Conservation energetics of beluga whales: using resting and swimming metabolism to understand threats to an endangered population.

The balance between energetic costs and acquisition in free-ranging species is essential for survival, and provides important insights regarding the physiological impact of anthropogenic disturbances on wild animals. For marine mammals such as beluga whales (Delphinapterus leucas), the first step in modeling this bioenergetic balance requires an examination of resting and active metabolic demands. Here, we used open-flow respirometry to measure oxygen consumption during surface rest and submerged swimming by trained beluga whales, and compared these measurements with those of a commonly studied odontocete, the Atlantic bottlenose dolphin (Tursiops truncatus). Both resting metabolic rate (3012±126.0 kJ h-1) and total cost of transport (1.4±0.1 J kg-1 m-1) of beluga whales were consistent with predicted values for moderately sized marine mammals in temperate to cold-water environments, including dolphins measured in the present study. By coupling the rate of oxygen consumption during submerged swimming with locomotor metrics from animal-borne accelerometer tags, we developed predictive relationships for assessing energetic costs from swim speed, stroke rate and partial dynamic acceleration. Combining these energetic data with calculated aerobic dive limits for beluga whales (8.8 min), we found that high-speed responses to disturbance markedly reduce the whale's capacity for prolonged submergence, pushing the cetaceans to costly anaerobic performances that require prolonged recovery periods. Together, these species-specific energetic measurements for beluga whales provide two important metrics, gait-related locomotor costs and aerobic capacity limits, for identifying relative levels of physiological vulnerability to anthropogenic disturbances that have become increasingly pervasive in their Arctic habitats.

Magnetic resonance imaging shows spinal curvature in Chinook salmon (Oncorhynchus tshawytscha) is associated with chronic inflammation of peri-vertebral soft tissues.

Chinook salmon (Oncorhynchus tshawytscha) farmed in New Zealand are known to develop abnormal spinal curvature late in seawater production. Its cause is presently unknown, but there is evidence to suggest a neuromuscular pathology. Using magnetic resonance imaging (MRI), we evaluated the relationship between soft tissue pathology and spinal curvature in farmed Chinook salmon. Regions of interest (ROIs) presenting as pathologic MRI signal hyper-intensity were identified from scans of 24 harvest-sized individuals: 13 with radiographically-detectable spinal curvature and 11 without. ROIs were excised from individuals using anatomical landmarks as reference points and histologically analysed. Pathologic MRI signal was observed more frequently in individuals with radiographic curvature (92%, n = 12) than those without (18%, n = 2), was localized to the peri-vertebral connective tissues and musculature, and presented as three forms: inflammation, fibrosis, or both. These pathologies are consistent with a chronic inflammatory process, such as that observed during recovery from a soft tissue injury, and suggest spinal curvature in farmed Chinook salmon may be associated with damage to and/or compromised integrity of the peri-vertebral soft tissues. Future research to ascertain the contributing factors is required.

A pragmatic randomized prospective trial of cooled radiofrequency ablation of the medial branch nerves versus facet joint injection of corticosteroid for the treatment of lumbar facet syndrome: 12 month outcomes.

BACKGROUND: Lumbar medial branch radiofrequency ablation (LRFA) and intraarticular facet steroid injections (FJI) are commonly performed for recalcitrant facet joint-mediated pain. However, no study has compared clinical outcomes of the two treatments in patients selected using dual medial branch blocks (MBBs) with an 80% relief threshold. OBJECTIVE: Compare the effectiveness of cooled LRFA (C-LRFA) to FIJ as assessed by pain and functional improvements. DESIGN: Prospective randomized comparative trial. METHODS: Patients with dual MBB-confirmed facet joint-mediated pain were randomized to receive C-LRFA or FIJ. Outcomes were assessed at 1, 3, 6, and 12 months. The primary outcome was ≥50% improvement in numerical pain rating scale (NPRS) score at 3 months. Secondary outcomes included ≥30% Oswestry Disability Index (ODI) improvement and Patient Global Impression of Chance (PGIC) ≥6 points, among others. Data were analyzed using contingency tables and mixed-effects logistic regression models. RESULTS: Of 1128 patients screened, 32 met eligibility criteria, were randomized, and received their allocated study treatment. In total, 20 (62.5%) and 12 (37.5%) participants received C-LRFA and FIJ, respectively. In the C-LRFA group, 70% (95% CI 48-85), 55% (95% CI 34-74), and 45% (95% CI 26-66) of participants met the NPRS responder definition, compared to 25% (95%CI 9-53), 25% (95% CI 9-53), and 17% (95% CI 5-45) in the FJI group at 3, 6, and 12 months, respectively (P = .014 at 3 months). The PGIC responder proportion was higher in the C-LRFA compared to FJI group at 3 and 6 months (P < .05). CONCLUSIONS: C-LRFA demonstrated superior success rates compared to FJI across pain and functional outcome domains. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov (NCT03614793); August 3, 2018.

The Relationship Between Patient Demographic and Clinical Characteristics and Successful Treatment Outcomes After Basivertebral Nerve Radiofrequency Ablation: A Pooled Cohort Study of Three Prospective Clinical Trials.

OBJECTIVE: Multiple studies have demonstrated the safety and effectiveness of basivertebral nerve radiofrequency ablation (BVN RFA) for improving low back pain related to the vertebral endplate. However, the influence of patient demographic and clinical characteristics on treatment outcome is unknown. DESIGN: Pooled cohort study of three clinical trials of patients with vertebral endplate pain identified by Type 1 and/or Type 2 Modic changes and a correlating presentation of anterior spinal element pain. SETTING: Thirty-three global study centers. SUBJECTS: Patients (n = 296) successfully treated with BVN RFA. METHODS: Participant demographic and clinical characteristics were analyzed with stepwise logistic regression to identify predictors of treatment success. Three definitions of treatment success were defined: 1) ≥50% visual analog scale pain improvement, 2) ≥15-point Oswestry Disability Index (ODI) improvement, and 3) ≥50% visual analog scale or ≥15-point ODI improvement from baseline. RESULTS: Low back pain of ≥5 years' duration and higher ODI scores at baseline increased the odds of treatment success, whereas baseline opioid use and higher Beck Depression Inventory scores reduced these odds. However, the three regression models demonstrated receiver-operating characteristics of 62-70% areas under the curve, and thus, limited predictive capacity. CONCLUSIONS: This analysis identified no demographic or clinical characteristic that meaningfully increased or reduced the odds of treatment success from BVN RFA. On the basis of these findings and the high response rates from the three analyzed trials, we recommend the use of objective imaging biomarkers (Type 1 and/or 2 Modic changes) and a correlating presentation of anterior spinal element pain to determine optimal candidacy for BVN RFA.

Pain Location and Exacerbating Activities Associated with Treatment Success Following Basivertebral Nerve Ablation: An Aggregated Cohort Study of Multicenter Prospective Clinical Trial Data.

OBJECTIVE: Develop pain location "maps" and investigate the relationship between low back pain (LBP)-exacerbating activities and treatment response to basivertebral nerve radiofrequency ablation (BVN RFA) in patients with clinically suspected vertebral endplate pain (VEP). DESIGN: Aggregated cohort study of 296 patients treated with BVN RFA at 33 centers in three prospective trials. METHODS: Participant demographics, pain diagrams, and LBP-exacerbating activities were analyzed for predictors using stepwise logistic regression. Treatment success definitions were: (1) ≥50% LBP visual analog scale (VAS), (2) ≥15-point Oswestry Disability Index (ODI), and (3) ≥50% VAS or ≥15-point ODI improvements at 3 months post-BVN RFA. RESULTS: Midline LBP correlated with BVN RFA treatment success in individuals with clinically-suspected VEP. Duration of pain ≥5 years (OR 2.366), lack of epidural steroid injection within 6 months before BVN RFA (OR 1.800), lack of baseline opioid use (OR 1.965), LBP exacerbation with activity (OR 2.099), and a lack of LBP with spinal extension (OR 1.845) were factors associated with increased odds of treatment success. Regressions areas under the curve (AUCs) were under 70%, indicative of low predictive value. CONCLUSIONS: This study demonstrates that midline LBP correlates with BVN RFA treatment success in individuals with VEP. While none of the regression models demonstrated strong predictive value, the pain location and exacerbating factors identified in this analysis may aid clinicians in identifying patients where VEP should be more strongly suspected. The use of objective imaging biomarkers (Type 1 and/or 2 Modic changes) and a correlating presentation of anterior spinal element pain remain the most useful patient selection factors for BVN RFA.

In-air hearing in Hawaiian monk seals: implications for understanding the auditory biology of Monachinae seals.

The auditory biology of Monachinae seals is poorly understood. Limited audiometric data and certain anatomical features suggest that these seals may have reduced sensitivity to airborne sounds compared to related species. Here, we describe the in-air hearing abilities of a Hawaiian monk seal (Neomonachus schauinslandi) trained to participate in a psychophysical paradigm. We report absolute (unmasked) thresholds for narrowband signals measured in quiet conditions across the range of hearing and masked thresholds measured in the presence of octave-band noise at two frequencies. The behavioral audiogram indicates a functional hearing range from 0.1 to 33 kHz and poor sensitivity, with detection thresholds above 40 dB re 20 µPa. Critical ratio measurements are elevated compared to those of other seals. The apparently reduced terrestrial hearing ability of this individual-considered with available auditory data for a northern elephant seal (Mirounga angustirostris)-suggests that hearing in Monachinae seals differs from that of the highly sensitive Phocinae seals. Exploration of phylogenetic relationships and anatomical traits support this claim. This work advances understanding of the evolution of hearing in amphibious marine mammals and provides updated information that can be used for management and conservation of endangered Hawaiian monk seals.

Metabolic trade-offs in tropical and subtropical marine mammals: unique maintenance and locomotion costs in West Indian manatees and Hawaiian monk seals.

Unlike the majority of marine mammal species, Hawaiian monk seals (Neomonachus schauinslandi) and West Indian manatees (Trichechus manatus latirostris) reside exclusively in tropical or subtropical waters. Although potentially providing an energetic benefit through reduced maintenance and thermal costs, little is known about the cascading effects that may alter energy expenditure during activity, dive responses and overall energy budgets for these warm-water species. To examine this, we used open-flow respirometry to measure the energy expended during resting and swimming in both species. We found that the average resting metabolic rates (RMRs) for both the adult monk seal (753.8±26.1 kJ h-1, mean±s.e.m.) and manatees (887.7±19.5 kJ h-1) were lower than predicted for cold-water marine mammal species of similar body mass. Despite these relatively low RMRs, both total cost per stroke and total cost of transport (COTTOT) during submerged swimming were similar to predictions for comparably sized marine mammals (adult monk seal: cost per stroke=5.0±0.2 J kg-1 stroke-1, COTTOT=1.7±0.1 J kg-1 m-1; manatees: cost per stroke=2.0±0.4 J kg-1 stroke-1, COTTOT=0.87±0.17 J kg-1 m-1). These lower maintenance costs result in less variability in adjustable metabolic costs that occur during submergence for warm-water species. However, these reduced maintenance costs do not appear to confer an advantage in overall energetic costs during activity, potentially limiting the capacity of warm-water species to respond to anthropogenic or environmental threats that require increased energy expenditure.

The Effectiveness of Intraosseous Basivertebral Nerve Radiofrequency Neurotomy for the Treatment of Chronic Low Back Pain in Patients with Modic Changes: A Systematic Review.

OBJECTIVE: Determine the effectiveness of intraosseous basivertebral nerve radiofrequency neurotomy for the treatment of chronic low back pain with type 1 or 2 Modic changes. DESIGN: Systematic review. POPULATION: Persons aged ≥18 years with chronic low back pain with type 1 or 2 Modic changes. INTERVENTION: Intraosseous basivertebral nerve radiofrequency neurotomy. COMPARISON: Sham, placebo procedure, active standard care treatment, or none. OUTCOMES: The primary outcome of interest was the proportion of individuals with ≥50% pain reduction. Secondary outcomes included ≥10-point improvement in function as measured by Oswestry Disability Index as well as ≥2-point reduction in pain score on the Visual Analog Scale or Numeric Rating Scale, and decreased use of pain medication. METHODS: Three reviewers independently assessed publications before May 15, 2020, in MEDLINE and Embase and the quality of evidence was evaluated using the Grades of Recommendation, Assessment, Development, and Evaluation framework. RESULTS: Of the 725 publications screened, seven publications with 321 participants were ultimately included. The reported 3-month success rate for ≥50% pain reduction ranged from 45% to 63%. Rates of functional improvement (≥10-point Oswestry Disability Index improvement threshold) ranged from 75% to 93%. For comparison to sham treatment, the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 1.25 (95% confidence interval [CI]: .88-1.77) and 1.38 (95% CI: 1.10-1.73), respectively. For comparison to continued standard care treatment the relative risk of treatment success defined by ≥50% pain reduction and ≥10-point Oswestry Disability Index improvement was 4.16 (95% CI: 2.12-8.14) and 2.32 (95% CI: 1.52-3.55), respectively. CONCLUSIONS: There is moderate-quality evidence that suggests this procedure is effective in reducing pain and disability in patients with chronic low back pain who are selected based on type 1 or 2 Modic changes, among other inclusion and exclusion criteria used in the published literature to date. Success of the procedure appears to be dependent on effective targeting of the BVN. Non-industry funded high-quality, large prospective studies are needed to confirm these findings.

The Total Synthesis of (-)-Scabrolide A.

The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels-Alder reaction and an enone-olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5-6-7] linear carbocyclic core of the molecule and complete the total synthesis.

Relationship between rheological properties and transverse relaxation time (T2) of artificial and porcine vitreous humour.

Vitreous liquefactive processes play an integral role in ocular health. Knowledge of the degree of liquefaction would allow better monitoring of ocular disease progression and enable more informed therapeutic dosing for an individual patient. Presently this process cannot be monitored in a non-invasive manner. Here, we evaluated whether magnetic resonance imaging (MRI) could predict the viscoelasticity and in turn liquefactive state of artificial and biological vitreous humour. Gels comprising identical concentrations of hyaluronic acid and agar ranging from 0.125 to 2.25 mg/ml of each polymer were prepared and their T2 was measured using a turbo-spin echo sequence via 3T clinical MRI. The gels were subsequently subjected to rheological frequency and flow sweeps and trends between T2 and rheological parameters were assessed. The relationship between T2 and vitreous humour rheology was further assessed using ex vivo porcine eyes. An optimised imaging technique improved homogeneity of obtained artificial vitreous humour T2 maps. Strong correlations were observed between T2 and various rheological parameters of the gels. Translation to porcine vitreous humour demonstrated that the T2 of biological tissue was related to its viscoelastic properties. This study shows that T2 can be correlated with various rheological parameters within gels. Future investigations will assess the translatability of these findings to live models.

Ex vivo cardiovascular magnetic resonance diffusion weighted imaging in congenital heart disease, an insight into the microstructures of tetralogy of Fallot, biventricular and univentricular systemic right ventricle.

PURPOSE: Common types of congenital heart disease exhibit a variety of structural and functional variations which may be accompanied by changes in the myocardial microstructure. We aimed to compare myocardial architecture from magnetic resonance diffusion tensor imaging (DTI) in preserved pathology specimens. MATERIALS AND METHODS: Pathology specimens (n = 24) formalin-fixed for 40.8 ± 7.9 years comprised tetralogy of Fallot (TOF, n = 10), dextro-transposition of great arteries (D-TGA, n = 8) five with ventricular septal defect (VSD), systemic right ventricle (n = 4), situs inversus totalis (SIT, n = 1) and levo-TGA (L-TGA, n = 1). Specimens were imaged using a custom spin-echo sequence and segmented automatically according to tissue volume fraction. In each specimen T1, T2, fractional anisotropy, mean diffusivity, helix angle (HA) and sheet angle (E2A) were quantified. Pathologies were compared according to their HA gradient, HA asymmetry and E2A mean value in each myocardial segment (anterior, posterior, septal and lateral walls). RESULTS: TOF and D-TGA with VSD had decreased helix angle gradient by - 0.34°/% and remained symmetric in the septum in comparison to D-TGA without VSD. Helix angle range was decreased by 45°. It was associated with a decreased HA gradient in the right ventricular (RV) wall, i.e. predominant circumferential myocytes. The sheet angle in the septum of TOF was opposing those of the left ventricular (LV) free wall. Univentricular systemic RV had the lowest HA gradient (- 0.43°/%) and the highest HA asymmetry (75%). HA in SIT was linear, asymmetric, and reversed with a sign change at about 70% of the depth at mid-ventricle. In L-TGA with VSD, HA was asymmetric (90%) and its gradients were decreased in the septum, anterior and lateral wall. CONCLUSION: The organization of the myocytes as determined by DTI differs between TOF, D-TGA, L-TGA, systemic RV and SIT specimens. These differences in cardiac structure may further enlighten our understanding of cardiac function in these diverse congenital heart diseases.

Prevalence and Discordance of the "Startle Response" with True Discogenic Pain According to Spine Intervention Society Guidelines for Provocation Discography: A Cohort Study.

SUMMARY OF BACKGROUND DATA: The literature on cervical provocation discography (C-PD) is sparse. A "Startle Response" during C-PD is a known phenomenon that might be mistaken as an indicator of discogenic pain at the provoked disc level, but this has not been quantitatively described. OBJECTIVES: To determine the incidence of the Startle Response and its concordance/discordance with true-positive C-PD in patients referred for surgical planning or evaluation after ruling out other axial pain generators. METHODS: Retrospective cohort study of consecutive patients who received C-PD at an outpatient spine center. The primary outcome was the rate of discordance of the Startle Response with true-positive C-PD according to the operational criteria of the Spine Intervention Society (SIS) guidelines. RESULTS: One hundred five discs were provoked in 36 individuals (19 female, mean age [SD] = 45.7 [10.9] years). C-PD was performed at a median of three levels (range = 1-5) with C4/5 (N = 30), C5/6 (N = 30), and C6/7 (N = 31) the most commonly evaluated. Twenty-six of 36 patients reported responses consistent with true-positive C-PD. A Startle Response was observed in 14 patients (39%, 95% confidence interval [CI] = 23-57%), and 22 of 105 (21%, 95% CI = 14-30%) provoked discs. Of the 14 patients who exhibited a Startle Response, four had negative C-PD results (29%, 95% CI = 8-58%). As assessed per disc, C-PD results were positive in 12 of the 22 (55%, 95% CI = 32-76%) provoked discs that generated a Startle Response. CONCLUSIONS: The present data demonstrate high discordance, 45% (95% CI = 24-68%), between the Startle Response and true-positive C-PD. Clinicians should be aware of this phenomenon and take care to distinguish it from a true-positive response during C-PD, as defined by the SIS guidelines. Misinterpretation of the Startle Response as a positive C-PD result may lead to inappropriate future care decisions in a substantial proportion of patients.

Genicular Nerve Radiofrequency Ablation for Chronic Knee Pain Using a Three-Tined Electrode: A Technical Description and Case Series.

BACKGROUND: Genicular nerve radiofrequency ablation (RFA) for the treatment of chronic knee pain has traditionally targeted the superomedial, superolateral, and inferomedial genicular nerves. However, recent cadaveric studies of knee neuroanatomy demonstrate varied locations of these specific nerves as well as additional articular nerves. This work suggests that traditional genicular nerve RFA lesion locations may be inadequate. OBJECTIVE: 1) To describe a novel protocol utilizing a three-tined RFA electrode to target the superomedial (SMGN), superolateral (SLGN), and inferomedial genicular nerves (IMGN), as well as the terminal articular branches of the nerves to the vastus medialis (NVM), intermedius (NVI), and lateralis (NVL). 2) To assess the ability of this technique to reduce chronic knee pain. METHODS: Case series of consecutive patients with six or more months of refractory knee pain who underwent genicular nerve RFA according to the novel protocol described. Seven discrete RFA lesions were placed to target the SMGN, NVM, NVI, NVL, SLGN, and IGMN. RESULTS: Eleven patients underwent RFA, nine with knee osteoarthritis and two postarthroplasty. At one month, 91% (95% CI = 59-100%), 82% (95% CI = 48-98%), and 9% (95% CI = 2-41%), of patients reported ≥50%, ≥80%, and 100% improvement in knee pain on the numeric rating scale, respectively. These results were sustained at six months. There were no complications. DISCUSSION/CONCLUSIONS: These preliminary data suggest the feasibility and possible effectiveness of genicular nerve RFA using the described novel protocol including a three-tined electrode. Larger-scale studies with comparative groups are warranted.

Does the Contrast Dispersion Pattern During Fluoroscopically Guided Cervical Transforaminal Epidural Steroid Injection Predict Short-Term Pain and Functional Outcomes? An Exploratory Analysis of Prospective Cohort Data.

SUMMARY OF BACKGROUND DATA: No study has evaluated the relationship between contrast dispersion patterns and outcomes after fluoroscopically guided cervical transforaminal epidural steroid injection (CTFESI). OBJECTIVES: Determine whether contrast dispersion patterns predict pain and functional outcomes after CTFESI. METHODS: Secondary analysis of data collected during two prospective studies of CTFESI for the treatment of refractory radicular pain. Contrast dispersion patterns visualized by true anteroposterior (AP) projections during CTFESIs were categorized by flow: 1) completely external to the lateral border of the neuroforamen (zone 1); 2) within the neuroforamen but without entry into the lateral epidural space (zone 2); and 3) with extension into the lateral epidural space (zone 3). At baseline and at 1 month post-CTFESI, neck pain, arm pain, and "dominant index pain" (the greater of arm or neck pain) were evaluated using a numeric rating scale (NRS); physical function was assessed using the Five-Item Version of the Neck Disability Index (NDI-5). RESULTS: One-month post-CTFESI, neck pain, arm pain, and "dominant index pain" reductions of ≥50% were observed in 39.4% (95% confidence interval [CI], 28.2-51.8), 55.6% (95% CI, 43.0-67.5), and 44.1% (95% CI, 32.7-56.2) of participants, respectively. Regarding "dominant index pain," 72.7% (95% CI, 40.8-91.2), 39.4% (95% CI, 24.2-57.0), and 37.5% (95% CI, 20.5-58.2) of participants reported ≥50% pain reduction when zone 1, zone 2, and zone 3 contrast flow patterns were observed. Contrast dispersion zone was not significantly associated with subgroup differences in neck pain, arm pain, or NDI-5 scores (P>0.05). CONCLUSION: Improvements in pain and function 1 month after treatment with CTFESI did not differ significantly based on the contrast dispersion pattern. Future study is needed to confirm or refute these findings in other procedural settings, in broader patient populations, and with longer-term outcome assessment.

The Effectiveness of Spinal Cord Stimulation for the Treatment of Axial Low Back Pain: A Systematic Review with Narrative Synthesis.

OBJECTIVE: Determine the effectiveness of spinal cord stimulation (SCS) for the treatment of axial low back pain (LBP) with or without leg pain. DESIGN: Systematic review. SUBJECTS: Persons aged ≥18 with axial LBP with or without accompanying leg pain. INTERVENTION: Traditional low-frequency, burst, or high-frequency SCS. COMPARISON: Sham, active standard of care treatment, or none. OUTCOMES: The primary outcome was ≥50% pain improvement, and the secondary outcome was functional improvement measured six or more months after treatment intervention. METHODS: Publications in PubMed, MEDLINE, and Cochrane databases were reviewed through September 19, 2019. Randomized or nonrandomized comparative studies and nonrandomized studies without internal controls were included. The Cochrane Risk of Bias Tool and GRADE system were used to assess individual study characteristics and overall quality. RESULTS: Query identified 262 publications; 17 were suitable for inclusion. For high-frequency SCS, the only level 1 study showed that 79% (95% confidence interval = 70-87%) of patients reported ≥50% pain improvement. For low-frequency SCS, the only level 1 study reported no categorical data for axial LBP-specific outcomes; axial LBP improved by a mean 14 mm on the visual analog scale at six months. Meta-analysis was not performed due to study heterogeneity. CONCLUSIONS: According to GRADE, there is low-quality evidence that high-frequency SCS compared with low-frequency SCS is effective in patients with axial LBP with concomitant leg pain. There is very low-quality evidence for low-frequency SCS for the treatment of axial LBP in patients with concomitant leg pain. There is insufficient evidence addressing the effectiveness of burst SCS to apply a GRADE rating.

A Randomized Comparative Trial of Targeted Steroid Injection via Epidural Catheter vs Standard Transforaminal Epidural Injection for the Treatment of Unilateral Cervical Radicular Pain: Six-Month Results.

OBJECTIVES: Compare the effectiveness of catheter-directed cervical interlaminar epidural steroid injection (C-CIESI) with triamcinolone to cervical transforaminal steroid injection (CTFESI) with dexamethasone for the treatment of refractory unilateral radicular pain. DESIGN: Prospective, randomized, comparative trial. METHODS: Primary outcome: proportion of participants with ≥50% numeric rating scale pain score reduction from baseline "dominant pain" (the greater of arm vs neck) at one month postinjection. Secondary outcomes: ≥30% Neck Disability Index (NDI-5) reduction and Patient Global Impression of Change (PGIC) response indicating "much improved" or "very much improved." RESULTS: One hundred twenty participants (55.6% females, 52.3 ± 12.5 years of age, BMI 28.2 ± 6.5 kg/m2), were enrolled. The proportions of participants who experienced ≥50% pain reduction at one, three, and six months were 68.5% (95% CI = 54.9-79.5%), 59.3% (95% CI = 45.7-71.6%), and 60.8% (95% CI = 46.7-73.2%), respectively, in the C-CIESI group compared with 49.1% (95% CI = 36.4-62.0%), 46.4% (95% CI = 33.8-59.6%), and 51.9% (95% CI = 38.4-65.2%), respectively, in the CTFESI group. The between-group difference at one month was significant (P = 0.038). The proportions of participants who experienced a ≥30% NDI-5 score improvement were 64.0% (95% CI = 49.8-76.1%) and 54.9% (95% CI = 41.1-68.0%) in the C-CIESI and CTFESI groups (P = 0.352). Participants reported similar PGIC improvement in both groups: At six months, 53.2% (95% CI 38.9-67.1%) and 54.5% (95% CI = 39.7-68.7%) of the C-CIESI and CTFESI groups reported being "much improved" or "very much improved," respectively (P = 0.897). CONCLUSIONS: Both C-CIESI with triamcinolone and CTFESI with dexamethasone are effective in reducing pain and disability associated with refractory unilateral cervical radiculopathy in a substantial proportion of participants for at least six months.

Assessing optimism and pessimism about genomic medicine: Development of a genomic orientation scale.

Efforts to characterize stakeholder attitudes about the implementation of genomic medicine would benefit from a validated instrument for measuring public views of the potential benefits and harms of genomic technologies, which would facilitate comparison across populations and clinical settings. We sought to develop a scale to evaluate attitudes about the future of genomic medicine. We developed a 21-item scale that examined the likelihood of various outcomes of genomic medicine. The scale was administered to participants in a genomic sequencing study. Exploratory factor analysis was conducted and bivariate correlations were calculated. The genomic orientation (GO) scale was completed by 2895 participants. A two-factor structure was identified, corresponding to an optimism subscale (16 items, α = 0.89) and a pessimism subscale (5 items, α = 0.63). Genomic optimism was positively associated with a perceived value of genetic test results, higher health literacy, and decreased decisional conflict about participation in a genomic research study. Genomic pessimism was associated with concerns about genetic testing, lower health literacy, and increased decisional conflict about the decision to participate in the study. The GO scale is a promising tool for measuring both positive and negative views regarding the future of genomic medicine and deserves further validation.

Enantioselective palladium-catalyzed allylic alkylation reactions in the synthesis of Aspidosperma and structurally related monoterpene indole alkaloids.

Covering: up to the end of 2017 Enantioselective Pd-catalyzed allylic alkylations of prochiral enolates represent a powerful tool for the construction of all-carbon quaternary stereocenters. This review describes the emergence of such reactions as strategic linchpins that enable efficient, stereocontrolled syntheses of Aspidosperma and related monoterpene indole alkaloids.

Swimming and diving energetics in dolphins: a stroke-by-stroke analysis for predicting the cost of flight responses in wild odontocetes.

Exponential increases in hydrodynamic drag and physical exertion occur when swimmers move quickly through water, and underlie the preference for relatively slow routine speeds by marine mammals regardless of body size. Because of this and the need to balance limited oxygen stores when submerged, flight (escape) responses may be especially challenging for this group. To examine this, we used open-flow respirometry to measure the energetic cost of producing a swimming stroke during different levels of exercise in bottlenose dolphins (Tursiops truncatus). These data were then used to model the energetic cost of high-speed escape responses by other odontocetes ranging in mass from 42 to 2738 kg. The total cost per stroke during routine swimming by dolphins, 3.31±0.20 J kg-1 stroke-1, was doubled during maximal aerobic performance. A comparative analysis of locomotor costs (LC; in J kg-1 stroke-1), representing the cost of moving the flukes, revealed that LC during routine swimming increased with body mass (M) for odontocetes according to LC=1.46±0.0005M; a separate relationship described LC during high-speed stroking. Using these relationships, we found that continuous stroking coupled with reduced glide time in response to oceanic noise resulted in a 30.5% increase in metabolic rate in the beaked whale, a deep-diving odontocete considered especially sensitive to disturbance. By integrating energetics with swimming behavior and dive characteristics, this study demonstrates the physiological consequences of oceanic noise on diving mammals, and provides a powerful tool for predicting the biological significance of escape responses by cetaceans facing anthropogenic disturbances.

A FISCHER INDOLIZATION STRATEGY TOWARD THE TOTAL SYNTHESIS OF (-)-GONIOMITINE.

A Fischer indolization strategy toward the core of (-)-goniomitine is reported. Initial investigations into the Pd-catalyzed asymmetric allylic alkylation of dihydropyrido[1,2-a]indolone (DHPI) substrates are also discussed.