Search

A fractional model for the kinetics of hepatitis B transmission was developed. The hepatitis B virus significantly affects the world's economic and health systems. Acute and chronic carrier phases play a crucial part in the spread of the HBV infection. The Hepatitis B infection can be spread by chronic carriers even though they show no symptoms. In this article, we looked into the Hepatitis B virus's various stages of infection-related transmission and built a nonlinear epidemic. Then, a fractional hepatitis B virus model using a Caputo derivative and vaccine effects is created. First, we determined the proposed model's essential reproductive value and equilibria. With the aid of Fixed Point Theory, a qualitative analysis of the problem's approximative root has been produced. The Adams-Bashforth predictor-corrector scheme is used to aid in the iterative approximate technique's evaluation of the fractional system under consideration that has the Caputo derivative. In the final section, a graphical representation compares various noninteger orders and displays the discovered scheme findings. In this study, we've utilized Artificial Neural Network (ANN) techniques to partition the dataset into three categories: training, testing, and validation. Our analysis delves deep into each category, comprehensively examining the dataset's characteristics and behaviors within these divisions. The study comprehensively analyzes the fractional HBV transmission model, incorporating both mathematical and computational approaches. The findings contribute to a better understanding of the dynamics of HBV infection and can inform the development of effective public health interventions., (© 2024. The Author(s).)

Complex fuzzy soft matrices play a crucial role in various applications, including decision-making, pattern recognition, signals processing, and image processing. The main objective of this study is to introduce the unique notions of complex Pythagorean fuzzy soft matrices (CPFSMs), which provide more flexibility and accuracy in modelling uncertainty. CPFSMs incorporate Pythagorean fuzzy soft matrices, allowing for more sophisticated uncertainty modeling. The key findings of CPFSMs, specific instances, and certain fundamental set-theoretic operations and principles were covered. A set of new distance metrics between two CPFSMs has been defined. In the context of complex Pythagorean fuzzy soft sets and complex Pythagorean fuzzy soft matrices, we created a CPFS decision-making technique. Moreover, the application's numerical example and comparison analysis have been effectively demonstrated. Thus, by integrating the concepts of Pythagorean fuzzy sets, soft matrices, and complex numbers, CPFSMs provide a robust framework with membership and non-membership degrees for complex decision-making modeling and analyzing uncertain data., (© 2024. The Author(s).)

A complex fuzzy distance measure (CFDMs) plays a significant role in applications involving complex or high-dimensional data where traditional distance measures may not adequately capture the nuances of the data relationships. The significance of CFDMs lies in their ability to handle uncertainty, imprecision, and complexity in various domains. Numerous researchers introduced different concepts of CFDMs, yet these CFDMs fails to convey any information regarding the hesitancy degree associated with an element. The main objective of this paper is to introduce some new distance measures based on complex fuzzy sets, called complex fuzzy hesitance distance measure and complex fuzzy Euclidean Hesitance distance measure, which is the generalization of complex fuzzy normalized Hamming distance measure and complex fuzzy Euclidean distance measure. Some new operations and primay results are discussed in the environment of proposed CFDMs and complex fuzzy operations. Moreover, we discussed the applications of the proposed CFDMs in addressing decision-making problems. We introduced a new decision-making algorithm that integrates CFDMs into decision-making processes, providing a robust methodology for handling real-world complexities. Further, the comparative study of the proposed CFDMs is discussed with some existing CFDMs., (© 2024. The Author(s).)

The creation of an explicit finite difference scheme with the express purpose of resolving initial boundary value issues with linear and semi-linear variable-order temporal fractional properties is presented in this study. The rationale behind the utilization of the Caputo derivative in this scheme stems from its known importance in fractional calculus, an area of study that has attracted significant interest in the mathematical sciences and physics. Because of its special capacity to accurately represent physical memory and inheritance, the Caputo derivative is a relevant and appropriate option for representing the fractional features present in the issues this study attempts to address. Moreover, a detailed Fourier analysis of the explicit finite difference scheme's stability is shown, demonstrating its conditional stability. Finally, certain numerical example solutions are reviewed and MATLAB-based graphic presentations are made., (© 2024. The Author(s).)

The application of artificial intelligence (AI) in predictive analytics is growing in popularity. It has the power to offer ground-breaking solutions for a range of social problems and real world societal difficulties. It is helpful in addressing some of the social issues that today's world seems incapable of solving. One of the most significant phenomena affecting people's lives is divorce. The goal of this paper is to study the use of machine learning algorithms to determine the effectiveness of divorce predictor scale (DPS) and identify the reasons that usually lead to divorce in the scenario of Hail region, KSA. For this purpose, in this study, the DPS, based on Gottman couples therapy, was used to predict divorce by applying different machine learning algorithms. There were 54 items of the DPS used as features or attributes for data collection. In addition to the DPS, a personal information form was utilized to gather participants' personal data in order to conduct this study in a more structured and traditional manner. Out of 148 participants 116 participants were married whereas 32 were divorced. With the use of algorithms artificial neural network (ANN), naïve bayes (NB), and random forest (RF), the effectiveness of DPS was examined in this study. The correlation based feature selection method was used to identify the top six features from the same dataset and the highest accuracy rate was 91.66% with RF. The results show that DPS can predict divorce. This scale can help family counselors and therapists in case formulation and intervention plan development process. Additionally, it may be argued that the Hail region, KSA sampling confirmed the Gottman couples treatment predictors., (© 2024. The Author(s).)

In this article, the dynamical behavior of a complex food chain model under a fractal fractional Caputo (FFC) derivative is investigated. The dynamical population of the proposed model is categorized as prey populations, intermediate predators, and top predators. The top predators are subdivided into mature predators and immature predators. Using fixed point theory, we calculate the existence, uniqueness, and stability of the solution. We examined the possibility of obtaining new dynamical results with fractal-fractional derivatives in the Caputo sense and present the results for several non-integer orders. The fractional Adams-Bashforth iterative technique is used for an approximate solution of the proposed model. It is observed that the effects of the applied scheme are more valuable and can be implemented to study the dynamical behavior of many nonlinear mathematical models with a variety of fractional orders and fractal dimensions.

Introduction: Research on young worker safety often relies on inconsistent definitions of young workers and poorly delineated indicators of occupational safety. This review aims to reconcile these fundamental issues by critically integrating research across disciplines and providing clear directions for future research on young worker safety., Method: We critically review the extant research on young worker safety., Results: We first reconcile the inconsistent definitions of young workers and specify the indicators of occupational safety used in young worker safety research. We next describe the prevalence of workplace injuries and population-level predictors of these injuries among young workers and then outline other factors that increase young workers' susceptibility to workplace injuries. Finally, we discuss the convergence of many of these issues on family farms-a context commonly studied in young worker safety research., Conclusions: Clearer definitions of young workers and indicators of occupational safety can improve the interpretation and comparability of extant research findings. Furthermore, the prevalence of workplace injuries and population-level predictors of injury among young workers are subject to the interactions among age, gender, minority status, and job characteristics. Other factors that increase young workers' susceptibility to injury include young workers' responses to hazardous work, individual differences stemming from young workers' biological and psychological development, managerial attitudes about young workers, and the limited safety training young workers are thus provided, the types of work that young workers typically perform, and the range of social influences on young workers., Practical Applications: Safety campaigns and safety training should consider interactions among young workers' age, gender, minority status, and job characteristics, rather than considering these features independently., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2022. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Conflict of Interest None.

This article is aimed to examine the relationship between socioeconomic factors and child mortality in South Asia because the relationship between child mortality and socioeconomic factors cannot be overlooked for better progress. Panel data were obtained from (World Development Indicators) and (Human Development Index) for the period 1990-2017. The data were quantitative. Levin, Lin, and Chu and I'm, Pesaran, and Shin test were used to check the stationarity of data. A cointegration test was applied to check the long-run association. Granger causality test was used to determine the direction of the relationship. Fully modified ordinary least squares and dynamic ordinary least squares techniques were used to examine the long-run and short-run impact of socioeconomic determinants on child mortality. The findings from this study showed the significant impact of education, unemployment, and health expenditure, access to improved water and sanitation facilities, and income inequality on child mortality. Overall results showed that there is a negative association between education and child mortality, access to improved water and access to sanitation facilities and child mortality, and health expenditure and child mortality, but there is a positive association between unemployment and income inequality with child mortality. The rate of child mortality is still very alarming in South Asian countries.

Preclinical as well as human studies indicate that melatonin is essential for a physiological sleep state, promotes analgesia and is involved in immunometabolic signaling by regulating neuroinflammatory pathways. Experimental and clinical neuromodulation studies for chronic pain treatment suggest that neurostimulation therapies such as spinal cord stimulation, vagus nerve stimulation and dorsal root ganglion stimulation have an impact on circulating inflammatory mediators in blood, cerebrospinal fluid and saliva. Herein, we provide an overview of current literature relevant for the shared pathways of sleep, pain and immunometabolism and elaborate the impact of melatonin on the crossroad of sleep, chronic pain and immunometabolism. Furthermore, we discuss the potential of melatonin as an adjunct to neurostimulation therapies. In this narrative review, we addressed these questions using the following search terms: melatonin, sleep, immunometabolism, obesity, chronic pain, neuromodulation, neurostimulation, neuroinflammation, molecular inflammatory phenotyping. So far, the majority of the published literature is derived from experimental studies and studies specifically assessing these relationships in context to neurostimulation are sparse. Thus, the adjunct potential of melatonin in clinical neurostimulation has not been evaluated under the umbrella of randomized-controlled trials and deserves increased attention as melatonin interacts and shares pathways relevant for noninvasive and invasive neurostimulation therapies.

Chronic refractory central post-stroke pain (CPSP), one of the most disabling consequences of cerebral stroke, occurs in up to 10% of patients with CPSP. Because a considerable proportion of these patients with chronic pain remain resistant to pharmacological and behavioral therapies, adjunctive invasive and non-invasive brain stimulation therapies are needed. We performed a review of human studies applying burst and conventional motor cortex stimulation (burstMCS and cMCS, respectively) for chronic pain states, on the basis of data sources identified through searches of PubMed, MEDLINE/OVID, and SCOPUS, as well as manual searches of the bibliographies of known primary and review articles. Our aim was to review and discuss clinical data on the indications of burstMCS for various chronic pain states originating from central stroke (excluding trigeminal facial pain). In addition, we assessed the efficacy and safety of burst versus cMCS for central post-stroke pain with an extended follow-up of 5 years in a 60-year-old man. According to our review, uncontrolled observational human cohort studies and one RCT using cMCS waveforms have revealed a meaningful clinical response; however, these studies lacked placebo groups and extended observation periods. In our case report, we found that 3 months of adjunctive cMCS reduced pain levels [visual analog scale (VAS) pre: 9/10 versus VAS post 7/10], whereas the pain decreased further under burstMCS (VAS pre: 7/10 versus VAS post: 2/10); the study involved a follow-up of 5 years and the following parameters: burst rate 40 Hz (500 Hz), 1-1.75 mA, 1 ms, bipolar configuration. To date, only limited evidence exists for the efficacy and safety of burst motor cortex stimulation for the treatment of refractory chronic pain. BurstMCS resulted in significantly decreased post-stroke pain observed after 5 years of cMCS. The available literature suggests similar efficacy as that of conventional (tonic) motor cortex stimulation, although the results are preliminary. Mechanistically, the precise mechanism of action is not fully understood. However, burstMCS may interact with the nociceptive thalamic-cingulate and descending spinal pain networks. To determine the potential utility of this treatment, large-scale sham-controlled trials comparing cMCS and burstMCS are highly recommended.

Leptin has been recognized as a potential tumor growth promoter in various cancers including cranial tumor pathologies such as pituitary adenomas, meningiomas and gliomas. Despite recent advances in adjunctive therapy and the established surgical resection, chemo- and radiotherapy regimen, glioblastoma multiforme remains a particular diagnostic and therapeutic challenge among the intracranial tumor pathologies, with a poor long-term prognosis. Systemic inflammation and immune-metabolic signaling through diverse pathways are thought to impact the genesis and recurrence of brain tumors, and glioblastoma multiforme in particular. Among the various circulating mediators, leptin has gained especial diagnostic and therapeutic interest, although the precise relationship between leptin and glioblastoma biology remains largely unknown. In this narrative review (MEDLINE/OVID, SCOPUS, PubMed and manual searches of the bibliographies of known primary and review articles), we discuss the current literature using the following search terms: leptin, glioblastoma multiforme, carcinogenesis, immunometabolism, biomarkers, metformin, antidiabetic medication and metabolic disorders. An increasing body of experimental evidence implicates a relationship between the development and maintenance of gliomas (and brain tumors in general) with a dysregulated central and peripheral immune-metabolic network mediated by circulating adipokines, chemokines and cellular components, and in particular the leptin adipokine. In this review, we summarize the current evidence of the role of leptin in glioblastoma pathophysiology. In addition, we describe the status of alternative diagnostic tools and adjunctive therapeutics targeting leptin, leptin-receptors, antidiabetic drugs and associated pathways. Further experimental and clinical trials are needed to elucidate the mechanism of action and the value of immune-metabolism molecular phenotyping (central and peripheral) in order to develop novel adjunctive diagnostics and therapeutics for newly diagnosed and recurrent glioblastoma patients.

Background: In a previous study, we reported that selective dorsal root ganglion stimulation (DRG STIM ) at DRG level L4 promoted a favorable outcome for complex regional pain syndrome (CRPS) patients along with DRG STIM -related changes of inflammatory biomarkers in blood and saliva. The impact on somatosensation is largely unknown. Herein, we assessed the quantitative sensory profile to quantify L4-DRG STIM effects in CRPS patients., Methods: Twelve refractory CRPS patients (4 female; 8 male; mean age 69 ± 9 years) received standardized quantitative sensory testing (QST) protocol at baseline and after 3 months of unilateral L4-DRG STIM assessing nociceptive and non-nociceptive thermal and mechanical sensitivity of the knee affected by CRPS and the contralateral non-painful knee area., Results: At baseline, CRPS subjects showed significantly increased thresholds for warmth, tactile and vibration detection (WDT, MDT and VDT) and exaggerated pain summation (WUR). After 3 months of unilateral L4-DRG STIM all pain parameters exhibited trends towards normalization of sensitivity accumulating to a significant overall normalization for pain sensitivity (effect size: 0.91, p < 0.01), while with the one exception of WDT all non-nociceptive QST parameters remained unchanged. Overall change of non-nociceptive detection was negligible (effect size: 0.25, p > 0.40). Notably, reduction of pain summation (WUR) correlated significantly with pain reduction after 3 months of L4-DRG STIM ., Conclusions: Selective L4-DRG STIM lowered ongoing pain in CRPS patients and evoked significant normalization in the pain domain of the somatosensory profile. Thermoreception and mechanoreception remained unchanged. However, larger randomized, sham-controlled trials are highly warranted to shed more light on effects and mechanisms of dorsal root ganglion stimulation on quantitative sensory characteristics. The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00011267.

Dihydroergotamine (DHE) is an ergot alkaloid derivative of substances produced by rye fungus. Ergotamine was first used in the field of gynecology and obstetrics, then used for migraine treatment a few years later. DHE was developed as a derivative of ergotamine. DHE, when compared to ergotamine, demonstrates greater alpha-adrenergic antagonist activity, lower arterial vasoconstriction, less dopaminergic agonism, and lower emetic potential. DHE can be delivered via several routes including intravenous (IV), intramuscular (IM), subcutaneous (SC), intranasal (IN), oral, and orally inhaled (although the latter two are not available in the USA and the last remains experimental only). DHE can be used in an outpatient basis in infusion centers, emergency departments, and urgent care centers, as well as inpatient treatment for admitted patients. There are protocols for adults as well as pediatric migraine treatment. DHE and other ergot alkaloids are considered contraindicated in pregnant women as they decrease uterine blood flow and increase uterine muscle contractility predisposing to spontaneous abortion. DHE during lactation is also not recommended as it can lead to gastrointestinal distress and weakness in infants; it can also suppress milk production. Caution should be taken before administering DHE in patients with cardiovascular risk factors. DHE is an older drug with an interesting history, yet it is still clinically useful today for patients with migraine attacks not responsive to triptans, who have a greater burden from migraine, and in refractory migraine., Competing Interests: Dr Stephanie Nahas reports personal fees from Alder/Lundbeck, Allergan, Amgen/Novartis, Biohaven, Eli Lilly, electroCore, Impel, Supernus, Teva, Theranica, Zosano, Springer, and Wolters-Kluwer outside the submitted work. The authors report no other conflicts of interest in this work., (© 2020 Shafqat et al.)

Chronic pain is a devastating condition affecting the physical, psychological, and socioeconomic status of the patient. Inflammation and immunometabolism play roles in the pathophysiology of chronic pain disorders. Electrical neuromodulation approaches have shown a meaningful success in otherwise drug-resistant chronic pain conditions, including failed back surgery, neuropathic pain, and migraine. A literature review (PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles) was performed using the following search terms: chronic pain disorders, systemic inflammation, immunometabolism, prediction, biomarkers, metabolic disorders, and neuromodulation for chronic pain. Experimental studies indicate a relationship between the development and maintenance of chronic pain conditions and a deteriorated immunometabolic state mediated by circulating cytokines, chemokines, and cellular components. A few uncontrolled in-human studies found increased levels of pro-inflammatory cytokines known to drive metabolic disorders in chronic pain patients undergoing neurostimulation therapies. In this narrative review, we summarize the current knowledge and possible relationships of available neurostimulation therapies for chronic pain with mediators of central and peripheral neuroinflammation and immunometabolism on a molecular level. However, to address the needs for predictive factors and biomarkers, large-scale databank driven clinical trials are needed to determine the clinical value of molecular profiling.

Background: In our recent clinical trial, increased peripheral concentrations of pro-inflammatory molecular mediators were determined in complex regional pain syndrome (CRPS) patients. After 3 months adjunctive unilateral, selective L4 dorsal root ganglion stimulation (L4-DRG STIM ), significantly decreased serum IL-10 and increased saliva oxytocin levels were assessed along with an improved pain and functional state. The current study extended molecular profiling towards gene expression analysis of genes known to be involved in the gonadotropin releasing hormone receptor and neuroinflammatory (cytokines/chemokines) signaling pathways., Methods: Blood samples were collected from 12 CRPS patients for whole-transcriptome profiling in order to assay 18,845 inflammation-associated genes from frozen blood at baseline and after 3 months L4-DRG STIM using PANTHER™ pathway enrichment analysis tool., Results: Pathway enrichment analyses tools (GOrilla™ and PANTHER™) showed predominant involvement of inflammation mediated by chemokines/cytokines and gonadotropin releasing hormone receptor pathways. Further, screening of differentially regulated genes showed changes in innate immune response related genes. Transcriptomic analysis showed that 21 genes (predominantly immunoinflammatory) were significantly changed after L4-DRG STIM . Seven genes including TLR1, FFAR2, IL1RAP, ILRN, C5, PKB and IL18 were down regulated and fourteen genes including CXCL2, CCL11, IL36G, CRP, SCGB1A1, IL-17F, TNFRSF4, PLA2G2A, CREB3L3, ADAMTS12, IL1F10, NOX1, CHIA and BDKRB1 were upregulated., Conclusions: In our sub-group analysis of L4-DRG STIM treated CRPS patients, we found either upregulated or downregulated genes involved in immunoinflammatory circuits relevant for the pathophysiology of CRPS indicating a possible relation. However, large biobank-based approaches are recommended to establish genetic phenotyping as a quantitative outcome measure in CRPS patients. Trial registration The study protocol was registered at the 15.11.2016 on German Register for Clinical Trials (DRKS ID 00011267). https://www.drks.de/drks&#95;web/navigate.do?navigationId=trial.HTML&TRIAL&#95;ID=DRKS00011267.

Objective: To assay peripheral inter-ictal cytokine serum levels and possible relations with non-invasive vagus nerve stimulation (nVNS) responsiveness in migraineurs., Methods: This double-blinded, sham-controlled study enrolled 48 subjects and measured headache severity, frequency [headache days/month, number of total and mild/moderate/severe classified attacks/month], functional state [sleep, mood, body weight, migraine-associated disability] and serum levels of inflammatory markers [inter-ictal] using enzyme-linked immunoassays at baseline and after 2 months of adjunctive nVNS compared to sham stimulation and suitably matched controls., Results: No significant differences were observed at baseline and after 2 months for headache severity, total attacks/month, headache days/month and functional outcome [sleep, mood, disability] between verum and sham nVNS. However, the number of severe attacks/month significantly decreased in the verum nVNS group and circulating pro-inflammatory IL-1β was elevated significantly in the sham group compared to nVNS. Levels of anti-inflammatory IL-10 were significantly higher at baseline in both groups compared to healthy controls, but not at 2 months follow-up [p < 0.05]. Concentrations of high-mobility group box-1 (HMGB-1), IL-6, tumor-necrosis factor-α (TNF-α), leptin, adiponectin, ghrelin remained unchanged [p > 0.05]. No severe device-/stimulation-related adverse events occurred., Conclusion: 2 months of adjunctive cervical nVNS significantly declined the number of severe attacks/month. Pro-inflammatory IL-1β plasma levels [inter-ictal] were higher in sham-treated migraine patients compared to verum nVNS. However, pro- [IL-6, HMGB-1, TNF-α, leptin] and anti-inflammatory [IL-10, adiponectin, ghrelin] mediators did not differ statistically. Profiling of neuroinflammatory circuits in migraine to predict nVNS responsiveness remains an experimental approach, which may be biased by pre-analytic variables warranting large-scale biobank-based systematic investigations [omics]., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Rising evidence indicate that oxytocin and IL-1β impact trigemino-nociceptive signaling. Current perspectives on migraine physiopathology emphasize a cytokine bias towards a pro-inflammatory status. The anti-nociceptive impact of oxytocin has been reported in preclinical and human trials. Cervical non-invasive vagus nerve stimulation (nVNS) emerges as an add-on treatment for the preventive and abortive use in migraine. Less is known about its potential to modulate saliva inflammatory signaling in migraine patients. The rationale was to perform inter-ictal saliva measures of oxytocin and IL-1ß along with headache assessment in migraine patients with 10 weeks adjunctive nVNS compared to healthy controls., Methods: 12 migraineurs and 12 suitably matched healthy control were studied with inter-ictal saliva assay of pro- and anti-neuroinflammatory cytokines using enzyme-linked immuno assay techniques along with assessment of headache severity/frequency and associated functional capacity at baseline and after 10 weeks adjunctive cervical nVNS., Results: nVNS significantly reduced headache severity (VAS), frequency (headache days and total number of attacks) and significantly improved sleep quality compared to baseline (p < 0.01). Inter-ictal saliva oxytocin and IL-1β were significantly elevated pre- as well as post-nVNS compared to healthy controls (p < 0.01) and similarly showed changes that may reflect the observed clinical effects., Conclusions: Our results add to accumulating evidence for a therapeutic efficacy of adjunct cervical non-invasive vagus nerve stimulation in migraine patients. This study failed to provide an evidence-derived conclusion addressed to the predictive value and usefulness of saliva assays due to its uncontrolled study design. However, saliva screening of mediators associated with trigemino-nociceptive traffic represents a novel approach, thus deserve future targeted headache research. Trial registration This study was indexed at the German Register for Clinical Trials (DRKS No. 00011089) registered on 21.09.2016.

Objectives: Complex regional pain syndrome (CRPS) and associated comorbidities have been linked to a pro-inflammatory state driven by different mediators. Targeted dorsal root ganglion stimulation (DRG STIM ) suppressed pain levels and improved functional capacity in intractable CRPS. However, clinical trials assessing the impact of DRG stimulation on the neuroimmune axis are lacking., Methods: This study enrolled 24 subjects (12 refractory CRPS patients plus suitably matched healthy controls) and performed immunoassays of inflammatory mediators in saliva and serum along with score-based assessments of pain, mood, and sleep quality at baseline and after three months of selective L4-DRG STIM ., Results: After three-month L4-DRG STIM CRPS associated pain significantly decreased. In addition, disturbed sleep and mood improved post-DRG STIM , although statistically not significant. Significantly increased serum values of pro-inflammatory markers were detected pre- and post L4-DRG STIM for high-mobility group box 1, tumor-necrosis factor α, interleukin (IL) 6, and leptin. IL-1β was significantly elevated pre-L4 DRG STIM , but not posttreatment. Elevated anti-inflammatory IL-10 significantly decreased after three months in serum, while saliva oxytocin concentrations increased in CRPS subjects after L4-DRG STIM (p = 0.65). No severe implantation and stimulation associated adverse events were recorded., Conclusions: Selective L4-DRG STIM improved neuropathic pain and functional impairment in CRPS as previously reported. CRPS patients displayed a pro-inflammatory molecular pattern in serum. Serum anti-inflammatory IL-10 significantly declined, while saliva oxytocin nonsignificantly increased after L4-DRG STIM . An evidence-based relational interpretation of our study is limited due to the uncontrolled study design. However, molecular profiling of biofluids (saliva, serum) represents a novel and experimental field in applied neuromodulation, which warrant further investigations to unveil mechanisms of neuroimmune modulation., (© 2018 International Neuromodulation Society.)

Objectives: To investigate the release of proinflammatory damage-associated molecular pattern molecule "high-mobility group box-1" in the serum of patients after aneurysmal subarachnoid hemorrhage and its association with cerebral vasospasm., Design: Retrospective observational study., Setting: University hospital., Patients: Aneurysmal subarachnoid hemorrhage patients admitted within 24 hours of ictus., Interventions: Standard subarachnoid hemorrhage treatment after clipping or coiling of aneurysm., Measurements and Main Results: We enrolled 53 aneurysmal subarachnoid hemorrhage patients from which peripheral venous blood was withdrawn on days 1, 3, 5, 7, 9, 11, and 13 and once from the controls to obtain the serum. Serum high-mobility group box-1 concentration was quantified by enzyme-linked immunosorbent assay. Serum interleukin-6 and peripheral blood leukocytes were also determined over the first 2 weeks after subarachnoid hemorrhage. Patients' data were recorded prospectively. Serum high-mobility group box-1 was significantly elevated in subarachnoid hemorrhage patients from day 1 to day 13 when compared with nonsubarachnoid hemorrhage patients (p < 0.05). Patients with cerebral vasospasm showed significantly higher high-mobility group box-1 starting from day 1 to day 13 when compared with patients without cerebral vasospasm. Cumulative levels of high-mobility group box-1 showed significant correlation with peripheral blood leukocytes and interleukin-6 levels (p < 0.05). Receiver operating characteristic curve analysis showed that serum high-mobility group box-1 level at admission may be a predictive biomarker for cerebral vasospasm with a sensitivity of 59% and a specificity of 82% at a cutoff value of 5.6 ng/mL., Conclusions: Serum high-mobility group box-1 is differentially elevated after subarachnoid hemorrhage. Serum high-mobility group box-1 levels were elevated early after subarachnoid hemorrhage (day 1) and remained significantly high until day 13 in patients who developed cerebral vasospasm. Our data suggest that serum high-mobility group box-1 may be a predictive biomarker for the detection of CVS.

Context: Diabetic peripheral neuropathy (DPN) is a common complication associated with long-term type 2 diabetes mellitus, although early diagnosis can improve prognosis., Objective: Our objective was to develop a simple protocol for early diagnosis of DPN in Chinese type 2 diabetic patients., Subjects and Methods: A total of 209 type 2 diabetic patients were included; these patients were categorized as symptomatic and asymptomatic group based on their symptoms. Clinical data of these patients were recorded and they were screened for DPN by vibration perception threshold test (VPT), 10-G nylon monofilament test, temperature identification, and the tendon reflex test., Results: The total combined rate of patients who were tested positive for DPN with all four screening methods was 68.7%. Patients tested positive for DPN were significantly older and had a longer disease duration than those who were tested negative (p<0.01); however, glycated hemoglobin levels, presence of hypertension, and gender did not differ significantly between them (p>0.05). Among screening methods, the highest positive rate observed among patients screened with the VPT test was 63.64% as compared to other tests. The total positive rate for temperature discrimination, 10-G monofilament and tendon reflex test were 26.79%, 11.96 % and 17.22 % respectively. In asymptomatic group VPT showed the highest positive rate for DPN (48.41%)., Conclusions: The combination of four simple methods can improve the detection rate of DPN and identify subclinical cases. Abnormal vibration perception was the most common feature of DPN and it was associated with both disease duration and the age of the patient., Competing Interests: The authors declare no potential conflict of interest.

Objectives: In our previous study, anti-inflammatory IL-10 serum levels were significantly elevated after burst spinal cord stimulation (SCS) in back pain patients and correlated with pain intensity. This current study extended cytokine analysis including metabolic-associated adipokine/cytokine serum assessment in chronic back pain patients with co-existing metabolic disorders such as diabetes, hypertension, and cardiovascular diseases., Methods: At baseline and after three months of burst SCS treatment, leptin (LP), adiponectin (AN), and ghrelin (GH) were recorded in non-/pre-obese chronic back pain patients with co-existing metabolic disorders and compared to age-/gender-matched healthy controls (HC)., Results: Mean BMI was 22 ± 0.81 kg/m 2 in 12 (five male/seven female) participants with diabetes in 6/12 (50%), hypertension in 9 (75%), and CVD in five patients (42%). Pre- and post-SCS LP levels were significantly higher compared to healthy controls: pre-SCS, 30567 (12,996-58,821) vs. HC, 7952 (4932-12,583) pg/mL, p = 0.029; post-SCS, 18,890 (7140-44,719) vs. HC, 7952 (4932-12,583) pg/mL, p = 0.035. Pre- and post-SCS changes of GH (p = 0.18) and AN (p = 0.8) did not differ significantly. GH serum levels correlated with AN (Spearman r = 0.5; p = 0.012; 95 CI 0.11 to -0.76) and AN levels were significantly correlated with higher age (Pearson correlation r = 0.8; p = 0.002; 95 CI 0.41-0.94) at baseline., Conclusions: This study determined serum changes of metabolic-associated cytokines/adipokines in non-obese chronic back pain patients responsive to burst SCS suggesting that neuroinflammation assessment may consider pain-associated mood, cognition, sleep, and metabolic state., (© 2017 International Neuromodulation Society.)

Objectives: Burst spinal cord stimulation (SCS) has been reported to reduce back pain and improve functional capacity in Failed Back Surgery Syndrome (FBSS). However, its mechanism of action is not completely understood. Systemic circulating cytokines have been associated with the development of chronic back pain., Methods: This prospective, feasibility study enrolled 12 refractory FBSS patients with predominant back pain (70% of overall pain) suitable for Burst SCS. Back and leg pain intensity (back pain [VAS B ]/leg pain [VAS L ]), functional capacity (sleep quality [PSQI]), depressive symptoms (BDI), body weight, stimulation parameters, and plasma levels of pro-inflammatory (Il-1b; TNF; HMGB1)/anti-inflammatory (Il-10) cytokines were collected at baseline and after three months of Burst SCS and compared to healthy controls., Results: Pain intensity (pre VAS B : 8.25 ± 0.75 vs. post 1.42 ± 1.24) and functional capacity (PSQI: pre 7.92 ± 3.92 vs. post 3.42 ± 1.24; BDI: pre 20.83 ± 3.56 vs. post 10.92 ± 0.75) significantly improved compared to baseline. Pro-inflammatory HMGB1 remained unchanged (preburst: 3.35 ± 3.25 vs. postburst: 3.78 ± 3.83 ng/mL; p = 0.27; W = -30) versus the HC group (2.53 ± 2.6 ng/mL; p = 0.47; U = 59), while anti-inflammatory IL-10 levels were significantly elevated after burst SCS as compared to baseline (preburst 12.54 ± 22.95 vs. postburst 43.16 ± 74.71 pg/mL; p = 0.03; W = -48) and HC group (HC: 7.03 ± 11.6 vs. postburst 43.16 ± 74.71 pg/mL; p = 0.03; W = -48; p = 0.04). Baseline preburst IL-10 values and preburst VAS B significantly correlated (Spearman correlation r = -0.66; p = 0.05; 95 CI -0.86 to -0.24), while correlation was not significant between postburst IL-10 values and postburst VAS B (Spearman correlation r = -0.49; p = 0.18; 95 CI -0.83 to -0.15). Postburst IL-10 values correlated significantly with postburst PSQI scores (Spearman correlation r = -0.66; p = 0.05; 95 CI -0.86 to -0.24), while no correlation was found between preburst and postburst changes related to the BDI., Conclusions: Burst SCS increased systemic circulating anti-inflammatory IL-10, improved FBSS back pain and back pain associated co-morbidities like disrupted sleep architecture and depressive symptoms in FBSS patients. Thus, suggesting a possible relationship between burst SCS and burst-evoked modulation of peripheral anti-inflammatory cytokine IL-10 in chronic back pain., (© 2017 International Neuromodulation Society.)