Mast Cells are Dependent on Glucose Transporter 1 (GLUT1) and GLUT3 for IgE-mediated Activation.

Mast cells (MCs) are known to have a pathological impact in a variety of settings, in particular in allergic conditions. There is also limited evidence implicating MCs in diabetes, raising the possibility that MC function may be influenced by alterations in glucose levels. However, it is not known whether MCs are directly affected by elevated glucose concentrations. Moreover, it is not known which glucose transporters that are expressed by MCs, and whether MCs are dependent on glucose transporters for activation. Here we addressed these issues. We show that MCs express high levels of both glucose transporter 1 (GLUT1/Slc2A1) and GLUT3 (Slc2A3). Further, we show that the inhibition of either GLUT1 or GLUT3 dampens both MC degranulation and cytokine induction in response to IgE receptor crosslinking, and that combined GLUT1 and GLUT3 inhibition causes an even more pronounced inhibition of these parameters. In contrast, the inhibition of GLUT1 or GLUT3, or combined GLUT1 and GLUT3 inhibition, had less impact on the ability of the MCs to respond to activation via compound 48/80. Elevated glucose concentrations did not affect MC viability, and had no stimulatory effect on MC responses to either IgE receptor crosslinking or compound 48/80. Altogether, these findings reveal that MCs are strongly dependent on glucose transport via GLUT1 and/or GLUT3 for optimal responses towards IgE-mediated activation, whereas MC functionality is minimally affected by elevated glucose levels. Based on these findings, antagonists of GLUT1 and GLUT3 may be considered for therapeutic intervention in allergic conditions.

Men's views on causes and consequences of erectile dysfunction or premature ejaculation in a primary care population: a qualitative study.

OBJECTIVE: To explore men's views on the causes and consequences of two common sexual dysfunctions - erectile dysfunction and premature ejaculation - and how this affects physical and mental health as well as social life and intimate or close relations. DESIGN: A qualitative design with semi-structured interviews using open-ended questions was employed. Individual interviews were conducted, audio recorded and transcribed, and a qualitative content analysis of the text was performed. SETTING: Informants were recruited from an outpatient primary care clinic in Sweden that offers consultation about sexual health to primarily younger men, age 20 years and above. SUBJECTS: A total of 18 participants were included in the study, ten with erectile dysfunction and eight with premature ejaculation or both. MAIN OUTCOME MEASURES: Using the content analysis, different views and strategies of erectile dysfunction and premature ejaculation were presented to illustrate a range of perceptions. RESULTS: The main theme emerged as 'Striving to understand and deal with the problem', which was divided into four categories: 'Reasons for seeking healthcare', 'Own perceptions/images about the problem and its cause', 'Experienced consequences on sex life' and 'Relationship qualities'.Participants experienced their problems in relation to a partner. Feelings of shame and fear of not being fit for desired sexual practices were common. They thought that underlying physical illness or previous sexual activities could have caused their problems. Decreased sexual desire and low self-esteem were seen as consequences, and participants wished for both medical treatment and counselling as support. CONCLUSION: Sexual dysfunction impairs general health and relationships with partners. While counselling is the basic treatment, those who are offered pharmaceutical treatment need follow-up concerning effectiveness and potential concerns.

People with sexual dysfunction may have decreased quality of life and poorer somatic and mental health in general.People with sexual dysfunction may have few places to turn to in a traditional primary health care setting.The participants expressed concerns about their physical health, their relationships with partners and motivation for treatment.Men's visits to primary care for sexual dysfunction provides opportunities to talk about lifestyle and relationships and discover other illnesses.

Observational study of selective screening for prediabetes and diabetes in a real-world setting: an interprofessional collaboration method between public dental services and primary health care in Sweden.

OBJECTIVE: Describe a method in a real-world setting to identify persons with undiagnosed prediabetes and type 2 diabetes through an interprofessional collaboration between Public Dental Services and Primary Health Care in Regions Stockholm. DESIGN: A descriptive observational study. SETTING: The study was conducted at seven sites in the region of Stockholm, Sweden. Each collaborating site consisted of a primary health clinic and dental clinic. SUBJECTS: Study participants included adults over 18 years of age who visited the Public Dental Services and did not have a medical history of prediabetes or type 2 diabetes. MAIN OUTCOME MEASURES: Selective screening is conducted in accordance with a risk assessment protocol at the Public Dental Services. In the investigated method, DentDi (Dental and Diabetes), adults diagnosed with caries and/or periodontitis over a cut-off value are referred to the Primary Health Care clinic for screening of prediabetes and type 2 diabetes. RESULTS: DentDi, introduced at seven sites, between the years 2017 and 2020, all of which continue to use the method today. A total of 863 participants from the Public Dental Services were referred to the Primary Health Care. Of those 396 accepted the invitation to undergo screening at the primary health care centre. Twenty-four individuals did not meet the inclusion criteria, resulting in a total of 372 persons being included in the study. Among the 372 participants, 27% (101) had elevated glucose levels, of which 12 were diagnosed with type 2 diabetes and 89 with prediabetes according to the study classification. CONCLUSIONS: DentDi is a feasible method of interprofessional collaboration where each profession contributes with the competence included in everyday clinical practice for early identification of persons with prediabetes and type 2 diabetes with a complete chain of care. The goal is to disseminate this method throughout Stockholm County and even other regions in Sweden.

Type 2 diabetes and poor oral health have a bidirectional association. The number of persons with undetected prediabetes and type 2 diabetes is high and rising globally.Through collaboration between Public Dental Services and Primary Health Care we have developed a feasible and novel method of selectively screening for prediabetes and type 2 diabetes in a real-world setting.By utilizing everyday practice within each discipline, this method has been implemented at seven sites in Region Stockholm.From the original number of 863 participants referred from the Public Dental Services to Primary Health Care 396 attended the medical screening. After excluding 24 participants, a total of 372 participants underwent screening for prediabetes and type 2 diabetes.The results of this study showed that almost 30% who were screened for prediabetes and type 2 diabetes had elevated blood glucose levels.

Impact of COVID-19 in patients with heart failure with mildly reduced or preserved ejection fraction enrolled in the DELIVER trial.

AIM: COVID-19 may affect clinical risk in patients with heart failure. DELIVER began before and was conducted during the COVID-19 pandemic. This study aimed to evaluate the association between COVID-19 and clinical outcomes among DELIVER participants. METHODS AND RESULTS: Participants with chronic heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) were randomized to dapagliflozin or placebo across 350 sites in 20 countries. COVID-19 was investigator-reported and the contribution of COVID-19 to death was centrally adjudicated. We assessed (i) the incidence of COVID-19, (ii) event rates before/during the pandemic, and (iii) risks of death after COVID-19 diagnosis compared to risks of death in participants without COVID-19. Further, we performed a sensitivity analysis assessing treatment effects of dapagliflozin vs. placebo censored at pandemic onset. Of 6263 participants, 589 (9.4%) developed COVID-19, of whom 307 (52%) required/prolonged hospitalization. A total of 155 deaths (15% of all deaths) were adjudicated as definitely/possibly COVID-19-related. COVID-19 cases and deaths did not differ by randomized assignment. Death rate in the 12 months following diagnosis was 56.1 (95% confidence interval [CI] 48.0-65.6) versus 6.4 (95% CI 6.0-6.8)/100 participant-years among trial participants with versus without COVID-19 (adjusted hazard ratio [aHR] 8.60, 95% CI 7.18-10.30). Risk was highest 0-3 months following diagnosis (153.5, 95% CI 130.3-180.8) and remained elevated at 3-6 months (12.6, 95% CI 6.6-24.3/100 participant-years). After excluding investigator-reported fatal COVID-19 events, all-cause death rates in the 12 months following diagnosis among COVID-19 survivors (n = 458) remained higher (aHR 2.46, 95% CI 1.83-3.33) than rates for all trial participants from randomization, with censoring of participants who developed COVID-19 at the time of diagnosis. Dapagliflozin reduced cardiovascular death/worsening HF events when censoring participants at COVID-19 diagnosis (HR 0.81, 95% CI 0.72-0.91) and pandemic onset (HR 0.72, 95% CI 0.58-0.89). There were no diabetic ketoacidosis or major hypoglycaemic events within 30 days of COVID-19. CONCLUSION: DELIVER is one of the most extensive experiences with COVID-19 of any cardiovascular trial, with >75% of follow-up time occurring during the pandemic. COVID-19 was common, with >50% of cases leading to hospitalization or death. Treatment benefits of dapagliflozin persisted when censoring at COVID-19 diagnosis and pandemic onset. Patients surviving COVID-19 had a high early residual risk. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03619213.

Generalized joint hypermobility and the risk of pregnancy-related pelvic girdle pain: Is body mass index of importance?-A prospective cohort study.

INTRODUCTION: Pelvic girdle pain (PGP) affects approximately 50% of pregnant women. The mechanisms are multifactorial but not fully understood. Women with generalized joint hypermobility (GJH) may be vulnerable to load in the pelvic joints during pregnancy. Our aim was to investigate if women with GJH had an increased risk of PGP and higher pain intensity during and after pregnancy, compared with women with normal joint mobility. We also studied if body mass index (BMI) in early pregnancy influenced that risk. MATERIAL AND METHODS: A prospective cohort study of 356 women, whose data were collected by self-reports and clinical examinations in early and in late pregnancy and 9 months after childbirth. GJH was present with ≥5/9 points on the Beighton score. PGP was defined by a pain drawing and ≥1 positive test. Pain intensity was measured with a visual analogue scale (0-100 mm). We adjusted for age and origin in logistic regression and ordinal logistic regression analysis. RESULTS: In early pregnancy, 47.1% of the women with GJH had PGP vs 32.6% of women with normal joint mobility (adjusted odds ratio [aOR] 1.76; 95% confidence interval [CI] 0.86-3.62) and had higher odds of reporting higher pain intensity (aOR 2.04; 95% CI 1.02-4.07). The odds of PGP were highest for women with GJH and BMI ≥25 kg/m2 (aOR 6.88; 95% CI 1.34-35.27) compared with women with normal joint mobility and BMI <25 kg/m2 . The estimated associations were weaker and not statistically significant in late pregnancy or after childbirth. CONCLUSIONS: Women with GJH did not have an increased risk of PGP during or after pregnancy but reported higher pain intensity in early pregnancy compared with women with normal joint mobility. Since women with combined GJH and BMI ≥25 kg/m2 had the highest odds of PGP in early pregnancy, our results may suggest that health care needs to pay attention to and develop methods to reduce the risk of PGP and delay the onset of pain during pregnancy in women with this combination.

Tendon pain - what are the mechanisms behind it?

OBJECTIVES: Management of chronic tendon pain is difficult and controversial. This is due to poor knowledge of the underlying pathophysiology of chronic tendon pain, priorly known as tendinitis but now termed tendinopathy. The objective of this topical review was to synthesize evolving information of mechanisms in tendon pain, using a comprehensive search of the available literature on this topic. CONTENT: This review found no correlations between tendon degeneration, collagen separation or neovascularization and chronic tendon pain. The synthesis demonstrated that chronic tendon pain, however, is characterized by excessive nerve sprouting with ingrowth in the tendon proper, which corresponds to alterations oberserved also in other connective tissues of chronic pain conditions. Healthy, painfree tendons are devoid of nerve fibers in the tendon proper, while innervation is confined to tendon surrounding structures, such as sheaths. Chronic painful tendons exhibit elevated amounts of pain neuromediators, such as glutamate and substance p as well as up-regulated expression and excitability of pain receptors, such as the glutamate receptor NMDAR1 and the SP receptor NK1, found on ingrown nerves and immune cells. Increasing evidence indicates that mast cells serve as an important link between the peripheral nervous system and the immune systems resulting in so called neurogenic inflammation. SUMMARY: Chronic painful tendons exhibit (1) protracted ingrowth of sensory nerves (2) elevated pain mediator levels and (3) up-regulated expression and excitability of pain receptors, participating in (4) neuro-immune pathways involved in pain regulation. Current treatments that entail the highest scientific evidence to mitigate chronic tendon pain include eccentric exercises and extracorporeal shockwave, which both target peripheral neoinnervation aiming at nerve regeneration. OUTLOOK: Potential mechanism-based pharmacological treatment approaches could be developed by blocking promotors of nerve ingrowth, such as NGF, and promoting inhibitors of nerve ingrowth, like semaphorins, as well as blocking glutamate-NMDA-receptor pathways, which are prominent in chronic tendon pain.

CSI Pollen: Diversity of Honey Bee Collected Pollen Studied by Citizen Scientists.

A diverse supply of pollen is an important factor for honey bee health, but information about the pollen diversity available to colonies at the landscape scale is largely missing. In this COLOSS study, beekeeper citizen scientists sampled and analyzed the diversity of pollen collected by honey bee colonies. As a simple measure of diversity, beekeepers determined the number of colors found in pollen samples that were collected in a coordinated and standardized way. Altogether, 750 beekeepers from 28 different regions from 24 countries participated in the two-year study and collected and analyzed almost 18,000 pollen samples. Pollen samples contained approximately six different colors in total throughout the sampling period, of which four colors were abundant. We ran generalized linear mixed models to test for possible effects of diverse factors such as collection, i.e., whether a minimum amount of pollen was collected or not, and habitat type on the number of colors found in pollen samples. To identify habitat effects on pollen diversity, beekeepers' descriptions of the surrounding landscape and CORINE land cover classes were investigated in two different models, which both showed that both the total number and the rare number of colors in pollen samples were positively affected by 'urban' habitats or 'artificial surfaces', respectively. This citizen science study underlines the importance of the habitat for pollen diversity for bees and suggests higher diversity in urban areas.

Web-based support for individuals with type 2 diabetes - a feasibility study.

BACKGROUND: Self-care is one of the cornerstones in the treatment of type 2 diabetes. Patients with type 2 diabetes struggle to maintain acceptable levels of blood sugar, blood pressure and lipids, the fundamental for the prevention of macro- and microvascular as well as neuropathic complications. The primary aim of the study was to evaluate the feasibility and describe patients' and caregivers' experiences of using the web- and smartphone-based system Triabetes. The secondary aim was to investigate if the use of the system could improve patients' clinical outcomes. METHODS: Feasibility was assessed with describing recruitment rate and the participant´s views of using the system. Laboratory and anthropometry data were also collected. RESULTS: The study showed that recruitment of patients to participate in the intervention was limited and compliance to the study protocol was low. A majority of the patients stated that the system was easy to get an overview of and that the system motivated them and made it easier and fun to handle lifestyle habits. A secondary finding of the study was that there was a significant lowering of LDL values. CONCLUSIONS: Feasibility in terms of recruitment rate was low. The participants agreed that the application overall was useful but suggested several improvements. Summarized lessons learned from this study are following: (1) we need more knowledge about what motivates a person to use a digital tool for a longer period of time; (2) the tool must be easy and less time consuming to use; (3) the technical structure needs to be improved and automatic recording of data must be improved.

Taxane-induced pain in breast cancer patients as perceived by nurses.

INTRODUCTION: Treatment with taxane-containing chemotherapy regimens is crucial for improving survival in patients with early-stage invasive breast cancer. Recent literature describes a high incidence of taxane-induced neuropathic pain or/and muscle and joint pain. For patients, oncology nurses can play an integral role as a resource for pain control. There is a knowledge gap regarding how nurses perceive patients' experienced taxane-induced pain and support from their organizations when caring for patients with such pain. AIM: Investigate nurses' perceptions of occurrence of taxane-induced pain and identify organizational support for managing such pain. MATERIAL AND METHODS: A cross-sectional observation study, conducted in 2017-2018, with a web-based questionnaire to 240 nurses working at oncology outpatient units in Sweden. The areas of concern were start-decline, duration, prevalence, intensity, and bodily distribution of taxane-induced pain. Patient information, guidelines, prophylactic analgesia, and perceived support were used to counteract such pain. Data were analyzed using descriptive statistics and a logistic regression model to estimate associations. RESULTS: One hundred sixty-one nurses completed the questionnaire, describing their perceptions of taxane-induced pain in patients with breast cancer. The prevalence and intensity of taxane-induced pain were experienced as divergent. Some consensus was found among the nurses regarding the start of the pain, but not when declined. The body areas where pain was expected to occur were the muscles, joints, legs, feet, and mainly the back of the trunk. Low use of local/national guidelines for managing taxane-induced pain was described. No relationship was found between factors related to the nurses' characteristics (age, work experience in oncology care, or specialist education in oncology) that significantly affected their perceptions regarding the occurrence of taxane-induced pain or pain intensity. Conclusion: This study highlights a need for attention to education and guidelines for how to observe, treat, and evaluate this particular type of pain.

Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells.

Mast cells are emerging as players in the communication between peripheral nerve endings and cells of the immune system. However, it is not clear the mechanism by which mast cells communicate with peripheral nerves. We previously found that mast cells located within healing tendons can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling. To evaluate this hypothesis, we stimulated primary mast cells with glutamate and showed that glutamate induced the profound upregulation of a panel of glutamate receptors of both the ionotropic type (NMDAR1, NMDAR2A, and NMDAR2B) and the metabotropic type (mGluR2 and mGluR7) at both the mRNA and protein levels. The binding of glutamate to glutamate receptors on the mast cell surface was confirmed. Further, glutamate had extensive effects on gene expression in the mast cells, including the upregulation of pro-inflammatory components such as IL-6 and CCL2. Glutamate also induced the upregulation of transcription factors, including Egr2, Egr3 and, in particular, FosB. The extensive induction of FosB was confirmed by immunofluorescence assessment. Glutamate receptor antagonists abrogated the responses of the mast cells to glutamate, supporting the supposition of a functional glutamate-glutamate receptor axis in mast cells. Finally, we provide in vivo evidence supporting a functional glutamate-glutamate receptor axis in the mast cells of injured tendons. Together, these findings establish glutamate as an effector of mast cell function, thereby introducing a novel principle for how cells in the immune system can communicate with nerve cells.

Effect of growth hormone treatment on circulating levels of NT-proBNP in patients with ischemic heart failure.

AIMS: Growth hormone (GH) therapy in heart failure (HF) is controversial. We investigated the cardiovascular effects of GH in patients with chronic HF due to ischemic heart disease. METHODS: In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66 years; 95% male) with ischemic HF (ejection fraction [EF] < 40%) to a 9-month treatment with either recombinant human GH (1.4 mg every other day) or placebo, with subsequent 3-month treatment-free follow-up. The primary outcome was change in left ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes included changes in New York Heat Association (NYHA) functional class and quality of life (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP). RESULTS: No changes in cardiac structure or systolic function were identified in either treatment group; nor did GH treatment affect QoL or functional class. In the GH group, circulating levels of IGF-1 doubled from baseline (+105%; p < 0.001) and NT-proBNP levels halved (-48%; p < 0.001) during the treatment period, with subsequently a partial return of both towards baseline levels. No changes in IGF-1 or NT-proBNP were observed in the placebo group at any time during the study. CONCLUSION: In patients with chronic ischemic HF, nine months of GH treatment was associated with significant increases in levels of IGF-1 and reductions in levels of NT-proBNP, but did not affect cardiac structure, systolic function or functional capacity.

Correction to: Glutamate triggers the expression of functional ionotropic and metabotropic glutamate receptors in mast cells.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Vibrotactile perception on the sole of the foot in an older group of people with normal glucose tolerance and type 2 diabetes.

OBJECTIVES: To evaluate vibrotactile sense in an older group of people with normal glucose tolerance and type 2 diabetes relative to other sensory tests. METHODS: Vibration perception thresholds on the sole of the foot (Multifrequency vibrametry and Biothesiometer) were compared to the results from evaluation of touch (monofilament), electrophysiology (sural nerve) and thermal sensation (Thermotest®). RESULTS: Vibration perception and temperature thresholds, as well as sural nerve function, differed between normal glucose tolerance and type 2 diabetes. Measuring vibration perception thresholds at lower frequencies with multifrequency vibrametry versus biothesiometer provided correlations similar to sural nerve amplitude. Temperature thresholds correlated with vibration perception thresholds and sural nerve function. Monofilaments revealed pathology in only a few participants with type 2 diabetes. CONCLUSIONS: In an older group of people, vibration perception thresholds show a correlation similar to sural nerve amplitude on tactile and non-tactile surfaces. Measuring a vibration perception threshold on a tactile surface in type 2 diabetes provides no clear advantage over measuring it on the medial malleolus. In older type 2 diabetes subjects, both large and small diameter nerve fibers are affected.

Do Mast Cells Have a Role in Tendon Healing and Inflammation?

Understanding the links between the tendon healing process, inflammatory mechanisms, and tendon homeostasis/pain after tissue damage is crucial in developing novel therapeutics for human tendon disorders. The inflammatory mechanisms that are operative in response to tendon injury are not fully understood, but it has been suggested that inflammation occurring in response to nerve signaling, i.e., neurogenic inflammation, has a pathogenic role. The mechanisms driving such neurogenic inflammation are presently not clear. However, it has recently been demonstrated that mast cells present within the injured tendon can express glutamate receptors, raising the possibility that mast cells may be sensitive to glutamate signaling and thereby modulate neurogenic inflammation following tissue injury. In this review, we discuss the role of mast cells in the communication with peripheral nerves, and their emerging role in tendon healing and inflammation after injury.

Peak expiratory flow rate and thoracic mobility in people with fibromyalgia. A cross sectional study.

BACKGROUND AND AIMS: Fibromyalgia (FM) is characterized by chronic widespread pain and affects approximately 1-3% of the general population. Respiratory function has not been given much consideration in people with FM. Few studies have been published concerning FM and respiratory function and conflicting data still exist. The aim of this study was to compare differences in forced expiration, but also to investigate chest expansion, spinal mobility and segmental pain intensity between a group with fibromyalgia and healthy controls. METHODS: Forty-one women with diagnosed FM based on American College of Rheumatology 1990 criteria and forty-one controls without pain matched for age and gender participated in this cross-sectional study. For evaluation of forced expiration, a Wright peak expiratory flow rate meter was used. A tape measure was used to measure the mobility of the thorax at maximum inhalation and exhalation known as chest expansion. Spinal mobility was measured with the Cervico-thoracic ratio method. The spinal mobility was measured as range of motion from C7 to 15 cm below in flexion and manual palpation was conducted between C7-T5. For differences in pain intensity a palpation-index was defined for each level, respectively; C7-T1, T1-2, T2-3, T3-4 and T4-5 by calculating the mean value for the four different palpation points for each motion segment. A combined measure of expiration and thoracic mobility (expiratory/inspiratory ratio) was calculated by dividing peak expiratory flow rate (L/min) with chest expansion (cm). Statistical analyses included descriptive statistics to describe subjects and controls, means and standard deviation to compare differences between groups and student-t and Chi-square (χ2) tests, using SPSS 22 software. Confidence interval was set to 95%. RESULTS: In the FM group 17 had the diagnosis for more than 5 years and 24 less than 5 years. The FM group demonstrated significantly lower forced expiration (p < 0.018), less thoracic expansion (p < 0.001), reduced spinal mobility (p < 0.029), higher expiratory-inspiratory ratio value (p < 0.001) and increased palpation pain over C7-T5 (p < 0.001) compared to healthy controls. There were more smokers in the FM group (n = 9) compared to the controls (n = 5) though this difference was not statistically significant (p < 0.24) and excluding the few smokers yielded similar result. No significant correlations for manual palpation, chest expansion, peak expiratory flow rate and spinal mobility were found in the FM group. CONCLUSIONS: Women with FM demonstrated significantly lower forced expiration and thoracic mobility compared to healthy controls. IMPLICATIONS: The results of this study point to a plausible restriction of respiratory function which in turn may have effect on physical endurance and work capacity in people with FM.

Colored body images reveal the perceived intensity and distribution of pain in women with breast cancer treated with adjuvant taxanes: a prospective multi-method study of pain experiences.

Background and aims Breast cancer is the most prevalent adult cancer worldwide. A broader use of screening for early detection and adjuvant systemic therapy with chemotherapy has resulted in improved survival rates. Taxane-containing chemotherapy is one of the cornerstones of the treatment. However, taxane-containing chemotherapy may result in acute chemotherapy-induced nociceptive and neuropathic pain. Since this pain may be an additional burden for the patient both during and after taxane chemotherapy, it is important to rapidly discover and treat it. There is yet no gold standard for assessing taxane-induced pain. In the clinic, applying multiple methods for collecting information on pain may better describe the patients' pain experiences. The aim was to document the pain during and after taxane through the contribution of different methods for collecting information on taxane-induced pain. Fifty-three women scheduled for adjuvant sequential chemotherapy at doses of ≥75 mg/m2 of docetaxel and epirubicin were enrolled in the study. Methods Prospective pain assessments were done on a visual analog scale (VAS) before and during each cycle of treatment for about 5 months, and using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire's (EORTC-QLQ-C30) two pain questions at baseline, 3 months, and 12 months. Participants scoring pain on the VAS >30 and undergoing an interview also colored their pain on a body image during treatment and at 12 months. Results Surprisingly widespread, intense pain was detected using a multi-method approach. The colored body image showed pain being perceived on 51% of the body surface area during treatment, and on 18% 12 months after inclusion. In general, the pain started and peaked in intensity after the first cycle of taxane. After Cycle 3, most women reported an increase in pain on the VAS. Some women continued to report some pain even during the epirubicin cycles. The VAS scores dropped after the last chemotherapy cycle, but not to the baseline level. At baseline, 3 months and 12 months after inclusion, the women who estimated VAS >30 reported higher levels of pain on the pain questions of the EORTC-QLQ-C30. Conclusions This study contributes information on how different pain assessment tools offer different information in the assessment of pain. The colored body image brings another dimension to pain diagnostics, providing additional information on the involved body areas and the pain intensities as experienced by the women. A multi-method approach to assessing pain offers many advantages. The timing of the assessment is important to properly assess pain. Implications Pain relief needs to be included in the chemotherapy treatment, with individual assessment and treatment of pain, in the same way as is done in chemotherapy-triggered nausea. There is a time window whereby the risk of pain development is at its highest within 24-48 h after receiving taxane chemotherapy. Proper attention to pain evaluation and treatment should be in focus during this time window.

Wide-field corneal subbasal nerve plexus mosaics in age-controlled healthy and type 2 diabetes populations.

A dense nerve plexus in the clear outer window of the eye, the cornea, can be imaged in vivo to enable non-invasive monitoring of peripheral nerve degeneration in diabetes. However, a limited field of view of corneal nerves, operator-dependent image quality, and subjective image sampling methods have led to difficulty in establishing robust diagnostic measures relating to the progression of diabetes and its complications. Here, we use machine-based algorithms to provide wide-area mosaics of the cornea's subbasal nerve plexus (SBP) also accounting for depth (axial) fluctuation of the plexus. Degradation of the SBP with age has been mitigated as a confounding factor by providing a dataset comprising healthy and type 2 diabetes subjects of the same age. To maximize reuse, the dataset includes bilateral eye data, associated clinical parameters, and machine-generated SBP nerve density values obtained through automatic segmentation and nerve tracing algorithms. The dataset can be used to examine nerve degradation patterns to develop tools to non-invasively monitor diabetes progression while avoiding narrow-field imaging and image selection biases.

Anatomical landmarks of the intra-pelvic side-wall as sources of pain in women with and without pregnancy-related chronic pelvic pain after childbirth: a descriptive study.

BACKGROUND: Chronic pelvic pain (CPP) affects 15-24% of women and can have a devastating impact on quality of life. Laparoscopy is often used in the investigation, although in one third of the examinations there is no visible pathology and the women may be dismissed without further investigation. Also, the contribution of skeletal, muscular, periosteal and ligamentous tissues to CPP remains to be further elucidated. The objective of the present study was to compare pain intensity provoked from anatomical landmarks of the intra-pelvic side-wall in women with pregnancy-related CPP after childbirth and women without such pain. METHODS: This is a descriptive study of 36 non-randomly selected parous women with CPP after childbirth and 29 likewise selected parous women after childbirth without CPP. Pain was determined by questionnaire and clinical examination. The primary outcome measure was reported pain intensity provoked on 13 anatomical landmarks of the intra-pelvic side-wall. All women reported their perceived pain intensity for each anatomical landmark on Likert scales and an individual sum score was calculated. RESULTS: Women with chronic pelvic pain were older than women without CPP. At several intra-pelvic landmarks high intensity pain was provoked in women with CPP compared with less intense pain provoked at fewer landmarks in women without low back or pelvic pain (p < 0.0001). The average sum of pain intensity scores was about 4 times higher in women with CPP (1.3) as compared with those without low back or pelvic pain (0.3), p < 0.0001. This association remained when adjusting for the age difference between the pain groups in linear regression analysis. In addition, reported pain intensity at worst past week was independently associated with sum of pain intensity scores. The maximum individual sum of pain intensity scores among women without CPP was exceeded by that of 85% of the women with CPP. CONCLUSIONS: Parous women with CPP after childbirth had a heightened pain intensity over 13 anatomical landmarks during pelvic examination compared with parous women without CPP. These results need to be confirmed in a larger cohort with different types of CPP.

Reduced Corneal Nerve Fiber Density in Type 2 Diabetes by Wide-Area Mosaic Analysis.

Purpose: To determine if corneal subbasal nerve plexus (SBP) parameters derived from wide-area depth-corrected mosaic images are associated with type 2 diabetes. Methods: One hundred sixty-three mosaics were produced from eyes of 82 subjects by laser-scanning in vivo confocal microscopy (IVCM). Subjects were of the same age, without (43 subjects) or with type 2 diabetes (39 subjects). Mosaic corneal nerve fiber length density (mCNFL) and apical whorl corneal nerve fiber length density (wCNFL) were quantified and related to the presence and duration of diabetes (short duration < 10 years and long duration ≥ 10 years). Results: In mosaics with a mean size of 6 mm2 in subjects aged 69.1 ± 1.2 years, mCNFL in type 2 diabetes was reduced relative to nondiabetic subjects (13.1 ± 4.2 vs. 15.0 ± 3.2 mm/mm2, P = 0.018). Also reduced relative to nondiabetic subjects was mCNFL in both short-duration (14.0 ± 4.0 mm/mm2, 3.2 ± 3.9 years since diagnosis) and long-duration diabetes (12.7 ± 4.2 mm/mm2, 15.4 ± 4.2 years since diagnosis; ANOVA P = 0.023). Lower mCNFL was associated with presence of diabetes (P = 0.032) and increased hemoglobin A1c (HbA1c) levels (P = 0.047). By contrast, wCNFL was unaffected by diabetes or HbA1c (P > 0.05). Global SBP patterns revealed marked degeneration of secondary nerve fiber branches outside the whorl region in long-duration diabetes. Conclusions: Wide-area mosaic images provide reference values for mCNFL and wCNFL and reveal a progressive degeneration of the SBP with increasing duration of type 2 diabetes.

Visualization of painful inflammation in patients with pain after traumatic ankle sprain using [11C]-D-deprenyl PET/CT.

BACKGROUND AND AIMS: Positron emission tomography (PET) with the radioligand [11C]-D-deprenyl has shown increased signal at location of pain in patients with rheumatoid arthritis and chronic whiplash injury. The binding site of [11C]-D-deprenyl in peripheral tissues is suggested to be mitochondrial monoamine oxidase in cells engaged in post-traumatic inflammation and tissue repair processes. The association between [11C]-D-deprenyl uptake and the transition from acute to chronic pain remain unknown. Further imaging studies of musculoskeletal pain at the molecular level would benefit from establishing a clinical model in a common and well-defined injury in otherwise healthy and drug-naïve subjects. The aim of this study was to investigate if [11C]-D-deprenyl uptake would be acutely elevated in unilateral ankle sprain and if tracer uptake would be reduced as a function of healing, and correlated with pain localizations and pain experience. METHODS: Eight otherwise healthy patients with unilateral ankle sprain were recruited at the emergency department. All underwent [11C]-D-deprenyl PET/CT in the acute phase, at one month and 6-14 months after injury. RESULTS: Acute [11C]-D-deprenyl uptake at the injury site was a factor of 10.7 (range 2.9-37.3) higher than the intact ankle. During healing, [11C]-D-deprenyl uptake decreased, but did not normalize until after 11 months. Patients experiencing persistent pain had prolonged [11C]-D-deprenyl uptake in painful locations. CONCLUSIONS AND IMPLICATIONS: The data provide further support that [11C]-D-deprenyl PET can visualize, quantify and follow processes in peripheral tissue that may relate to soft tissue injuries, inflammation and associated nociceptive signaling. Such an objective correlate would represent a progress in pain research, as well as in clinical pain diagnostics and management.