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We previously reported that the cell cycle-related cyclin-dependent kinase 4-retinoblastoma (RB) transcriptional corepressor pathway is essential for stroke-induced cell death both in vitro and in vivo However, how this signaling pathway induces cell death is unclear. Previously, we found that the cyclin-dependent kinase 4 pathway activates the pro-apoptotic transcriptional co-regulator Cited2 in vitro after DNA damage. In the present study, we report that Cited2 protein expression is also dramatically increased following stroke/ischemic insult. Critically, utilizing conditional knockout mice, we show that Cited2 is required for neuronal cell death, both in culture and in mice after ischemic insult. Importantly, determining the mechanism by which Cited2 levels are regulated, we found that E2F transcription factor (E2F) family members participate in Cited2 regulation. First, E2F1 expression induced Cited2 transcription, and E2F1 deficiency reduced Cited2 expression. Moreover, determining the potential E2F-binding regions on the Cited2 gene regulatory sequence by ChIP analysis, we provide evidence that E2F1/4 proteins bind to this DNA region. A luciferase reporter assay to probe the functional outcomes of this interaction revealed that E2F1 activates and E2F4 inhibits Cited2 transcription. Moreover, we identified the functional binding motif for E2F1 in the Cited2 gene promoter by demonstrating that mutation of this site dramatically reduces E2F1-mediated Cited2 transcription. Finally, E2F1 and E2F4 regulated Cited2 expression in neurons after stroke-related insults. Taken together, these results indicate that the E2F- Cited2 regulatory pathway is critically involved in stroke injury., (© 2019 Huang et al.)

Background: Roux-en-Y gastric bypass is the gold standard for weight loss surgery. This procedure creates two to three mesenteric defects, depending on ante-colic versus retro-colic technique. Current literature supports mesenteric defect closure, but there is no consensus on how to best close these defects. Described options include running separate suture lines for each defect, or employing endoscopic staplers for defect closure., Methods: This is a video/dynamic manuscript on operative technique., Results: We describe an alternative technique that does not require an extra laparoscopic instrument and is more efficient than traditional suture lines due to less suturing., Conclusions: The technique maintains low gastric bypass complication rates by closing mesenteric defects, while keeping intra-operative costs low, and minimizing time spent on the defect closures.

To raise awareness for surgeons encountering bariatric patients with anatomy that deviates from the standard Roux-en-Y gastric bypass (RYGB). This is a single-institution retrospective case series over 12 years (2003-2014) involving patients who believed they received RYGBs, but actually did not. Data was obtained reviewing physician encounters, imaging, and operative reports. There were six cases with confusing clinical pictures, found to have aberrant RYGB anatomy: (1) gastric bypass with jejuno-jejunostomy only without gastrojejunostomy, (2) distal partial vertical gastrectomy without expected prosthetic band, (3) inverse vertical banded gastroplasty, (4) non-divided gastric bypass with no gastrojejunostomy, (5) 20-cm Roux limb, with gastro-gastric fistula, and (6) 200-cm bilio-pancreatic limb similar to the traditional Scopinaro procedure. There are cases of "Roux-en-Y gastric bypasses" that have no resemblance to the named procedure at all. Adjunctive upper gastrointestinal studies and upper endoscopies help surgeons make diagnoses that are incongruent with the surgical history. It is important to keep in mind that there could be anatomic or surgical variations which were born out of necessity or based on other surgeons' creativities.

Background: Data regarding outcomes after peripheral nerve injuries is limited, and the optimal management strategy for an acute injury is unclear. The aim of this study was to examine timing of repair and specific factors that impact motor-sensory outcomes after peripheral nerve injury., Methods: This was a single-center, retrospective study. Patients with traumatic peripheral nerve injury from January 2010 to June 2015 were included. Patients who died, required amputation, suffered brachial plexus injury, or had missing motor-sensory examinations were excluded. Motor-sensory examinations were graded 0 to 5 by the Modified British Medical Research Council system. Operative repair of peripheral nerves was analyzed for patient characteristics, anatomic nerve injured, level of injury, associated injuries, days until repair, and repair method., Results: Three hundred eleven patients met inclusion criteria. Two hundred fifty-eight (83%) patients underwent operative management, and 53 (17%) underwent nonoperative management. Those who required operative intervention had significantly more penetrating injuries 85.7% versus 64.2% (p < 0.001), worse initial motor scores 1.19 versus 2.23 (p = 0.004), and worse initial sensory examination scores 1.75 versus 2.28 (p = 0.029). Predictors of improved operative motor outcomes on univariate analysis were Injury Severity Score less than 15 (p = 0.013) and male sex (p = 0.006). Upper arm level of injury was a predictor of poor outcome (p = 0.041). Multivariate analysis confirmed male sex as a predictor of good motor outcome (p = 0.014; Adjusted Odds Ratio, 3.88 [1.28-11.80]). Univariate analysis identified distal forearm level of injury (p = 0.026) and autograft repair (p = 0.048) as predictors of poor sensory outcome. Damage control surgery for unstable patients undergoing laparotomy (p = 0.257) and days to nerve repair (p = 0.834) did not influence motor-sensory outcome. Outcomes did not differ significantly in patients who underwent repair 24 hours or longer versus those who were repaired later., Conclusion: Outcomes were primarily influenced by patient characteristics and injury level rather than operative characteristics. Peripheral nerve injuries can be repaired after damage control surgery without detriment to outcomes., Level of Evidence: Prognostic study, level III.

A pilot-scale study was conducted using electrocoagulation technology to treat chlorine dioxide bleaching-stage effluent of a local pulp mill, with the purpose of evaluating the treatment performance. The operating variables were the current density (0 ~ 133.3 A/m(2)) and hydraulic retention time (HRT, 6.5 ~ 16.25 minutes). Water quality indicators investigated were the conductivity, suspended solids (SS), chemical oxygen demand (COD), true color, and hardness. The results showed that electrocoagulation technology can be used to treat D-stage bleaching effluent for water reuse. Under the operating conditions studied, the removal of conductivity and COD always increased with increases in either the current density or HRT. The highest removals obtained at 133.3 A/m(2) and an HRT of 16.25 minutes for conductivity, SS, COD, true color, and hardness were respectively 44.2, 98.5, 75.0, 85.9, and 36.9% with aluminum electrodes. Iron electrodes were not applicable to the D-stage effluent due to formation of dark-colored ferric complexes.

Objective: To report a case of successful treatment of a patient with spontaneous intracranial hypotension correlated with MRI finding of cerebrospinal fluid (CSF) leak with extradural collection at the upper cervical spinal level., Design: Case report., Setting: An academic tertiary pain management center., Methods: Fluoroscopically guided placement of an 18-gauge epidural needle into epidural space at the C7-T1 level was performed; an epidural catheter (Braun Perifix 20G) was advanced to C2 level (first patch) and C3 level (second patch). An epidurogram with Omnipaque injections confirmed contrast in the posterior and lateral epidural space. Autologous venous blood was then administered through the catheter., Results: This patient received two lumbar epidural blood patches without lasting relief. Given the radiographic evidence of prominent CSF leak with extradural fluid collection at C1-2 level, the patient was then treated with a cervical epidural blood patch, which provided headache pain relief lasting 6 months. A second cervical epidural blood patch was performed, and the patient has been headache-free for nearly one year to date., Conclusion: Based on the successful treatment of this patient's spontaneous intracranial hypotension, we advocate that patients undergo epidural blood patches to target the site of any CSF leak identified by imaging studies to improve the efficacy of this intervention. This case demonstrates that cervical epidural blood patch, despite its inherent risks, may be more effective than lumbar epidural blood patch in treatment of cervical CSF leak., (Wiley Periodicals, Inc.)

Cervicogenic headache (CGH) is defined as referred pain from various cervical structures innervated by the upper three cervical spinal nerves. Such structures are potential pain generators, and include the atlanto-occipital joint, atlantoaxial joint, C2-3 zygapophysial joint, C2-3 intervertebral disc, cervical myofascial trigger points, as well as the cervical spinal nerves. Various interventional techniques, including cervical epidural steroid injection (CESI), have been proposed to treat this disorder. And while steroids administered by cervical epidural injection have been used in clinical practice to provide anti-inflammatory and analgesic effects that may alleviate pain in patients with CGH, the use of CESI in the diagnosis and treatment of CGH remains controversial. This article describes the neuroanatomy, neurophysiology, and classification of CGH as well as a review of the available literature describing CESI as treatment for this debilitating condition.

A 42-year-old African American woman with a 5-year history of neuromyelitis optica was found to have an incongruous homonymous hemianopia. Optical coherence tomography (OCT) showed corresponding left homonymous hemimacular thinning. Magnetic resonance imaging of the brain demonstrated a demyelinating lesion in the left optic tract (OT) just anterior to the lateral geniculate nucleus and diffusion tensor magnetic resonance tractography confirmed axonal fiber loss in the left OT. This case illustrates the complementary and confirmatory roles of visual field testing, macular OCT, and neuroimaging in an OT lesion, which caused selective hemimacular thinning through retrograde degeneration.

Much recent research has demonstrated that honokiol, a phenolic compound originally isolated from Magnolia officinalis, has potent anticancer activities; however, the detailed molecular mechanism of its anti-inflammatory activity has not yet been fully addressed. In this study we demonstrated that honokiol inhibited lipopolysaccharide (LPS)-induced tumor necrosis factor-alpha secretion in macrophages, without affecting the activity of the tumor necrosis factor-alpha converting enzyme. At the same time, honokiol not only inhibited nitric oxide expression in LPS-stimulated murine macrophages but also inhibited the LPS-induced phosphorylation of ERK1/2, JNK1/2, and p38. By means of confocal microscope analysis we demonstrated that phosphorylation and membrane translocation of protein kinase C-alpha, as well as NF-kappaB activation, were inhibited by honokiol in LPS-stimulated macrophages. Furthermore, it was found that honokiol neither antagonizes the binding of LPS to cells nor alters the cell surface expression of toll-like receptor 4 and CD14. Our current results have exhaustively described the anti-inflammatory properties of honokiol, which could lead to the possibility of its future pharmaceutical application in the realm of immunomodulation.

Neurons within the olfactory system undergo functional turnover throughout life. This process of cell death and compensatory neurogenesis requires feedback between neuronal populations of different developmental ages. We examined the role of NT-3 in this process. NT-3 was localized within both the olfactory bulb and olfactory epithelium. Mice null for NT-3 showed increased numbers of immature neurons, without change in the number of mature neurons. This was due to compensatory alterations in apoptosis of mature and immature neuronal populations. Using a primary olfactory neuronal culture, NT-3 was found to directly activate the PI3K/Akt pathway and indirectly activate the MAPK and PLC pathways. Activated PI3K/Akt promoted mature neuronal survival and induced the release of secondary factors, which activated the MAPK and PLC pathways to reduce neuronal precursor proliferation and inhibit neuronal maturation. These effects of NT-3 serve to maintain homeostasis between neuronal populations within the olfactory epithelium.