Epidural Spinal Cord Stimulation for Spinal Cord Injury in Humans: A Systematic Review.

(1) Background: Spinal cord injury (SCI) represents a major health challenge, often leading to significant and permanent sensorimotor and autonomic dysfunctions. This study reviews the evolving role of epidural spinal cord stimulation (eSCS) in treating chronic SCI, focusing on its efficacy and safety. The objective was to analyze how eSCS contributes to the recovery of neurological functions in SCI patients. (2) Methods: We utilized the PRISMA guidelines and performed a comprehensive search across MEDLINE/PubMed, Embase, Web of Science, and IEEE Xplore databases up until September 2023. We identified studies relevant to eSCS in SCI and extracted assessments of locomotor, cardiovascular, pulmonary, and genitourinary functions. (3) Results: A total of 64 studies encompassing 306 patients were identified. Studies investigated various stimulation devices, parameters, and rehabilitation methods. Results indicated significant improvements in motor function: 44% of patients achieved assisted or independent stepping or standing; 87% showed enhanced muscle activity; 65% experienced faster walking speeds; and 80% improved in overground walking. Additionally, eSCS led to better autonomic function, evidenced by improvements in bladder and sexual functions, airway pressures, and bowel movements. Notable adverse effects included device migration, infections, and post-implant autonomic dysreflexia, although these were infrequent. (4) Conclusion: Epidural spinal cord stimulation is emerging as an effective and generally safe treatment for chronic SCI, particularly when combined with intensive physical rehabilitation. Future research on standardized stimulation parameters and well-defined therapy regimens will optimize benefits for specific patient populations.

First Leptophobic Dark Matter Search from the Coherent-CAPTAIN-Mills Liquid Argon Detector.

We report the first results of a search for leptophobic dark matter (DM) from the Coherent-CAPTAIN-Mills (CCM) liquid argon (LAr) detector. An engineering run with 120 photomultiplier tubes (PMTs) and 17.9×10^{20} protons on target (POT) was performed in fall 2019 to study the characteristics of the CCM detector. The operation of this 10-ton detector was strictly light based with a threshold of 50 keV and used coherent elastic scattering off argon nuclei to detect DM. Despite only 1.5 months of accumulated luminosity, contaminated LAr, and nonoptimized shielding, CCM's first engineering run has already achieved sensitivity to previously unexplored parameter space of light dark matter models with a baryonic vector portal. With an expected background of 115 005 events, we observe 115 005+16.5 events which is compatible with background expectations. For a benchmark mediator-to-DM mass ratio of m_{V_{B}}/m_{χ}=2.1, DM masses within the range 9 MeV≲m_{χ}≲50 MeV are excluded at 90% C. L. in the leptophobic model after applying the Feldman-Cousins test statistic. CCM's upgraded run with 200 PMTs, filtered LAr, improved shielding, and 10 times more POT will be able to exclude the remaining thermal relic density parameter space of this model, as well as probe new parameter space of other leptophobic DM models.

Behavioural responses of infective-stage copepodids of the salmon louse (Lepeophtheirus salmonis, Copepoda:Caligidae) to host-related sensory cues.

The salmon louse (Lepeophtheirus salmonis [Krøyer]) is an ectoparasitic copepod that causes disease in farmed Atlantic salmon (Salmo salar) and may play a role in the decline of some wild salmonid populations. Controlling lice infestations is a major cost for the salmon industry; this has stimulated the pursuit of alternative approaches to controlling them. One such approach involves determining, and then disrupting, the sensory cues used by the parasite to find its host. In this context, we examined the behavioural responses of lice copepodids to light flicker-simulating light reflecting from the sides of the salmon host and/or the shadows cast by fish passing overhead-and water-soluble chemicals released from the skin of the salmon. From these observations, we estimate that visual cues such as those presented here would operate at relatively long range (metres to tens of metres). A diffuse host-related olfactory cue stimulated swimming, however, it remains unclear whether olfactory cues provide directional information. The observations presented herein could be used to disrupt the link between the parasite and host fish, using a large number of traps deployed at a distance from a salmon farm, for example, thereby reducing sea lice infestation pressure.

Associations between human breast milk hormones and adipocytokines and infant growth and body composition in the first 6 months of life.

BACKGROUND: Much is to be learnt about human breast milk (HBM). OBJECTIVES: The purpose of this study is to extend our knowledge of HBM by investigating the role of maternal body mass index (BMI), sex and stage of lactation (month 1 vs. 6) on HBM insulin, glucose, leptin, IL-6 and TNF-α and their associations with infant body composition. METHODS: Thirty-seven exclusively breastfeeding infants (n = 37; 16♀, 21♂), and their mothers (19-47 kg m-2 ) were studied at 1 and 6 months of lactation. Infants had body composition measured (using dual-energy X-ray absorptiometry) and HBM collected. RESULTS: A significant interaction between maternal BMI and infant sex on insulin levels (p = 0.0322) was observed such that insulin was 229% higher in obese mothers nursing female infants than in normal weight mothers nursing female infants and 179% higher than obese mothers nursing male infants. For leptin, a significant association with BMI category was observed (p < 0.0001) such that overweight and obese mothers had 96.5% and 315.1% higher leptin levels than normal weight mothers, respectively. Leptin was also found to have a significant (p = 0.0004) 33.7% decrease from months 1 to 6, controlling for BMI category and sex. A significant inverse relationship between month 1 leptin levels and infant length (p = 0.0257), percent fat (p = 0.0223), total fat mass (p = 0.0226) and trunk fat mass (p = 0.0111) at month 6 was also found. No associations or interactions were observed for glucose, TNF-α or IL-6. CONCLUSIONS: These data demonstrate that maternal BMI, infant sex and stage of lactation affect the compositional make-up of insulin and leptin.

Divergent cAMP signaling differentially regulates serotonin-induced spinal motor plasticity.

Spinal metabotropic serotonin receptors encode transient experiences into long-lasting changes in motor behavior (i.e. motor plasticity). While interactions between serotonin receptor subtypes are known to regulate plasticity, the significance of molecular divergence in downstream G protein coupled receptor signaling is not well understood. Here we tested the hypothesis that distinct cAMP dependent signaling pathways differentially regulate serotonin-induced phrenic motor facilitation (pMF); a well-studied model of spinal motor plasticity. Specifically, we studied the capacity of cAMP-dependent protein kinase A (PKA) and exchange protein activated by cAMP (EPAC) to regulate 5-HT2A receptor-induced pMF within adult male rats. Although spinal PKA, EPAC and 5-HT2A each elicit pMF when activated alone, concurrent PKA and 5-HT2A activation interact via mutual inhibition thereby blocking pMF expression. Conversely, concurrent EPAC and 5-HT2A activation enhance pMF expression reflecting additive contributions from both mechanisms. Thus, we demonstrate that distinct downstream cAMP signaling pathways enable differential regulation of 5-HT2A-induced pMF. Conditional activation of independent signaling mechanisms may explain experience amendable changes in plasticity expression (i.e. metaplasticity), an emerging concept thought to enable flexible motor control within the adult central nervous system.

Plasticity in respiratory motor neurons in response to reduced synaptic inputs: A form of homeostatic plasticity in respiratory control?

For most individuals, the respiratory control system produces a remarkably stable and coordinated motor output-recognizable as a breath-from birth until death. Very little is understood regarding the processes by which the respiratory control system maintains network stability in the presence of changing physiological demands and network properties that occur throughout life. An emerging principle of neuroscience is that neural activity is sensed and adjusted locally to assure that neurons continue to operate in an optimal range, yet to date, it is unknown whether such homeostatic plasticity is a feature of the neurons controlling breathing. Here, we review the evidence that local mechanisms sense and respond to perturbations in respiratory neural activity, with a focus on plasticity in respiratory motor neurons. We discuss whether these forms of plasticity represent homeostatic plasticity in respiratory control. We present new analyses demonstrating that reductions in synaptic inputs to phrenic motor neurons elicit a compensatory enhancement of phrenic inspiratory motor output, a form of plasticity termed inactivity-induced phrenic motor facilitation (iPMF), that is proportional to the magnitude of activity deprivation. Although the physiological role of iPMF is not understood, we hypothesize that it has an important role in protecting the drive to breathe during conditions of prolonged or intermittent reductions in respiratory neural activity, such as following spinal cord injury or during central sleep apnea.

Deletion of murine Arv1 results in a lean phenotype with increased energy expenditure.

BACKGROUND: ACAT-related enzyme 2 required for viability 1 (ARV1) is a putative lipid transporter of the endoplasmic reticulum that is conserved across eukaryotic species. The ARV1 protein contains a conserved N-terminal cytosolic zinc ribbon motif known as the ARV1 homology domain, followed by multiple transmembrane regions anchoring it in the ER. Deletion of ARV1 in yeast results in defective sterol trafficking, aberrant lipid synthesis, ER stress, membrane disorganization and hypersensitivity to fatty acids (FAs). We sought to investigate the role of Arv1 in mammalian lipid metabolism. METHODS: Homologous recombination was used to disrupt the Arv1 gene in mice. Animals were examined for alterations in lipid and lipoprotein levels, body weight, body composition, glucose tolerance and energy expenditure. RESULTS: Global loss of Arv1 significantly decreased total cholesterol and high-density lipoprotein cholesterol levels in the plasma. Arv1 knockout mice exhibited a dramatic lean phenotype, with major reductions in white adipose tissue (WAT) mass and body weight on a chow diet. This loss of WAT is accompanied by improved glucose tolerance, higher adiponectin levels, increased energy expenditure and greater rates of whole-body FA oxidation. CONCLUSIONS: This work identifies Arv1 as an important player in mammalian lipid metabolism and whole-body energy homeostasis.

Spinal 5-HT7 receptors induce phrenic motor facilitation via EPAC-mTORC1 signaling.

Spinal serotonin type 7 (5-HT7) receptors elicit complex effects on motor activity. Whereas 5-HT7 receptor activation gives rise to long-lasting phrenic motor facilitation (pMF), it also constrains 5-HT2 receptor-induced pMF via "cross-talk inhibition." We hypothesized that divergent cAMP-dependent signaling pathways give rise to these distinct 5-HT7 receptor actions. Specifically, we hypothesized that protein kinase A (PKA) mediates cross-talk inhibition of 5-HT2 receptor-induced pMF whereas 5-HT7 receptor-induced pMF results from exchange protein activated by cAMP (EPAC) signaling. Anesthetized, paralyzed, and ventilated rats receiving intrathecal (C4) 5-HT7 receptor agonist (AS-19) injections expressed pMF for >90 min, an effect abolished by pretreatment with a selective EPAC inhibitor (ESI-05) but not a selective PKA inhibitor (KT-5720). Furthermore, intrathecal injections of a selective EPAC activator (8-pCPT-2'-Me-cAMP) were sufficient to elicit pMF. Finally, spinal mammalian target of rapamycin complex-1 (mTORC1) inhibition via intrathecal rapamycin abolished 5-HT7 receptor- and EPAC-induced pMF, demonstrating that spinal 5-HT7 receptors elicit pMF by an EPAC-mTORC1 signaling pathway. Thus 5-HT7 receptors elicit and constrain spinal phrenic motor plasticity via distinct signaling mechanisms that diverge at cAMP (EPAC vs. PKA). Selective manipulation of these molecules may enable refined regulation of serotonin-dependent spinal motor plasticity for therapeutic advantage.

Evaluation of DXA vs. MRI for body composition measures in 1-month olds.

BACKGROUND: Detailed measures of infant body composition are needed for understanding the impact of genes and environment on growth early in life. OBJECTIVE: The purpose of this study was to compare the accuracy and bias of body composition in infants. METHODS: Dual energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) were used to determine body composition and the trunk depot. The depots measured were total fat mass (FM), total fat-free mass (FFM) and trunk FM and FFM using DXA and MRI in 14 infants. RESULTS: None of the regression lines between DXA and MRI significantly deviate from the line of identity for any of the depots studied. However, Bland-Altman analyses revealed bias for trunk FM and trunk FFM. CONCLUSION: Our data showed DXA to be accurate (regression not significantly deviating from the line of identity), with high agreement (indicated by high R(2) ) and without bias (non-significant Bland-Altman) when estimating total FM and FFM. This could not be said for trunk estimates.

Relationship of insulin, glucose, leptin, IL-6 and TNF-α in human breast milk with infant growth and body composition.

BACKGROUND: Numerous appetite, growth, obesity-related hormones and inflammatory factors are found in human breast-milk, but there is little evidence on their relationship with infant body composition. OBJECTVIE: The purpose of the present cross-sectional pilot study was to assess the cross-sectional associations of appetite-regulating hormones and growth factors (leptin, insulin and glucose) and inflammatory factors (interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α)) in human breast-milk with infant size, adiposity, and lean tissue at 1-month of age in healthy term infants. METHODS: Human breast-milk was collected from nineteen exclusively breast-feeding mothers using one full breast expression between 8:00 and 10:00 a.m. The milk was then mixed, aliquoted, stored at -80°C and then centrifuged to remove the milk fat, prior to analyses using commercially available immunoassay kits; milk analytes were natural log transformed prior to analysis. Infant body composition was assessed using a Lunar iDXA v11-30.062 scanner (Infant whole body analysis enCore 2007 software, GE, Fairfield, CT). RESULTS: Maternal pre-pregnancy BMI was positively associated with milk leptin concentration (P = 0.0027), and so maternal-BMI-adjusted Spearman correlations were examined between breast-milk analytes and infant growth and body composition variables. As previously reported, greater milk leptin was associated with lower BMIZ (BMI-for-age z-score based on WHO 2006 growth charts; r = -0.54, P = 0.03). Glucose was positively associated with relative weight (r = 0.6, P = 0.01), and both fat and lean mass (0.43-0.44, P < 0.10). Higher concentrations of milk insulin were associated with lower infant weight, relative weight, and lean mass (r = -0.49-0.58, P < 0.06). Higher milk IL-6 was associated with lower relative weight, weight gain, percent fat, and fat mass (r = -0.55-0.70, P < 0.03 for all), while higher TNF-α was associated with lower lean mass (r = -0.58, P = 0.05), but not measures of adiposity. CONCLUSIONS: These preliminary data suggest for the first time that in the first months of life, breast-milk concentrations of insulin, glucose, IL-6 and TNF-α, in addition to leptin, may be bioactive and differentially influence the accrual of fat and lean body mass.

Body composition and power changes in elite judo athletes.

The purpose of this study was to analyse the association between body composition changes, from a weight stable period to prior competition, on upper-body power in judo athletes. 27 top-level male athletes were evaluated at baseline (weight stable period) and 1-3 days before competition, with a time difference of approximately 1 month. Total body and extracellular water were estimated by dilution techniques (deuterium and bromide, respectively) and intracellular water was calculated as the difference. Body composition was assessed by DXA. A power-load spectrum was used to assess upper-body power output in a bench-press position. Comparison of means, bivariate, and partial correlations were used. Results indicate that though no significant mean changes were found in body composition and upper-body power, individual variability was large. Among all body composition changes, only total-body water (r=0.672; p<0.001) and intracellular water (r=0.596; p=0.001) were related to upper-body power variation. These associations remained significant after controlling for weight and arm lean-soft tissue changes (r=0.594, p=0.002 for total-body water; r=0.524, p=0.007 for intracellular water). These findings highlight the need for tracking total-body water, specifically the intracellular compartment in elite judo athletes in order to avoid reductions in upper-body power when a target body weight is desired prior to competition.

Changes in thoracic gas volume with air-displacement plethysmography after a weight loss program in overweight and obese women.

OBJECTIVE: This study was designed to compare measured and predicted thoracic gas volume (V (TG)) after weight loss and to analyze the effect of body composition confounders such as waist circumference (WC) on measured V (TG) changes. DESIGN: Prospective intervention study. SETTING: Outpatient University Laboratory, Lisbon, Portugal. SUBJECTS: Eighty-five overweight and obese women (body mass index = 30.0+/-3.5 kg/m(2); age = 39.0+/-5.7 years) participating in a 16-month university-based weight control program designed to increase physical activity and improve diet. METHODS: Body weight (Wb), body volume (Vb), body density (Db), fat mass (FM), percent fat mass (%FM) and fat-free mass (FFM) were assessed by air-displacement plethysmography (ADP) at baseline and at post-intervention (16 months). The ADP assessment included a protocol to measure V (TG) and a software-based predicted V (TG). Dual-energy X-ray absorptiometry (DXA) (Hologic QDR 1500) was also used to estimate FM, %FM and FFM. Maximal oxygen uptake (VO(2) max) was assessed with a modified Balke cardiopulmonary exercise testing protocol with a breath-by-breath gas analysis. RESULTS: Significant differences between the baseline and post-weight loss intervention were observed for body weight and composition (Vb, Db, %FM, FM and FFM), and measures of V (TG) (measured: Delta=0.2 l, P<0.001; predicted: Delta=0.01 l, P<0.010) variables. Measured V (TG) change was negatively associated with the change in the WC (P=0.008), controlling for VO(2) max and age (P=0.007, P=0.511 and P=0.331). Linear regression analysis results indicated that %FM and FM using the measured and predicted V (TG) explained 72 and 76%, and 86 and 90% respectively, of the variance in %FM and FM changes using dual-energy x-ray absorptiometry. CONCLUSIONS: After weight loss, measured V (TG) increased significantly, which was partially attributed to changes is an indicator of body fat distribution such as WC. Consequently, measured and predicted V (TG) should not be used interchangeably when tracking changes in body composition. The mechanisms relating the reduction of an upper body fat distribution with an increase measured V (TG) are worthy of future investigation.

Chemoreception in the salmon louse Lepeophtheirus salmonis: an electrophysiology approach.

The search for effective and long-term solutions to the problems caused by salmon lice Lepeophtheirus salmonis (Krøyer, 1837) has increasingly included biological/ecological mechanisms to combat infestation. One aspect of this work focuses on the host-associated stimuli that parasites use to locate and discriminate a compatible host. In this study we used electrophysiological recordings made directly from the antennule of adult lice to investigate the chemosensitivity of L. salmonis to putative chemical attractants from fish flesh, prepared by soaking whole fish tissue in seawater. There was a clear physiological response to whole fish extract (WFX) with threshold sensitivity at a dilution of 10 . When WFX was size fractionated, L. salmonis showed the greatest responses to the water-soluble fractions containing compounds between 1 and 10 kDa. The results suggest that the low molecular weight, water-soluble compounds found in salmon flesh may be important in salmon lice host choice.

Inhibition of ClC-2 chloride channels by a peptide component or components of scorpion venom.

ClC chloride channels play essential roles in membrane excitability and maintenance of osmotic balance. Despite the recent crystallization of two bacterial ClC-like proteins, the gating mechanism for these channels remains unclear. In this study we tested scorpion venom for the presence of novel peptide inhibitors of ClC channels, which might be useful tools for dissecting the mechanisms underlying ClC channel gating. Recently, it has been shown that a peptide component of venom from the scorpion L. quinquestriatus hebraeus inhibits the CFTR chloride channel from the intracellular side. Using two-electrode voltage clamp we studied the effect of scorpion venom on ClC-0, -1, and -2, and found both dose- and voltage-dependent inhibition only of ClC-2. Comparison of voltage-dependence of inhibition by venom to that of known pore blockers revealed opposite voltage dependencies, suggesting different mechanisms of inhibition. Kinetic data show that venom induced slower activation kinetics compared to pre-venom records, suggesting that the active component(s) of venom may function as a gating modifier at ClC-2. Trypsinization abolished the inhibitory activity of venom, suggesting that the component(s) of scorpion venom that inhibits ClC-2 is a peptide.

Measurement of spin-transfer observables in p p-->Lambda Lambda at 1.637 GeV/c.

Spin-transfer observables for p p-->Lambda Lambda have been measured using a transversely polarized frozen-spin target and a beam momentum of 1.637 GeV/c. Current models of the reaction near threshold are in good agreement with existing measurements performed with unpolarized particles in the initial state but produce conflicting predictions for the spin-transfer observables Dnn and Knn (the normal-to-normal depolarization and polarization transfer), which are measurable only with polarized target or beam. Measurements of Dnn and Knn presented here are found to be in disagreement with predictions from these models.

Measurement of analyzing power for proton-carbon elastic scattering in the coulomb-nuclear interference region with a 22-GeV/c polarized proton beam.

The analyzing power for proton-carbon elastic scattering in the Coulomb-nuclear interference region of momentum transfer, 9.0x10(-3)<-t<4.1x10(-2) (GeV/c)(2), was measured with a 21.7 GeV/c polarized proton beam at the Alternating Gradient Synchrotron of Brookhaven National Laboratory. The ratio of hadronic spin-flip to nonflip amplitude, r(5), was obtained from the analyzing power to be Rer(5)=0.088+/-0.058 and Imr(5)=-0.161+/-0.226.

Comparison of the BOD POD with the four-compartment model in adult females.

PURPOSE: This study was designed to compare the accuracy and bias in estimates of total body density (Db) by hydrostatic weighing (HW) and the BOD POD, and percent body fat (%fat) by the BOD POD with the four-compartment model (4C model) in 42 adult females. Furthermore, the role of the aqueous and mineral fractions in the estimation of body fat by the BOD POD was examined. METHODS: Total body water was determined by isotope dilution ((2)H(2)0) and bone mineral was determined by dual-energy x-ray absorptiometry. Db and %fat were determined by the BOD POD and HW. The 4C model of Baumgartner was used as the criterion measure of body fat. RESULTS: HW Db (1.0352 g x cm(-3)) was not statistically different (P = 0.35) from BOD POD Db (1.0349 g x cm(-3)). The regression between Db by HW and the BOD POD significantly deviated from the line of identity (Db by HW = 0.90 x Db by BOD POD + 0.099; R(2) = 0.94). BOD POD %fat (28.8%) was significantly lower (P < 0.01) than %fat by the 4C model (30.6%). The regression between %fat by the 4C model and the BOD POD significantly deviated from the line of identity (%fat by 4C model = 0.88 x %fat by BOD POD + 5.41%; R(2) = 0.92). BOD POD Db and %fat showed no bias across the range of fatness. Only the aqueous fraction of the fat-free mass (FFM) had a significant correlation with the difference in %fat between the 4C model and the BOD POD. CONCLUSION: These data indicate that the BOD POD underpredicted body fat as compared with the 4C model, and the aqueous fraction of the FFM had a significant effect on estimates of %fat by the BOD POD.

Effect of scalp and facial hair on air displacement plethysmography estimates of percentage of body fat.

OBJECTIVE: The objective of this study was to determine the effect of body hair (scalp and facial) on air displacement plethysmography (BOD POD) estimates of percentage of body fat. RESEARCH METHODS AND PROCEDURES: A total of 25 men (31.4 +/- 8.0 years, 83.4 +/- 12.2 kg, 181.8 +/- 6.9 cm) agreed to grow a beard for 3 weeks to participate in the study. Total body density (g/cm(3)) and percentage of body fat were evaluated by BOD POD. To observe the effect of trapped isothermal air in body hair, BOD POD measures were performed in four conditions: criterion method (the beard was shaven and a swimcap was worn), facial hair and swimcap, facial hair and no swimcap, and no facial hair and no swimcap(.) RESULTS: The presence of only a beard (facial hair and swimcap) resulted in a significant underestimation of percentage of body fat (16.2%, 1.0618 g/cm(3)) vs. the criterion method (17.1%, 1.0597 g/cm(3), p < 0.001). The effect of scalp hair (no swim cap worn) resulted in a significant underestimation in percentage of body fat relative to the criterion method, either with facial hair (facial hair and no swimcap; 14.8%, 1.0649 g/cm(3)) or without facial hair (no facial hair and no swimcap; 14.8%, 1.0650 g/cm(3), p < 0.001 for both). DISCUSSION: A significant underestimation of percentage of body fat was observed with the presence of facial hair ( approximately 1%) and scalp hair ( approximately 2.3%). This underestimation in percentage of body fat may be caused by the effect of trapped isothermal air in body hair on body-volume estimates. Thus, excess facial hair should be kept to a minimum and a swimcap should be worn at all times to ensure accurate estimates of body fat when using the BOD POD.

SAMIE: statistical algorithm for modeling interaction energies.

We are investigating the rules that govern protein-DNA interactions, using a statistical mechanics based formalism that is related to the Boltzmann Machine of the neural net literature. Our approach is data-driven, in which probabilistic algorithms are used to model protein-DNA interactions, given SELEX and/or phage data as input. In the current report, we trained the network using SELEX data, under the "one-to-one" model of interactions (i.e. one amino acid contacts one base). The trained network was able to successfully identify the wild-type binding sites of EGR and MIG protein families. The predictions using our method are the same or better than that of methods existing in the literature. However our methodology offers the potential to capitalise in quantitative detail, as well as to be used to explore more general model of interactions, given availability of data.