Plasma proteomic analysis on neuropathic pain in idiopathic peripheral neuropathy patients.

BACKGROUND AND AIMS: Why only half of the idiopathic peripheral neuropathy (IPN) patients develop neuropathic pain remains unknown. By conducting a proteomics analysis on IPN patients, we aimed to discover proteins and new pathways that are associated with neuropathic pain. METHODS: We conducted unbiased mass-spectrometry proteomics analysis on blood plasma from 31 IPN patients with severe neuropathic pain and 29 IPN patients with no pain, to investigate protein biomarkers and protein-protein interactions associated with neuropathic pain. Univariate modeling was done with linear mixed modeling (LMM) and corrected for multiple testing. Multivariate modeling was performed using elastic net analysis and validated with internal cross-validation and bootstrapping. RESULTS: In the univariate analysis, 73 proteins showed a p-value <.05 and 12 proteins showed a p-value <.01. None were significant after Benjamini-Hochberg adjustment for multiple testing. Elastic net analysis created a model containing 12 proteins with reasonable discriminatory power to differentiate between painful and painless IPN (false-negative rate 0.10, false-positive rate 0.18, and an area under the curve 0.75). Eight of these 12 proteins were clustered into one interaction network, significantly enriched for the complement and coagulation pathway (Benjamini-Hochberg adjusted p-value = .0057), with complement component 3 (C3) as the central node. Bootstrap validation identified insulin-like growth factor-binding protein 2 (IGFBP2), complement factor H-related protein 4 (CFHR4), and ferritin light chain (FTL), as the most discriminatory proteins of the original 12 identified. INTERPRETATION: This proteomics analysis suggests a role for the complement system in neuropathic pain in IPN.

Safety and Efficacy of Topiramate in Individuals With Cryptogenic Sensory Peripheral Neuropathy With Metabolic Syndrome: The TopCSPN Randomized Clinical Trial.

Importance: Cryptogenic sensory peripheral neuropathy (CSPN) is highly prevalent and often disabling due to neuropathic pain. Metabolic syndrome and its components increase neuropathy risk. Diet and exercise have shown promise but are limited by poor adherence. Objective: To determine whether topiramate can slow decline in intraepidermal nerve fiber density (IENFD) and/or neuropathy-specific quality of life measured using the Norfolk Quality of Life-Diabetic Neuropathy (NQOL-DN) scale. Design, Setting, and Participants: Topiramate as a Disease-Modifying Therapy for CSPN (TopCSPN) was a double-blind, placebo-controlled, randomized clinical trial conducted between February 2018 and October 2021. TopCSPN was performed at 20 sites in the National Institutes of Health-funded Network for Excellence in Neurosciences Clinical Trials (NeuroNEXT). Individuals with CSPN and metabolic syndrome aged 18 to 80 years were screened and randomly assigned by body mass index (<30 vs ≥30), which is calculated as weight in kilograms divided by height in meters squared. Patients were excluded if they had poorly controlled diabetes, prior topiramate treatment, recurrent nephrolithiasis, type 1 diabetes, use of insulin within 3 months before screening, history of foot ulceration, planned bariatric surgery, history of alcohol or drug overuse in the 2 years before screening, family history of a hereditary neuropathy, or an alternative neuropathy cause. Interventions: Participants received topiramate or matched placebo titrated to a maximum-tolerated dose of 100 mg per day. Main Outcomes and Measures: IENFD and NQOL-DN score were co-primary outcome measures. A positive study was defined as efficacy in both or efficacy in one and noninferiority in the other. Results: A total of 211 individuals were screened, and 132 were randomly assigned to treatment groups: 66 in the topiramate group and 66 in the placebo group. Age and sex were similar between groups (topiramate: mean [SD] age, 61 (10) years; 38 male [58%]; placebo: mean [SD] age, 62 (11) years; 44 male [67%]). The difference in change in IENFD and NQOL-DN score was noninferior but not superior in the intention-to-treat (ITT) analysis (IENFD, 0.21 fibers/mm per year; 95% CI, -0.43 to ∞ fibers/mm per year and NQOL-DN score, -1.52 points per year; 95% CI, -∞ to 1.19 points per year). A per-protocol analysis excluding noncompliant participants based on serum topiramate levels and those with major protocol deviations demonstrated superiority in NQOL-DN score (-3.69 points per year; 95% CI, -∞ to -0.73 points per year). Patients treated with topiramate had a mean (SD) annual change in IENFD of 0.56 fibers/mm per year relative to placebo (95% CI, -0.21 to ∞ fibers/mm per year). Although IENFD was stable in the topiramate group compared with a decline consistent with expected natural history, this difference did not demonstrate superiority. Conclusion and Relevance: Topiramate did not slow IENFD decline or affect NQOL-DN score in the primary ITT analysis. Some participants were intolerant of topiramate. NQOL-DN score was superior among those compliant based on serum levels and without major protocol deviations. Trial Registration: ClinicalTrials.gov Identifier: NCT02878798.

Transfusing Convalescent Plasma as Post-Exposure Prophylaxis Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection: A Double-Blinded, Phase 2 Randomized, Controlled Trial.

BACKGROUND: The efficacy of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320 by Euroimmun ELISA) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed coronavirus disease 2019 (COVID-19) in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was new SARS-CoV-2 infection. RESULTS: In total, 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for screening SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) positivity. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs 25.2 days; P = .49) and COVID-19 (26.3 vs 25.9 days; P = .35) was similar for both groups. CONCLUSIONS: Administration of high-titer CCP as post-exposure prophylaxis, although appearing safe, did not prevent SARS-CoV-2 infection. CLINICAL TRIALS REGISTRATION: NCT04323800.

Exercise as Treatment for Neuropathy in the Setting of Diabetes and Prediabetic Metabolic Syndrome: A Review of Animal Models and Human Trials.

BACKGROUND: Peripheral neuropathy is among the most common complications of diabetes, but a phenotypically identical distal sensory predominant, painful axonopathy afflicts patients with prediabetic metabolic syndrome, exemplifying a spectrum of risk and continuity of pathogenesis. No pharmacological treatment convincingly improves neuropathy in the setting of metabolic syndrome, but evolving data suggest that exercise may be a promising alternative. OBJECTIVE: The aim of the study was to review in depth the current literature regarding exercise treatment of metabolic syndrome neuropathy in humans and animal models, highlight the diverse mechanisms by which exercise exerts beneficial effects, and examine adherence limitations, safety aspects, modes and dose of exercise. RESULTS: Rodent models that recapitulate the organismal milieu of prediabetic metabolic syndrome and the phenotype of its neuropathy provide a strong platform to dissect exercise effects on neuropathy pathogenesis. In these models, exercise reverses hyperglycemia and consequent oxidative and nitrosative stress, improves microvascular vasoreactivity, enhances axonal transport, ameliorates the lipotoxicity and inflammatory effects of hyperlipidemia and obesity, supports neuronal survival and regeneration following injury, and enhances mitochondrial bioenergetics at the distal axon. Prospective human studies are limited in scale but suggest exercise to improve cutaneous nerve regenerative capacity, neuropathic pain, and task-specific functional performance measures of gait and balance. Like other heath behavioral interventions, the benefits of exercise are limited by patient adherence. CONCLUSION: Exercise is an integrative therapy that potently reduces cellular inflammatory state and improves distal axonal oxidative metabolism to ameliorate features of neuropathy in metabolic syndrome. The intensity of exercise need not improve cardinal features of metabolic syndrome, including weight, glucose control, to exert beneficial effects.

Role of Mechanoinsensitive Nociceptors in Painful Diabetic Peripheral Neuropathy.

The cutaneous mechanisms that trigger spontaneous neuropathic pain in diabetic peripheral neuropathy (PDPN) are far from clear. Two types of nociceptors are found within the epidermal and dermal skin layers. Small-diameter lightly myelinated Aδ and unmyelinated C cutaneous mechano and heat-sensitive (AMH and CMH) and C mechanoinsensitive (CMi) nociceptors transmit pain from the periphery to central nervous system. AMH and CMH fibers are mainly located in the epidermis, and CMi fibers are distributed in the dermis. In DPN, dying back intra-epidermal AMH and CMH fibers leads to reduced pain sensitivity, and the patients exhibit significantly increased pain thresholds to acute pain when tested using traditional methods. The role of CMi fibers in painful neuropathies has not been fully explored. Microneurography has been the only tool to access CMi fibers and differentiate AMH, CMH, and CMi fiber types. Due to the complexity, its use is impractical in clinical settings. In contrast, a newly developed diode laser fiber selective stimulation (DLss) technique allows to safely and selectively stimulate Aδ and C fibers in the superficial and deep skin layers. DLss data demonstrate that patients with painful DPN have increased Aδ fiber pain thresholds, while C-fiber thresholds are intact because, in these patients, CMi fibers are abnormally spontaneously active. It is also possible to determine the involvement of CMi fibers by measuring the area of DLss-induced neurogenic axon reflex flare. The differences in AMH, CMH, and CMi fibers identify patients with painful and painless neuropathy. In this review, we will discuss the role of CMi fibers in PDPN.

Vitamin B6 levels do not correlate with severity of neuropathy in chronic idiopathic axonal polyneuropathy.

Pyridoxine (vitamin B6) toxicity is known to cause a length-dependent, sensory predominant axonal polyneuropathy. There is debate regarding the threshold at which intake levels can cause neurological symptoms through pyridoxine toxicity. We asked if elevated plasma vitamin B6 levels were related to outcome measures in a well-characterized cohort of patients with chronic idiopathic axonal polyneuropathy (CIAP). We included 261 patients enrolled in the Peripheral Neuropathy Research Registry who had a complete dataset including a plasma vitamin B6 value. Patients with vitamin B6 deficiency (0-4.9 µg/L) were excluded. We performed a chi-square test for independence and analyzed the logistic relation of elevated plasma B6 level to nerve conduction studies (NCS), neurological examination findings, and patient-reported symptoms controlling for age and time elapsed since neuropathy symptom onset. Plasma B6 level was not related to neuropathy severity. There was no logistic relation of elevated plasma B6 level to NCS results, examination features including toe strength, vibration sense, and deep tendon reflexes, or patient-reported numbness or pain intensity. This study suggests that moderately elevated plasma B6 levels, even in the 100 to 200 µg/L range, are not associated with significantly worse neuropathy signs or symptoms. Although standard supplementation of B6 does not appear to have a major negative affect on CIAP, this study does not directly answer whether stopping supplementation will have a beneficial effect. Very few patients in the study had vitamin B6 levels >300 µg/L, suggesting that screening for vitamin B6 toxicity may be left to the discretion of the physician.

Randomized controlled trial transfusing convalescent plasma as post-exposure prophylaxis against SARS-CoV-2 infection.

BACKGROUND: The efficacy of SARS-CoV-2 convalescent plasma (CCP) for preventing infection in exposed, uninfected individuals is unknown. We hypothesized that CCP might prevent infection when administered before symptoms or laboratory evidence of infection. METHODS: This double-blinded, phase 2 randomized, controlled trial (RCT) compared the efficacy and safety of prophylactic high titer (≥1:320) CCP with standard plasma. Asymptomatic participants aged ≥18 years with close contact exposure to a person with confirmed COVID-19 in the previous 120 hours and negative SARS-CoV-2 test within 24 hours before transfusion were eligible. The primary outcome was development of SARS-CoV-2 infection. RESULTS: 180 participants were enrolled; 87 were assigned to CCP and 93 to control plasma, and 170 transfused at 19 sites across the United States from June 2020 to March 2021. Two were excluded for SARS-CoV-2 RT-PCR positivity at screening. Of the remaining 168 participants, 12/81 (14.8%) CCP and 13/87 (14.9%) control recipients developed SARS-CoV-2 infection; 6 (7.4%) CCP and 7 (8%) control recipients developed COVID-19 (infection with symptoms). There were no COVID-19-related hospitalizations in CCP and 2 in control recipients. There were 28 adverse events in CCP and 58 in control recipients. Efficacy by restricted mean infection free time (RMIFT) by 28 days for all SARS-CoV-2 infections (25.3 vs. 25.2 days; p=0.49) and COVID-19 (26.3 vs. 25.9 days; p=0.35) were similar for both groups. CONCLUSION: In this trial, which enrolled persons with recent exposure to a person with confirmed COVID-19, high titer CCP as post-exposure prophylaxis appeared safe, but did not prevent SARS-CoV-2 infection. TRIAL REGISTRATION: Clinicaltrial.gov number NCT04323800 .

Microvascular Anatomy and Intrinsic Gene Expression of Menisci From Young Adults.

BACKGROUND: Meniscal vascular supply is an important determinant of its healing potential. It has been reported that only the peripheral 30% of the meniscus is vascularized in cadavers aged 53 to 94 years; however, the vascularity in young patients, in whom meniscal repair is more often performed, is unknown. PURPOSE: The primary objective was to analyze and measure the microvascular anatomy of the meniscus in adult cadaveric specimens <35 years old. The secondary objective was to assess angiogenic potential by quantifying regional gene expression in a meniscal allograft cohort <45 years old. STUDY DESIGN: Descriptive laboratory study. METHODS: In part 1 of this study, 13 fresh-frozen cadaveric knees (age range, 22-34 years; mean, 28.5 years) underwent popliteal artery India ink injection and tissue clearing using a Spalteholz technique, followed by microvascular vascular measurement. In part 2, mRNA was isolated from 13 meniscal allografts (age range, 17-43 years; mean, 27.2 years), and expression of angiogenic genes, vascular endothelial growth factor (VEGF), and vascular endothelial growth factor receptor 1 (FLT1) was quantified using real-time polymerase chain reaction. RESULTS: The maximal depth of vascular penetration into the periphery of the medial and lateral menisci ranged from 0% to 42% and 0% to 48%, respectively. There was variation in the degree of vascular penetration within the medial meniscus, with the posterior horn having a significantly smaller depth of penetration (median, 8.7%) than that of the anterior horn (median, 17.4%; P < .0001) or midbody (median, 17.5%; P = .0003). There were no differences in angiogenesis gene expression (VEGF/FLT1) based on circumferential or radial meniscal locations. CONCLUSION: The vascular supply of the medial and lateral menisci in specimens from adults <35 years of age extended farther than what was reported in specimens from older individuals; however, median values remained consistent. Gene expression of the angiogenic marker VEGF was low throughout all regions of uninjured menisci from young adults, which is consistent with reports in older specimens. CLINICAL RELEVANCE: Improved understanding of meniscal vascular supply in young adults is critical to informing clinical treatment decisions.

Idiopathic distal sensory polyneuropathy: ACTTION diagnostic criteria.

OBJECTIVE: To present standardized diagnostic criteria for idiopathic distal sensory polyneuropathy (iDSP) and its subtypes: idiopathic mixed fiber sensory neuropathy (iMFN), idiopathic small fiber sensory neuropathy (iSFN), and idiopathic large fiber sensory neuropathy (iLFN) for use in research. METHODS: The Analgesic, Anesthetic, and Addiction Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION) public-private partnership with the Food and Drug Administration convened a meeting to develop consensus diagnostic criteria for iMFN, iSFN, and iLFN. After background presentations, a collaborative, iterative approach was used to develop expert consensus for new criteria. RESULTS: An iDSP diagnosis requires at least 1 small fiber (SF) or large fiber (LF) symptom, at least 1 SF or LF sign, abnormalities in sensory nerve conduction studies (NCS) or distal intraepidermal nerve fiber density (IENFD), and exclusion of known etiologies. An iMFN diagnosis requires that at least 1 of the above clinical features is SF and 1 clinical feature is LF with abnormalities in sensory NCS or IENFD. Diagnostic criteria for iSFN require at least 1 SF symptom and at least 1 SF sign with abnormal IENFD, normal sensory NCS, and the absence of LF symptoms and signs. Diagnostic criteria for iLFN require at least 1 LF symptom and at least 1 LF sign with normal IENFD, abnormal sensory NCS, and absence of SF symptoms and signs. CONCLUSION: Adoption of these standardized diagnostic criteria will advance research and clinical trials and spur development of novel therapies for iDSPs.

Unconventional Field-Induced Spin Gap in an S=1/2 Chiral Staggered Chain.

We investigate the low-temperature magnetic properties of the molecule-based chiral spin chain [Cu(pym)(H_{2}O)_{4}]SiF_{6}·H_{2}O (pym=pyrimidine). Electron-spin resonance, magnetometry and heat capacity measurements reveal the presence of staggered g tensors, a rich low-temperature excitation spectrum, a staggered susceptibility, and a spin gap that opens on the application of a magnetic field. These phenomena are reminiscent of those previously observed in nonchiral staggered chains, which are explicable within the sine-Gordon quantum-field theory. In the present case, however, although the sine-Gordon model accounts well for the form of the temperature dependence of the heat capacity, the size of the gap and its measured linear field dependence do not fit with the sine-Gordon theory as it stands. We propose that the differences arise due to additional terms in the Hamiltonian resulting from the chiral structure of [Cu(pym)(H_{2}O)_{4}]SiF_{6}·H_{2}O, particularly a uniform Dzyaloshinskii-Moriya coupling and a fourfold periodic staggered field.

Peripheral Neuropathy Research Registry: A prospective cohort.

The Peripheral Neuropathy Research Registry (PNRR) is a prospective cohort of peripheral neuropathy (PN) patients focused on idiopathic axonal peripheral neuropathy. Patients with diabetic, human immunodeficiency virus-, and chemotherapy-induced peripheral neuropathies are enrolled as comparison groups. The PNRR is a multi-center collaboration initiated and funded by the Foundation for Peripheral Neuropathy (FPN) with the objective to recruit a well characterized cohort of patients with different phenotypes and symptoms in each diagnostic category, and to advance research through development of biomarkers and identification of previously unknown causes of PN. The overall goal of the initiative is to find disease-altering treatments and better symptom relief for patients. We present the study design, types of data collected, and characteristics of the first 1150 patients enrolled. We also discuss ongoing analyses on this dataset, including untargeted-omics methodologies.

Counting the cost of an outbreak of carbapenemase-producing Enterobacteriaceae: an economic evaluation from a hospital perspective.

OBJECTIVE: To perform an economic evaluation on the cost associated with an outbreak of carbapenemase-producing Enterobacteriaceae (CPE). METHODS: We performed an observational economic evaluation of an outbreak of CPE (NDM-producing Klebsiella pneumoniae) affecting 40 patients in a group of five hospitals across three sites in West London. Costs were split into actual expenditure (including anti-infective costs, enhanced CPE screening, contact precautions, temporary ward-based monitors of hand and environmental practice, and environmental decontamination), and 'opportunity cost' (staff time, bed closures and elective surgical missed revenue). Costs are estimated from the hospital perspective over the 10-month duration of the outbreak. RESULTS: The outbreak cost €1.1m over 10 months (range €0.9-1.4m), comprising €312 000 actual expenditure, and €822 000 (range €631 000-€1.1m) in opportunity cost. An additional €153 000 was spent on Estates renovations prompted by the outbreak. Actual expenditure comprised: €54 000 on anti-infectives for 18 patients treated, €94 000 on laboratory costs for screening, €73 000 on contact precautions for 1831 contact precautions patient-days, €42 000 for hydrogen peroxide vapour decontamination of 24 single rooms, €43 000 on 2592 hours of ward-based monitors, and €6000 of expenditure related to ward and bay closures. Opportunity costs comprised: €244 000 related to 1206 lost bed-days (range 366-2562 bed-days, €77 000-€512 000), €349 000 in missed revenue from 72 elective surgical procedures, and €228 000 in staff time (range €205 000-€251 000). Reduced capacity to perform elective surgical procedures related to bed closures (€349 000) represented the greatest cost. CONCLUSIONS: The cost estimates that we present suggest that CPE outbreaks are highly costly.

Activity for Diabetic Polyneuropathy (ADAPT): Study Design and Protocol for a 2-Site Randomized Controlled Trial.

Background: Half of all patients with diabetes develop diabetic peripheral neuropathy (DPN), a complication leading to reduced mobility and quality of life. Although there are no proven pharmacologic approaches to reduce DPN risk or slow its progression, evidence suggests that physical activity may improve symptoms and enhance peripheral nerve regeneration. Objective: The aim of the study will be to determine the impact of an intense lifestyle intervention on neuropathy progression and quality of life in individuals with DPN. Design: The study will be a randomized controlled trial. Setting: The study will be conducted at 2 academic medical centers. Participants: The participants will be 140 individuals with type 2 diabetes and mild to moderate DPN. Intervention: The intervention group will receive 18 months of supervised exercise training, actigraphy-based counseling to reduce sedentary behavior, and individualized dietary counseling. Control group participants will receive diet and activity counseling at baseline and at 9 months. Measurements: The primary outcomes are neuropathy progression as measured by intraepidermal nerve fiber density in a distal thigh skin biopsy and the Norfolk Quality of Life-Diabetic Neuropathy score. Secondary outcomes include pain, gait, balance, and mobility measures. Limitations: Due to the combined intervention approach, this protocol will not be able to determine which intervention components influence outcomes. There also may be difficulty with participant attrition during the 18-month study intervention. Conclusions: The Activity for Diabetic Polyneuropathy (ADAPT) protocol resulted from a collaboration between physical therapists and neurologist researchers that includes as primary outcomes both a quality-of-life measure (NQOL-DN) and a physiologic biomarker (IENFD). It has the potential to demonstrate that an intensive lifestyle intervention may be a sustainable, clinically effective approach for people with DPN that improves patient outcomes and can have an immediate impact on patient care and future clinical trials.

The Association of Chemotherapy-Induced Peripheral Neuropathy Symptoms and the Risk of Falling.

IMPORTANCE: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of neurotoxic chemotherapy resulting in pain, sensory loss, and decreased quality of life. Few studies have prospectively examined the relationship between sensory neuropathy symptoms, falls, and fall-related injuries for patients receiving neurotoxic chemotherapy. OBJECTIVE: To determine the association between the symptoms of CIPN and the risk of falls for patients receiving neurotoxic chemotherapy. DESIGN, SETTING, AND PARTICIPANTS: In this secondary analysis of a prospective study, 116 patients with breast, ovarian, or lung cancer who were beginning neurotoxic chemotherapy with a taxane or platinum agent were recruited from oncology clinics. These patients would call a novel automated telephone system daily for 1 full course of chemotherapy. The telephone system (SymptomCare@Home) used a series of relevant CIPN questions to track symptoms on a 0 to 10 ordinal scale and contained a questionnaire about falls. Those reporting a numbness and tingling severity score of 3 or greater for at least 10 days were considered to have significant CIPN symptoms and were compared with those patients who did not. Data analysis was performed in November 2015. EXPOSURE: Chemotherapy with a neurotoxic taxane or platinum agent. MAIN OUTCOMES AND MEASURES: Patient-reported falls or near falls and fall-related injuries. The hypothesis was generated after data collection but prior to data analysis. RESULTS: Of the 116 patients who started neurotoxic chemotherapy (mean [SD] age was 55.5 [11.9] years, and 109 [94.0%] were female), 32 met the predetermined criteria for CIPN symptoms. The mean duration of follow-up was 62 days, with 51 telephone calls completed per participant. Seventy-four falls or near falls were reported. The participants with CIPN symptoms were nearly 3 times more likely to report a fall or near fall than the participants without CIPN symptoms (hazard ratio, 2.67 [95% CI, 1.62-4.41]; P < .001). The participants with CIPN symptoms were more likely than the participants without CIPN symptoms to obtain medical care for falls (8 of 32 participants with CIPN symptoms [25.0%] vs 6 of 84 participants without CIPN symptoms [7.1%]; P = .01). CONCLUSIONS AND RELEVANCE: These findings suggest that the sensory symptoms of CIPN are an indicator of an increased risk of falling and an increased use of health care resources. This study demonstrates the utility of a novel telephone-based system to track neuropathy symptoms. Careful monitoring and coaching of patients receiving neurotoxic chemotherapy for new sensory symptoms may facilitate more effective fall prevention strategies.

Normative Values for Electrochemical Skin Conductances and Impact of Ethnicity on Quantitative Assessment of Sudomotor Function.

BACKGROUND: Sudomotor dysfunction is one of the earliest pathophysiologic abnormalities in diabetes. Sudoscan™ (Impeto Medical, Paris, France) was developed as a noninvasive, rapid, and quantitative assessment of sudomotor function and has been shown to be sensitive in the detection of neuropathy. This global collaborative analysis aimed to establish reference values in healthy subjects of different ethnic groups, age, and gender, to define factors potentially affecting results, and to provide standardization of the methodology. MATERIALS AND METHODS: Data from 1,350 generally healthy study participants who underwent sudomotor function testing were collected and analyzed. The relationship between age, height, weight, gender, glycemic and lipid profiles, ethnicity, and hand and foot electrochemical skin conductance (ESC) was assessed among subgroups of participants. RESULTS: Lower mean hands and feet ESC values were observed in African American, Indian, and Chinese subjects (P < 0.0001). No participant discomfort or safety concern was reported in 1,376 tests. No significant difference in ESC was observed between women and men at the hands (75 [57-87] vs. 76 [56-89] µS; P = 0.35) or feet (83.5 [71-90] vs. 82.5 [70-91] µS; P = 0.12). The coefficient of correlation between right and left side ESC was r = 0.96, P < 0.0001 for hands and r = 0.97, P < 0.0001 for feet. A significant but weak correlation was observed between ESC and age: for hands, r = -0.17, P < 0.0001; for feet, r = -0.19, P < 0.0001. CONCLUSIONS: A normative reference range was established in whites showing that there was no effect of sex or body mass index and a slight decrease in ESC with age. Ethnicity influenced ESC scores, but additional studies are necessary to validate this effect and determine its mechanism and impact on nerve function.

Frustrated magnetism in the spin-chain metal Yb2Fe12P7.

Magnetization measurements for magnetic fields [Formula: see text] up to 60 T are reported for the noncentrosymmetric spin-chain metal Yb2Fe12P7. These measurements reveal behavior that is consistent with Ising-like spin chain magnetism that produces pronounced spin degeneracy. In particular, we find that although a Brillouin field dependence is observed in M(H) for [Formula: see text] with a saturation moment that is close to the expected value for free ions of Yb(3+) , non-Brillouin-like behavior is seen for [Formula: see text] with an initial saturation moment that is nearly half the free ion value. In addition, hysteretic behavior that extends above the ordering temperature [Formula: see text] is seen for [Formula: see text] but not for [Formula: see text], suggesting out-of-equilibrium physics. This point of view is strengthened by the observation of a spin reconfiguration in the ordered state for [Formula: see text] which is only seen for [Formula: see text] and after polarizing the spins. Together with the heat capacity data, these results suggest that the anomalous low temperature phenomena that were previously reported (Baumbach 2010 et al Phys. Rev. Lett. 105 106403) are driven by spin degeneracy that is related to the Ising-like one dimensional chain-like configuration of the Yb ions.

Exercise as Therapy for Diabetic and Prediabetic Neuropathy.

Length-dependent neuropathy is the most common and costly complication of diabetes and frequently causes injury primarily to small-diameter cutaneous nociceptive fibers. Not only persistent hyperglycemia but also metabolic, endocrine, and inflammatory effects of obesity and dyslipidemia appear to play an important role in the development of diabetic neuropathy. Rational therapies aimed at direct control of glucose or its increased entry into the polyol pathway, oxidative or nitrosative stress, advanced glycation end product formation or signaling, microvascular ischemia, or adipocyte-derived toxicity have each failed in human trials of diabetic neuropathy. Aerobic exercise produces salutary effects in many of these pathogenic pathways simultaneously and, in both animal models and human trials, has been shown to improve symptoms of neuropathy and promote re-growth of cutaneous small-diameter fibers. Behavioral reduction in periods of seated, awake inactivity produces multimodal metabolic benefits similar to exercise, and the two strategies when combined may offer sustained benefit to peripheral nerve function.

Precision chemical heating for diagnostic devices.

Decoupling nucleic acid amplification assays from infrastructure requirements such as grid electricity is critical for providing effective diagnosis and treatment at the point of care in low-resource settings. Here, we outline a complete strategy for the design of electricity-free precision heaters compatible with medical diagnostic applications requiring isothermal conditions, including nucleic acid amplification and lysis. Low-cost, highly energy dense components with better end-of-life disposal options than conventional batteries are proposed as an alternative to conventional heating methods to satisfy the unique needs of point of care use.