Autofluorescence is a biomarker of neural stem cell activation state.

Neural stem cells (NSCs) must exit quiescence to produce neurons; however, our understanding of this process remains constrained by the technical limitations of current technologies. Fluorescence lifetime imaging (FLIM) of autofluorescent metabolic cofactors has been used in other cell types to study shifts in cell states driven by metabolic remodeling that change the optical properties of these endogenous fluorophores. Using this non-destructive, live-cell, and label-free strategy, we found that quiescent NSCs (qNSCs) and activated NSCs (aNSCs) have unique autofluorescence profiles. Specifically, qNSCs display an enrichment of autofluorescence localizing to a subset of lysosomes, which can be used as a graded marker of NSC quiescence to predict cell behavior at single-cell resolution. Coupling autofluorescence imaging with single-cell RNA sequencing, we provide resources revealing transcriptional features linked to deep quiescence and rapid NSC activation. Together, we describe an approach for tracking mouse NSC activation state and expand our understanding of adult neurogenesis.

Intra-Articular Platelet Rich Plasma vs Corticosteroid Injections for Sacroiliac Joint Pain: A Double-Blinded, Randomized Clinical Trial.

OBJECTIVE: Using stringent inclusion criteria, a double-blinded study protocol, and fluoroscopically guided injections, we compare intra-articular sacroiliac joint platelet-rich plasma injections with intra-articular steroids. DESIGN: Double-blind, randomized controlled trial. SETTING: Two large university-based interdisciplinary spine centers. SUBJECTS: A total of 26 patients with a positive diagnostic block (>80% relief). METHODS: Subjects who had a positive diagnostic block were randomized to undergo either a fluoroscopically guided intra-articular injection of steroid or a platelet-rich plasma injection. Follow-up was at 1 month, 3 months, and 6 months. Outcomes included level of pain, as indicated on a 0- to 100-mm numeric pain rating scale, and functional disability score, obtained via the Oswestry Disability Index (ODI). RESULTS: At 1, 3, and 6 months, both groups improved; however, subjects who received steroid injections reported lower pain scores than did subjects who received platelet-rich plasma. Using categorical data, we observed significantly more responders (defined as pain scores that improved by 50% or more from baseline) at 1 and 3 months in the group who received steroids than in the group who received platelet-rich plasma. CONCLUSION: Although both groups showed improvements in pain and function, the steroid group had significantly greater response and significantly more responders than did the platelet-rich plasma group.

Investigation of genicular neurotomy of the knee: MRI characterization of anatomy and implications for intervention.

BACKGROUND: Genicular nerve block and subsequent radiofrequency neurotomy (RFN) has emerged as a novel intervention and alternative for total knee arthroplasty in patients with refractory pain from knee osteoarthritis (OA). To our knowledge, there is no cited report correlating the accuracy of localizing the genicular nerves using bony landmarks on magnetic resonance imaging (MRI). OBJECTIVES: To quantify the proximity of superomedial genicular nerve (SMGN), superolateral genicular nerve (SLGN), and inferomedial genicular nerve (IMGN) from a target point. The target point was an intersection marked by a line parallel to the diaphysis and a separate line parallel to the metaphyseal flare along the cortical surfaces of both the femur and tibia. DESIGN: Retrospective chart review. PATIENTS: A total of 25 de-identified knee MRIs were reviewed. METHODS: The coronal proton density fat suppressed sequence was used for identification and localization of the SLGN, SMGN, and IMGN. The neurovascular bundles were traced from posterior location along their origin as they wrap around the distal diaphysis. The nerve locations were determined by consensus measurements performed by two board-certified radiologists with certificates of added qualification in neuroradiology and interventional radiology. The proximity of each respective genicular nerves was measured by drawing a perpendicular line from each genicular nerve to the height of the target point. All measurements were taken on the mid-coronal view at the point of maximal epiphyseal flare. MAIN OUTCOME MEASUREMENTS: Positive values indicated the location of the neurovascular bundle to be superior to the target point. Negative values indicated the location of the neurovascular bundle to be inferior to the target point. RESULTS: The distance between our target point and the inferior border of SLGN ranged from -3 mm to 6 mm. Twenty-three out of 25 (92%) SLGN lied exactly at or above our target intersection. The distance between our target point and the inferior border of SMGN ranged from -1 mm to 2 mm with twenty-two out of 25 (88%) SMGN lied exactly at or above our target point. The distance between our target point and the superior border of IMGN ranged from 0 mm to 3 mm with all (100%) IMGN lying exactly at or above the target point. CONCLUSION: The intersection of the femoral diaphyseal shaft to a line along the metaphyseal flare and the intersection of the tibial diaphyseal shaft to a line along the medial metaphyseal can be used as a target point to localize the genicular nerves with close proximity.

Ultrasound for Lumbar Spinal Procedures.

Ultrasonography has become an increasingly valuable and promising tool for performing image-guided spine interventions. The increase in the use of ultrasound utilization has led to more studies evaluating ultrasound-guided interventional spine procedures in comparison to fluoroscopy and computed tomography. Several studies have investigated the use of ultrasound for lumbosacral pain management procedures with favorable outcomes.

Myofascial Pelvic Pain and Related Disorders.

Myofascial pelvic pain refers to pain in the pelvic floor muscles, the pelvic floor connective tissue, and the surrounding fascia. The cause is often multifactorial and requires treatment that encompasses multiple modalities. This type of pain is often associated with other abdominopelvic disorders, so providers in these specialties need to be aware of these connections. A comprehensive musculoskeletal examination, including evaluation of the pelvic floor muscles, and history are key to diagnosing myofascial pelvic pain. Treatments include physical therapy, muscle relaxers, oral neuromodulators, cognitive-behavioral therapy, and pelvic floor muscle injections.

Treatment of muscle invasive bladder cancer in the elderly: navigating the trade-offs of risk and benefit.

PURPOSE: Despite the fact that bladder cancer patients have the highest median age of any type of cancer, older patients with muscle invasion are often under-treated. METHODS: In this review, we report the most up to date literature on the patterns of care and treatment of older patients with muscle invasive bladder cancer. Data on under-treatment, geriatric principles, cystectomy, perioperative chemotherapy, and bladder preservation for older patients are presented and analyzed. CONCLUSION: Chronologic age should not exclude patients from curative-intent therapy. Functional age as determined by geriatric assessments and multidisciplinary evaluation can help clinicians decide on the best course of treatment for individual patients. Cystectomy, perioperative chemotherapy, and curative-intent bladder preservation are reasonable options in healthy older adults. Observation should be limited to patients with extremely poor performance status and very limited life expectancy.

Secondary acute lymphoblastic leukemia is an independent predictor of poor prognosis.

Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic leukemia (sALL) is poorly characterized. We utilized data from the Surveillance, Epidemiology, and End Results (SEER) 13 database to further elucidate patient characteristics and prognostic factors in sALL. Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers or lymphoma with a latency period of at least 12 months were identified within the SEER 13 database. Survival in sALL and de novo ALL were compared after propensity matching based on age, gender, race, ALL subtype, and year of diagnosis. 4124 cases of de novo ALL and 79 cases of sALL were identified. sALL patients were older at diagnosis (median 62 years vs. 44 years; p<0.01). Overall survival (OS) in sALL was lower than de novo ALL (median 8 months vs. 11 months), 1 year OS: 35% vs. 47% (p=0.05), 2 year OS: 16% vs. 31% (p<0.01), and 5 year OS: 7% vs. 21% (p<0.01). Multivariate analysis revealed sALL as an independent predictor of worsened survival (adjusted HR 1.54; 95% CI 1.16-2.04, p<0.01) after propensity matching.

Ultra low concentrations of morphine increase neurite outgrowth in cultured rat spinal cord and cerebral cortical neurons.

The present study was undertaken to evaluate the effects of ultra low concentrations (10(-9) or 10(-14)M) of morphine on neurite elongation in cultured neurons dissociated from rat spinal cords and cerebral cortex. In fetal serum (FS) or fetal serum-free supplemented with cAMP media, the length of longest neurite was significantly increased by 10(-9) or 10(-14)M morphine. For example, 10(-14)M morphine increased neurite length by 24 +/- 0.5% and 27 +/- 0.3% in spinal cord neurons, and 18 +/- 0.2% and 17 +/- 0.6% in cortical neurons. Morphine (10(-6)M) had no significant effect on neurite length of spinal and cortical neurons. The relative frequency distribution of neurite length revealed 61 +/- 2.7% of spinal neurons and 48 +/- 2.6% of cortical neurons are responsive to ultra low concentrations of morphine. In the responsive populations, morphine (10(-14)M) enhanced the neurite outgrowth in spinal neurons by 58 +/- 0.9% and 48 +/- 1.2% and in cortical neurons by 31 +/- 0.6% and 28 +/- 0.9% in FS and cAMP-supplemented media, respectively. Pretreatment with naloxone did not prevent the morphine effect. The result shows that morphine at ultra low concentrations enhances neurite outgrowth of spinal and cortical neurons via a naloxone-independent mechanism.

Beacon/ubiquitin-like 5-immunoreactivity in the hypothalamus and pituitary of the mouse.

Beacon is a 73-amino acid peptide encoded by a novel gene in the hypothalamus of Israeli sand rat Psammomys obesus. Reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemical techniques were used to investigate the presence of beacon mRNA and the distribution of beacon-immunoreactivity (irBC) in the hypothalamus of ICR mice. RT-PCR experiments revealed beacon mRNA in the mouse hypothalamus. Using a rabbit polyclonal antiserum directed against the synthetic C-terminal peptide fragment (47-73), irBC was detected in the mouse hypothalamus and pituitary. In the hypothalamus, irBC was concentrated in perikarya of the supraoptic (SO), paraventricular (PVH) and accessory neurosecretory nuclei and in cell processes of the median eminence and pituitary stalk. In the pituitary, irBC was noted mainly in the posterior lobe. Double-labeling the hypothalamic sections with guinea-pig vasopressin-antiserum or mouse monoclonal oxytocin-antibody and beacon-antiserum revealed that <30% of vasopressin-immunoreactive neurons and nearly all oxytocin-immunoreactive neurons in the PVH and SO were irBC. The result shows the presence of beacon mRNA in the mouse hypothalamus, and the distribution of irBC is distinctively different from that reported in the hypothalamus of Psammomys obesus, but similar to that of the Sprague-Dawley rats described in our earlier study. More interestingly, Blast search uncovered a 73-amino acid peptide, human ubiquitin-like 5, which has the same exact sequence as beacon. Thus, irBC observed in the mouse brain could be that of ubiquitin-like 5.