making by nurses and (3) describe barriers to evidence-based practice across various settings., Background: Publication of practice guidelines, which address fever management, has not yielded improvements in nursing care. This may be related to differences in ways nurses define and approach fever., Method: The collective case study approach was used to guide the process of data collection and analysis. Data were collected during 2006-7. Transcripts were coded using the constant comparative method until themes were identified. Cross-case comparison was conducted. The nursing process was used as an analytical filter for refinement and presentation of the findings., Findings: Nurses across settings defined fever as a (single) elevated temperature that exceeded some established protocol. Regardless of practice setting, interventions chosen by nurses were frequently based on trial and error or individual conventions -'what works'- rather than evidence-based practice. Some nurses' accounts indicated use of interventions that were clearly contraindicated by the literature. Participants working on dedicated neuroscience units articulated specific differences in patient care more than those working on mixed units., Conclusions: By defining a set temperature for intervention, protocols may serve as a barrier to critical clinical judgment. We recommend that protocols be developed in an interdisciplinary manner to foster local adaptation of best practices. This could further best practice by encouraging individual nurses to think of protocols not as a recipe, but rather as a guide when individualizing patient care. There is value of specialty knowledge in narrowing the translational gap, offering institutions evidence for planning and structuring the organization of care., (© 2010 The Authors. Journal of Advanced Nursing © 2010 Blackwell Publishing Ltd.)

The neuropathic pain syndrome is complex. Current drugs to treat neuropathic pain, including anticonvulsivants and antidepressants, fail in up to 40-50% of the patients, while in the rest of them total alleviation is not normally achieved. Increased research advances in the neurobiology of neuropathic pain have not translated in more successful pharmacological treatments by the moment, but recent progress in the experimental methods available for this purpose could result in significant advances in the short term. One rational possibility for the pharmaceutical development of new drugs, including target identification, drug design and evaluation studies, could be to focus on mimicking what organism does to limit nerve damage or to enhance the regeneration of injured axons. Following this strategy, neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) have been postulated as potential pharmacological targets to treat neuropathic pain. In addition, during the last few years, strong scientific evidences point to novel neurotrophic factors, such as pleiotrophin (PTN), as important factors to limit neuropathic pain development because of their remodeling and angiogenic actions in the injured area. This review focuses on recent research advances identifying new pharmacological targets in the treatment of the cause, not only the symptoms, of neuropathic pain.

Purpose: In this study, prophylactic penile rehabilitation (PR) with sildenafil before and after a cavernosal nerve (CN) injury was analyzed in an animal model., Materials and Methods: Thirty-six animals were divided into six groups as follows: (1) those with no CN injury (i.e., sham), (2) those with a bilateral CN injury (i.e., control), (3, 4) those with a bilateral CN injury treated with 10-20 mg/kg of sildenafil subcutaneously (SC) on a daily basis commencing 1 month prior to and after nerve injuries, respectively, (5, 6) those with a bilateral CN injury treated daily with 10-20 mg/kg of sildenafil SC after the nerve injuries, respectively. Mean arterial pressure (MAP) and intracavernosal pressure (ICP) were measured in response to CN stimulation to assess erectile function (EF). Neuronal nitric oxide synthase (nNOS) immunohistochemical analysis and real-time polymerase chain reaction (RT-PCR) were performed., Results: The maximal ICP/MAP ratio was 60 ± 18% in the sham, 22 ± 5% in the control, 28 ± 9% in Group III, 45 ± 16% in Group IV, 45 ± 17% in Group V, and 49 ± 21% in Group VI. Although EF was improved with sildenafil treatment in a dose-dependent fashion, no statistically significant difference was observed between the preemptive and standard rehabilitation groups. Again, nNOS immunoreactivity and RT-PCR results showed the beneficial effect of sildenafil, but the study did not support the efficacy of preemptive rehabilitation when compared to the standard rehabilitation group., Conclusions: Although, a dose-response relationship was observed for PR treatment with sildenafil; i.e., outcomes improved at higher doses of sildenafil for PR, preemptive PR should not be pursued as an alternative rehabilitation modality.