Diagnosis and prevalence of diabetic polyneuropathy: a cross-sectional study of Danish patients with type 2 diabetes.

BACKGROUND AND PURPOSE: Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes. METHODS: A questionnaire on neuropathy and pain was sent to a cohort of 5514 Danish type 2 diabetes patients. A sample of 389 patients underwent a detailed clinical examination and completed neuropathy questionnaires and scales. RESULTS: Of the 389 patients with a median diabetes duration of 5.9 years, 126 had definite DPN (including 53 with painful DPN), 88 had probable DPN and 53 had possible DPN. There were 49 patients with other causes of polyneuropathy, neuropathy symptoms or pain, 10 with subclinical DPN and 63 without DPN. The sensitivity of the Michigan Neuropathy Screening Instrument questionnaire to detect DPN was 25.7% and the specificity 84.6%. The sensitivity of the Toronto Clinical Neuropathy Scoring System, including questionnaire and clinical examination, was 62.9% and the specificity was 74.6%. CONCLUSIONS: Diabetic polyneuropathy affects approximately one in five Danish patients with recently diagnosed type 2 diabetes but neuropathic pain is not as common as previously reported. Neuropathy scales with clinical examination perform better compared with questionnaires alone, but better scales are needed for future epidemiological studies.

Compact, low-threshold squeezed light source.

Strongly squeezed light finds many important applications within the fields of quantum metrology, quantum communication and quantum computation. However, due to the bulkiness and complexity of most squeezed light sources of today, they are still not a standard tool in quantum optics labs. We have taken the first steps in realizing a compact, high-performance 1550 nm squeezing source based on commercially available fiber components combined with a free-space double-resonant parametric down-conversion source. The whole setup, including single-pass second-harmonic generation in a waveguide, fits on a 30 cm×45 cm breadboard and produces 9.3 dB of squeezing at a 5 MHz sideband-frequency. The setup is currently limited by phase noise, but further optimization and development should allow for a 19" sized turn-key squeezing source capable of delivering more than 10 dB of squeezing.

Early-onset type 2 diabetes: Age gradient in clinical and behavioural risk factors in 5115 persons with newly diagnosed type 2 diabetes-Results from the DD2 study.

AIM: To examine the association between early onset of type 2 diabetes mellitus (DM) and clinical and behavioural risk factors for later complications of diabetes. METHODS: We conducted a cross-sectional study of 5115 persons with incident type 2 DM enrolled during 2010-2015 in the Danish Centre for Strategic Research in Type 2 Diabetes-cohort. We compared risk factors at time of diagnosis among those diagnosed at ≤45 years (early onset) with diagnosis age 46 to 55, 56 to 65 (average onset = reference), 66 to 75, and >75 years (late onset). Prevalence ratios (PRs) were computed by using Poisson regression. RESULTS: Poor glucose control, ie, HbA1c ≥ 75 mmol/mol (≥9.0%) in the early-, average-, and late-onset groups was observed in 12%, 7%, and 1%, respectively (PR 1.70 [95% confidence intervals (CI) 1.27, 2.28] and PR 0.17 [95% CI 0.06, 0.45]). A similar age gradient was observed for severe obesity (body mass index > 40 kg/m2 : 19% vs. 8% vs. 2%; PR 2.41 [95% CI 1.83, 3.18] and 0.21 (95% CI 0.08, 0.57]), dyslipidemia (90% vs. 79% vs. 68%; PR 1.14 [95% CI 1.10, 1.19] and 0.86 [95% CI 0.79, 0.93]), and low-grade inflammation (C-reactive protein > 3.0 mg/L: 53% vs. 38% vs. 26%; PR 1.41 [95% CI 1.12, 1.78] and 0.68 [95% CI 0.42, 1.11]). Daily smoking was more frequent and meeting physical activity recommendations less likely in persons with early-onset type 2 DM. CONCLUSIONS: We found a clear age gradient, with increasing prevalence of clinical and behavioural risk factors the younger the onset age of type 2 DM. Younger persons with early-onset type 2 DM need clinical awareness and support.

Towards water sensitive cities in Asia: an interdisciplinary journey.

Rapid urbanisation, population growth and the effects of climate change drive the need for sustainable urban water management (SUWM) in Asian cities. The complexity of this challenge calls for the integration of knowledge from different disciplines and collaborative approaches. This paper identifies key issues and sets the stage for interdisciplinary research on SUWM in Asia. It reports on the initial stages of a SUWM research programme being undertaken at Monash University, Australia, and proposes a framework to guide the process of interdisciplinary research in urban water management. Three key themes are identified: (1) Technology and Innovation, (2) Urban Planning and Design, and (3) Governance and Society. Within these themes 12 research projects are being undertaken across Indonesia, China, India and Bangladesh. This outward-looking, interdisciplinary approach guides our research in an effort to transgress single-discipline solutions and contribute on-ground impact to SUWM practices in Asia.

Expression of NK cell and monocyte receptors in critically ill patients--potential biomarkers of sepsis.

UNLABELLED: Sepsis is characterized by activation of both the innate and adaptive immune systems as a response to infection. During sepsis, the expression of surface receptors expressed on immune competent cells, such as NKG2D and NKp30 on NK cells and TLR4 and CD14 on monocytes, is partly regulated by pro- and anti-inflammatory mediators. In this observational study, we aimed to explore whether the expression of these receptors could be used as diagnostic and/or prognostic biomarkers in sepsis. Patients with severe sepsis or septic shock (n = 21) were compared with critically ill non-septic patients (n = 15). Healthy volunteers (n = 15) served as controls. To elucidate variations over time, all patients were followed for 4 days. Cell surface expression of NKG2D, NKp30, TLR4 and CD14 and serum levels of IL-1ß, IL-6, IFN-γ, TNF-α, IL-4 and IL-10 was estimated by flow cytometry. We found that NK cell expression of NKG2D and monocyte expression of CD14 were lower in the septic patients compared with the non-septic patients, both at ICU admission and during the observation period (P < 0.01 for all comparisons). Both at ICU admission, and during the observation period, levels of IL-6 and IL-10 were higher in the septic patients compared with the non-septic patients (P < 0.001 for all comparisons). CONCLUSION: As both NKG2D and CD14 levels appear to distinguish between septic and non-septic patients, both NKG2D and CD14 may be considered potential diagnostic biomarkers of severe sepsis and septic shock.

Prescribing practices and clinical predictors of glucose-lowering therapy within the first year in people with newly diagnosed Type 2 diabetes.

AIM: To examine prescribing practices and predictors of glucose-lowering therapy within the first year following diagnosis of Type 2 diabetes mellitus in a clinical care setting. METHODS: We followed people enrolled in the Danish Centre for Strategic Research in Type 2 Diabetes (DD2) cohort from outpatient hospital clinics and general practices throughout Denmark in 2010-2013. We used Poisson regression to compute age- and gender-adjusted risk ratios (RRs). RESULTS: Among 1158 new Type 2 diabetes mellitus patients, 302 (26%) did not receive glucose-lowering therapy within the first year, 723 (62%) received monotherapy [685 (95%) with metformin], and 133 (12%) received more than one drug. Predictors of receiving any vs. no therapy and combination vs. monotherapy were: age < 40 years [RR: 1.29 (95% CI: 1.16-1.44) and 3.60 (95% CI: 2.36-5.50)]; high Charlson Comorbidity Index [RRs: 1.20 (95% CI: 1.05-1.38) and 2.08 (95% CI: 1.16-3.72)]; central obesity [RRs: 1.23 (95% CI: 1.04-1.44) and 1.93 (95% CI: 0.76-4.94)]; fasting blood glucose of ≥ 7.5 mmol/l [RRs: 1.25 (95% CI: 1.10-1.42) and 1.94 (95% CI: 1.02-3.71)]; and HbA1c ≥ 59 mmol/mol (≥ 7.5%) [RR: 1.26 (95% CI: 1.20-1.32) and 2.86 (95% CI: 1.97-4.14)]. Weight gain ≥ 30 kg since age 20, lack of physical exercise and C-peptide of < 300 pmol/l also predicted therapy. CONCLUSIONS: Comorbidity, young age, central obesity and poor baseline glycaemic control are important predictors of therapy one year after Type 2 diabetes mellitus debut.

Nuclear magnetic resonance metabolomic profiling of Day 3 and 5 embryo culture medium does not predict pregnancy outcome in good prognosis patients: a prospective cohort study on single transferred embryos.

STUDY QUESTION: Does the metabolomic profile, obtained with nuclear magnetic resonance (NMR), of spent culture media from human embryos correlate with reproductive potential in a cohort of good prognosis patients? SUMMARY ANSWER: In a large cohort of single transferred blastocysts from a homogeneous group of good prognosis patients, we find a high degree of individual variation in the metabolome that, however, has no relation to pregnancy outcome. WHAT IS KNOWN ALREADY: Differences among various specific metabolites have been linked to reproductive potential. Although results from retrospective near infrared (NIR) spectroscopy analyses of spent culture medias from transferred embryos were promising, randomized controlled trials were unable to demonstrate that NIR analysis improved pregnancy rates. Therefore, a more detailed investigation of the relation between embryo metabolism and reproductive potential is required. NMR is a powerful technique that provides detailed structural and dynamic information. STUDY DESIGN, SIZE, DURATION: A prospective cohort study was conducted at the Fertility Clinic, Aarhus University Hospital between February 2011 and July 2012. Infertile patients aged <38 years without endometriosis were offered participation and their embryos were included if greater than or equal to eight oocytes were retrieved. In total, 161 infertile patients were included in the cohort. PARTICIPANTS/MATERIALS, SETTING, METHODS: Spent culture media was collected on Days 3 and 5 after oocyte retrieval from 148 single transferred embryos. NMR spectra were obtained from 12 µl of spent media. Data were quantitatively analysed using multivariate analysis with respect to pregnancy outcome, defined as a live fetus by ultrasound in gestational Week 8, along with patient and treatment related variables such as embryo score, age, BMI, fertilization method and cause of infertility. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 148 cycles were included in the analysis [embryo transfer cancelled (n = 12), no media collected (n = 1)]. Clinical pregnancy was confirmed in 47 patients (32%). We obtained high quality NMR spectra for 141 Day 3 and 137 Day 5 samples. Our spectra show a high degree of individual variation. Multivariate data analysis was performed on spectral data with several different pre-processing combinations, i.e. binning, alignment, normalization and scaling in the attempt to develop a valid prediction model. Different strategies of multivariate analysis showed, however, no correlation between the NMR profiles and pregnancy outcome, patient or treatment characteristics. No model could therefore be developed for prediction of pregnancy outcome. We conclude that within this group of good prognosis patients, large-scale metabolic variations between embryos detected with NMR have no apparent association with pregnancy outcome. LIMITATIONS, REASONS FOR CAUTION: Although this study is the largest we know of using NMR to investigate metabolomic profiles of single-transferred embryos, there may be differences that would be detected with a larger study. When analysing such a small sample volume, even small variations in the amount of media and dilution may introduce a large uncertainty in the results. WIDER IMPLICATIONS OF THE FINDINGS: Our study questions the usefulness of the entire metabolome for embryo selection, which should direct the search for viability markers in the culture media towards individual components. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by Aarhus University, the Lippert Foundation, the Toyota Foundation, the Aase og Einar Danielsen foundation. Research at the Fertility Clinic, Aarhus Universtity Hospital is supported by an unrestricted grant from MSD and Ferring. The authors declare no competing interest. TRIAL REGISTRATION NUMBER: NCT01139268.

Rough-Form Lipopolysaccharide Increases Apoptosis in Human CD4⁺ and CD8⁺ T Lymphocytes.

Immunosuppression induced by lymphocyte apoptosis is considered an important factor in the pathogenesis of sepsis and has been demonstrated in both animal models of lipopolysaccharide (LPS)-induced endotoxemia and septic patients. As rough-form LPS (R-LPS) has recently been shown to elicit a stronger immunological response than regular smooth-form LPS (S-LPS), we aimed to assess the apoptosis-inducing capabilities of R-LPS in different subsets of lymphocytes (CD4(+) T cells, CD8(+) T cell, B cells and NK cells). Using multicolour flow cytometry on human peripheral blood mononuclear cells, we found that R-LPS increased apoptosis in CD4(+) and CD8(+) T cells assessed by annexin V and propidium iodide (AV(+) PI(-)), compared with both S-LPS-stimulated and unstimulated cells. 7-Amino-actinomycin D and staining for intracellular active caspase-3, which are considered later signs of apoptosis, did not reveal the same results. Both forms appeared to inhibit apoptosis in B cells, but no LPS-form-specific effect was seen on B or NK cells. Our results indicate that R-LPS induces a stronger AV(+) PI(-)-assessed apoptotic response in T cells than S-LPS. Our findings emphasize the importance of T cell apoptosis in endotoxemia and advocates for control of LPS form in both endotoxemia research and clinical trials with Gram-negative infections.

Scope insensitivity in contingent valuation studies of health care services: should we ask twice?

The main purpose of the present study was to test for outcome scope insensitivity. Respondents were initially asked to value one of two severe health states by way of a time-trade-off (TTO) exercise. Subsequent to the TTO exercise all respondents were asked to value an intervention, which offered a reduction in risk of falling into the health state they had evaluated. All respondents were subsequent to this initial CV exercise asked to value the same risk reduction, but in this case the outcome was death. Although our study passes the internal scope test, there is not a high degree of sensitivity to outcome. As many as 68% of respondents stated an identical maximum WTP in first and second CV valuation exercise implying that they value the interventions equally despite the fact that the health state presented in the initial CV question was deemed far better than death according to the TTO responses given by the same respondents. In contrast, the external scope test (comparison of response to initial CV across study arms) fared much better.

Factors related to pain during routine photodynamic therapy: a descriptive study of 301 patients.

BACKGROUND: Pain may be a limiting factor in the use of photodynamic therapy (PDT). The consequences of the pain i.e. the resources spent on pain-intervention during routine PDT therapy are poorly described. OBJECTIVES: To describe the consequences of pain during PDT by describing the use of pain-reducing interventions in routine use. We studied the frequency as well as level of pain-reducing intervention. METHODS: Descriptive data from PDT treated patients. The level of pain-reducing intervention was graded 0, no intervention; +, cold water spray and ++, pause or nerve block. RESULTS: Data from 983 PDT treatments on 579 lesions distributed on 301 patients: 56% did not require pain-reducing intervention, 35% required spraying of cold water, while 9% required pause or nerve block. Ordinate logistic regression revealed an association between lesion size and pain-reducing intervention: the larger the lesion, the more frequent the intervention. Lesion size did not, however, appear associated with the level of intervention. Intervention was most frequently required when treating the scalp/forehead and the extremities. The scalp/forehead also required the highest level of intervention. No significant association between pain-reducing intervention and diagnosis, pre-treatment, gender or age was found. CONCLUSIONS: Pain-reducing intervention was required in 44% of the PDT treatments. Intervention was particularly required when treating lesions in areas suited for PDT therapy for cosmetic reasons such as the scalp/forehead or extremities. Treatment of large areas more frequently calls for pain intervention than treatment of small areas.

Time gating of heralded single photons for atomic memories.

We demonstrate a method for time gating the standard heralded cw spontaneous parametric downconverted single-photon source by using pulsed pumping of an optical parametric oscillator below threshold. The narrow bandwidth, high purity, high spectral brightness, and pseudodeterministic character make the source highly suitable for light-atom interfaces with atomic memories.

High purity bright single photon source.

Using cavity-enhanced non-degenerate parametric down-conversion, we have built a frequency tunable source of heralded single photons with a narrow bandwidth of 8 MHz, making it compatible with atomic quantum memories. The photon state is 70% pure single photon as characterized by a tomographic measurement and reconstruction of the quantum state, revealing a clearly negative Wigner function. Furthermore, it has a spectral brightness of ~1,500 photons/s per MHz bandwidth, making it one of the brightest single photon sources available. We also investigate the correlation function of the down-converted fields using a combination of two very distinct detection methods; photon counting and homodyne measurement.

Phospho-imaging as a tool for visualization and noninvasive measurement of P transport dynamics in arbuscular mycorrhizas.

• A new method is described for monitoring hyphal 32 P transport in compartmented, monoxenic mycorrhizal root cultures. Nondestructive time-course measurements of P transport in hyphae were obtained by capturing digital autoradiograms on P-imaging screens, and comparing with growth observed by optical scanning. 32 P distribution measured by densitometry on the day of harvest closely agreed with values obtained by liquid scintillation counting after destructive harvest. • Virtually all labeled PO4 was absorbed by arbuscular mycorrhizal (AM) hyphae, but transfer to the roots appeared to be incomplete. P transport was not unidirectional towards the roots, as 32 P was also transported from the root compartment to the hyphal compartment. Net P flux rates were calculated for hyphae crossing between compartments, taking bidirectional flow into account. • Amounts of transported P were poorly correlated with extra-radical hyphal length and root d. wt, but highly correlated with the number of hyphae crossing the barrier separating the two compartments. Such correlations were highest when only hyphae with detectable protoplasmic streaming were considered. • The method was tested using radiolabeled P sources, H2 PO4 - and cytidine triphosphate (CTP), and the AM fungi, Glomus intraradices and G. proliferum. Fungal transport of 32 P from CTP was much slower than from PO4 for both fungi.

[Residual metastases from testicular cancer. CT as a diagnostic and strategic adjuvant]. / Restmetastaser fra cancer testis. CT som diagnostisk og strategisk adjuvans.

Forty-nine young males with advanced testicular cancer treated between March 1982 and June 1989 comprised a 49/588 (8%) subgroup with distant metastases to the retroperitoneum, mediastinum and lungs, and required mandatory surgery on basis of the risk for reactivation of "slumbering" malignant components in tumor tissue temporarily inactivated by chemotherapy and/or radiotherapy. Preoperative CAT-scan was carried out with the intention of mapping regional pathology related to the size, number, burden of the tumor tissue, and the occasional and prognostic ominous invasion of the great vessels. Regarding radical surgery, the positive predictive value of CAT-scan was found to be 33/34 (97%). The negative predictive value was 5/15 (33%) and was interpreted as an expression of the radiologist's cautious assessment. 14/49 (29%) died before March 1990. Poor prognosis was related to invasion of major vessels and was found in 14 patients of whom eight died. It seems established that CAT-scan presents an extremely valuable preoperative investigation when it comes to planning of surgical strategy in a patient population with testicular cancer metastases with difficult access.

[Acute porphyria and multiple organ failure during treatment with lamotrigine]. / Akut porfyri og multiorgansvigt under behandling med lamotrigin.

A 38-year-old female suffered from an acute porphyric attack, multi-organ failure and disseminated intravascular coagulation (DIC) within two weeks of starting lamotrigine, a new antiepileptic drug. The porphyric attack was characterized by excess urinary excretion of aminolevulinic acid (ALA), porphobilinogen (PBG) and coproporphyrin III, a pattern similar to that seen in hereditary coproporphyria, however the diagnostic criteria for this specific porphyria were not fulfilled. We suggest that the observed clinical picture represents a rare adverse reaction to lamotrigine.

[Incapacitating angina pectoris treated with electric stimulation of the spinal cord]. / Invaliderende angina pectoris behandlet med elektrisk rygmarvsstimulation (ERS).

Thirty patients who had severe incapacitating angina pectoris which had not reacted to the conventional therapeutic measures and which required massive daily opioid consumption were treated with electrical spinal cord stimulation (SCS) by means of a completely implantable stimulation system. The therapeutic effect was good in 87% of the patients who experienced considerably reduced frequency of attacks and markedly reduced opioid consumption (p less than 0.00005). Nine of the patients could reduce opioid consumption and 14 out of 27 could cease their otherwise daily opioid consumption. In four patients, the therapeutic effect was unsatisfactory. In the first 22 patients in whom a unipolar electrode was introduced, displacement of the electrode and subsequent reoperation was a frequent problem. This problem disappeared after change to multipolar electrodes as slight changes in placing of the electrode could easily be compensated for via the external programming equipment. This investigation reveals that SCS is a good therapeutic alternative for this selected patient category.

[Endocarditis--clinical picture of native valve infection]. / Endocarditis--klinisk billede ved infektiøs affektion af native klapper.

In a population of 930,000 inhabitants all records of native valve infective endocarditis diagnosed in the decade 1980-89 were reviewed. One hundred and thirty-two cases were found, of whom 23 were not diagnosed until postmortem. Median prehospital duration of symptoms was 20 days (range 0-180) and median in-hospital diagnostic delay five days (range 0-54). Known cardiac disease was found in 42%, possible portal of entry in 33%, but in 36% no predisposing factors were found. During the clinical course 55% experienced cardiac failure and 17% embolic episodes. Surgery was required in 19 patients. Of 111 culture positive cases, streptococci were found in 61 and staphylococci in 45 cases. Overall mortality was 33% with a mortality of clinically diagnosed cases of 18%. Native valve endocarditis is thus associated with a significant mortality in part due to significant diagnostic delays and a large number of post-mortem diagnosed cases. Only by securing a high level of alertness towards endocarditis can we expect a reduced mortality.