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Introduction: Small fiber neuropathy (SFN) is a common cause of neuropathic pain in peripheral neuropathies. Good accessibility of diagnostics and treatment is necessary for an accurate diagnosis and treatment of SFN. Evidence is lacking on the quality performance of the diagnostic SFN service in the Netherlands. Our aim was to determine the patient satisfaction and -accessibility of the diagnostic SFN service, and to identify areas for improvement. Methods: In a single-center, prospective, survey-based cohort study, 100 visiting patients were asked to fill in the SFN patient satisfaction questionnaire (SFN-PSQ), with 10 domains and 51 items. Cut-off point for improvement was defined as ≥ 25% dissatisfaction on an item. A chi-square test and linear regression analyses was used for significant differences and associations of patient satisfaction. Results: From November 2020 to May 2021, 98 patients with SFN-related complaints filled in the online SFN-PSQ within 20 minutes. In 84% of the patients SFN was confirmed, average age was 55.1 (52.5–57.8) years and 67% was female. High satisfaction was seen in the domains 'Waiting List Period', Chest X-ray', 'Consultation with the Doctor or Nurse Practitioner (NP)', 'Separate Consultation with the Doctor or NP about Psychological Symptoms', and 'General' of the SFN service. Overall average patient satisfaction score was 8.7 (IQR 8–10) on a 1-to-10 rating scale. Main area for improvement was shortening the 8-week period for receiving the results of the diagnostic testing (p < 0.05). General health status was statistically significant associated with patient satisfaction (p < 0.05) Conclusion: A good reflection of the high patient satisfaction and -accessibility of the SFN-service is shown, with important points for improvement. These results could help hospitals widely to optimize the logistic and diagnostic pathway of SFN analysis, benchmarking patient satisfaction results among the hospitals, and to improve the quality of care of comparable SFN services. [ABSTRACT FROM AUTHOR]

Purpose: Post-acute non-arteritic ischemic optic neuropathy (NAION) and glaucomatous optic neuropathy (GON) can be difficult to differentiate clinically. Our objective was to identify optical coherence tomography (OCT) parameters to help differentiate these optic neuropathies. Methods: We compared 12 eyes of 8 patients with NAION and 12 eyes of 12 patients with GON, matched for age and visual field mean deviation (MD). All patients underwent clinical assessment, automated perimetry (Humphrey Field Analyzer II; Carl Zeiss Meditec, Dublin, CA, USA), and OCT imaging (Spectralis OCT2; Heidelberg Engineering, Heidelberg, Germany) of the optic nerve head and macula. We derived the neuroretinal minimum rim width (MRW), peripapillary retinal nerve fibre layer (RNFL) thickness, central anterior lamina cribrosa depth, and macular retinal thickness. Results: MRW was markedly thicker, both globally and in all sectors, in the NAION group compared to the GON group. There was no significant group difference in RFNL thickness, globally or in any sector, with the exception of the temporal sector that was thinner in the NAION group. The group difference in MRW increased with increasing visual field loss. Other differences observed included lamina cribrosa depth significantly greater in the GON group and significantly thinner central macular retinal layers in the NAION group. The ganglion cell layer was not significantly different between the groups. Conclusions: The neuroretinal rim is altered in a dissimilar manner in NAION and GON and MRW is a clinically useful index for differentiating these two neuropathies. The fact that the difference in MRW between the two groups increased with disease severity suggests distinct remodelling patterns in response to differing insults with NAION and GON. [ABSTRACT FROM AUTHOR]

Background: Despite being a new entity, there is a large amount of information on the characteristics of SARS-CoV-2 infection and the symptoms of the acute phase; however, there are still many unknowns about the clinical features and pathophysiology of post-COVID syndrome. Refractory chronic cough is one of the most prevalent symptoms and carries both a medical problem and a social stigma. Many recent studies have highlighted the role of SARS-CoV-2 neurotropism, but no studies have demonstrated vagus nerve neuropathy as a cause of persistent chronic cough or other COVID-19 long-term effects. Objective: The main objective was to assess the involvement of the vagus nerve neuropathy as a cause of chronic cough and other post-COVID syndrome symptoms. Material and methods: This was a single-center observational study with prospective clinical data collected from 38 patients with chronic cough and post-COVID-19 syndrome. Clinical characteristics and laryngeal electromyographic findings were analyzed. Results: Clinical data from 38 patients with chronic cough after 12 weeks of the acute phase of COVID-19 infection were analyzed. Of these patients, 81.6% suffered from other post-COVID conditions and, 73.6% reported fluctuating evolution of symptoms. Laryngeal electromyography (LEMG) of the thyroarytenoid (TA) muscles and cricothyroid (CT) muscles was pathological in 76.3% of the patients. Of the patients with abnormal LEMG, chronic denervation was the most frequent finding (82.8%), 10.3% presented acute denervation signs, and 6.9% presented myopathic pattern in LEMG. Conclusions: LEMG studies suggest the existence of postviral vagus nerve neuropathy after SARS-CoV-2 infection that could explain chronic cough in post-COVID syndrome. [ABSTRACT FROM AUTHOR]

Membranous glomerulonephritis (MGN) is a common cause of nephrotic syndrome in adults, mediated by glomerular antibody deposition to an increasing number of newly recognised antigens. Previous case reports have suggested an association between patients with anti-contactin-1 (CNTN1)-mediated neuropathies and MGN. In an observational study we investigated the pathobiology and extent of this potential cause of MGN by examining the association of antibodies against CNTN1 with the clinical features of a cohort of 468 patients with suspected immune-mediated neuropathies, 295 with idiopathic MGN, and 256 controls. Neuronal and glomerular binding of patient IgG, serum CNTN1 antibody and protein levels, as well as immune-complex deposition were determined. We identified 15 patients with immune-mediated neuropathy and concurrent nephrotic syndrome (biopsy proven MGN in 12/12), and 4 patients with isolated MGN from an idiopathic MGN cohort, all seropositive for IgG4 CNTN1 antibodies. CNTN1-containing immune complexes were found in the renal glomeruli of patients with CNTN1 antibodies, but not in control kidneys. CNTN1 peptides were identified in glomeruli by mass spectroscopy. CNTN1 seropositive patients were largely resistant to first-line neuropathy treatments but achieved a good outcome with escalation therapies. Neurological and renal function improved in parallel with suppressed antibody titres. The reason for isolated MGN without clinical neuropathy is unclear. We show that CNTN1, found in peripheral nerves and kidney glomeruli, is a common target for autoantibody-mediated pathology and may account for between 1 and 2% of idiopathic MGN cases. Greater awareness of this cross-system syndrome should facilitate earlier diagnosis and more timely use of effective treatment. [ABSTRACT FROM AUTHOR]

The present study investigates the spectrum and analysis of mitochondrial DNA (mtDNA) variants associated with Leber hereditary optic neuropathy (LHON) in an Argentinean cohort, analyzing 3 LHON-associated mitochondrial genes. In 32% of the cases, molecular confirmation of the diagnosis could be established, due to the identification of disease-causing variants. A total of 54 variants were observed in a cohort of 100 patients tested with direct sequencing analysis. The frequent causative mutations m.11778G>A in MT-ND4, m.3460G>A in MT-ND1, and m.14484T>C in MT-ND6 were identified in 28% of the cases of our cohort. Secondary mutations in this Argentinean LHON cohort were m.11253T>C p.Ile165Thr in MT-ND4, identified in three patients (3/100, 3%) and m.3395A>G p.Tyr30Cys in MT-ND1, in one of the patients studied (1%). This study shows, for the first time, the analysis of mtDNA variants in patients with a probable diagnosis of LHON in Argentina. Standard molecular methods are an effective first approach in order to achieve genetic diagnosis of the disease, leaving NGS tests for those patients with negative results. [ABSTRACT FROM AUTHOR]

The diagnosis of pure neural leprosy is more challenging because patients share characteristics with other common pathologies, such as ulnar compression, which should be taken into consideration for differential diagnosis. In this study, we identify ulnar nerve conduction characteristics to aid in the differential diagnosis of ulnar neuropathy (UN) in leprosy and that of non-leprosy etiology. In addition, we include putative markers to better understand the inflammatory process that may occur in the nerve. Data were extracted from a database of people affected by leprosy (leprosy group) diagnosed with UN at leprosy diagnosis. A non-leprosy group of patients diagnosed with mechanical neuropathy (compressive, traumatic) was also included. Both groups were submitted to clinical, neurological, neurophysiological and immunological studies. Nerve enlargement and sensory impairment were significantly higher in leprosy patients than in patients with compressive UN. Bilateral impairment was significantly higher in the leprosy group than in the non-leprosy group. Leprosy reactions were associated to focal demyelinating lesions at the elbow and to temporal dispersion (TD). Clinical signs such as sensory impairment, nerve enlargement and bilateral ulnar nerve injury associated with eletrodiagnostic criteria such as demyelinating finds, specifically temporal dispersion, could be tools to help us decided on the best conduct in patients with elbow ulnar neuropathy and specifically decide if we should perform a nerve biopsy for diagnosis of pure neural leprosy. [ABSTRACT FROM AUTHOR]

The rodent model of nonarteritic anterior ischemic optic neuropathy (rNAION) is similar in many of its pathophysiological responses to clinical NAION. Like human NAION, there is significant variability in the severity of the lesion produced, and little is known of the parameters associated with rNAION induction severity or if pre- or early post-induction biomarkers can be identified that enable prediction of lesion severity and ultimate loss of retinal ganglion cells (RGCs). Adult male Sprague-Dawley outbred rats were evaluated for various parameters including physiological characteristics (heart rate, respiratory rate, temperature, hematocrit [Hct]), optic nerve head (ONH) appearance, pre- and post-induction mean diameter, and intravenous fluorescein and indocyanine green angiographic patterns of vascular leakage at 5 hours post-induction, performed using a spectral domain-optical coherence tomography (SD-OCT) instrument. Early changes were correlated with ultimate RGC loss by Brn3a (+) immunohistology. RGC loss also was correlated with the relative level of laser exposure. The severity of ONH edema 2d, but not 5hr, post induction was most closely associated with the degree of RGC loss, revealing a threshold effect, and consistent with a compartment syndrome where a minimum level of capillary compression within a tight space is responsible for damage. RGC loss increased dramatically as the degree of laser exposure increased. Neither physiological parameters nor the degree of capillary leakage 5hr post induction were informative as to the ultimate degree of RGC loss. Similar to human NAION, the rNAION model exhibits marked variability in lesion severity. Unlike clinical NAION, pre-induction ONH diameter likely does not contribute to ultimate lesion severity; however, cross-sectional ONH edema can be used as a biomarker 2d post-induction to determine randomization of subjects prior to inclusion in specific neuroprotection or neuroregeneration studies. [ABSTRACT FROM AUTHOR]

Background: Non-arteritic ischemic optic neuropathy (NAION) is the most common acute optic neuropathy over the age of 50 years. NAION is commonly associated with systemic vascular risk factors (diabetes, hypertension, hyperlipidemia) and small cup-to-disc-ratio. We have assessed the prevalence risk factors of NAION and the visual outcome in patients referred to a tertiary ophthalmology center in Kuwait. Materials and methods: A retrospective review of new cases of NAION presenting within 2 weeks of onset were included and baseline clinical and demographics characteristic were determined. The prevalence of risk factors and the visual outcome (change in logMAR visual acuity, mean deviation of visual field) was compared between young NAION patients (below 50 years of age) and older NAION patients (over 50 years of age). The odds ratio of a final favorable visual outcome (visual acuity 20/40 or better) by age category was determined. Results: Seventy-eight eyes of 78 patients with recent onset NAION were included in the study. The most prevalent risk factors for NAION in our subjects were diabetes (64.1%), small cup-to-disc ratio (61.5%), hyperlipidemia (51.3%) and hypertension (38.5%). Young NAION patients had better final logMAR visual acuity (0.55 +- 0.57) then older NAION patients (0.9 +- 0.73), (p = 0.03). Furthermore, young NAION patients were 2.8 times more likely to have a final visual acuity of 20/40 or better than older NAION patients, odds ratio (OR), 2.87; 95% confidence interval (CI), 1.12–7.40, Chi-square p-value = 0.03). Conclusion: There is a high prevalence of systemic vascular risk factors and small cup-to-disc ratio in NAION patients referred to our center across different age groups (below and above 50 years). Patients below the age of 50 years with NAION are more likely to have a final visual acuity of 20/40 or better than NAION patients above the age of 50 years. [ABSTRACT FROM AUTHOR]

Background: Ulnar neuropathy at the elbow is an entrapment neuropathy, while ulnar nerve dislocation might also be involved in its incidence and severity. Wheelchair marathon athletes may be at an increased risk for Ulnar Neuropathy. However, there is a paucity of research into the prevalence of Ulnar Neuropathy and ulnar nerve dislocation in this population. Objective: To investigate the prevalence of ulnar neuropathy at the elbow and ulnar nerve dislocation in wheelchair marathon athletes. Participants: Wheelchair marathon athletes (N = 38) who participated in the 2017, 2018, and 2019 Oita International Wheelchair Marathon. 2 athletes participated only one time, 36 athletes repeatedly. Data from athletes'latest assessment were used. Methods: The day before the race, questionnaires, physical examinations, and ultrasonography were conducted to screen for Ulnar Neuropathy in both upper limbs. Ulnar nerve dislocation was confirmed by physical examination and ultrasonography. Results: 11 (29%) athletes were diagnosed with Ulnar Neuropathy. There were no significant differences in age, height, weight, Body Mass Index, or history of primary illness between athletes with and without Ulnar Neuropathy. In the group without Ulnar Neuropathy, 44% of athletes reported to have been engaging in other wheelchair sports, compared to 9% in the group with Ulnar Neuropathy (p = 0.037). Ulnar nerve dislocation was diagnosed in 15 (39%) athletes by ultrasonography. Out of the 14 elbows of 11 athletes diagnosed with Ulnar Neuropathy, 9 (64%) elbows had ulnar nerve dislocation. Conclusion: The prevalence of Ulnar Neuropathy in wheelchair marathon athletes was higher than previously reported in able-bodied, non-athlete individuals and lower than in non-athletes with lower limb dysfunction. Therefore, while wheelchair sports may provide some protection against Ulnar Neuropathy, this study further supports the importance of screening for Ulnar Neuropathy, as well as for ulnar nerve dislocation as a potential risk factor for the development of Ulnar Neuropathy. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to utilise corneal confocal microscopy to quantify corneal nerve morphology and establish the presence of sub-clinical small fibre damage and peripheral neuropathy in children with celiac disease. Methods: This is a cross-sectional cohort study of twenty children with celiac disease and 20 healthy controls who underwent clinical and laboratory assessments and corneal confocal microscopy. Corneal nerve fiber density (no.mm2), corneal nerve branch density (no.mm2), corneal nerve fiber length (mm.mm2), corneal nerve fiber tortuosity and inferior whorl length (mm.mm2) were quantified manually. Results: Corneal nerve fiber density (34.7±8.6 vs. 32.9±8.6; P = 0.5), corneal nerve branch density (47.2±24.5 vs. 47.3±20.0; P = 0.1) and corneal nerve fiber length (20.0±5.1 vs. 19.5±4.5; P = 0.8) did not differ between children with celiac disease and healthy controls. Corneal nerve fiber tortuosity (11.4±1.9 vs 13.5±3.0; P = 0.01) was significantly lower and inferior whorl length (20.0±5.5 vs 23.0±3.8; P = 0.06) showed a non-significant reduction in children with celiac disease compared to healthy controls. Inferior whorl length correlated significantly with corneal nerve fiber density (P = 0.005), corneal nerve branch density (P = 0.04), and corneal nerve fiber length (P = 0.002). Conclusion: Corneal confocal microscopy demonstrates minimal evidence of neuropathy in children with celiac disease. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate ways to improve the generalizability of a deep learning algorithm for identifying glaucomatous optic neuropathy (GON) using a limited number of fundus photographs, as well as the key features being used for classification. Methods: A total of 944 fundus images from Taipei Veterans General Hospital (TVGH) were retrospectively collected. Clinical and demographic characteristics, including structural and functional measurements of the images with GON, were recorded. Transfer learning based on VGGNet was used to construct a convolutional neural network (CNN) to identify GON. To avoid missing cases with advanced GON, an ensemble model was adopted in which a support vector machine classifier would make final classification based on cup-to-disc ratio if the CNN classifier had low-confidence score. The CNN classifier was first established using TVGH dataset, and then fine-tuned by combining the training images of TVGH and Drishti-GS datasets. Class activation map (CAM) was used to identify key features used for CNN classification. Performance of each classifier was determined through area under receiver operating characteristic curve (AUC) and compared with the ensemble model by diagnostic accuracy. Results: In 187 TVGH test images, the accuracy, sensitivity, and specificity of the CNN classifier were 95.0%, 95.7%, and 94.2%, respectively, and the AUC was 0.992 compared to the 92.8% accuracy rate of the ensemble model. For the Drishti-GS test images, the accuracy of the CNN, the fine-tuned CNN and ensemble model was 33.3%, 80.3%, and 80.3%, respectively. The CNN classifier did not misclassify images with moderate to severe diseases. Class-discriminative regions revealed by CAM co-localized with known characteristics of GON. Conclusions: The ensemble model or a fine-tuned CNN classifier may be potential designs to build a generalizable deep learning model for glaucoma detection when large image databases are not available. [ABSTRACT FROM AUTHOR]

We investigated the presence of cerebral small vessel disease (SVD) in patients with nonarteritic anterior ischemic optic neuropathy (NAION) compared to control subjects without NAION to identify the association between NAION and cerebral SVD. We retrospectively reviewed the cases of 63 patients with NAION and 2749 control subjects without any neurologic and ocular diseases including NAION who underwent careful medical interviews, ophthalmic examinations, and magnetic resonance imaging (MRI) studies of the brain. We assessed and compared the degree of cerebral SVD on the MRIs. The patients with NAION presented with cerebral SVD more frequently than controls (68% versus 37%, respectively, p<0.001), which was also observed after adjusting for age, sex, comorbid conditions including hypertension, diabetes, and dyslipidemia, and smoking using the standardized mortality ratio (68% vs. 37%, p<0.001). A multivariate logistic regression analysis showed that the odds of cerebral SVD were 4.86 (95% CI, 2.10 to 11.24, p<0.001) times higher in patients with NAION than in the controls. We found that there was an association between cerebral SVD and NAION even after adjusting for age, sex, and medical histories. Clinicians should consider brain MRI scans in patients with NAION to prevent neurological impairment after cerebral SVD. [ABSTRACT FROM AUTHOR]

Background: Vitamin B-12 deficiency is often considered synonymous with pernicious anemia, a rare condition in which severe malabsorption of the vitamin requires high-dose parenteral treatment. In developing countries such as India, inadequate dietary intake of B-12 due to socio-cultural factors leads to widely prevalent asymptomatic low B-12 status. In this scenario, lower doses of oral B-12 may be effective, safer and more affordable. Objective: To examine the effects of oral B-12 treatment at physiological doses on hematological and biochemical indices and peripheral nerve function in B-12 deficient rural Indian adolescent women. Methods: Thirty-nine women with B-12 deficiency who were excluded from a community based B-12 supplementation trial (Pune Rural Intervention in Young Adolescents (PRIYA)) received oral B-12 2μg/day, either alone (n = 19) or with multiple micronutrients (UNIMAPP formula + 20gm milk powder, n = 20) for 11 months. Hematological indices, nutrients (B-12, folate), metabolites (homocysteine) and peripheral nerve function (SUDOSCAN, Impetomedical, Paris and sensory nerve conduction velocity (NCV) of median and sural nerves) were assessed at baseline and after 11 months of B-12 treatment. Results: Results were similar in the two treatment allocation groups, which were therefore combined. At baseline, all women had B-12 concentration <100pmol/L, 79% were anemic and 33% had macrocytosis, but none had neuropathy. After 11 months of treatment, B-12 levels increased, while folate did not change. The prevalence of anemia fell to 59% and mean corpuscular volume (MCV) and plasma homocysteine concentrations decreased. Sudomotor nerve function in the feet improved by an average of 14.7%, and sensory conduction velocity in median and sural nerves increased by 16.2% and 29.4% respectively. Conclusion: We document clinically beneficial effects of supplementation with a physiological dose of oral B-12 in asymptomatic rural Indian adolescent women with very low B-12 status. These findings support a public health approach to tackle the widely prevalent low B-12 status in young Indians. [ABSTRACT FROM AUTHOR]

Context: Multiple factors contribute to sexual dysfunction in men with obesity. Sex hormone levels are commonly abnormal in men with obesity and this abnormality is often the focus of management in clinical practice. The role of small fibre neuropathy in obesity-related sexual dysfunction is not well established. Objective: We aimed to investigate the relationship between sexual function, sex hormone levels and small nerve fibre morphology in men with severe obesity. Materials and methods: A prospective study of 29 men with severe obesity was undertaken. Sexual function was assessed using the European Male Ageing Study Sexual Function Questionnaire. Small nerve fibre morphology was quantified using corneal confocal microscopy. Sex hormone levels were measured by mass spectrophotometry. Results: Erectile dysfunction was present in 72% of the cohort with a higher prevalence of diabetes among the symptomatic group (88% vs 38%, p = 0.006). Corneal nerve fibre length (CNFL) and corneal nerve fibre density (CNFD) were both significantly lower in participants with erectile dysfunction compared to those without (p = 0.039 and p = 0.048 respectively). The erectile function score correlated with CNFL (r = -0.418, p = 0.034) and CNFD (r = -0.411, p = 0.037). Total testosterone and calculated free testosterone levels did not differ significantly between men with or without erectile dysfunction (median 8.8 nmol/L vs 9.0 nmol/L, p = 0.914; and median 176 pmol/L vs 179 pmol/L, p = 0.351 respectively), infrequent sexual thoughts (median 8.1 nmol/L vs 9.2 nmol/L, p = 0.650; and median 184 pmol/L, vs 176 pmol/L, p = 0.619 respectively) and decreased morning erections (median 9.0 nmol/L vs 8.8 nmol/L, p = 0.655; and median 170 pmol/L vs 193 pmol/L, p = 0.278 respectively). Conclusion: Sexual dysfunction is highly prevalent in men with severe obesity. We found an association between small fibre neuropathy with erectile dysfunction with presence of diabetes a likely a significant contributing factor. We found no associations between testosterone levels with sexual symptoms (including frequency of sexual thoughts). The influence of small nerve fibre neuropathy on response to therapeutic interventions and whether interventions that improve small fibre neuropathy can improve erectile function in this population merits further study. [ABSTRACT FROM AUTHOR]

The difficulty in obtaining as well as maintaining weight loss, together with the impairment of metabolic control in conditions like diabetes and cardiovascular disease, may represent pathological situations of inadequate neural communication between the brain and peripheral organs and tissues. Innervation of adipose tissues by peripheral nerves provides a means of communication between the master metabolic regulator in the brain (chiefly the hypothalamus), and energy-expending and energy-storing cells in the body (primarily adipocytes). Although chemical and surgical denervation studies have clearly demonstrated how crucial adipose tissue neural innervation is for maintaining proper metabolic health, we have uncovered that adipose tissue becomes neuropathic (ie: reduction in neurites) in various conditions of metabolic dysregulation. Here, utilizing both human and mouse adipose tissues, we present evidence of adipose tissue neuropathy, or loss of proper innervation, under pathophysiological conditions such as obesity, diabetes, and aging, all of which are concomitant with insult to the adipose organ as well as metabolic dysfunction. Neuropathy is indicated by loss of nerve fiber protein expression, reduction in synaptic markers, and lower neurotrophic factor expression in adipose tissue. Aging-related adipose neuropathy particularly results in loss of innervation around the tissue vasculature, which cannot be reversed by exercise. Together with indications of neuropathy in muscle and bone, these findings underscore that peripheral neuropathy is not restricted to classic tissues like the skin of distal extremities, and that loss of innervation to adipose may trigger or exacerbate metabolic diseases. In addition, we have demonstrated stimulation of adipose tissue neural plasticity with cold exposure, which may ameliorate adipose neuropathy and be a potential therapeutic option to re-innervate adipose and restore metabolic health. [ABSTRACT FROM AUTHOR]

Background: To evaluate the risk of developing optic neuropathy (ON) in patient with both non-surgery and surgery-indicated chronic rhinosinusitis (CRS) via the national health insurance research database in Taiwan. Methodology/Principal findings: 44,176 Patients with a diagnostic code of CRS was selected, which included 6,678 received functional endoscopic sinus surgery (FESS) regarded as the surgery-indicated CRS. Each individual in the study group was matched to two non-CRS patients by age and gender. The outcome was set as the occurrence of ON according to the diagnostic codes occurred after the index date. Poisson regression was used to calculate the adjusted relative risk (aRR) and conditional Cox proportional model was used to estimate the adjusted hazard ratio (aHR). There were 131 and 144 events of ON occurred in the study group and the control group respectively during the follow-up period. The whole study group, whether received FESS or not, demonstrated both significant aRR and aHR compared to the control group after adjusting demographic data, prominent ocular diseases, and systemic co-morbidities. In addition, both the aRR and aHR were higher in CRS patient received FESS than those with CRS but without FESS management. Conclusion: The existence of CRS, especially the surgery-indicated CRS is a significant risk factor for the following ON using multivariable analysis. [ABSTRACT FROM AUTHOR]

Aims: The aim of the present study was to investigate the major determinants of diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes (T2D), considering the traditional and newly discovered risk factors, including hypoglycaemia and glycemic variability. Methods: This retrospective case-control study was conducted in a tertiary care hospital in Taiwan. A total of 2,837 patients with T2D were recruited, medical history and biochemical data were obtained, and patients were screened for DPN using the Michigan Neuropathy Screening Instrument (MNSI). DPN was defined as an MNSI exam score > 2. A stepwise selection of variables was used based on the Akaike Information Criterion (AIC) and the Schwarz Criterion (SC). Multivariate analysis was performed using the identified variables obtained from the stepwise selection. Results: Among the recruited patients, 604 (21.3%) were found to have DPN. 275 patients with DPN were selected because of longer follow up period before enrollment and complete data of glycemic parameters, and paired with 351 patients with T2D without DPN and matched for age, gender, and diabetes duration. The results of the stepwise selection showed that the presence of moderately and severely increased albuminuria yielded the lowest values of AIC and SC, which indicate the best predictive performance. Multivariate analysis demonstrated that moderately and severely increased albuminuria and greater long-term glycemic variability significantly increased the risk of DPN, with a corresponding odds ratio of 1.85 and 1.61 (95%confidence intervals of 1.25–2.73and1.02–2.55, respectively), after adjusted for hypoglycaemia and types of diabetes treatment. Conclusions: Albuminuria is a potent predictor of DPN, and greater long-term glycemic variabilityis clearly associated with DPN in adults with T2D. These findings indicate that, in addition to achieve average blood glucose control, screening for albuminuria and reducing blood glucose fluctuations might be useful for improving diabetic microvascular complications. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy is common and disabling despite glycemic control. Novel neuroprotective approaches are needed. Thrombin and hypercoagulability are associated with diabetes and nerve conduction dysfunction. Our aim was to study the role of thrombin in diabetic neuropathy. We measured thrombin activity by a biochemical assay in streptozotocin (STZ)-induced diabetic neuropathy in male Sprague-Dawley rats. Neuropathy severity was assessed by thermal latency and nerve conduction measures. Thermal latencies were longer in diabetic rats, and improved with the non-specific serine-protease inhibitor Tosyl-L-lysine-chloromethyl ketone (TLCK) treatment (p<0.01). The tail nerve of diabetic rats showed slow conduction velocity (p˂0.01), and interestingly, increased thrombin activity was noted in the sciatic nerve (p˂0.001). Sciatic nodes of Ranvier and the thrombin receptor, protease activated receptor 1 (PAR1) reactivity showed abnormal morphology in diabetic animals by immunofluorescence staining (p<0.0001). Treatment of diabetic animals with either the specific thrombin inhibitor, N-alpha 2 naphtalenesulfonylglycyl alpha-4 amidino-phenylalaninepiperidide (NAPAP) or TLCK preserved normal conduction velocity, (p˂0.01 and p = 0.01 respectively), and prevented disruption of morphology (p˂0.05 and p˂0.03). The results establish for the first time an association between diabetic neuropathy and excessive activation of the thrombin pathway. Treatment of diabetic animals with thrombin inhibitors ameliorates both biochemical, structural and electrophysiological deficits. The thrombin pathway inhibition may be a novel neuroprotective therapeutic target in the diabetic neuropathy pathology. [ABSTRACT FROM AUTHOR]

Aims: To develop and validate the content of a free web-based software (desktop and mobile applications) for the self-management of and customised foot-ankle exercises for people with diabetes and diabetic neuropathy. Methods: The development of the programme was based on gamification principles and addressed three main areas: foot care recommendations; self-assessment of feet according to the main complications of diabetic neuropathy; and customised foot-ankle exercises to strengthen muscles, increase the range of motion and improve functionality. The content was validated using the Delphi methodology and a quantitative approach in two rounds with diabetes specialists (n = 9) and users with diabetes (n = 20). A 70% approval rate was considered sufficient in the second round for final validation purposes. The data analysis was conducted using descriptive statistics, absolute and relative frequencies and the content-validity index (CVI). Results: Among specialists, the CVI was 0.812 after the first round, and final approval was 100% after the second round. Among users, the CVI was 0.902 in the first round, and the final approval was 97%. Conclusion: This free access web software was developed based on the high agreement rating between specialists and users and has the potential to prevent complications arising from diabetic polyneuropathy. It allows for self-monitoring and promotes personalised exercises, following a preventive model that can be applied in primary and secondary care services as a complementary treatment for chronic complications. However, further steps to validate the software in a larger population are recommended. [ABSTRACT FROM AUTHOR]

Background: Disability related to the progressive and degenerative neuropathies known collectively as Charcot-Marie-Tooth disease (CMT) affects gait and function, increasing with age and influencing physical activity in adults with CMT. The relationship between CMT-related disability, ambulatory function and physical activity in children and adolescents with CMT is unknown. Method: A cross-sectional case-controlled study of physical activity in 50 children with CMT and age- and gender-matched typically developing (TD) controls [mean age 12.5 (SD 3.9) years]. A 7-day recall questionnaire assessed physical activity; CMT-related disability and gait-related function were measured to explore factors associated with physical activity. Results: Children with CMT were less active than TD controls (estimated weekly moderate to vigorous physical activity CMT 283.6 (SD 211.6) minutes, TD 315.8 (SD 204.0) minutes; p < 0.001). The children with CMT had moderate disability [CMT Pediatric Scale mean score 17 (SD 8) /44] and reduced ambulatory capacity in a six-minute walk test [CMT 507.7 (SD 137.3) metres, TD 643.3 (74.6) metres; p < 0.001]. Physical activity correlated with greater disability (ρ = -0.56, p < 0.001) and normalised six-minute walk distance (ρ = 0.74, p < 0.001). Conclusions: CMT-related disability affects physical activity and gait-related function in children and adolescents with CMT compared to TD peers. Reduced physical activity adversely affects function across the timespan of childhood and adolescence into adulthood in people with CMT. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the sex-based differences in the carpal arch morphology. Carpal arch morphology was quantified using palmar bowing and area of the arch formed by the transverse carpal ligament. The carpal arch was imaged at the distal and proximal tunnel levels using ultrasonography in 20 healthy young adults (10 women and 10 men). It was found that females had a smaller carpal arch height compared to men at both distal and proximal levels (p<0.05) and smaller carpal arch width only at the proximal level (p<0.05) but not distally. Palmar bowing index, the carpal arch height to width ratio, was significantly smaller in females at the distal level (p<0.05) but not at the proximal level. Carpal arch cross-sectional area normalized to the wrist cross-sectional area was found to be significantly smaller in females at both tunnel levels compared to men (p<0.05). This study demonstrates that females have a smaller carpal arch compared to men with a reduced palmar bowing distally and a smaller arch area at both tunnel levels. The findings help explain the higher incidence of carpal tunnel syndrome in women as a smaller carpal arch makes the median nerve more vulnerable to compression neuropathy. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FM) is one of the most frequent generalized pain disorders with poorly understood neurobiological mechanisms. This condition accounts for an enormous proportion of healthcare costs. Despite extensive research, the etiology of FM is unknown and thus, there is no disease modifying therapy available for this condition. We show that most (if not all) patients with FM belong to a distinct population that can be segregated from a control group by their glycated hemoglobin A1c (HbA1c) levels, a surrogate marker of insulin resistance (IR). This was demonstrated by analyzing the data after introducing an age stratification correction into a linear regression model. This strategy showed highly significant differences between FM patients and control subjects (p < 0.0001 and p = 0.0002, for two separate control populations, respectively). A subgroup of patients meeting criteria for pre-diabetes or diabetes (patients with HbA1c values of 5.7% or greater) who had undergone treatment with metformin showed dramatic improvements of their widespread myofascial pain, as shown by their scores using a pre and post-treatment numerical pain rating scale (NPRS) for evaluation. Although preliminary, these findings suggest a pathogenetic relationship between FM and IR, which may lead to a radical paradigm shift in the management of this disorder. [ABSTRACT FROM AUTHOR]

Purpose: To longitudinally evaluate the visual function and structure of patients taking ethambutol by various modalities and identify useful tests for detection of subclinical ethambutol-induced optic toxicity. Methods: This retrospective study enrolled 84 patients with newly diagnosed tuberculosis treated with ethambutol. Best-corrected visual acuity (BCVA), color vision, contrast sensitivity, fundus and retinal nerve fiber layer (RNFL) photography, automated visual field (VF) test, and optical coherence tomography (OCT) were performed: prior to starting; every month during administration, and 1 month after stoppage. We longitudinally compared visual function and structure with the baseline and identified the occurrence of subclinical toxicity. Results: BCVA, color vision, and contrast sensitivity showed no change from the baseline. Mean temporal RNFL thickness was significantly increased at 6 months (p = 0.014). Subclinical toxicity was found in 22 eyes of 14 patients (i.e., 13% of 168 eyes), in the forms of VFI decrease (VF index, 9 eyes of 6 patients), quadrant RNFL thickness increase (5 eyes of 4 patients), and VF pattern defect (12 eyes of 6 patients). 73% of the patients showed recovery to the baseline at 1 month post-stoppage. The risk factors for occurrence of subclinical toxicity were age, cumulative dose, and medication duration. Conclusion: Mean temporal RNFL thickness increased after administration. The VFI, quadrant RNFL thickness, and VF pattern defect could prove useful in assessment of subclinical toxicity. Medication duration was shown to be a strong risk factor for occurrence of subclinical toxicity. [ABSTRACT FROM AUTHOR]

Background: Leprosy can be considered to be the most common peripheral neuropathy of infectious etiology and constitutes a public health problem. The standard routine examination for assessing sensory impairment in leprosy neuropathy basically evaluates hands, feet and eyes. However, evaluation of facial cutaneous sensation is not routinely performed. Objectives: The aim of this study was to evaluate facial cutaneous sensation in patients with different clinical forms of leprosy and compare the findings with those from healthy individuals. Methodology: 19 healthy controls and 71 leprosy patients who were being treated at a national reference center for leprosy in Brazil underwent facial sensation assessment using the Semmes-Weinstein monofilament test. This test was applied over the facial areas corresponding to the ophthalmic, maxillary and mandibular distal branches of the trigeminal nerve. Results: The predominant clinical form in terms of changes to facial cutaneous sensation was lepromatous leprosy (LL), followed by the borderline-borderline (BB), and borderline-lepromatous (BL) forms, in comparison with healthy individuals. The distal branches most affected were the zygomatic (28.2%; 20/71), buccal (23.9%; 17/71) and nasal (22.5%; 16/71). There was asymmetrical sensory impairment of the face in 62.5% (20/32) of the cases. Conclusion: The face is just as impaired in leprosy as are the feet, hands and eyes, but facial impairment is underdiagnosed. Our evaluation on the different sensory branches and evidence of asymmetrical impairment of the face confirm the classically described pattern of leprosy neuropathy, i.e. consisting of asymmetrical and predominantly sensory peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether multi-frequency measurement of vibration perception thresholds (VPTs) can identify individuals with a high risk of developing diabetic foot ulcer or neuropathic symptoms. Methods: VPTs were measured at six different frequencies (4, 8, 16, 32, 64 and 125 Hz) on metatarsal heads 1 and 5 on the sole of the foot using a standard VibroSense Meter device in 535 type 1 diabetic (T1DM) patients and 717 non-diabetic control subjects. VPTs in control subjects were used to establish normal values for five different age groups for male and female subjects respectively. Normal values were defined as a VPT below the mean plus 1.66 x standard deviation for each group. Various definitions of abnormal VPTs were tested using either all frequencies, only lowest VPT frequencies (4 and 8 Hz) or only highest VPT frequencies (64 and 125 Hz). Results: The VPTs were higher in T1DM patients than in non-diabetic control subjects matched for age and gender. The low frequencies, 4 and 8 Hz, particularly were associated with the risk of diabetic foot ulcer (OR 40.7 [5.4–308.4], p = 0.0003) and with difficulties in balance and or gait (OR 1.89 [1.04–3.46], p = 0.04) difficulties and weakness (OR 2.77 [1.25–6.16], p = 0.01). The VPTs at the 125 Hz frequency were higher in short duration (≤ 10 yrs.) T1DM patients compared to age- and gender-matched control subjects. Conclusions: Vibration perception thresholds at low frequencies seem to be a better indicator of the risk of developing diabetic foot ulcers, gait or balance problems or weakness of the foot. The 125 Hz frequency, however, seemed to be impaired earlier and it was the only pathological VPT frequency in patients with short duration of diabetes.This study suggests that at least four different frequencies (4, 8, 64 and 125 Hz) should be included in any examination in order to obtain a complete evaluation of the risk factors for diabetic neuropathy and diabetic foot ulcers. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated if people at risk of foot ulceration actually wear the footwear recommended by best practice guidelines to prevent foot ulceration. This study aimed to investigate the prevalence of, and factors associated with, wearing inadequate outdoor footwear in those with diabetes or peripheral neuropathy in an inpatient population. Methods: This was a secondary analysis of a multi-site cross-sectional study investigating foot conditions in a large representative inpatient population admitted into hospital for any medical reason on one day. A range of explanatory variables were collected from all participants including sociodemographic, medical and foot condition factors. The outcome variable for this study was the self-reported outdoor footwear type worn most by participants outside the house in the year prior to hospitalisation. The self-reported footwear type was then categorised into adequate and inadequate according to footwear features recommended in guidelines for populations at risk of foot ulceration. Logistic regression identified factors independently associated with inadequate footwear in all inpatient participants, and diabetes and neuropathy subgroups. Results: Overall, 47% of a total of 726 inpatients wore inadequate outdoor footwear; 49% of the 171 in the diabetes subgroup and 43% of 159 in the neuropathy subgroup. Wearing inadequate outdoor footwear was independently associated (Odds Ratio (95% Confidence Interval)) with being female in the diabetes (2.7 (1.4–5.2)) and neuropathy subgroups (3.7 (1.8–7.9)) and being female (5.1 (3.7–7.1)), having critical peripheral arterial disease (2.5 (1.1–5.9)) and an amputation (0.3 (0.1–0.7)) in all inpatients (all, p<0.05). Conclusions: Almost half of all inpatients at risk of foot ulceration reported wearing outdoor footwear most of the time that did not meet recommendations for prevention. We found women were much more likely to wear inadequate footwear. More work needs to be done to increase the uptake of footwear recommendations in these populations to prevent foot ulceration. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy (DPN), the most common chronic complication of diabetes, has become an important public health crisis worldwide. Given that DPN is extremely difficult to treat, determining its risk factors and controlling it at an early stage is critical to preventing its serious consequences and the burden of social disease. Current studies suggest that the risk factors for diabetic peripheral neuropathy are the duration of diabetes, age, glycosylated hemoglobin A1c (HbA1c), diabetic retinopathy (DR), smoking, and body mass Index (BMI). However, most of the aforementioned studies are cross-sectional, and the sample sizes are very limited, so the strength of causal reasoning is relatively low. The current study systematically evaluated DPN’s influencing factors in patients with type 2 diabetes using evidence-based medicine. Overall, 16 included studies (14 cross-sectional studies and 2 case-control studies including 12,116 cases) that conformed to the present criteria were included in the final analysis. The results suggested that the duration of diabetes (MD 2.5, 95% CI 1.71~3.29), age (MD 4.00, 95% CI 3.05~4.95), HbA1c (MD 0.48, 95% CI 0.33~0.64), and DR (OR 2.34, 95% CI 1.74~3.16) are associated with significantly increased risks of DPN among diabetic patients, while BMI, smoking, total triglyceride (TG), and total cholesterol (TC) did not indicate any risks of increasing DPN. The findings provide a scientific basis for a further understanding of the causes of type 2 diabetes complicated with peripheral neuropathy and the improvement of preventive strategies. The next step is to conduct further high-quality prospective cohort studies to validate this paper’s findings. [ABSTRACT FROM AUTHOR]

Objectives: To examine whether post-treatment Lyme disease syndrome (PTLDS) defined by fatigue, cognitive complaints and widespread pain following the treatment of Lyme disease is associated with small fiber neuropathy (SFN) manifesting as autonomic and sensory dysfunction. Methods: This single center, retrospective study evaluated subjects with PTLDS. Skin biopsies for assessment of epidermal nerve fiber density (ENFD), sweat gland nerve fiber density (SGNFD) and functional autonomic testing (deep breathing, Valsalva maneuver and tilt test) were performed to assess SFN, severity of dysautonomia and cerebral blood flow abnormalities. Heart rate, end tidal CO2, blood pressure, and cerebral blood flow velocity (CBFv) from middle cerebral artery using transcranial Doppler were monitored. Results: 10 participants, 5/5 women/men, age 51.3 ± 14.7 years, BMI 27.6 ± 7.3 were analyzed. All participants were positive for Lyme infection by CDC criteria. At least one skin biopsy was abnormal in all ten participants. Abnormal ENFD was found in 9 participants, abnormal SGNFD in 5 participants, and both abnormal ENFD and SGNFD were detected in 4 participants. Parasympathetic failure was found in 7 participants and mild or moderate sympathetic adrenergic failure in all participants. Abnormal total CBFv score was found in all ten participants. Low orthostatic CBFv was found in 7 participants, three additional participants had abnormally reduced supine CBFv. Conclusions: SFN appears to be associated with PTLDS and may be responsible for certain sensory symptoms. In addition, dysautonomia related to SFN and abnormal CBFv also seem to be linked to PTLDS. Reduced orthostatic CBFv can be associated with cerebral hypoperfusion and may lead to cognitive dysfunction. Autonomic failure detected in PTLDS is mild to moderate. SFN evaluation may be useful in PTLDS. [ABSTRACT FROM AUTHOR]

Aim: To compare the risks of hospitalization for heart failure (HHF) associated with sulfonylurea (SU), dipeptidyl peptidase-4 inhibitor (DPP-4i), and thiazolidinedione (TZD) as add-on medications to metformin (MET) therapy using the data of Korean adults with type-2 diabetes from the Korean National Health Insurance database. Methods: We identified 98,383 people who received SU (n = 42,683), DPP-4i (n = 50,310), or TZD (n = 5,390) added to initial treatment of MET monotherapy in patients with type-2 diabetes. The main outcome was the hospitalization for HHF. Hazard ratios for HHF by type of second-line glucose-lowering medication were estimated by Cox-proportional hazard models. Sex, age, duration of MET monotherapy, Charlson Comorbidity Index and additional comorbidities, and calendar year were controlled as potential confounders. Results: The observed numbers (rate per 100,000 person-years) of HHF events were 1,129 (658) for MET+SU users, 710 (455) for MET+DPP-4i users, and 110 (570) for MET+TZD users. Compared to that for MET+SU users (reference group), the adjusted hazard ratios for HHF events were 0.76 (95% confidence interval 0.69–0.84) for MET+DPP-4i users and 0.96 (95% confidence interval 0.79–1.17) for MET+TZD users. Conclusion: DPP-4i as an add-on therapy to MET may lower the risks of HHF compared with SU. [ABSTRACT FROM AUTHOR]

CMT is the most common hereditary neuromuscular disorder of the peripheral nervous system with a prevalence of 1/2500 individuals and it is caused by mutations in more than 80 genes. LRSAM1, a RING finger ubiquitin ligase also known as TSG101-associated ligase (TAL), has been associated with Charcot-Marie-Tooth disease type 2P (CMT2P) and to date eight causative mutations have been identified. Little is currently known on the pathogenetic mechanisms that lead to the disease. We investigated the effect of LRSAM1 deregulation on possible LRSAM1 interacting molecules in cell based models. Possible LRSAM1 interacting molecules were identified using protein-protein interaction databases and literature data. Expression analysis of these molecules was performed in both CMT2P patient and control lymphoblastoid cell lines as well as in LRSAM1 and TSG101 downregulated SH-SY5Y cells.TSG101, UBE2N, VPS28, EGFR and MDM2 levels were significantly decreased in the CMT2P patient lymphoblastoid cell line as well as in LRSAM1 downregulated cells. TSG101 downregulation had a significant effect only on the expression of VPS28 and MDM2 and it did not affect the levels of LRSAM1. This study confirms that LRSAM1 is a regulator of TSG101 expression. Furthermore, deregulation of LRSAM1 significantly affects the levels of UBE2N, VPS28, EGFR and MDM2. [ABSTRACT FROM AUTHOR]

Background: Antiretroviral therapy has surely increased the life expectancy of people living with HIV. However, long term complications like HIV associated sensory neuropathy has a negative impact on quality of life among people living with HIV (PLHIV). In Ethiopia, lack of data on magnitude of the burden and predictors of HIV associated sensory neuropathy in many resource limited setting has led to under diagnosis and eventually under management of HIV-SN. Hence, this study was set out to establish the burden of HIV-associated sensory neuropathy and, its association with demographic, health and clinical characteristics among people living with HIV in Ethiopia. Methods: Cross-sectional study was conducted to assess the prevalence of HIV-associated sensory neuropathy and the associated factors among adult HIV patients at University of Gondar Teaching Hospital, Gondar, Ethiopia. Brief Peripheral Neuropathy Screening tool validated by AIDs Clinical trial group was used for screening HIV-associated sensory neuropathy. Data were analyzed descriptively and through uni- and multivariate logistic regression. Results: In total 359 adult PLHIV with a mean age of 36.5± 9.07 years participated, their median duration of HIV infection was 60 months (IQR 36–84) and their median CD4 count 143cells/μL (IQR 69.5–201.5). Age above 40 years, anti-tuberculosis regimen, tallness, and exposure to didanosine contained antiretroviral therapy were found to be associated with HIV-associated sensory neuropathy (AOR 1.82, 1.84, 1.98 and 4.33 respectively). Conclusions: More than half of the HIV patients who attended HIV care clinic at University of Gondar hospital during the study period were found to present with peripheral sensory neuropathy. Higher age, tallness, TB medication, and didanosine in ART were significantly associated with HIV-SN as screened by effective diagnostic (BPNS) tool. [ABSTRACT FROM AUTHOR]

Background: Carpal tunnel syndrome is a common neuropathy disorder for which surgical treatment consists of release and reconstruction of the flexor retinaculum. Reports of postoperative clinical outcomes after carpal tunnel release with or without flexor retinaculum reconstruction in several studies are controversial. This meta-analysis aimed to compare the efficacy and safety of carpal tunnel release with or without flexor retinaculum reconstruction. Methods: The PubMed, EMBASE, Web of Science, Ovid, Cochrane Library and Clinical Tri Org databases were searched for randomized controlled trials that compared carpal release with and without transverse carpal ligament reconstruction for carpal tunnel syndrome. Outcomes included postoperative Boston Carpal Tunnel Questionnaire Symptom Severity Scale (SSS), Functional Status Scale (FSS), grip strength and complications. The follow-up time was categorized into short-term (0-3mon) and long-term(>3mon). Results: A total of 7 studies with 613 patients met the inclusion criteria and were analyzed in detail. Statistical analysis showed no significant difference between two groups on postoperative long-term grip strength (MD 5.85, 95% CI -1.05 to 12.76) long-term SSS (MD -0.31, 95% CI -0.75 to 0.13) and occurrence of complications (RR 1.14, 95% CI 0.84 to 1.54), whereas statistically significant difference was found between groups regarding short-term grip strength (MD 1.51, 95% CI 0.86 to 2.17) and long-term FSS (MD -0.34, 95% CI -0.47 to -0.21). Conclusion: Carpal tunnel release with flexor retinaculum reconstruction for carpal tunnel syndrome may result in improved long-term functional status while there’s no advantage regarding grip strength, symptom severity and safety over individual carpal tunnel release in short- and long-term outcomes. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced peripheral neuropathy (CiPN) is a serious adverse effect in the clinic, but nonclinical assessment methods in animal studies are limited to labor intensive behavioral tests or semi-quantitative microscopic evaluation. Hence, microRNA (miRNA) biomarkers and automated in-life behavioral tracking were assessed for their utility as non-invasive methods. To address the lack of diagnostic biomarkers, we explored miR-124, miR-183 and miR-338 in a CiPN model induced by paclitaxel, a well-known neurotoxic agent. In addition, conventional and Vium’s innovative Digital Vivarium technology-based in-life behavioral tests and postmortem microscopic examination of the dorsal root ganglion (DRG) and the sciatic nerve were performed. Terminal blood was collected on days 8 or 16, after 20 mg/kg paclitaxel was administered every other day for total of 4 or 7 doses, respectively, for plasma miRNA quantification by RT-qPCR. DRG and sciatic nerve samples were collected from mice sacrificed on day 16 for miRNA quantification. Among the three miRNAs analyzed, only miR-124 was statistically significantly increased (5 fold and 10 fold on day 8 and day 16, respectively). The increase in circulating miR-124 correlated with cold allodynia and axonal degeneration in both DRG and sciatic nerve. Automated home cage motion analysis revealed for the first time that nighttime motion was significantly decreased (P < 0.05) in paclitaxel-dosed animals. Although both increase in circulating miR-124 and decrease in nighttime motion are compelling, our results provide positive evidence warranting further testing using additional peripheral nerve toxicants and diverse experimental CiPN models. [ABSTRACT FROM AUTHOR]

Pyrrole adducts are specific reaction products of 2,5-hexadione (2,5-HD) in vivo and are considered highly relevant to the pathogenesis of peripheral nerve impairments after exposure to n-hexane, though the exact mechanism remains unclear. In this study, 40 male Wistar rats were randomly divided into three experimental groups and one control group, in which all rat’s hair were shaved completely at the beginning. The rats in three experimental groups were treated with 2,5-HD by gavage at dosages of 100, 200 and 300 mg/kg per day respectively, six times per week for 8 weeks. Abnormality of gait and changes in the rota-rod latency were surveilled. Pyrrole adducts in hair, urine and serum of all rats were measured at the endpoint. Results showed that the increased pyrrole adducts in hair, urine and serum accumulated in dose-response relationship. Spearman’s correlation analysis between pyrrole adducts and gait scores showed that hair pyrrole adducts were highly relevant to the gait scores. Moreover, we treated rats with n-hexane and succeed to verify the results aforesaid. Further, multiply linear regression analysis showed that hair pyrrole adducts have higher partial correlation coefficients than these in serum and urine in both 2,5-HD and n-hexane treated models. Our findings draw the conclusion that the hair pyrrole adducts might serve as a promising biomarker of n-hexane induced peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular autonomic neuropathy (CAN) is a known complication of diabetes, but is also diagnosed in patients without diabetes. CAN may be related to perioperative hemodynamic instability. Our objective was to investigate if patients with diabetes would have a higher prevalence of CAN compared to patients without diabetes undergoing surgery. We further studied its relation to changes in post-induction hemodynamic variables. Methods: We prospectively included 82 adult patients, 55 with DM, 27 without DM, scheduled for major abdominal or cardiac surgery. Patients performed four autonomic function tests on the day before surgery. Primary outcomes were the prevalence of CAN and the relation between CAN and severe post-induction hypotension, defined as mean arterial pressure (MAP) < 50 mmHg or ≥ 50% decrease from baseline. Secondary outcomes were the relation between CAN, intraoperative hypotension, MAP < 65 mmHg for more than 13 minutes, and the use of vasopressor therapy. Results: The prevalence of CAN in patients with or without DM was 71% versus 63%, (p = 0.437). CAN was not associated with severe post induction hypotension (CAN+ vs. CAN–: 21% vs. 19.2%, p = 0.819) nor with intraoperative hypotension (16% vs. 15%, p = 0.937). Patients with definite CAN received more norepinephrine in the perioperative period compared to patients with mild CAN or no CAN (0.07 mcg kg-1 min-1 (0.05–0.08) vs. 0.03 (0.01–0.07) vs. 0.02 (0.01–0.06) respectively, p = 0.001). Conclusions: The majority of patients studied had mild to moderate CAN, regardless of the presence of DM. Assessing CAN before surgery did not identify patients at risk for post induction and intraoperative hypotension in our cohort. Trial registration: Dutch Trial Registry () . [ABSTRACT FROM AUTHOR]

The concept of frailty has been used in the clinical and research field for more than two decades. It is usually described as a clinical state of heightened vulnerability to poor resolution of homeostasis after a stressor event, which thereby increases the risk of adverse outcomes, including falls, delirium, disability and mortality. Here we report the results of the first genome-wide association scan and comparative gene ontology analyses where we aimed to identify genes and pathways associated with the deficit model of frailty. We used a discovery-replication design with two independent, nationally representative samples of older adults. The square-root transformed Frailty Index (FI) was the outcome variable, and age and sex were included as covariates. We report one hit exceeding genome-wide significance: the rs6765037 A allele was significantly associated with a decrease in the square-root transformed FI score in the Discovery sample (beta = -0.01958, p = 2.14E-08), without confirmation in the Replication sample. We also report a nominal replication: the rs7134291 A allele was significantly associated with a decrease in the square-root transformed FI score (Discovery sample: beta = -0.01021, p = 1.85E-06, Replication sample: beta = -0.005013, p = 0.03433). These hits represent the KBTBD12 and the GRIN2B genes, respectively. Comparative gene ontology analysis identified the pathways ‘Neuropathic pain signalling in dorsal horn neurons’ and the ‘GPCR-Mediated Nutrient Sensing in Enteroendocrine Cells’, exceeding the p = 0.01 significance in both samples, although this result does not survive correction for multiple testing. Considering the crucial role of GRIN2B in brain development, synaptic plasticity and cognition, this gene appears to be a potential candidate to play a role in frailty. In conclusion, we conducted genome-wide association scan and pathway analyses and have identified genes and pathways with potential roles in frailty. However, frailty is a complex condition. Therefore, further research is required to confirm our results and more thoroughly identify relevant biological mechanisms. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate, through (OCT), alterations in retinal thickness, secondary to use of ethambutol in the treatment of patients with tuberculosis. In addition to studying the use of simpler semiological tools, such as Amsler and Ishihara, in the screening of these cases. Methods: Thirty patients with ethambutol were recruited from the reference service of tuberculosis treatment at the Federal University of Espírito Santo from May 2015 to July 2016. After clinical history, the following parameters were analyzed; best corrected visual acuity, biomicroscopy, tonometry, photomotor reflex testing, Ishihara test, Amsler’s grid test, color digital retinography and optical coherence tomography with CIRRUS HD-OCT (Humphrey-Zeiss) every 2 months during treatment with ethambutol. They were divided into two groups according to the treatment: (1) standard group, two months of ethambutol; (2) extended group, nine to twelve months of ethambutol. Results: There was a significant reduction in OCT thickness between the pre and post treatment times in ten eyes of the extended group, mean reduction of 7,8 microns and in seven eyes of the standard group, with an average of 5.57 microns. During the study, a significant reduction of retinal thickness was observed in both groups at two months of treatment, and the delta percentage was higher in those patients who presented reduction of visual acuity and / or change in the Ishihara test. Conclusion: There was a significant reduction in the thickness of the nerve fiber layer by OCT in the patients studied, being more pronounced in those submitted to the extended treatment regimen. This reduction was observed two months after the start of therapy, and was more significant in the cases that presented changes in the Ishihara test. [ABSTRACT FROM AUTHOR]

Background: Approximately two thirds of patients with lumbar spinal stenosis (LSS) who undergo surgical treatment benefit from the surgery. The objective of this study was to derive a prognostic probability function (PPF) to identify patients with a high probability of post-surgical improvement because there is currently no method available. Methods: In this multicenter, prospective, observational study, we collected data from eight medical centers in Switzerland in which patients underwent surgery for LSS. The endpoints were meaningful clinically important differences (MCID) in pain and disability one year after baseline. We developed a PPF named PROCESS (PostopeRative OutComE Spinal Stenosis), based on a large set of prognostic indicators extracted from the literature. The PPF was derived using data from a random subset of two thirds of the patients and validated in the remaining third. We addressed overfitting by shrinking the regression coefficients. The area under the ROC curve (AUC) and calibration determined the accuracy of the PPF. Results: In this study, 452 LSS patients received surgery. 73% of the 300 patients in the derivation subset reached an MCID in pain and 68% reached an MCID in disability. The corresponding values were 70% and 63% in the validation subset, respectively. In the derivation subsample, the AUC was 0.64 (95% CI 0.57 to 0.71) for of the PPF predicting MCID in pain and 0.71 (0.64 to 0.77) for MCID in disability, after shrinkage. The corresponding numbers were 0.62 (0.52 to 0.72) and 0.70 (0.60 to 0.79) in the validation subsample, and the PPF showed good calibration. Conclusions: Surgical treatment for patients with lumbar spinal stenosis is being performed with increasing frequency. PROCESS is conditional on the individual pattern of preoperatively available prognostic indicators, and may be helpful for clinicians in counselling patients and in guiding the discussion on individual treatment decision in the era of personalized medicine. [ABSTRACT FROM AUTHOR]

Objective: In Western countries, chronic pain patients with neuropathic characteristics have more intense pain, greater negative impact in quality of life and worse psychological well-being. The aim of this study was to compare the outcomes, impact, and health seeking behaviours in Chinese chronic pain patients with and without neuropathic characteristics in Hong Kong. Methods: Random telephone survey was conducted on the general Hong Kong population, and based on the Nuprin Pain Report. Specific questions on chronic and neuropathic pain were included. Respondents with pain lasting three months or more were asked to indicate their two most painful sites. Chi-square and Mann-Whitney U-test were used to investigate differences between variables in patients with and without neuropathic characteristics. P<0.05 was regarded as significant. Results: The response rate was 32.3%. Chronic pain patients with neuropathic characteristics reported higher pain scores and longer duration of pain (p = 0.0001). They reported greater negative impact on work and effect on daily life (p = 0.0131); were significantly more likely to consult pain specialists (p = 0.0006), Chinese medicine practitioners (p = 0.0203), and psychiatrists (p = 0.0212); and were significantly less likely to be prescribed oral analgesics (p = 0.0226), to feel ‘very satisfied’ (p = 0.0263) with prescribed treatment and to find oral analgesics ‘very useful’ (p = 0.0215). There was no difference in oral analgesic medications taken. Conclusion: Chinese individuals having chronic pain with neuropathic characteristics had worse pain related outcomes. Differences in help-seeking behaviour were observed. Lack of appropriate analgesic prescription suggests that identification and management of chronic neuropathic pain in Hong Kong needs to be improved. [ABSTRACT FROM AUTHOR]

Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is a rare neurological disorder of the peripheral nervous system. The economic burden of CIDP is not well understood. Objectives: To assess the economic and clinical burden of CIDP and to compare the incremental burden relative to a matched control group without CIDP. Methods: This retrospective case-control analysis was conducted using data from the IQVIA Real-World Data Adjudicated Claims. Adults newly diagnosed with CIDP between 7/1/2010 and 6/30/2014 were identified and direct matched to controls without CIDP. Baseline characteristics were assessed and compared over a 6-month pre-index period. Healthcare resource use, costs and clinical characteristics were assessed and compared over a 2-year follow-up. Total cost differences over the 2-year follow-up were compared between matched cohorts using a generalized estimating equation model. Results: The final sample comprised a total of 790 cases matched to 790 controls. Over the 2-year follow-up, cases more frequently experienced neuropathic pain, back pain and osteoarthritis and more commonly utilized opioids, anti-convulsants and anti-depressants. Compared to controls, more cases had ≥1 hospitalization (26.2% vs. 9.0%), and cases had a higher mean number of outpatient prescription fills (62.8 vs. 32.0) and physician office visits (34.7 vs. 13.0) (all p<0.0001). Cases had 7.5x higher mean total costs ($116,330 vs. $15,586, p<0.0001). Important cost drivers were costs for outpatient ancillary, radiology and HCPCS drugs (mean $76,366 vs. $4,292) and costs for inpatient care (mean $16,357 vs. $2,862) (both p<0.0001). Among cases, CIDP therapy (inclusive of both outpatient pharmacy and medical claims) accounted for 51.2% of mean total costs. After further adjusting for baseline clinical characteristics, cases were associated with a 6.1x increase in total costs compared to controls (p<0.0001). Conclusions: Our findings suggest a substantial clinical and economic burden among patients with CIDP relative to matched controls over a 2-year follow-up. [ABSTRACT FROM AUTHOR]

Aims: To compare the prevalence of vitamin B12 deficiency and peripheral neuropathy between two groups of type 2 diabetes mellitus (T2DM) patients treated with or without metformin, and to determine factors associated with vitamin B12 deficiency therapy and dietary intake of vitamin B12. Methods: In this retrospective study, we recruited 412 individuals with T2DM: 319 taking metformin, and 93 non-metformin users. Demographics, dietary assessment for vitamin B12 intakes, and medical history were collected. Participants were assessed for peripheral neuropathy. Blood specimens were collected and checked for serum vitamin B12 levels. The differences between the two groups were analyzed using an independent t-test for continuous data, and the Chi-squared or Fisher's exact test was used for categorical data. The relationship of vitamin B12 deficiency with demographics and clinical characteristics was modeled using logistic regression. Results: The prevalence of B12 deficiency was 7.8% overall, but 9.4% and 2.2% in metformin users and non-metformin users, respectively. The odds ratio for serum vitamin B12 deficiency in metformin users was 4.72 (95% CI, 1.11–20.15, P = 0.036). There were no significant differences in a test of peripheral neuropathy between the metformin users and non-metformin users (P > 0.05). Low levels of vitamin B12 occurred when metformin was taken at a dose of more than 2,000 mg/day (AOR, 21.67; 95% CI, 2.87–163.47) or for more than 4 years (AOR, 6.35; 95% CI, 1.47–24.47). Conclusion: Individuals with T2DM treated with metformin, particularly those who use metformin at large dosages (> 2,000 mg/day) and for a longer duration (> 4 years), should be regularly screened for vitamin B12 deficiency and metformin is associated with B12 deficiency, but this is not associated with peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Charcot Marie Tooth disease (CMT) has negative functional impact on postural control of children; however, it has not been widely studied. Stabilometry can provide insights about postural control and guide preventive interventions in immature perceptual and musculoskeletal systems as those seen in children with CMT. This cross-sectional study aimed to identify and interpret stabilometric variables that reflect the postural control of children with CMT. 53 subjects (age 6–17) were assigned to one of the two groups: CMT (15 males and 14 females with CMT) or Control (13 males and 11 females healthy). Quiet standing was tested in different conditions: with open and closed eyes on regular surface (open-regular, closed-regular) and foam surface (open-foam, closed-foam) using a force platform. The minimum of 2 and maximum of 3 trials of 30 seconds for each test condition provided the classical stabilometric variables and Romberg Quotient (RQv). CMT group showed increase of confidence ellipse area, mean velocity, mediolateral and anteroposterior velocities associated with decreased mean body oscillation frequency, as the complexity of tasks increased. CMT postural deficit was identified by greater and faster sway associated with these lower frequencies, when compared to Control. [ABSTRACT FROM AUTHOR]

The antinociceptive effects of the carbon monoxide-releasing molecule tricarbonyldichlororuthenium (II) dimer (CORM-2) during chronic pain are well documented, but most of its possible side-effects remain poorly understood. In this work, we examine the impact of CORM-2 treatment on the lipoprotein profile and two main atheroprotective functions attributed to high-density lipoprotein (HDL) in a mouse model of type 1 diabetes while analyzing the effect of this drug on diabetic neuropathy. Streptozotocin (Stz)-induced diabetic mice treated with CORM-2 (Stz-CORM-2) or vehicle (Stz-vehicle) were used to evaluate the effect of this drug on the modulation of painful diabetic neuropathy using nociceptive behavioral tests. Plasma and tissue samples were used for chemical and functional analyses, as appropriate. Two main antiatherogenic properties of HDL, i.e., the ability of HDL to protect low-density lipoprotein (LDL) from oxidation and to promote reverse cholesterol transport from macrophages to the liver and feces in vivo (m-RCT), were also assessed. Stz-induced diabetic mice displayed hyperglycemia, dyslipidemia and pain hypersensitivity. The administration of 10 mg/kg CORM-2 during five consecutive days inhibited allodynia and hyperalgesia and significantly ameliorated spinal cord markers (Cybb and Bdkrb1expression) of neuropathic pain in Stz mice, but it did not reduce the combined dyslipidemia shown in Stz-treated mice. Its administration to Stz-treated mice led to a significant increase in the plasma levels of cholesterol (∼ 1.4-fold vs. Ctrl, ∼ 1.3- fold vs. Stz-vehicle; p < 0.05) and was attributed to significant elevations in both non-HDL (∼ 1.8-fold vs. Ctrl; ∼ 1.6-fold vs. Stz-vehicle; p < 0.05) and HDL cholesterol (∼ 1.3-fold vs. Ctrl, ∼ 1.2-fold vs. Stz-vehicle; p < 0.05). The increased HDL in plasma was not accompanied by a commensurate elevation in m-RCT in Stz-CORM-2 compared to Stz-vehicle mice; instead, it was worsened as revealed by decreased [3H]-tracer trafficking into the feces in vivo. Furthermore, the HDL-mediated protection against LDL oxidation ex vivo shown by the HDL isolated from Stz-CORM-2 mice did not differ from that obtained in Stz-vehicle mice. In conclusion, the antinociceptive effects produced by a high dose of CORM-2 were accompanied by antioxidative effects but were without favorable effects on the dyslipidemia manifested in diabetic mice. [ABSTRACT FROM AUTHOR]

Backgrounds: Cardiac autonomic neuropathy is a common but always overlooked. More convenient diagnostic methods are needed. Hypothesis: Cardiac autonomic neuropathy risk score evaluated by SUDOSCAN has a fine diagnostic efficacy detecting cardiac autonomic neuropathy. Methods: This is a cross-sectional study among patients with diabetes mellitus. Subjects undertook SUDOSCAN tests and cardiac autonomic reflex tests, including heart rate variability due to Valsalva maneuver, heart rate response due to deep breathing and heart rate response due to standing up. Presenting 2 abnormal results was defined as cardiac autonomic neuropathy. Results: Subjects with cardiac autonomic neuropathy has significantly higher cardiac autonomic neuropathy risk score (32.88±1.60 vs 27.64±1.24,P = 0.010). Cardiac autonomic neuropathy risk score was correlated significantly with the heart rate response due to deep breathing(P = 0.004). Multiple regression analysis including significant variables showed an independent association of cardiac autonomic neuropathy risk score and heart rate response due to deep breathing (P = 0.031) and age (P = 0.000). In receiver operating characteristic curve analysis evaluating the relationship between cardiac autonomic neuropathy risk score and cardiac autonomic neuropathy, The cut-off value was 20.5, with the sensitivity of 90.48%, the specificity of 29.5%, and the positive predictive value of 46.9%. In two-step diagnostic methods, Setting 20.5 as the cut-off value of cardiac autonomic neuropathy risk score and abnormal heart rate response due to standing up as the second diagnostic step’s positive result, and setting 16.5 as the cut-off value of cardiac autonomic neuropathy risk score and abnormal heart rate response due to deep breathing as the second diagnostic step’s positive result, both achieved good diagnostic efficacy. Conclusion: Cardiac autonomic neuropathy risk score evaluated by SUDOSCAN is a good screening test for cardiac autonomic neuropathy. The two-step diagnostic methods could be considered as surrogate diagnostic methods. [ABSTRACT FROM AUTHOR]

Background: The use of the HIV antiretroviral drug stavudine (d4T), a thymidine analogue, is associated with the development of mitochondrial toxicities such as sensory neuropathy (SN). Genetic variation in genes relating to d4T transport and metabolism, as well as genetic variation in the thymidine synthesis pathway, could influence occurrence of d4T-related toxicity. Methods: We examined this hypothesis in a cohort of HIV-positive South African adults exposed to d4T, including 143 cases with SN and 120 controls without SN. Ten SNPs in four genes associated with stavudine transport, and 16 SNPs in seven genes of the thymidine synthesis / phosphorylation pathway were genotyped using Agena mass spectrometry methods. Associations between sensory neuropathy and genetic variants were evaluated using PLINK by univariate and multivariable analyses. Results: Age and height were significantly associated with SN occurrence. Using logistic regression with age and height as covariates, and uncorrected empirical p-values, genetic variation in SLC28A1, SAMHD1, MTHFR and RRM2B was associated with SN in South Africans using d4T. Conclusion: Variation in genes relating to d4T transport and metabolism, as well as genetic variation in the thymidine synthesis pathway may influence occurrence of d4T-related SN. These data contribute to the characterisation of African pharmacogenetic variation and its role in adverse response to antiretroviral therapy. [ABSTRACT FROM AUTHOR]

Object: In patients with focal nerve injury and neuropathic pain cutting the nerve to obtain permanent pain reduction can be considered. Surgery is indicated only if a diagnostic nerve block provides temporary pain relief. We evaluated the predictive value of a block on the outcome of surgery. Methods: In total, three blocks were performed at two week intervals. Patients were blinded to injections containing lidocaine 1% and a placebo was included. Surgery was offered regardless of the effect of the blocks. Twenty-four patients received 72 blocks. Sixteen patients opted for surgery, 5 patients refrained from surgery, and in 3 the blocks provided permanent pain relief. The predictive ability of the block on the outcome of surgery was assessed by calculating the area under a Receiver Operating Characteristic curve (AUC). Results: The AUC of the first lidocaine block was 0.35 with a 95% confidence interval from 0.077 to 0.62. At 95% confidence (two-sided), the AUC is less than 0.62, and hence the predictive ability of the block was poor. The outcome of the second lidocaine block and saline block did not change the conclusion of the first block. Conclusions: We conclude that the use of blocks to select patients for surgery should be critically appraised. Perspective: A pain relieving response to one open block is currently considered mandatory before patients with focal nerve injury and neuropathic pain are offered surgery. Blinded blocks including a placebo show that responses for selection should be carefully interpreted because they may not be as predictive as generally presumed. [ABSTRACT FROM AUTHOR]

Introduction: Familial amyloid polyneuropathy (FAP) is a genetic disease leading to the production of a variant transthyretin (TTR) or a beta variant β2-microglobulin. FAP may be associated with refractory diarrhoea. In this study, we assessed the efficacy and tolerance of somatostatin analogues in refractory diarrhoea associated with FAP. Methods: FAP patients from the French national referral center who received somatostatin analogues for a refractory diarrhoea were retrospectively studied. We assessed remission of diarrhoea, as defined by a stool consistence of five or less on the Bristol stool scale, assessed after three to six months of follow-up. Stool frequency and continence before and after three to six months of treatment were also compared by the means of Wilcoxon and McNemar's exact tests, respectively. Results: Fourteen patients treated with somatostatin analogues were evaluable. After three to six months of follow-up, 9/14 patients (64% 95%CI = [35%; 87%]) had remission of diarrhoea. This was significantly higher than a theoretical remission rate of 20% (p = 0.0004). There was a significant decrease of daily bowel movement from 6 to 2.5 per day (p = 0.002). Twelve/14 (85%) patients had incontinence at baseline vs 8/14 (57%) after three to six months of follow-up (p = 0.134). Three out of 14 patients (21%) had a severe adverse event; two patients had hypoglycaemia, and one had endocarditis due to an injection-site bacterial infection. Conclusion: This study suggests that somatostatin analogues may benefit to patients with FAP and refractory diarrhoea. Approximately 20% of patients had severe adverse events, including hypoglycaemia. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate B-mode ultrasound as a novel method for objective and quantitative assessment of a relative afferent pupillary defect (RAPD) in a prospective case-control study. Methods: Seventeen patients with unilateral optic neuropathy and a clinically detectable RAPD and 17 age and sex matched healthy controls were examined with B-mode ultrasound using an Esaote-Mylab25 system according to current guidelines for orbital insonation. The swinging flashlight test was performed during ultrasound assessment with a standardized light stimulus using a penlight. Results: B-mode ultrasound RAPD examination was doable in approximately 5 minutes only and was well tolerated by all participants. Compared to the unaffected contralateral eyes, eyes with RAPD showed lower absolute constriction amplitude of the pupillary diameter (mean [SD] 0.8 [0.4] vs. 2.1 [0.4] mm; p = 0.009) and a longer pupillary constriction time after ipsilateral light stimulus (mean [SD] 1240 [180] vs. 710 [200] ms; p = 0.008). In eyes affected by RAPD, visual acuity correlated with the absolute constriction amplitude (r = 0.75, p = 0.001). Conclusions: B-mode ultrasound enables fast, easy and objective quantification of a RAPD and can thus be applied in clinical practice to document a RAPD. [ABSTRACT FROM AUTHOR]

This study explored whether cataract surgery precipitates diabetic retinopathy (DR) development in diabetic patients without previous DR. Patients with the diagnosis of type II diabetes but without DR were selected from the Longitudinal Health Insurance Database 2000. Patients who received cataract surgery between January 1, 2000, and December 31, 2010, were included in the case group, and the control group was matched to the case group by age, sex, and index year. The postoperative incidence rates of nonproliferative diabetic retinopathy (NPDR), proliferative diabetic retinopathy (PDR), and diabetic macular edema (DME) were the main outcomes studied and were adjusted by age, sex, comorbidities, and statin, fibrate, angiotensin-converting-enzyme inhibitor (ACEI), oral hypoglycemic agents (OHA), and insulin use. In our cohort, patients who had dyslipidemia and used statins were more likely to undergo cataract surgery. Among diabetic patients without previous DR, patients receiving cataract surgery had a higher risk of NDPR development (adjusted hazard ratio = 1.48, 95% confidence interval = 1.15–1.91). No statistical difference was observed in PDR or DME development between operative and nonoperative groups. In additional stratified analyses, female sex, older age, comorbidities, surgery within 5 years, statin ACEI, OHA, and insulin use increased the risk of NPDR development. In an adjusted Cox regression model, cataract surgery, OHA and insulin use were found to be risk factors for NPDR development. Cataract surgery with complications increased post-operative risks for NPDR were even higher, and the significant influence from cataract surgery persisted 5 years after surgery. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy is a common complication associated with diabetes mellitus with a pathogenesis that is incompletely understood. By regulating RNA silencing and post-transcriptional gene expression, microRNAs participate in various biological processes and human diseases. However, the relationship between microRNAs and the progress of diabetic peripheral neuropathy still lacks a thorough exploration. Here we used microarray microRNA and mRNA expression profiling to analyze the microRNAs and mRNAs which are aberrantly expressed in dorsal root ganglia from streptozotocin-induced diabetic rats. We found that 37 microRNAs and 1357 mRNAs were differentially expressed in comparison to non-diabetic samples. Bioinformatics analysis indicated that 399 gene ontology terms and 29 Kyoto Encyclopedia of Genes and Genomes pathways were significantly enriched in diabetic rats. Additionally, a microRNA-gene network evaluation identified rno-miR-330-5p, rno-miR-17-1-3p and rno-miR-346 as important players for network regulation. Finally, quantitative real-time polymerase chain reaction analysis was used to confirm the microarray results. In conclusion, this study provides a systematic perspective of microRNA and mRNA expression in dorsal root ganglia from diabetic rats, and suggests that dysregulated microRNAs and mRNAs may be important promotors of peripheral neuropathy. Our results may be the underlying framework of future studies regarding the effect of the aberrantly expressed genes on the pathophysiology of diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]