Mucosal integrin α4ß7 blockade fails to reduce the seeding and size of viral reservoirs in SIV-infected rhesus macaques.

Cellular viral reservoirs are rapidly established in tissues upon HIV-1/SIV infection, which persist throughout viral infection, even under long-term antiretroviral therapy (ART). Specific integrins are involved in the homing of cells to gut-associated lymphoid tissues (GALT) and inflamed tissues, which may promote the seeding and dissemination of HIV-1/SIV to these tissue sites. In this study, we investigated the efficacy of prophylactic integrin blockade (α4ß7 antibody or α4ß7/α4ß1 dual antagonist TR-14035) on viral infection, as well as dissemination and seeding of viral reservoirs in systemic and lymphoid compartments post-SIV inoculation. The results showed that blockade of α4ß7/α4ß1 did not decrease viral infection, replication, or reduce viral reservoir size in tissues of rhesus macaques after SIV infection, as indicated by equivalent levels of plasma viremia and cell-associated SIV RNA/DNA to controls. Surprisingly, TR-14035 administration in acute SIV infection resulted in consistently higher viremia and more rapid disease progression. These findings suggest that integrin blockade alone fails to effectively control viral infection, replication, dissemination, and reservoir establishment in HIV-1/SIV infection. The use of integrin blockade for prevention or/and therapeutic strategies requires further investigation.

Causation and gravitation in George Cheyne's Newtonian natural philosophy.

This paper analyzes the metaphysical system developed in Cheyne's Philosophical Principles of Religion. Cheyne was an early proponent of Newtonianism and tackled several philosophical questions raised by Newton's work. The most pressing of these concerned the causal origin of gravitational attraction. Cheyne rejected the occasionalist explanations offered by several of his contemporaries in favor of a model on which God delegated special causal powers to bodies. Additionally, he developed an innovative approach to divine conservation. This allowed him to argue that Newton's findings provided evidence for God's existence and providence without the need for continuous divine intervention in the universe.

Spatial complexity reduces interaction strengths in the meta-food web of a river floodplain mosaic.

Theory states that both the spatial complexity of landscapes and the strength of interactions between consumers and their resources are important for maintaining biodiversity and the balance of nature. Spatial complexity is hypothesized to promote biodiversity by reducing the potential for competitive exclusion; whereas, models show that weak trophic interactions can enhance stability and maintain biodiversity by dampening destabilizing oscillations associated with strong interactions. Here, we show that spatial complexity can reduce the strength of consumer-resource interactions in natural food webs. By sequentially aggregating food webs of individual aquatic habitat patches across a floodplain mosaic, we found that increasing spatial complexity resulted in decreases in the strength of interactions between predators and prey, owing to a greater proportion of weak interactions and a reduced proportion of strong interactions in the meta-food web. The main mechanism behind this pattern was that some patches provided predation refugia for species that were often strongly preyed upon in other patches. If weak trophic interactions do indeed promote stability, then our findings may signal an additional mechanism by which complexity and stability are linked in nature. In turn, this may have implications for how the values of landscape complexity, and the costs of biophysical homogenization, are assessed.

Lockean superaddition and Lockean humility.

This paper offers a new approach to an old debate about superaddition in Locke. Did Locke claim that some objects have powers that are unrelated to their natures or real essences? The question has split commentators. Some (Wilson, Stuart, Langton) claim the answer is yes and others (Ayers, Downing, Ott) claim the answer is no. This paper argues that both of these positions may be mistaken. I show that Locke embraced a robust epistemic humility. This epistemic humility includes ignorance of the real essences of bodies, of the causal processes underlying the production of natural phenomena, and of God's method of creation. I show how this epistemic humility offers strong support for an agnostic response to the question of superaddition. Locke did not intend to claim that bodies either do or do not have properties unrelated to their real essences. Instead, his primary goal in discussing the topic was to emphasize the strict limits to human knowledge.

Improvement in non-24-h sleep-wake rhythm disorder in a sighted individual treated with a melatonin receptor agonist.

Non-24-hour sleep-wake rhythm disorder (N24SWD) typically presents in patients with visual impairments that disrupt the ability to entrain to the 24 hour solar cycle. We discuss a 43 year old sighted man who presented with periodic daytime hypersomnia and nighttime insomnia, occasionally leading to <3 hours of sleep per day. Previous polysomnography showed an apnea hypopnea index of 6.2 events per hour. A sleep log of 3 months showed irregular time of sleep onset, and an average of 3 hours of sleep per day. Wrist actigraphy confirmed N24SWD. A trial of tasimelteon 20 mg/day resulting in improved daytime hypersomnia (pre-Epworth Sleepiness Scale (ESS) = 21/24, post-ESS = 5/24; a score of > 10/24 is considered sleepy). Follow-up actigraphy showed marked resolution of phase delay with an average of five hours of sleep. The case demonstrates that tasimelteon is a possible treatment for N24SWD in sighted individuals.

The floodplain food web mosaic: a study of its importance to salmon and steelhead with implications for their recovery.

Although numerous studies have attempted to place species of interest within the context of food webs, such efforts have generally occurred at small scales or disregard potentially important spatial heterogeneity. If food web approaches are to be employed to manage species, studies are needed that evaluate the multiple habitats and associated webs of interactions in which these species participate. Here, we quantify the food webs that sustain rearing salmon and steelhead within a floodplain landscape of the Methow River, Washington, USA, a location where restoration has been proposed to restore side channels in an attempt to recover anadromous fishes. We combined year-long measures of production, food demand, and diet composition for the fish assemblage with estimates of invertebrate prey productivity to quantify food webs within the main channel and five different, intact, side channels; ranging from channels that remained connected to the main channel at low flow to those reduced to floodplain ponds. Although we found that habitats within the floodplain had similar invertebrate prey production, these habitats hosted different local food webs. In the main channel, 95% of total prey consumption flowed to fishes that are not the target of proposed restoration. These fishes consumed 64% and 47% of the prey resources that were found to be important to fueling chinook and steelhead production in the main channel, respectively. Conversely, in side channels, a greater proportion of prey was consumed by anadromous salmonids. As a result, carrying capacity estimates based on food were 251% higher, on average, for anadromous salmonids in side channels than the main channel. However, salmon and steelhead production was generally well below estimated capacity in both the main and side channels, suggesting these habitats are under-seeded with respect to food, and that much larger populations could be supported. Overall, this study demonstrates that floodplain heterogeneity is associated with the occurrence of a mosaic of food webs, all of which were utilized by anadromous salmonids, and all of which may be important to their recovery and persistence. In the long term, these and other fishes would'likely benefit from restoring the processes that maintain floodplain complexity.

An international survey of deep brain stimulation procedural steps.

BACKGROUND: Deep brain stimulation (DBS) surgery is standard of care for the treatment of certain movement disorders. OBJECTIVE: We sought to characterize the spectrum of steps performed in DBS surgery, at centers around the world where this surgery is performed. METHODS: We identified the main steps in DBS surgery workflow and grouped these 19 steps into 3 phases (preoperative, operative, and postoperative). A survey tool, informed by a pilot survey, was administered internationally by trained study personnel at high- and low-volume DBS centers. Procedural components, duration, and surgeon motivational factors were assessed. Cluster analysis was used to identify procedural and behavioral clusters. RESULTS: One hundred eighty-five procedure workflow surveys (143 DBS centers) and 65 online surveys of surgeon motivational drivers were completed (45% response rate). Significant heterogeneity in technique, operative time, and surgeon motivational drivers was reported across centers. CONCLUSIONS: We provide a description of the procedural steps involved in DBS surgery and the duration of these steps, based on an international survey. These data will enable individual surgeons and centers to examine their own experience relative to colleagues at other centers and in other countries. Such information could also be useful in comparing efficiencies and identifying workflow obstacles between different hospital environments.

Does intraoperative neurophysiological monitoring have predictive value for functional recovery following spinal cord injury? A case report.

To present a case report of a patient with an ASIA B spinal cord injury with partially intact baseline IONM who made a complete functional recovery postoperatively. A thirty-three year old male presented after a motor vehicle accident. Imaging studies revealed a C4-C5 bilateral facet dislocation. On presentation the patient had 4/5 strength in bilateral biceps and wrist extensors, 3/5 strength in bilateral triceps, and 0/5 strength in the finger flexors, intrinsics and all lower extremity muscles. Motor level was C7. Sensation was grossly intact to light touch throughout all extremities, intact to pinprick from C2 to T7, and absent to pinprick caudal to T7. Rectal tone and contraction were absent. After attempts at closed reduction failed the patient underwent an open reduction and posterior C4-C5 fusion. Intraoperative neurophysiologic monitoring (IONM) revealed the presence of baseline responses to the posterior tibial nerve using somatosensory evoked potentials and to the right abductor hallucis using transcranial motor evoked potentials. At the 6 weeks postoperative visit the patient had full 5/5 motor strength to all muscles except the left deltoid that was 4/5 due to a rotator cuff injury. This case illustrates a potential prognostic value of IONM. Despite lack of clinical motor function at the time of surgery, IONM was able to illicit a motor response in the right lower extremity. Further prospective studies are needed for further investigation.

Error reduction with routine checklist use during deep brain stimulation surgery.

BACKGROUND: The use of checklists to reduce error rates in procedural literature has led our group to employ this strategy during deep brain stimulation (DBS) surgery. OBJECTIVES: We sought to examine the improvement in the number of errors made during DBS surgery after long-term use of a checklist. METHODS: Our checklist has been used for all DBS cases at our institution since the beginning of this study's enrollment in 2008. The number of cases in which errors were detected after 1 year of routine use (group B, n = 11) was compared in one cohort of DBS subjects to that of an earlier cohort of patients (group A, n = 17), which underwent DBS exactly 1 year prior. RESULTS: Eleven of the 14 cases where major errors were detected occurred in group A; 6 of the 9 cases where only minor errors were detected were also in group A; of the patients without any error, all 5 were in group B. We found a significant difference in these proportions between group A and group B [χ(2)(2) = 9.73; p < 0.008]. CONCLUSIONS: After 1 year of checklist use, the total number of major and minor errors made was reduced, indicating an improvement in error rate after long-term routine incorporation of this checklist.

Is there a difference between simultaneous or staged decompressions for combined cervical and lumbar stenosis?

STUDY DESIGN: We evaluated 43 patients diagnosed with tandem spinal stenosis (TSS) from 1999 to 2005 in an academic hospital. OBJECTIVE: The purpose of this study is to compare outcomes after simultaneous decompression of the cervical and lumbar spine versus staged operations. SUMMARY OF BACKGROUND DATA: TSS is a rare degenerative disease affecting multiple spinal levels with limited research describing operative management. METHODS: Of our patients, 21 underwent simultaneous decompression of both the cervical and lumbar spine and 22 underwent staged decompression of the cervical spine followed by the lumbar spine at a later date. Medical records were reviewed for patient demographics, type and duration of symptoms, operative time, combined blood loss, cervical myelopathy modified Japan Orthopaedic Association Score, Oswestry Disability Index (ODI), major and minor complications, and average length of follow up. Each category was evaluated by Pearson correlations and unpaired Student t tests. RESULTS: With a mean follow-up of 7 years, both groups improved in JOA and ODI without a significant difference between the 2 operative groups in terms of major or minor complications, JOA, or ODI. Independent of the surgical algorithm, age above 68 years, estimated blood loss ≥400 mL, and operative time ≥150 minutes significantly increased the number of complications. CONCLUSIONS: These results indicate that TSS can be effectively managed by either surgical intervention, simultaneous, or staged decompressions. However, patient age, blood loss, and operative time do significantly impact outcomes. Therefore, operative management should be tailored to the patient's age and the option which will limit blood loss and operative time, whether that is by simultaneous or staged procedures.

Does the ACS NSQIP Surgical Risk Calculator Accurately Predict Complications Rates After Anterior Lumbar Interbody Fusion Procedures?

STUDY DESIGN: Clinical case series. OBJECTIVE: The aim of this study was to determine the effectiveness of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator in the prediction of complications after anterior lumbar interbody fusion (ALIF). SUMMARY OF BACKGROUND DATA: Identifying at-risk patients may aid in the prevention of complications after spine procedures. The ACS NSQIP surgical risk calculator was developed to predict 30-day postoperative complications for a variety of operative procedures. METHODS: Medical records of patients undergoing ALIF at our institution from 2009 to 2019 were retrospectively reviewed. Demographic and comorbidity variables were entered into the ACS NSQIP surgical risk calculator to generate percentage predictions for complication incidence within 30 days postoperatively. The observed incidences of these complications were also abstracted from the medical record. The predictive ability of the ACS NSQIP surgical risk calculator was assessed in comparison to the observed incidence of complications using area under the curve (AUC) analyses. RESULTS: Two hundred fifty-three (253) patients were analyzed. The ACS NSQIP surgical risk calculator was a fair predictor of discharge to non-home facility (AUC 0.71) and surgical site infection (AUC 0.70). The ACS NSQIP surgical risk calculator was a good predictor of acute kidney injury/progressive renal insufficiency (AUC 0.81). The ACS NSQIP surgical risk calculator was not an adequate predictive tool for any other category, including: pneumonia, urinary tract infections, venous thromboembolism, readmission, reoperations, and aggregate complications (AUC < 0.70). CONCLUSION: The ACS NSQIP surgical risk calculator is an adequate predictive tool for a subset of complications after ALIF including acute kidney injury/progressive renal insufficiency, surgical site infections, and discharge to non-home facilities. However, it is a poor predictor for all other complication groups. The reliability of the ACS NSQIP surgical risk calculator is limited, and further identification of models for risk stratification is necessary for patients undergoing ALIF.Level of Evidence: 3.

Feasibility of an operational standardized checklist for movement disorder surgery. A pilot study.

Despite the clinical success of deep brain stimulation (DBS), it remains to be elucidated where within the work process the surgical result could diverge from the surgical plan. We sought to determine this. We implemented a standardized checklist to detect and remediate procedural errors. A consecutive series of 13 patients was studied. Revisions, explantations and thermal lesions were excluded. We tabulated the number and type of errors that could occur when implementing a surgical plan. Errors were categorized as minor or major. The elapsed time was also assessed. A mean of two errors per case were identified: 1.15 major errors/case and 0.85 minor errors per case. The total number of errors identified per case did not change significantly over the course of the series. Time to complete the checklist decreased monotonically from 4 min 5 s to 1 min 10 s. The checklist applied in this scenario is a useful tool to identify and remediate errors during DBS, adding minimal additional operative time and consistently identifying errors.

Sleeping in Airports.

This essay describes the author's experience of sleeping in an airport because of an April blizzard.

Landscape context and the biophysical response of rivers to dam removal in the United States.

Dams have been a fundamental part of the U.S. national agenda over the past two hundred years. Recently, however, dam removal has emerged as a strategy for addressing aging, obsolete infrastructure and more than 1,100 dams have been removed since the 1970s. However, only 130 of these removals had any ecological or geomorphic assessments, and fewer than half of those included before- and after-removal (BAR) studies. In addition, this growing, but limited collection of dam-removal studies is limited to distinct landscape settings. We conducted a meta-analysis to compare the landscape context of existing and removed dams and assessed the biophysical responses to dam removal for 63 BAR studies. The highest concentration of removed dams was in the Northeast and Upper Midwest, and most have been removed from 3rd and 4th order streams, in low-elevation (< 500 m) and low-slope (< 5%) watersheds that have small to moderate upstream watershed areas (10-1000 km2) with a low risk of habitat degradation. Many of the BAR-studied removals also have these characteristics, suggesting that our understanding of responses to dam removals is based on a limited range of landscape settings, which limits predictive capacity in other environmental settings. Biophysical responses to dam removal varied by landscape cluster, indicating that landscape features are likely to affect biophysical responses to dam removal. However, biophysical data were not equally distributed across variables or clusters, making it difficult to determine which landscape features have the strongest effect on dam-removal response. To address the inconsistencies across dam-removal studies, we provide suggestions for prioritizing and standardizing data collection associated with dam removal activities.

Identical excimer laser PTK treatments in rabbits result in two distinct haze responses.

PURPOSE: To obtain objective light-scattering measurements to test a hypothesis that identical PTK treatments cause distinct low- and high-level light-scattering responses in rabbit corneas. METHODS: An excimer laser was used to produce identical 6-mm diameter phototherapeutic keratectomy treatments (PTK) in 32 pigmented rabbits. Eyes were treated by performing a 40-microm epithelial ablation, followed by a 100-mum stromal PTK. Objective scattering measurements were made before treatment, weekly up to 5 weeks, and then biweekly to 9 weeks. Confocal microscopy was performed on several corneas at 4 and 7 weeks. RESULTS: Mean scattering levels split into distinct low- and high-scattering groups 2 weeks after treatment and remained distinct until week 7 (P < 0.003). Scattering in the low group reached a broad peak that lasted from weeks 2 to 4 at approximately 3 times the pretreatment level. Scattering in the high group peaked at 3 weeks at approximately 12 times the pretreatment level. Scattering levels diminished after reaching their peaks. Confocal images showed a band of highly reflective material in the anterior stroma that extended much deeper in corneas from the high group. The reflective band in the highly scattering corneas obscured the posterior stroma from view for up to 5 weeks. CONCLUSIONS: Quantitative scattering data obtained with the scatterometer suggest that identical PTK treatments indeed result in distinct low- and high-level light-scattering responses in rabbits.

Aneurysm observation versus intervention: a literature review.

Aneurysmal subarachnoid hemorrhage (SAH) is a devastating illness that affects persons at the peaks of their lives. The 1990s witnessed rapid growth in noninvasive vascular imaging technologies, which allowed safe diagnosis of unruptured saccular intracranial aneurysms. Presently, it is unclear who will benefit from screening. Mass screening is neither feasible nor cost-effective. The current literature suggests that persons in a family with two or more relatives with a history of SAH are most likely to benefit from screening. Individuals with a history of SAH, with aneurysms greater than 10 mm in diameter or with symptomatic aneurysms are clearly at increased risk for SAH. These aneurysms should be treated, though the method of treatment remains open to question. Treatment of older patients or those with smaller aneurysms has been modeled by decision analysis, but has yet to be verified in a prospective clinical trial. Future directions for aneurysm management are explored.

Use of a cyanoacrylate skin adhesive to reduce external ventricular drain infection rates.

UNLABELLED: OBJECT.: Ventriculitis related to external ventricular drain (EVD) placement is a significant source of morbidity in neurological intensive care patients. Current rates of EVD-related infections range from 2% to 45% in the literature. The authors sought to determine if a 2-octyl cyanoacrylate adhesive would result in lower infection rate than standard semiocclusive dressings. METHODS: The authors tracked ventriculitis rates via CSF cultures among 259 patients whose EVD sites were dressed with sterile semiocclusive dressings and underwent routine sterile dressing exchanges every 48 hours. They analyzed data obtained in an additional 113 patients whose EVD sites were dressed one time with a surgical adhesive, 2-octyl cyanoacrylate. RESULTS: Ventriculitis rate in patients with standard bioocclusive dressings and wound care was 15.1%, whereas that in patients with a 2-octyl cyanoacrylate dressing was 3.54% (p = 0.002). Staphylococcus genus accounted for 79.5% of instances of ventriculitis among patients with bioocclusive dressings and routine wound care, whereas it accounted for 25.0% of the instances of ventriculitis among patients with a liquid polymer sealant dressing. A 90% reduction in Staphylococcus infection completely accounts for the observed effect (p = 0.04). CONCLUSIONS: The one-time application of 2-octyl cyanoacrylate to EVD wounds and exit sites provided superior protection against EVD-related ventriculitis compared to conventional EVD-site wound care. Likely this protection results from a barrier to the entry of gram-positive skin flora along the EVD exit tract. The results should be validated in a randomized trial.

Deep brain stimulation of the globus pallidus suppresses post-traumatic dystonic tremor.

Dystonic tremor is an unusual movement disorder that is highly disabling and difficult to treat medically. We describe an 18-year-old patient with dystonic tremor whose medical treatment failed, and was considered for surgery. The patient had a long-standing dystonic tremor and was recommended for globus pallidus (GP) deep brain stimulation. At 2 year follow-up, we observed substantial tremor suppression and best clinical effect with contact three, which, radiographically, is located in the internal globus pallidus/external globus pallidus transition area. The stimulation was more rostral than expected. We conclude that the GP is a potentially useful therapeutic target for dystonic tremor.