Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insu...Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.展开更多
This paper focuses on the characteristics of solutions of nonlinear oscillatory systems in the limit of very high oscillation energy, E;specifically, systems, in which the nonlinear driving force grows with energy muc...This paper focuses on the characteristics of solutions of nonlinear oscillatory systems in the limit of very high oscillation energy, E;specifically, systems, in which the nonlinear driving force grows with energy much faster for x(t) close to the turning point, a(E), than at any position, x(t), that is not too close to a(E). This behavior dominates important aspects of the solutions. It will be called “nonlinear violence”. In the vicinity of a turning point, the solution of a nonlinear oscillatory systems that is affected by nonlinear violence exhibits the characteristics of boundary-layer behavior (independently of whether the equation of motion of the system can or cannot be cast in the traditional form of a boundary-layer problem.): close to a(E), x(t) varies very rapidly over a short time interval (which vanishes for E → ∞). In traditional boundary layer systems this would be called the “inner” solution. Outside this interval, x(t) soon evolves into a moderate profile (e.g. linear in time, or constant)—the “outer” solution. In (1 + 1)-dimensional nonlinear energy-conserving oscillators, if the solution is reflection-invariant, nonlinear violence determines the characteristics of the whole solution. For large families of nonlinear oscillatory systems, as E → ∞, the solutions for x(t) tend to common, indistinguishable profiles, such as periodic saw-tooth profiles or step-functions. If such profiles are observed experimentally in high-energy oscillations, it may be difficult to decipher the dynamical equations that govern the motion. The solution of motion in a central field with a non-zero angular momentum exhibits extremely fast rotation around a turning point that is affected by nonlinear violence. This provides an example for the possibility of interesting phenomena in (1 + 2)-dimensional oscillatory systems.展开更多
A novel X-shaped variable stiffness vibration isolator(X-VSVI)is proposed.The Runge-Kutta method,harmonic balance method,and wavelet transform spectra are introduced to evaluate the performance of the X-VSVI under var...A novel X-shaped variable stiffness vibration isolator(X-VSVI)is proposed.The Runge-Kutta method,harmonic balance method,and wavelet transform spectra are introduced to evaluate the performance of the X-VSVI under various excitations.The layer number,the installation angle of the X-shaped structure,the stiffness,and the active control parameters are systematically analyzed.In addition,a prototype of the X-VSVI is manufactured,and vibration tests are carried out.The results show that the proposed X-VSVI has a superior adaptability to that of a traditional X-shaped mechanism,and shows excellent vibration isolation performance in response to different amplitudes and forms of excitations.Moreover,the vibration isolation efficiency of the device can be improved by appropriate adjustment of parameters.展开更多
BACKGROUND Improved adenoma detection rate(ADR)has been demonstrated with artificial intelligence(AI)-assisted colonoscopy.However,data on the real-world appli-cation of AI and its effect on colorectal cancer(CRC)scre...BACKGROUND Improved adenoma detection rate(ADR)has been demonstrated with artificial intelligence(AI)-assisted colonoscopy.However,data on the real-world appli-cation of AI and its effect on colorectal cancer(CRC)screening outcomes is limited.AIM To analyze the long-term impact of AI on a diverse at-risk patient population undergoing diagnostic colonoscopy for positive CRC screening tests or sympt-oms.METHODS AI software(GI Genius,Medtronic)was implemented into the standard proced-ure protocol in November 2022.Data was collected on patient demographics,procedure indication,polyp size,location,and pathology.CRC screening outcomes were evaluated before and at different intervals after AI introduction with one year of follow-up.RESULTS We evaluated 1008 colonoscopies(278 pre-AI,255 early post-AI,285 established post-AI,and 190 late post-AI).The ADR was 38.1%pre-AI,42.0%early post-AI(P=0.77),40.0%established post-AI(P=0.44),and 39.5%late post-AI(P=0.77).There were no significant differences in polyp detection rate(PDR,baseline 59.7%),advanced ADR(baseline 16.2%),and non-neoplastic PDR(baseline 30.0%)before and after AI introduction.CONCLUSION In patients with an increased pre-test probability of having an abnormal colonoscopy,the current generation of AI did not yield enhanced CRC screening metrics over high-quality colonoscopy.Although the potential of AI in colonoscopy is undisputed,current AI technology may not universally elevate screening metrics across all situations and patient populations.Future studies that analyze different AI systems across various patient populations are needed to determine the most effective role of AI in optimizing CRC screening in clinical practice.展开更多
Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy r...Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.展开更多
Artemisia ordosica Krasch. is a dominant shrub occurring mainly on stable sand dunes in the Gobi Desert of China, in the Mongolian phytogeographic region. Achenes of A. ordosica germinate in light but poorly in ...Artemisia ordosica Krasch. is a dominant shrub occurring mainly on stable sand dunes in the Gobi Desert of China, in the Mongolian phytogeographic region. Achenes of A. ordosica germinate in light but poorly in dark and light is the limiting factor regulating the achene germination in sand depth. Achenes germinate in spring or autumn with an optimal temperature of 20 ℃. Achene mucilage can absorb large amounts of water and has important ecological function. Salt concentrations and sand moisture may regulate achene germination in sand. A. ordosica, A. sphaerocephala Krasch. and A. monosperma Delile. from different climates have similar responses to light, the underground location of achene, and sand moisture. Percentage of seedling emergence from different levels of sand depth is depends on the specific, temperature and intensity of light penetrating through the sand depths, as well as on sand moisture. The desert sand habitat seems to have had a dominant influence on the evolution of the germination strategies of these 3 Artemisia species.展开更多
A multidisciplinary approach-anatomy, histochemistry and phytochemistry-was used to investigate the leaf structure, the content and the storage location of barbaloin in the leaves of Aloe vera L. var. chinensis (Haw.)...A multidisciplinary approach-anatomy, histochemistry and phytochemistry-was used to investigate the leaf structure, the content and the storage location of barbaloin in the leaves of Aloe vera L. var. chinensis (Haw.) Berg. Xeromorphic characteristics including secondary thickened epidermal cell walls, thicker cuticle, ambiguous differentiation of spongy and palisade tissues in the chlorenchyma, and well-developed aquiferous tissue could be seen in the leaves. Several large parenchymatous cells were observed at the phloem pole of the first ring of vascular bundles. The secondary ring of vascular bundles in the leaf base and the stomata, which are surrounded by five cells, have some classification significance in this species. The density of vascular bundles, the content of barbaloin and the intensity of histochemical reaction differed among leaf numbers Ll (annual leaf), L2 (biennial leaf), L3 (triennial leaf) and L4 (quadrennial leaf), and in different parts of the leaf. These three factors were highest in the youngest leaf, Ll, and top parts of all the leaves and lowest in the basal parts and the oldest leaf, L4. The density of vascular bundles had a positive correlation to the content of barbaloin. The histochemical results revealed that the small sheath cells that surrounded the bundles might be the location of barbaloin synthesis and the large parenchymatous cells beneath the sheath might be the storage places of this metabolite.展开更多
Multiple sclerosis(MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but...Multiple sclerosis(MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus(EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory B-cells, the primary reservoir site where EBV latency occurs. In addition, EBV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EBV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on B-cells and in vivo imaging. Addressing the potential link between EBV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to B-cell depleting intervention.展开更多
Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is W...Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration （WD）, which occurs after acute axonal injury. In the peripheral nervous system （PNS）, WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system （CNS）, WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well documented that Schwann cells （SCs） have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs ＇sense＇ axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent 昀ndings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss.展开更多
文摘Type 1 diabetes(T1D)is a chronic autoimmune condition that destroys insulinproducing beta cells in the pancreas,leading to insulin deficiency and hyperglycemia.The management of T1D primarily focuses on exogenous insulin replacement to control blood glucose levels.However,this approach does not address the underlying autoimmune process or prevent the progressive loss of beta cells.Recent research has explored the potential of glucagon-like peptide-1 receptor agonists(GLP-1RAs)as a novel intervention to modify the disease course and delay the onset of T1D.GLP-1RAs are medications initially developed for treating type 2 diabetes.They exert their effects by enhancing glucose-dependent insulin secretion,suppressing glucagon secretion,and slowing gastric emptying.Emerging evidence suggests that GLP-1RAs may also benefit the treatment of newly diagnosed patients with T1D.This article aims to highlight the potential of GLP-1RAs as an intervention to delay the onset of T1D,possibly through their potential immunomodulatory and anti-inflammatory effects and preservation of beta-cells.This article aims to explore the potential of shifting the paradigm of T1D management from reactive insulin replacement to proactive disease modification,which should open new avenues for preventing and treating T1D,improving the quality of life and long-term outcomes for individuals at risk of T1D.
文摘This paper focuses on the characteristics of solutions of nonlinear oscillatory systems in the limit of very high oscillation energy, E;specifically, systems, in which the nonlinear driving force grows with energy much faster for x(t) close to the turning point, a(E), than at any position, x(t), that is not too close to a(E). This behavior dominates important aspects of the solutions. It will be called “nonlinear violence”. In the vicinity of a turning point, the solution of a nonlinear oscillatory systems that is affected by nonlinear violence exhibits the characteristics of boundary-layer behavior (independently of whether the equation of motion of the system can or cannot be cast in the traditional form of a boundary-layer problem.): close to a(E), x(t) varies very rapidly over a short time interval (which vanishes for E → ∞). In traditional boundary layer systems this would be called the “inner” solution. Outside this interval, x(t) soon evolves into a moderate profile (e.g. linear in time, or constant)—the “outer” solution. In (1 + 1)-dimensional nonlinear energy-conserving oscillators, if the solution is reflection-invariant, nonlinear violence determines the characteristics of the whole solution. For large families of nonlinear oscillatory systems, as E → ∞, the solutions for x(t) tend to common, indistinguishable profiles, such as periodic saw-tooth profiles or step-functions. If such profiles are observed experimentally in high-energy oscillations, it may be difficult to decipher the dynamical equations that govern the motion. The solution of motion in a central field with a non-zero angular momentum exhibits extremely fast rotation around a turning point that is affected by nonlinear violence. This provides an example for the possibility of interesting phenomena in (1 + 2)-dimensional oscillatory systems.
基金Project supported by the National Natural Science Foundation of China(Nos.12022213,12002329,U23A2066,12272240,and 12002217)。
文摘A novel X-shaped variable stiffness vibration isolator(X-VSVI)is proposed.The Runge-Kutta method,harmonic balance method,and wavelet transform spectra are introduced to evaluate the performance of the X-VSVI under various excitations.The layer number,the installation angle of the X-shaped structure,the stiffness,and the active control parameters are systematically analyzed.In addition,a prototype of the X-VSVI is manufactured,and vibration tests are carried out.The results show that the proposed X-VSVI has a superior adaptability to that of a traditional X-shaped mechanism,and shows excellent vibration isolation performance in response to different amplitudes and forms of excitations.Moreover,the vibration isolation efficiency of the device can be improved by appropriate adjustment of parameters.
基金This study was approved by the Institutional Review Board(IRB number:18CR-31902-01)of the Lundquist Institute at Harbor-UCLA.
文摘BACKGROUND Improved adenoma detection rate(ADR)has been demonstrated with artificial intelligence(AI)-assisted colonoscopy.However,data on the real-world appli-cation of AI and its effect on colorectal cancer(CRC)screening outcomes is limited.AIM To analyze the long-term impact of AI on a diverse at-risk patient population undergoing diagnostic colonoscopy for positive CRC screening tests or sympt-oms.METHODS AI software(GI Genius,Medtronic)was implemented into the standard proced-ure protocol in November 2022.Data was collected on patient demographics,procedure indication,polyp size,location,and pathology.CRC screening outcomes were evaluated before and at different intervals after AI introduction with one year of follow-up.RESULTS We evaluated 1008 colonoscopies(278 pre-AI,255 early post-AI,285 established post-AI,and 190 late post-AI).The ADR was 38.1%pre-AI,42.0%early post-AI(P=0.77),40.0%established post-AI(P=0.44),and 39.5%late post-AI(P=0.77).There were no significant differences in polyp detection rate(PDR,baseline 59.7%),advanced ADR(baseline 16.2%),and non-neoplastic PDR(baseline 30.0%)before and after AI introduction.CONCLUSION In patients with an increased pre-test probability of having an abnormal colonoscopy,the current generation of AI did not yield enhanced CRC screening metrics over high-quality colonoscopy.Although the potential of AI in colonoscopy is undisputed,current AI technology may not universally elevate screening metrics across all situations and patient populations.Future studies that analyze different AI systems across various patient populations are needed to determine the most effective role of AI in optimizing CRC screening in clinical practice.
文摘Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN®) to help induce “dopamine homeostasis” in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN®), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.
文摘Artemisia ordosica Krasch. is a dominant shrub occurring mainly on stable sand dunes in the Gobi Desert of China, in the Mongolian phytogeographic region. Achenes of A. ordosica germinate in light but poorly in dark and light is the limiting factor regulating the achene germination in sand depth. Achenes germinate in spring or autumn with an optimal temperature of 20 ℃. Achene mucilage can absorb large amounts of water and has important ecological function. Salt concentrations and sand moisture may regulate achene germination in sand. A. ordosica, A. sphaerocephala Krasch. and A. monosperma Delile. from different climates have similar responses to light, the underground location of achene, and sand moisture. Percentage of seedling emergence from different levels of sand depth is depends on the specific, temperature and intensity of light penetrating through the sand depths, as well as on sand moisture. The desert sand habitat seems to have had a dominant influence on the evolution of the germination strategies of these 3 Artemisia species.
文摘A multidisciplinary approach-anatomy, histochemistry and phytochemistry-was used to investigate the leaf structure, the content and the storage location of barbaloin in the leaves of Aloe vera L. var. chinensis (Haw.) Berg. Xeromorphic characteristics including secondary thickened epidermal cell walls, thicker cuticle, ambiguous differentiation of spongy and palisade tissues in the chlorenchyma, and well-developed aquiferous tissue could be seen in the leaves. Several large parenchymatous cells were observed at the phloem pole of the first ring of vascular bundles. The secondary ring of vascular bundles in the leaf base and the stomata, which are surrounded by five cells, have some classification significance in this species. The density of vascular bundles, the content of barbaloin and the intensity of histochemical reaction differed among leaf numbers Ll (annual leaf), L2 (biennial leaf), L3 (triennial leaf) and L4 (quadrennial leaf), and in different parts of the leaf. These three factors were highest in the youngest leaf, Ll, and top parts of all the leaves and lowest in the basal parts and the oldest leaf, L4. The density of vascular bundles had a positive correlation to the content of barbaloin. The histochemical results revealed that the small sheath cells that surrounded the bundles might be the location of barbaloin synthesis and the large parenchymatous cells beneath the sheath might be the storage places of this metabolite.
文摘Multiple sclerosis(MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus(EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W. The emerging B-cell depleting therapies, particularly anti-CD20 agents such as rituximab, ocrelizumab, as well as the fully human ofatumumab, have shown promising clinical and magnetic resonance imaging benefit. One potential effect of these therapies is the depletion of memory B-cells, the primary reservoir site where EBV latency occurs. In addition, EBV potentially interacts with both genetic and other environmental factors to increase susceptibility and disease severity of MS. This review examines the role of EBV in MS pathophysiology and summarizes the recent clinical and radiological findings, with a focus on B-cells and in vivo imaging. Addressing the potential link between EBV and MS allows the better understanding of MS pathogenesis and helps to identify additional disease biomarkers that may be responsive to B-cell depleting intervention.
基金supported by Muscular Dystrophy Association grants#292306 and#236648Empire State Development Corporation for HJKRI Grants W753 and U446+1 种基金Hunter’s Hope FoundationUniversity at Buffalo IMPACT funding
文摘Axonal degeneration is a pivotal feature of many neurodegenerative conditions and substantially accounts for neurological morbidity. A widely used experimental model to study the mechanisms of axonal degeneration is Wallerian degeneration （WD）, which occurs after acute axonal injury. In the peripheral nervous system （PNS）, WD is characterized by swift dismantling and clearance of injured axons with their myelin sheaths. This is a prerequisite for successful axonal regeneration. In the central nervous system （CNS）, WD is much slower, which significantly contributes to failed axonal regeneration. Although it is well documented that Schwann cells （SCs） have a critical role in the regenerative potential of the PNS, to date we have only scarce knowledge as to how SCs ＇sense＇ axonal injury and immediately respond to it. In this regard, it remains unknown as to whether SCs play the role of a passive bystander or an active director during the execution of the highly orchestrated disintegration program of axons. Older reports, together with more recent studies, suggest that SCs mount dynamic injury responses minutes after axonal injury, long before axonal breakdown occurs. The swift SC response to axonal injury could play either a pro degenerative role, or alternatively a supportive role, to the integrity of distressed axons that have not yet committed to degenerate. Indeed, supporting the latter concept, recent 昀ndings in a chronic PNS neurodegeneration model indicate that deactivation of a key molecule promoting SC injury responses exacerbates axonal loss. If this holds true in a broader spectrum of conditions, it may provide the grounds for the development of new glia-centric therapeutic approaches to counteract axonal loss.
