Widespread horse-based mobility arose around 2,200 BCE in Eurasia.

Horses revolutionized human history with fast mobility1. However, the timeline between their domestication and widespread integration as a means of transportation remains contentious2-4. Here we assemble a large collection of 475 ancient horse genomes to assess the period when these animals were first reshaped by human agency in Eurasia. We find that reproductive control of the modern domestic lineage emerged ~2,200 BCE (Before Common Era), through close kin mating and shortened generation times. Reproductive control emerged following a severe domestication bottleneck starting no earlier than ~2,700 BCE, and coincided with a sudden expansion across Eurasia that ultimately resulted in the replacement of nearly every local horse lineage. This expansion marked the rise of widespread horse-based mobility in human history, which refutes the commonly-held narrative of large horse herds accompanying the massive migration of steppe peoples across Europe ~3,000 BCE and earlier3,5. Finally, we detect significantly shortened generation times at Botai ~3,500 BCE, a settlement from Central Asia associated with corrals and a subsistence economy centered on horses6,7. This supports local horse husbandry before the rise of modern domestic bloodlines.

Insignificant influence of the intertransverse process block for major breast cancer surgery: a randomized, blinded, placebo-controlled, clinical trial.

INTRODUCTION: The intertransverse process (ITP) block mimics the thoracic paravertebral block and allegedly ameliorates hemithoracic postoperative pain. However, concerning major reconstructive breast cancer surgery the modality has never been tested against placebo in a randomized clinical trial. We aimed to assess the efficacy of the multiple-injection ITP block and hypothesized that the blockade would reduce postoperative opioid consumption. METHODS: We screened 58 patients with breast cancer scheduled for unilateral subpectoral implant-based primary breast reconstruction, involving mastectomy with complete fascial dissection of the major pectoral muscle. A randomization procedure allowed for the allocation of 36 patients to receive either unilateral multiple-injection active ITP block (0.5% ropivacaine 3×10 mL) or placebo ITP block (isotonic saline 3×10 mL) at T2, T4, T6 in a prospective, blinded, clinical trial. The primary outcome was total opioid consumption within the first 24 postoperative hours. Secondary outcomes included opioid consumption at 4-hour intervals, postoperative pain, patient satisfaction with block application, time to first opioid, ambulation and discharge, opioid-related side effects, and quality of recovery. RESULTS: Opioid consumption within the first 24 postoperative hours showed no significant reduction when comparing the active and placebo group median (IQR): 75.0 mg (45-135) vs 62.5 mg (30-115), p=0.5, respectively. We did not find any consequential clinically relevant results of the secondary outcomes. CONCLUSIONS: Following major reconstructive breast cancer surgery, a preoperative multiple-injection ITP block neither reduces 24-hour opioid consumption postoperatively nor promotes substantial clinical positive outcomes. TRIAL REGISTRATION NUMBER: EudraCT2019-001016-35.

Electronic patient-reported outcome measures to enable systematic follow-up in treatment and care of women diagnosed with breast cancer: a feasibility study protocol.

INTRODUCTION: The use of patient-reported outcome measures (PROMs) in clinical practice has the potential to promote person-centred care and improve patients' health-related quality of life. We aimed to develop an intervention centred around electronic PROMs (ePROMs) for systematic follow-up in patients diagnosed with breast cancer and to evaluate its feasibility. METHODS AND ANALYSIS: We developed a nurse-oriented and surgeon-oriented intervention in PROMs, including (1) an education programme for nurses and surgeons; (2) administration of BREAST-Q as proactive ePROMs during follow-up in patients diagnosed with breast cancer and (3) feedback to nurses and surgeons on PROM scores and a guidance manual for healthcare practitioners. Subsequently, we designed a non-controlled feasibility evaluation on the outcomes acceptability, demand, implementation, practicality and integration. The feasibility evaluation includes qualitative ethnographic studies exploring the user perspectives of patients, nurses and surgeons and quantitative studies to explore the characteristics of the patient population regarding demographic background, response rates and response patterns. The feasibility study was initiated in September 2021, will continue until 2024 and will include approximately 900 patients. EPROMs are collected at the following assessment time points: baseline (after diagnosis, before surgery), 1-year follow-up and 3-year endpoint. ETHICS AND DISSEMINATION: The study will be conducted according to the General Data Protection Regulation and the fifth version of the Helsinki Declaration. The National Committee on Health Research Ethics approved the study according to the law of the Committee § 1, part 4. All data will be anonymised before its publication. The results of the feasibility study will be published in peer-reviewed, international journals.

Novel chicken two-dimensional intestinal model comprising all key epithelial cell types and a mesenchymal sub-layer.

The intestinal epithelium plays a variety of roles including providing an effective physical barrier and innate immune protection against infection. Two-dimensional models of the intestinal epithelium, 2D enteroids, are a valuable resource to investigate intestinal cell biology and innate immune functions and are suitable for high throughput studies of paracellular transport and epithelial integrity. We have developed a chicken 2D enteroid model that recapitulates all major differentiated cell lineages, including enterocytes, Paneth cells, Goblet cells, enteroendocrine cells and leukocytes, and self-organises into an epithelial and mesenchymal sub-layer. Functional studies demonstrated the 2D enteroids formed a tight cell layer with minimal paracellular flux and a robust epithelial integrity, which was maintained or rescued following damage. The 2D enteroids were also able to demonstrate appropriate innate immune responses following exposure to bacterial endotoxins, from Salmonella enterica serotype Typhimurium and Bacillus subtilis. Frozen 2D enteroids cells when thawed were comparable to freshly isolated cells. The chicken 2D enteroids provide a useful ex vivo model to study intestinal cell biology and innate immune function, and have potential uses in screening of nutritional supplements, pharmaceuticals, and bioactive compounds.

Peripheral blood immune markers in breast cancer: Differences in regulatory T cell abundance are related to clinical parameters.

BACKGROUND: Cancer development is among other factors driven by tumor immune escape and tumor-mediated changes in the immune response. Investigating systemic immune changes may provide important knowledge for the improvement of patient prognosis and treatment opportunities. METHODS: The systemic immune profile of patients with ER-positive breast cancer (n = 22) and healthy controls (n = 30) was investigated based on complete blood counts, flow cytometric analysis of T cell subsets including regulatory T cells (Tregs), and immune assays investigating soluble (s)HLA-G and the cytokine profile in plasma. We further examined the correlation between the immune markers and clinical parameters including tumor size, tumor grade and lymph node involvement. RESULTS: Results indicated that breast cancer patients possessed a higher amount of neutrophils and monocytes and fewer lymphocytes and eosinophils compared with healthy controls. Breast cancer patients had significantly more CD25+CD127low Tregs than controls, and both lymphocyte and Treg numbers were negatively correlated with tumor size. Furthermore, Treg numbers were elevated in grade I tumors compared with grade II tumors and with healthy controls. No difference in sHLA-G levels was observed between patients and controls. Higher levels of IL-6 and TNF-α were observed in breast cancer patients. Cytokine and sHLA-G levels were not associated with clinical parameters. CONCLUSION: The results of this exploratory study contribute to the elucidation of the systemic immune response in breast cancer indicating a potential use of peripheral immune cell counts and Tregs to distinguish patients from healthy controls and as potential diagnostic and prognostic biomarkers to be investigated in future studies.

Immunogenicity of the Novel Glucagon Analogue Dasiglucagon: Results of a Dedicated Immunogenicity Trial in Type 1 Diabetes.

Dasiglucagon is a next-generation glucagon analogue that is stable in aqueous formulation. This dedicated immunogenicity trial to support use as rescue treatment for severe hypoglycemia was conducted to evaluate the immunogenicity of repeated subcutaneous doses of dasiglucagon in subjects with type 1 diabetes. A total of 112 subjects were randomized 1:1 to receive three subcutaneous weekly doses of either 0.6 mg dasiglucagon or 1.0 mg recombinant glucagon (GlucaGen®) according to a double-blind parallel-group trial design. Subjects were followed for 15 weeks, with a multitiered testing approach planned for assessment of antidrug antibody (ADA) formation. For the primary immunogenicity endpoint, the overall ADA incidence was zero, as no subject demonstrated any treatment-induced or treatment-boosted ADA response at any time point in this trial involving three consecutive weekly doses of trial drug. No injection site reactions were reported for subjects receiving dasiglucagon. There were no unexpected safety findings for the trial.

Cardiovascular adaptations after 10 months of daily 12-min bouts of intense school-based physical training for 8-10-year-old children.

The present study examined cardiovascular adaptations in 8-10-year-old schoolchildren after a full school year (10 months) of 5 × 12 min/wk. of intense physical training, including small-sided ball games (soccer, basketball and floorball) or interval running. The study involved 8-10-year-old healthy Danish schoolchildren (n = 232), who were cluster-randomized to a small-sided games group (SSG, n = 60), an interval running group (IR, n = 57) or a control group (CON, n = 115). Comprehensive transthoracic echocardiography, resting heart rate and blood pressure measurements were performed at baseline and post intervention. For interval running, analysis of baseline-to-10-months changes showed significant (P < 0.05) between-group differences in delta scores for diastolic blood pressure (BP) and mean arterial BP (IR -3.2 ±â€¯5.7 and - 2.2 ±â€¯6.5 mmHg vs. CON 0.2 ±â€¯5.3 and 0.4 ±â€¯6.4 mmHg, respectively). Delta scores also showed a trend for reduction of mean arterial BP in SSG compared to CON (-2.1 ±â€¯6.0 vs. 0.2 ±â€¯5.3 mmHg, P = 0.067). Moreover, there were between-group differences in delta scores (P < 0.05) for selected echocardiographic parameters, i.e. in SSG vs. CON for interventricular septum thickness and peak transmitral flow velocity in early diastole, and in IR vs. CON for left ventricular systolic diameter. In conclusion, 10 months of 5 × 12 min/wk. of IR in 8-10-year-old children decreased diastolic BP, while both IR and SSG elicited cardiac adaptations. The results suggest that frequent low volume, intense physical training can have effects on the cardiovascular health profile in healthy children.

[Mastitis].

Mastitis is defined as an inflammation of the breast and may or may not be accompanied by infection. It usually affects fertile women but can be seen at all ages and even in males. Mastitis is commonly divided into two groups: lactational mastitis which occurs in breastfeeding women, and non-lactational mastitis. A timely diagnosis and correct management is essential to avoid complications. In this review, we assess different types of inflammations of the breast and elucidate important differential diagnoses, such as inflammatory breast cancer.

Cardiovascular adaptations after 10 months of intense school-based physical training for 8- to 10-year-old children.

This study examined cardiovascular adaptations in 8- to 10-year-old schoolchildren after 10 months (a full school year) of 3 × 40 minute per week of small-sided ball games (SSG, including football, basketball, and/or floorball) or circuit strength training (CST). The study involved 291 Danish schoolchildren, 8-10 years old, cluster-randomized to SSG (n = 93, 4 schools, 5 classes), CST (n = 83, 4 schools, 4 classes), or a control group (CON, n = 115, 2 schools, 5 classes). Before and after the 10-month intervention, resting heart rate and blood pressure measurements were performed as well as comprehensive transthoracic echocardiography and peripheral arterial tonometry (PAT). Analysis of baseline-to-10-months changes showed between-group differences (P < 0.05) after both training interventions in diastolic blood pressure (delta scores: SSG -2.1 ± 6.0 mm Hg; CST -3.0 ± 7.1 mm Hg; CON 0.2 ± 5.3 mm Hg). Moreover, there were between-group differences in delta scores (P < 0.05) in interventricular septum thickness (SSG 0.17 ± 0.87 mm; CST 0.30 ± 0.94 mm; CON -0.15 ± 0.68 mm), left-atrial volume index (SSG 0.32 ± 5.13 mL/m2 ; CON 2.60 ± 5.94 mL/m2 ), and tricuspid annular plane systolic excursion (SSG -0.4 ± 3.3 mm; CON: 0.1 ± 3.6 mm). No significant between-group differences were observed for the PAT-derived reactive hyperemia index. In conclusion, 10 months of 3 × 40 minutes per week of SSG and CST in 8- to 10-year-old children decreased diastolic blood pressure and elicited discrete cardiac adaptations, suggesting that intense physical exercise in school classes can have effects on cardiovascular health in children.

Positive effects on bone mineralisation and muscular fitness after 10†months of intense school-based physical training for children aged 8-10†years: the FIT FIRST randomised controlled trial.

OBJECTIVES: We investigated whether musculoskeletal fitness of school children aged 8-10 years was affected by frequent intense PE sessions. DESIGN AND PARTICIPANTS: 295 Danish school children aged 8-10 years were cluster randomised to a small-sided ball game group (SSG) (n=96, four schools, five classes), a circuit strength training group (CST) (n=83, four schools, four classes) or a control group (CON, n=116, two schools, five classes). INTERVENTION: SSG or CST was performed 3×40 min/week over 10 months. Whole-body dual-energy X-ray absorptiometry (DXA) scans were used to determine areal bone mineral density (aBMD), bone mineral content (BMC) and lean body mass (LBM). Flamingo balance, standing long jump and 20-m sprint tests were used to determine muscular fitness. RESULTS: Analysis of baseline-to-10 months change scores showed between-group differences in favour of the interventions in whole-body aBMD (SSG vs CON: 8 mg/cm2, 95% CI 3 to 13; CST vs CON: 7 mg/cm2, 95% CI 2 to 13, p<0.05) and leg BMC (SSG vs CON: 11 g, 95% CI 4 to 18; CST vs CON: 11 g, 95% CI 3 to 18, p<0.05). SSG had higher change scores in leg aBMD compared with CON and CST (SSG vs CON: 19 mg/cm2, 95% CI 11 to 39, p<0.05; SSG vs CST: 12 mg/cm2, 95% CI 3 to 21, p<0.05), and CST had higher change scores in whole-body BMC compared with CON (CST vs CON: 25 g, 95% CI 10 to 39, p<0.05). Both training types resulted in higher change scores in postural balance (SSG vs CON: 2.4 fewer falls/min, 95% CI 0.3 to 4.5, CST vs CON: 3.6 fewer falls/min, 95% CI 1.3 to 5.9, p<0.05) and jump length (SSG vs CON: 10%, 95% CI 5 to 16%; CST vs CON: 9%, 95% CI 3 to 15%, p<0.05). No between-group differences were observed for sprint performance or LBM (p>0.05). CONCLUSIONS: In conclusion, 3×40 min/week with SSG or CST over a full school year improves bone mineralisation and several aspects of muscular fitness of children aged 8-10 years, suggesting that well-organised intense physical education classes can contribute positively to develop musculoskeletal health in young children. TRIAL REGISTRATION NUMBER: NCT02000492, post results.

Physical Fitness and Body Composition in 10-12-Year-Old Danish Children in Relation to Leisure-Time Club-Based Sporting Activities.

This study investigated whether the physical fitness and body composition of 10-12-year-old Danish children are related to participation in leisure-time club-based sporting activities. The study involved 544 Danish 10-12-year-old 5th-grade municipal schoolchildren (269 boys and 275 girls, 11.1 ± 0.4 years). After answering a questionnaire about leisure-time sporting activities, the children were divided into four groups: football club participation (FC; n=141), other ball games (OBG; n=42), other sports (OS; n=194), and no sports-club participation (NSC; n=167). The children completed a battery of health and fitness tests, including a 20 m sprint test, a standing long-jump test, the Yo-Yo IR1 children's test (YYIR1C), and body composition, blood pressure, resting heart rate (HRrest), and the flamingo balance test. The children engaged in club-based ball games (FC and OBG) had higher (p<0.05) lean body mass than NSC (FC: 17.5 ± 2.9; OBG: 18.4 ± 2.6; OS: 16.7 ± 2.9; NSC: 16.4 ± 2.8 kg), performed better (p<0.05) in the YYIR1C test (FC: 1083 ± 527; OBG: 968 ± 448; OS: 776 ± 398; NSC: 687 ± 378 m), and had lower (p<0.05) %HRmax after 1, 2, and 3 min of YYIR1C. Moreover, HRrest was lower (p<0.05) for FC than for OS and NSC (FC: 68 ± 9 vs OS: 72 ± 10 and NSC: 75 ± 10 bpm), and lower (p<0.05) for OBG than for NSC (OBG: 70 ± 10 vs NSC: 75 ± 10 bpm). This study found that 10-12-year-old Danish children engaged in club-based football and other ball games had better exercise capacity, lower resting heart rate, and higher muscle mass than children not engaged in leisure-time sports. Thus, participation in club-based leisure-time ball-game activities seems to be of importance for the fitness and health profile of prepubertal children.

Physical Fitness and Body Composition in 8-10-Year-Old Danish Children Are Associated With Sports Club Participation.

Larsen, MN, Nielsen, CM, Ørntoft, CØ, Randers, M, Manniche, V, Hansen, L, Hansen, PR, Bangsbo, J, and Krustrup, P. Physical fitness and body composition in 8-10-year-old Danish children are associated with sports club participation. J Strength Cond Res 31(12): 3425-3434, 2017-We investigated whether physical fitness and body composition in 8-10-year-old Danish children are associated with sports club participation. The study included 423 schoolchildren, comprising 209 girls and 214 boys, of whom 67 and 74%, respectively, were active in sports clubs. Yo-Yo intermittent recovery level 1 for children (YYIR1C), balance, jump and coordination tests, together with dual-energy X-ray absorptiometry, were used to determine exercise capacity and body composition. Children active in sports clubs had better (p < 0.05) YYIR1C (33%, 767 ± 26 vs. 575 ± 29 m), 20-m sprint (3%, 4.33 ± 0.03 vs. 4.48 ± 0.04 seconds), coordination (6%, 68 ± 1 vs. 72 ± 1 second), and balance test performances (9%, 19.3 ± 0.5 vs. 21.2 ± 0.7 falls·min) and lower fat mass index (16%, 3.8 ± 0.1 vs. 4.5 ± 0.2 kg[fat]·m) than children not active in sports clubs. Ball game players had better (p < 0.05) YYIR1C (38%, 925 ± 39 vs. 671 ± 28 m), 20-m sprint (4%, 4.25 ± 0.03 vs. 4.42 ± 0.04 seconds), and coordination test performances (5%, 65 ± 1 vs. 69 ± 1 second), along with higher (p < 0.05) lean body mass (5%, 24.00 ± 0.22 vs. 22.83 ± 0.25 kg) and whole-body BMD (2%, 0.90 ± < 0.01 vs. 0.88 ± <0.01 g·cm) compared with children active in other sports. The study showed that 8[FIGURE DASH]10-year-old Danish children engaged in sports-club activity, especially ball game players, have better exercise capacity and superior body composition compared with children not active in sports clubs.

Fitness Effects of 10-Month Frequent Low-Volume Ball Game Training or Interval Running for 8-10-Year-Old School Children.

We investigated the exercise intensity and fitness effects of frequent school-based low-volume high-intensity training for 10 months in 8-10-year-old children. 239 Danish 3rd-grade school children from four schools were cluster-randomised into a control group (CON, n = 116) or two training groups performing either 5 × 12 min/wk small-sided football plus other ball games (SSG, n = 62) or interval running (IR, n = 61). Whole-body DXA scans, flamingo balance, standing long-jump, 20 m sprint, and Yo-Yo IR1 children's tests (YYIR1C) were performed before and after the intervention. Mean running velocity was higher (p < 0.05) in SSG than in IR (0.88 ± 0.14 versus 0.63 ± 0.20 m/s), while more time (p < 0.05) was spent in the highest player load zone (>2; 5.6 ± 3.4 versus 3.7 ± 3.4%) and highest HR zone (>90% HRmax; 12.4 ± 8.9 versus 8.4 ± 8.0%) in IR compared to SSG. After 10 months, no significant between-group differences were observed for YYIR1C performance and HR after 2 min of YYIR1C (HRsubmax), but median-split analyses showed that HRsubmax was reduced (p < 0.05) in both training groups compared to CON for those with the lowest aerobic fitness (SSG versus CON: 3.2% HRmax [95% CI: 0.8-5.5]; IR versus CON: 2.6% HRmax [95% CI: 1.1-5.2]). After 10 months, IR had improved (p < 0.05) 20 m sprint performance (IR versus CON: 154 ms [95% CI: 61-241]). No between-group differences (p > 0.05) were observed for whole-body or leg aBMD, lean mass, postural balance, or jump length. In conclusion, frequent low-volume ball games and interval running can be conducted over a full school year with high intensity rate but has limited positive fitness effects in 8-10-year-old children.

A Fast-Track Referral System for Skin Lesions Suspicious of Melanoma: Population-Based Cross-Sectional Study from a Plastic Surgery Center.

Introduction. To minimize delay between presentation, diagnosis, and treatment of cutaneous melanoma (CM), a national fast-track referral system (FTRS) was implemented in Denmark. The aim of this study was to analyze the referral patterns to our department of skin lesions suspicious of melanoma in the FTRS. Methods. Patients referred to the Department of Plastic Surgery and Breast Surgery in Zealand University Hospital were registered prospectively over a 1-year period in 2014. A cross-sectional study was performed analyzing referral patterns, including patient and tumor characteristics. Results. A total of 556 patients were registered as referred to the center in the FTRS for skin lesions suspicious of melanoma. Among these, a total of 312 patients (56.1%) were diagnosed with CM. Additionally, 41 (7.4%) of the referred patients were diagnosed with in situ melanoma. Conclusion. In total, 353 (63.5%) patients had a malignant or premalignant melanocytic skin lesion. When only considering patients who where referred without a biopsy, the diagnostic accuracy for GPs and dermatologists was 29% and 45%, respectively. We suggest that efforts of adequate training for the referring physicians in diagnosing melanocytic skin lesions will increase diagnostic accuracy, leading to larger capacity in secondary care for the required treatment of malignant skin lesions.

Behavioral responses of juvenile Daphnia magna after exposure to glyphosate and glyphosate-copper complexes.

Glyphosate (N-(phosphonomethyl)glycine) is the active ingredient in a range of popular broad-spectrum herbicide formulations. Glyphosate is a chelating agent that can form stable complexes with divalent metal ions including Cu(II). Little is known about the bioavailability and ecotoxicity of glyphosate-Cu(II) complexes to aquatic organisms. In this study, we used video tracking and behavior analysis to investigate sublethal effects of binary mixtures of glyphosate and Cu(II) to juvenile D. magna. Behavioral responses were quantified for individual D. magna after 24h and 48h exposure to glyphosate and glyhosate-Cu(II) mixtures. Sublethal concentrations resulted in decreases in swimming velocity, acceleration speed, and distance moved whereas inactive time of D. magna increased. Distance moved and inactive time were the most responsive parameters to glyphosate and glyphosate-Cu(II) exposure. On a molar basis, glyphosate-Cu(II) complexes appeared more toxic to D. magna than glyphosate alone. The 48h EC50 for glyphosate and glyphosate-Cu(II) determined from swimming distance were 75.2µM and 8.4µM, respectively. In comparison, traditional visual observation of mobility resulted in 48h EC50 values of 52.8µM and 25.5µM for glyphosate and glyphosate-Cu(II), respectively. The behavioral responses indicated that exposure of D. magna to mixtures of glyphosate and Cu(II) attenuated acute metal toxicity but increased apparent glyphosate toxicity due to complexation with Cu(II). The study suggests that glyphosate is a likely mediator of aquatic metal toxicity, and that video tracking provides an opportunity for quantitative studies of sublethal effects of pesticide complexes.

Poor adherence to clinical guidelines for women undergoing breast reduction.

INTRODUCTION: Indication for breast reduction in a publically funded or an insurance-funded setting depends on the severity of the subjective symptoms and on the clinical evaluation. The purpose of this study was to evaluate whether Danish surgeons follow a clinical practice recommending a minimum tissue resection weight of 400-500 g per breast. METHODS: Included in the study were a total of 366 female patients with breast hypertrophy who underwent bilateral breast reduction surgery at three large university hospitals in Denmark in the period from August 2008 to November 2013. The patients' height, weight and standard breast measurement were registered as was the weight of breast tissue resection. The preoperative breast volume was measured using transparent plastic cups designed for this purpose. RESULTS: Among the 366 female participants, the median age was 40 years, the median BMI was 24 kg/m2, and the median breast volume was 1,050 cc on each side. Only 201 (55%) cases met the resection criterion of a minimum of 400 g tissue per breast, and 130 (36%) had 500 g or more resected. We found a highly significant correlation between the amount of resected breast tissue and the preoperative breast volume (p < 0.001, n = 366). CONCLUSIONS: Many surgeons did not follow the clinical practice of resecting 400-500 g of breast tissue in women who underwent breast reduction surgery at three large hospitals in Denmark in the 2008-2013 period. Our findings are surprising and beg the question if the guidelines should be revised to reflect the current practice or vice versa. FUNDING: none. TRIAL REGISTRATION: not relevant.

Interpretation of the skin cancer quality of life score: a validated quality of life questionnaire for non-melanoma skin cancer.

BACKGROUND: Health-related quality of life (HRQoL) instruments are used increasingly. In order to assign clinical meaning to HRQoL scores, the interpretation of instruments is essential but lagging in dermatology. OBJECTIVE: To establish a clinical interpretation of the Skin Cancer Quality of Life questionnaire (SCQoL), a newly validated HRQoL instrument for patients with non-melanoma skin cancer (NMSC), using an anchor-based method, and to test the responsiveness. METHODS: Receiver-operating characteristic analysis was used to propose clinically meaningful cut-off scores for SCQoL including 101 patients with NMSC. RESULTS: The following bands were established: score 0-3 corresponds to no impairment, 4-6 corresponds to mild impairment, 7-10 to moderate impairment and 11-27 to severe impairment of HRQoL. Testing the responsiveness shows a moderate effect size and significantly lower scores only for the domain emotion and the global item. CONCLUSION: Using proposed clinical cut-off scores for SCQoL may help clinicians in their decision-making, help monitoring clinical improvement and classify patients just as e.g. the Dermatology Life Quality Index can.

Risk of metabolic syndrome and diabetes among young twins and singletons in Guinea-Bissau.

OBJECTIVE: Twins in Africa may be at increased risk of metabolic disorders due to strained conditions in utero, including high exposure to infections. We studied metabolic syndrome (MS) and diabetes mellitus (DM) among young twins and singletons in Guinea-Bissau. RESEARCH DESIGN AND METHODS: The study was cross-sectional and occurred from October 2009 until August 2011 at the Bandim Health Project, a demographic surveillance site in the capital Bissau. Twins and singleton controls between 5 and 32 years were visited at home. Fasting blood samples for metabolic measurements were collected. Zygosity was established genetically for a subset. DM was defined as HbA1c ≥6.5% (48 mmol/mol) and MS by the International Diabetes Federation criteria. RESULTS: HbA1c was available for 574 twins and 463 singletons. Mean age was 15.3 years versus 15.8 years, respectively. Eighteen percent of twins were monozygotic. There were no DM cases among twins but one among singletons. A total of 1.4% (8 of 574) of twins had elevated HbA1c (6.0-6.4%, 42-46 mmol/mol) compared with 2.4% (11 of 463) of singletons (P = 0.28). Mean HbA1c was 5.3% (34 mmol/mol) for both groups. MS data were available for 364 twins and 360 singletons. The MS prevalence was 3.0% (11 of 364) among twins and 3.6% (13 of 360) among singletons (P = 0.66). The prevalence of fasting blood glucose (F-glucose) ≥5.6 mmol/L was 34.9% (127 of 364) for twins versus 24.7% (89 of 360) for singletons (P = 0.003). Median homeostasis model assessment-insulin resistance did not differ (P = 0.34). CONCLUSIONS: The MS and DM prevalences among young individuals in Guinea-Bissau were low. Twins did not have a higher MS and DM burden than singletons, though elevated F-glucose was more common among twins.

Assessment of the effects of intramuscular administration of alfaxalone with and without medetomidine in Horsfield's tortoises (Agrionemys horsfieldii).

OBJECTIVE: To characterise four different intramuscular (IM) anaesthetic protocols, two with alfaxalone and two with alfaxalone in combination with medetomidine in terrestrial tortoises. STUDY DESIGN: Blinded, randomized, cross-over experimental study. ANIMALS: Nine healthy adult male Horsfield's tortoises (Agrionemys horsfieldii). METHODS: Each tortoise was randomly assigned to one of four different protocols: 1) 10 mg kg(-1) alfaxalone; 2) 10 mg kg(-1) alfaxalone + 0.10 mg kg(-1) medetomidine; 3) 20 mg kg(-1) alfaxalone; and 4) 20 mg kg(-1) alfaxalone + 0.05 mg kg(-1) medetomidine. During the experiment, the following variables were recorded: heart rate; respiratory rate; peripheral nociceptive responses; muscle strength; ability to intubate; palpebral, corneal and tap reflexes; and cloacal temperature. RESULTS: Protocols 1 and 2 resulted in moderate sedation with no analgesia, and moderate to deep sedation with minimal analgesia, respectively. Protocols 3 and 4 resulted in deep sedation or anaesthesia with variable analgesic effect; these two protocols had the longest total anaesthetic time and allowed intubation in 6/9 and 8/9 tortoises respectively. The total anaesthesia/sedation time produced by alfaxalone was significantly increased (p < 0.05) by the addition of medetomidine. There were no significant differences regarding time to plateau phase and duration of plateau phase. Baseline heart rate of 53 ± 6 beats minute(-1) decreased significantly (p < 0.05) with all protocols, and was lower (p < 0.05) in protocols 3 and 4. Heart rate increased after atipamezole administration, but the increase was transient. In two tortoises, extreme bradycardia with no cardiac activity for 10 minutes was observed with protocols 3 and 4. CONCLUSION AND CLINICAL RELEVANCE: Alfaxalone 10 and 20 mg kg(-1) IM can be used for sedation for non-painful procedures. Alfaxalone in combination with medetomidine can be used for deeper sedation or anaesthesia, but the observed respiratory and cardiovascular depression may limit its use.

Changed activation, oxygenation, and pain response of chronically painful muscles to repetitive work after training interventions: a randomized controlled trial.

The aim of this randomized controlled trial was to assess changes in myalgic trapezius activation, muscle oxygenation, and pain intensity during repetitive and stressful work tasks in response to 10 weeks of training. In total, 39 women with a clinical diagnosis of trapezius myalgia were randomly assigned to: (1) general fitness training performed as leg-bicycling (GFT); (2) specific strength training of the neck/shoulder muscles (SST) or (3) reference intervention without physical exercise. Electromyographic activity (EMG), tissue oxygenation (near infrared spectroscopy), and pain intensity were measured in trapezius during pegboard and stress tasks before and after the intervention period. During the pegboard task, GFT improved trapezius oxygenation from a relative decrease of -0.83 ± 1.48 µM to an increase of 0.05 ± 1.32 µM, and decreased pain development by 43%, but did not affect resting levels of pain. SST lowered the relative EMG amplitude by 36%, and decreased pain during resting and working conditions by 52 and 38%, respectively, without affecting trapezius oxygenation. In conclusion, GFT performed as leg-bicycling decreased pain development during repetitive work tasks, possibly due to improved oxygenation of the painful muscles. SST lowered the overall level of pain both during rest and work, possibly due to a lowered relative exposure as evidenced by a lowered relative EMG. The results demonstrate differential adaptive mechanisms of contrasting physical exercise interventions on chronic muscle pain at rest and during repetitive work tasks.