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Abstract Background Reviews of the literature on the health and work environment of ambulance personnel have indicated an increased risk of work-related health problems in this occupation. The aim of this study was to compare health status and exposure to different work environmental factors among ambulance personnel and the core work force in Denmark. In addition, to examine the association between physical and psychosocial work environment factors and different measures of health among ambulance personnel. Methods Data were taken from a nationwide sample of ambulance personnel and fire fighters (n = 1,691) and was compared to reference samples of the Danish work force. The questionnaire contained measures of physical and psychosocial work environment as well as measures of musculoskeletal pain, mental health, self-rated health and sleep quality. Results Ambulance personnel have half the prevalence of poor self-rated health compared to the core work force (5% vs. 10%). Levels of mental health were the same across the two samples whereas a substantially higher proportion of the ambulance personnel reported musculoskeletal pain (42% vs. 29%). The ambulance personnel had higher levels of emotional demands and meaningfulness of and commitment to work, and substantially lower levels of quantitative demands and influence at work. Only one out of ten aspects of physical work environment was consistently associated with higher levels of musculoskeletal pain. Emotional demands was the only psychosocial work factor that was associated with both poorer mental health and worse sleep quality. Conclusions Ambulance personnel have similar levels of mental health but substantially higher levels of musculoskeletal pain than the work force in general. They are more exposed to emotional demands and these demands are associated with higher levels of poor mental health and poor sleep quality. To improve work environment, attention should be paid to musculoskeletal problems and the presence of positive organizational support mechanisms that can prevent negative effects from the high levels of emotional demands.

The current study presents preliminary efficacy findings of a pilot randomized controlled trial of Positive Change © ( +Change © ). +Change © utilizes personalized normative feedback to target alcohol use, sexual assault (SA) victimization, SA perpetration, and bystander intervention tailored for heterosexual cisgender men, heterosexual cisgender women, and sexual and gender-minoritized (SGM) groups. Participants included 165 undergraduate students aged 18 to 25 years old from a large public university in the Southwestern U.S. who engaged in past month heavy episodic drinking. Participants (57 cisgender heterosexual men; 54 cisgender heterosexual women; and 54 SGM) were randomized to +Change © ( n  = 83) or an assessment-only control ( n  = 82) and completed surveys online at baseline and 3-month follow-up in a parallel design with a 1:1 ratio (NCT04089137). The current study presents the secondary outcomes of the pilot randomized controlled trial which include alcohol use, SA victimization, SA perpetration, and bystander intervention behavior. +Change © was associated with significantly less severe SA victimization and more bystander intervention behavior at 3-month follow-up relative to the control. There were no significant differences between conditions in alcohol use at 3-month follow-up, however, the magnitude of decreases in drinking in the +Change © condition in this pilot study were consistent with other personalized normative feedback interventions. The present study was unable to assess differences in SA perpetration due to low base rates. No adverse effects among those receiving the intervention were observed. Findings suggested that +Change © may be a feasible strategy to prevent SA, by reducing student SA victimization and increasing bystander intervention. A fully powered randomized clinical trial is needed to examine the effects of +Change © ., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Background: During shortages, elastomeric half-mask respirators (EHMRs) are an alternative to reusing N95 filtering facepiece respirators but require between-use disinfection. The objectives of this study were to (a) measure microbial reductions on EHMR surfaces under laboratory conditions by a standardized procedure using wipes impregnated with health care disinfectants and to (b) measure microbial reductions on EHMRs disinfected by volunteer health care providers., Method: We inoculated EHMR (Honeywell model RU8500) surfaces with Pseudomonas aeruginosa, Bacillus atrophaeus spores, and bacteriophages MS2 and Φ6, and disinfected them using two wipes with hydrogen peroxide (HP), alcohols, and quaternary ammonium compounds (QACs). Then, we randomized 54 volunteer subjects into three groups (Group 1: two wipes with instructions, Group 2: five wipes with instructions, Group 3: no instructions or set number of wipes) and used 0.5% HP wipes without precleaning on EHMRs inoculated with Raoultella terrigena and MS2., Findings: The laboratory study demonstrated that all organisms achieved at least 4 log 10 median reductions (HP>QAC/alcohol>QAC>QAC/saline). Pseudomonas was highly susceptible to HP and QAC/alcohol and Φ6 to all disinfectants. MS2 reduction was highest using HP and lowest using QAC/saline. Bacillus was least susceptible. The volunteer study showed a 3 to 4 log 10 average reductions of bacteria and virus; Raoultella reductions were greater than MS2, with variability within and between subjects. Conclusions : HP disinfectant wipes used in laboratory and by volunteers reduce bacteria and viruses on EHMRs by 3 to 4 log 10 on average., Implications for Practice: Commercially available hospital disinfectant wipes reduce bacteria and viruses on EHMRs and can fill the need for between-use disinfection. HP and combination QAC/alcohol have the greatest efficacy under our test conditions., Competing Interests: Conflict of InterestThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: There is growing interest in use of transcutaneous spinal stimulation (TSS) for people with neurologic conditions both to augment volitional control (by facilitating motoneuron excitability), and to decrease spasticity (by activating inhibitory networks). Various electrode montages are used during TSS, with little understanding of how electrode position influences spinal circuit activation. We sought to identify the thoracolumbar electrode montage associated with the most robust activation of spinal circuits by comparing posterior root-muscle reflexes (PRM reflexes) elicited by 6 montages. Additionally, we assessed tolerability of the stimulation during PRM reflex testing., Methods: Fifteen adults with intact neurological systems participated in this randomized crossover study. PRM reflexes were evoked transcutaneously using electrode montages with dorsal-ventral (DV) or dorsal-midline (DM) current flow. DV montages included: [1] cathode over T11/T12, anodes over iliac crests (DV-I), [2] cathode over T11/T12, anodes over umbilicus (DV-U), [3] dual paraspinal cathodes at T11/12, anodes over iliac crests (DV-PI), and [4] dual paraspinal cathodes at T11/12, anodes over umbilicus (DV-PU). DM montages included: [5] cathode over T11/12, anode 5cm caudal (DM-C), and [6] cathode over T11/12, anode 5cm rostral (DM-R). PRM reflex recruitment curves were obtained in the soleus muscle of both lower extremities., Results: DV-U and DV-I montages elicited bilateral reflexes with lower reflex thresholds and larger recruitment curve area than other montages. There were no differences in response amplitude at 120% of RT(1.2xRT) or tolerability among montages., Conclusions: Differences in spinal circuit recruitment are reflected in the response amplitude of the PRM reflexes. DV-I and DV-U montages were associated with lower reflex thresholds, indicating that motor responses can be evoked with lower stimulation intensity. DV-I and DV-U montages therefore have the potential for lower and more tolerable interventional stimulation intensities. Our findings optimize electrode placement for interventional TSS and PRM reflex assessments., Competing Interests: Competing Interests: Author ECF-F serves as a consultant to the medical device company ONWARD Inc.

Suicide is a serious public health problem in the United States. Alcohol use has been substantially documented as a risk factors for suicide, yet it is unclear how alcohol is associated with suicidal ideation (SI) and behavior (SIB) at the event level. We examined the association between alcohol use and SI using a mixed methods approach that included daily assessments from 13 adults who engage in heavy episodic drinking with current SI and qualitative interviews among 12 of those adults. Participants were recruited on social media. Separate mixed effects logistic regression models indicated that individuals' alcohol use on a given day was associated with SI (OR = 1.37), and suicidal urges (OR = 1.41). Adjusting for repeated measures, the expected marginal mean for intensity of SI (EMM = 3.33) and urges (EMM = 2.94) were higher on days with reported drinking behavior than days without reported drinking (EMM = 2.68 and EMM = 2.62 respectively). Qualitative data indicated that the association between alcohol use and SIB is more complex than a single directionality. Instead, the association can be unidirectional, bidirectional, and/or dependent on factors including mental health and amount of alcohol consumed. Overall, these findings emphasize a need for integrated alcohol and SIB interventions while providing insight on possible daily, just-in-time adaptations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Rheumatoid arthritis (RA) poses a significant health burden, with patients facing a twofold higher risk of cardiovascular diseases compared to the general population. As a results, the international recommendations set forth by the European Alliance of Associations for Rheumatology, advocate for a structured cardiovascular (CV) risk management and adherence to a healthy lifestyle for patients with RA. Unhealthy lifestyle factors not only impact overall health but also worsen inflammation and hinder treatment response in patients with RA Despite these recommendations, there remains a knowledge gap regarding patients' attitudes towards screening participation and lifestyle changes. Therefore, the aims of this study were firstly to explore the perspectives of patients with rheumatoid arthritis on participation and adherence to cardiovascular screening. Secondly, to explore patients' perspectives on lifestyle changes., Methods: Semi-structured interviews based on a hermeneutic approach were conducted. The analysis was guided by qualitative content analysis, employing an inductive approach., Results: Nine women and seven men, aged 47 to 76 years, diagnosed with RA, and who had attended at least one CV screening session, took part in the study. Two primary themes, along with four sub-themes, emerged from the analysis. The first main theme, Accepting an offer, encompassed the sub-themes of Engagement in the screening consultation and Risk awareness, reflecting participants' views on their involvement in, and commitment to, CV screening. The second theme pertained to participants' perspectives on lifestyle changes: Living with a chronic disease and embracing changes, described through the sub-themes of Motivation for lifestyle changes and Strategies to achieve lifestyle changes., Conclusion: Motivations for taking part in the screening differed among the participants, ranging from simply accepting an invitation to joining as a proactive precaution. In general, there was unanimous agreement among the participants that the screening proved to be a positive encounter. While it may not have immediately prompted significant lifestyle alterations, it did enhance their awareness of risks and underscored the significance of maintaining a healthy lifestyle. Overall, the individual guidance and support for patients with rheumatoid arthritis should entail awareness of CV risk combined with support to lifestyle changes the participants want to pursue., (© 2024. The Author(s).)

Young women living in Kampala, Uganda, often face adversities related to Social Determinants of Mental Health (SDoMH) including poverty, food scarcity, environmental stressors such as high levels of community violence, and lack of adequate healthcare access. Two consecutive pilot studies were conducted to assess the feasibility and acceptability of survey questions, wearable fitness trackers, and daily diaries before launching a larger prospective cohort study. Preliminary associations between SDoMH factors with depressive symptoms, stress levels, and life satisfaction were examined among the total sample of 60 women across two pilot studies. A total of 32.2% of respondents (out of n = 59) reported being depressed most or all of the time in the past 30 days. Frequent depressive symptoms correlated with food insecurity (χ2 = 5.38, df = 1, p = 0.02). Higher stress levels were significantly associated with lower overall life satisfaction scores ( t = 2.74, df = 6.20, p = 0.03). Additionally, frequent depressive symptoms were associated with lower satisfaction scores in the living conditions and lifestyle domain ( t = 2.22, df = 36.18, p = 0.03). However, overall life satisfaction scores and other domains (social relationships and personal independence) were not statistically associated with frequent depressive symptoms. Identifying the most impactful SDoMH factors among young women in Kampala can inform targeted approaches to improve mental health outcomes.

Access to sexual health education, such as education on sexual consent, is limited in the US. Artificial intelligence (AI), such as ChatGPT, provides a potential opportunity to increase access to sexual consent information and education. However, what ChatGPT knows about sexual consent and if this aligns with the current evidence-based literature on sexual consent is unclear. The goal of this research commentary was to explore what ChatGPT knows about sexual consent with a focus on: 1) the definition of consent, 2) how consent could be communicated, and 3) the impact that substances have on consent. We also examined the reliability of ChatGPT's responses by having three different researchers ask ChatGPT the same set of questions. Across our questions, ChatGPT provided similar and comprehensive responses that discussed key features of consent - that consent is freely given or reversible. ChatGPT provided examples of different verbal and nonverbal cues people can use to communicate and interpret consent and discussed the ways that substances can impact consent communication. Overall, ChatGPT could be a potential resource for educators and young people who seek information about sexual consent; however, we should proceed with caution. ChatGPT is not a replacement for an educator but rather a way to increase access to education.

The purpose of this study was to evaluate in vivo endothelial function and nitric oxide (NO)-dependent vasodilation between women in either menstrual or placebo pill phases of their respective hormonal exposure [either naturally cycling (NC) or using oral contraceptive pills (OCPs)] and men. A planned subgroup analysis was then completed to assess endothelial function and NO-dependent vasodilation between NC women, women using OCP, and men. Endothelium-dependent and NO-dependent vasodilation were assessed in the cutaneous microvasculature using laser-Doppler flowmetry, a rapid local heating protocol (39°C, 0.1 °C/s), and pharmacological perfusion through intradermal microdialysis fibers. Data are represented as means ± standard deviation. Men displayed greater endothelium-dependent vasodilation (plateau, men: 71 ± 16 vs. women: 52 ± 20%CVC max , P < 0.01), but lower NO-dependent vasodilation (men: 52 ± 11 vs. women: 63 ± 17%NO, P = 0.05) compared with all women. Subgroup analysis revealed NC women had lower endothelium-dependent vasodilation (plateau, NC women: 48 ± 21%CVC max , P = 0.01) but similar NO-dependent vasodilation (NC women: 52 ± 14%NO, P > 0.99), compared with men. Endothelium-dependent vasodilation did not differ between women using OCP and men ( P = 0.12) or NC women ( P = 0.64), but NO-dependent vasodilation was significantly greater in women using OCP (74 ± 11%NO) than both NC women and men ( P < 0.01 for both). This study highlights the importance of directly quantifying NO-dependent vasodilation in cutaneous microvascular studies. This study also provides important implications for experimental design and data interpretation. NEW & NOTEWORTHY This study supports differences in microvascular endothelial function and nitric oxide (NO)-dependent vasodilation between women in low hormone phases of two hormonal exposures and men. However, when separated into subgroups of hormonal exposure, women during placebo pills of oral contraceptive pill (OCP) use have greater NO-dependent vasodilation than naturally cycling women in their menstrual phase and men. These data improve knowledge of sex differences and the effect of OCP use on microvascular endothelial function.

Background: The percentage of Neisseria gonorrhoeae (GC) isolates with resistance or elevated minimum inhibitory concentrations to antimicrobials has steadily increased. Current estimates are based on the Gonococcal Isolate Surveillance Project (GISP), a sentinel surveillance study of male GC in the United States. This analysis seeks to assess for adjustment before treating aggregated GISP estimates as nationally representative of all reported male urogenital infections., Methods: We used multilevel regression with poststratification (MRP) to compute national estimates of the proportion of antimicrobial resistance (AMR) (defined as exceeding minimum inhibitory concentration thresholds) in male GC using data from 2008 to 2018 GISP and case reports. Sensitivity analyses investigated the impact of analysis assumptions and unmeasured variables. We additionally produced estimates of 2018 AMR GC cases among US men., Results: National estimates were consistent with unweighted estimates. The estimated proportion of incident AMR GC infections in men with urogenital GC in 2018 was 51.5% (95% confidence interval [CI], 50.1%-52.9%), equating to an estimated 366,300 incident AMR GC infections in US men aged 15 to 39 years. Estimates of AMR for tested antimicrobials in male GC infections in 2018 ranged from 0.16% (95% CI, 0.08%-0.24%) for ceftriaxone to 29.9% (95% CI, 28.6%-31.1%) for ciprofloxacin. Sensitivity analyses revealed that unmeasured data on sex of sex partners could substantially impact weighted estimates., Conclusions: Antimicrobial resistance among reported incident male urogenital GC infections remains rare for ceftriaxone, the current standard of care. Aggregated GISP data are generally representative of men in the US who are reported with urogenital gonorrhea., Competing Interests: Conflicts of Interest: Office of Management and Budget/Centers for Disease Control and Prevention Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention., (Copyright © 2022 American Sexually Transmitted Diseases Association. All rights reserved.)

New Findings: What is the main observation in this case? The main observation of this case report is substantial improvement in cutaneous microvascular endothelial function after cessation of long-term use of a fourth-generation oral contraceptive pill. This improvement appears independent of relative changes in the contribution of nitric oxide. What insights does it reveal? Our findings suggest that cessation of long-term, fourth-generation oral contraceptive pill use improves endothelial function within 20 months of cessation., Abstract: The purpose of this case report was to evaluate in vivo endothelial function and nitric oxide (NO)-dependent vasodilatation before and after the cessation of long-term (11-12 years) fourth-generation oral contraceptive pill (OCP) use in one young, healthy and premenopausal woman. This retrospective analysis includes data from six experimental visits: three visits during months 133-144 of fourth-generation OCP use and three visits 19-22 months after OCP cessation. Endothelium-dependent and NO-dependent vasodilatation were assessed in the cutaneous microvasculature using laser-Doppler flowmetry, a rapid local heating protocol (39°C, 0.1°C/s) and pharmacological perfusion through intradermal microdialysis fibres. The participant had consistent medical history and lifestyle behaviours throughout both hormonal exposures. Data are presented as the mean (SD). Endothelium-dependent vasodilatation was 42 (10)% of site-specific maximal cutaneous vascular conductance (CVC max ) during OCP use and 63 (10)%CVC max after OCP cessation (49% increase). Nitric oxide-dependent vasodilatation was 70 (5)% contribution of NO during OCP use and 60 (15)%NO after OCP cessation (15% reduction). Baseline blood flow was greater after OCP cessation, but maximal blood flow was reduced. Data from this case report support a substantial increase in cutaneous microvascular endothelial function assessed via local heating after cessation of long-term use of a fourth-generation OCP, which does not appear to be attributable to increased NO bioavailability. Overall, these data suggest an improvement in endothelial and microvascular function after the cessation of long-term use of a fourth-generation OCP., (© 2022 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.)

The lifespan of humans varies greatly between individuals. Here, we aimed to explore what biological roles miRNAs may have on old age mortality-variation. Circulating miRNAs were measured in plasma from 43 monozygotic twin pairs (73-95 years of age) and mortality analyses were applied using Cox regression survival analyses and linear regression analyses of lifespan. In general, nominally significant miRNAs were mainly upregulated with shorter lifespan, both in Cox analysis (72 % upregulated) and in linear regression analysis (81 % upregulated). A total of 29 miRNAs were associated to mortality at a nominal significance level (p < 0.05) in the survival analysis, but no miRNAs passed the FDR adjusted level of significance. Seven of the 29 miRNAs; hsa-miR-140-3p, hsa-miR-16-5p, hsa-miR-487b-3p, hsa-miR-19a-3p, hsa-let-7d-5p, hsa-miR-320a, hsa-miR-375, were nominally significant across two linear twin-paired analyses and the cox analysis. Pathway analyses of the 29 nominally significant miRNAs from the individual level analyses resulted in two nominally significant associated Reactome pathways (unadjusted p < 0.05); 'Negative regulation of FGFR signaling' and 'Neurotransmitter receptor binding and downstream transmission in the postsynaptic cell', and two significantly associated KEGG pathways; 'Linoleic acid metabolism' and 'Toxoplasmosis'. Additional pathway analyses and results of previous studies support that miRNAs linked to mortality at age 70 years or older play a role in lipid metabolism, tissues maintenance and morphology., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Behavioral science researchers are increasingly collecting detailed location data such as second-by-second GPS tracking on participants due to increased ease and affordability. While intraindividual variability has been discussed in the travel literature for decades, traditional methods designed for studying individual differences in central tendencies limit the extent to which novel questions about variability in lived experiences can be answered. Thus, new methods of quantifying behavior that focus on intraindividual variability are needed to address the context in which the behavior occurs and the location tracking data from which behavior is derived., Methods: We propose deviations from typical paths as a data processing technique to separate individual-level typical travel behavior from a location tracking data set in order to highlight atypical travel behavior as an outcome measure., Results: A simulated data example shows how the method works to produce deviation measures from a location dataset. Analysis of these deviations offers additional insights compared to traditional measures of maximum daily distance from home., Conclusions: This process can be integrated into larger research questions to explore predictors of atypical behavior and potential mechanisms of behavior change., (© 2022. The Author(s).)

Background and Objectives: Research has not yet investigated how the association between alcohol and alcohol-related consequences differs across cisgender heterosexual women (CHW), cisgender heterosexual men (CHM), and sexual and gender minority (SGM) college students., Methods: Participants were N = 754 college students (34.5% CHW [n = 260]; 34.5% CHM [n = 260]; 31.0% SGM [n = 234]) between the ages 18 and 25 who completed a survey on sexual orientation, gender identity, alcohol use (i.e., average drinks per week), and alcohol-related consequences., Results: Among individuals who reported alcohol use, CHM reported significantly more drinks per week compared to CHW and SGM. The logistic model of a zero-inflated negative binomial regression indicated that excess zeros in the alcohol-related consequences were more likely among (1) nondrinkers and (2) SGM compared to CHM. The count portion of the model indicated that, among drinkers, there was a positive association between drinks per week and alcohol-related consequences. Estimated alcohol-related consequences per drink were 1.90% higher among CHW than CHM and 2.76% higher among SGM than CHM. Exploratory analyses did not find significant differences in outcomes between cisgender female and male sexual minority students., Discussion and Conclusion: Findings suggest that although CHW and SGM students consume less alcohol than CHM, these students experience more alcohol-related consequences per drink., Scientific Significance: This study advances the field's knowledge of alcohol use patterns and consequences among SGM college students. There is a need for alcohol education programming that is tailored to the unique experiences, identities, and minority stressors of SGM college students., (© 2022 American Academy of Addiction Psychiatry.)

Background and Objectives: Hand arthritis can limit upper-limb instrumental activities of daily living (IADLs) and require the recruitment of additional cognitive and motor resources to support performance. We devised a dual-task protocol for dishwashing to examine cognitive-motor performance costs and prioritizations under increased demands, processes of adaptation, and individual differences in performance costs., Research Design and Methods: Sixty women with hand arthritis (aged 60-91) completed a standardized dishwashing protocol. Motor demand was increased via the properties of the soap dispenser. Cognitive demand was increased using audial attention and response inhibition tasks. The protocol was completed twice per lab visit on 3 occasions. Response time and dishwashing time provided measures of cognitive and motor task performance. Prioritization was determined by comparing the magnitude of dual-task cost (DTC) across tasks. Adaptation to the dishwashing protocol and novel dispenser was assessed by change in DTC across lab visits. Individual differences in cognitive and physical ability were assessed with the trail making B test and gait speed., Results: Estimates from linear mixed-effects models revealed that response time increased, whereas dishwashing time decreased, during the dual-task study stages. Cognitive-motor prioritization effects were most pronounced among women with lower cognitive and physical ability. Evidence of prioritization and individual differences in DTC diminished across lab visits., Discussion and Implications: The pattern of results suggests that older women with arthritis prioritize the motor over cognitive components of dishwashing, a common IADL. Adaptation across lab visits resulted in improved performance, reduced evidence of prioritization, and attenuated differences in DTC across physical and cognitive abilities., (© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.)

Aim: Diabetic foot ulcer (DFU) is a major complication of both Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D); however research into risk factors for DFU does not separate between these two types. The purpose of the present investigation was to identify risk factors for development of first time DFU (FTDFU) over a period of 15 years in patients with T1D and T2D separately., Methods: This retrospective cohort study included 25,220 feet from 5588 patients with T1D and 7113 patients with T2D treated in the period 2001-2015. Data on baseline characteristics and comorbidities were collected from electronic patient records. Influences of various risk factors for the development of FTDFU were assessed by hazard ratios (HR) from Cox proportional hazard regression models on time from enrolment to FTDFU diagnosis or end-of-follow-up., Results: In T1D independent risk factors were male sex, age >60 years, high HbA1c, long diabetes duration, history of cardiovascular disease, macro-albuminuria, decreased visual acuity, advanced diabetic retinopathy, decreased/absent vibration sense, presence of patient reported symptoms of neuropathy, and absence of foot pulses. In T2D the independent risk factors were the same except age >60 years, a history of cardiovascular disease, and long diabetes duration., Conclusions: This study documents that much of the standard clinical information obtained as part of the routine follow-up are also independent risk factors for development of FTDFU. This may be used to create a basis for in which patient and when prevention should be started., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ice accretion causes damage on power generation infrastructure, leading to mechanical failure. Icephobic materials are being researched so that ice buildup on these surfaces will be shed before the weight of the ice causes catastrophic damage. Lubricated materials have imposed the lowest-recorded forces of ice adhesion, and therefore lubricated materials are considered the state-of-the-art in this area. Slippery lubricant-infused porous surfaces (SLIPS) are one type of such materials. SLIPS are initially very effective at repelling ice, but the trapped fluid layer that affords their icephobic properties is easily depleted by repeated icing/deicing cycles, even after one deicing event. UV-cured siloxane resins were infused into SLIPS to observe effects on icephobicity and durability. These UV-cured polymer networks enhanced both the icephobicity and longevity of the SLIPS; values of ice adhesion below 10 kPa were recorded, and appreciable icephobicity was maintained up to 10 icing/deicing cycles.

Aim: Diabetic foot ulcer (DFU) is a serious complication to diabetes. The aim was to study the incidence of first DFU among patients with type 1 (T1DM) and type 2 diabetes (T2DM), stratified according to etiology: neuropathic, neuro-ischemic or ischemic, over a period of 14years (2001-2014)., Methods: DFU incidence rates were calculated from electronic patient record data from patients with T1DM and complicated T2DM from a large specialized diabetes hospital with a multidisciplinary foot clinic in Denmark. Poisson regression was used to model incidence of first DFU according to calendar year, diabetes type and etiology., Results: Among 5640 patients with T1DM 255 developed a DFU, corresponding to an incidence of 5.8 (95% confidence interval (95%CI) 5.1-6.5) per 1000 patient years; this incidence dropped from 8.1 (95%CI 5.4-11.9) per 1000 patient years in 2002 to 2.6 (95%CI 1.3-5.3) in 2014 (p=0.0059). Among 6953 patients with T2DM 310 developed a DFU, corresponding to an incidence of 11.3 (95%CI 10.1-12.6) per 1000 patient years; this incidence dropped from 17.0 (95%CI 12.2-23.8) per 1000 patient years in 2002 to 8.7 (95%CI 5.3-14.1) per 1000 patient year (p=0.0260) in 2014., Conclusion: The incidence of DFU has decreased substantially in T1DM as well as in T2DM. This change was driven by a decrease in incidence of neuropathic ulcers., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Aim: To study toe ulcer healing in patients with diabetic foot ulcers attending a multidisciplinary foot clinic over a 10 years period., Methods: The study was retrospective, consecutive and observational during 2001 through 2011. The patients were treated according to the International Consensus on the Diabetic Foot. During the period the chiropodist staffing in the foot clinic was doubled; new offloading material and orthopedic foot corrections for recalcitrant ulcers were introduced. Healing was investigated in toe ulcers in Cox regression models., Results: 2634 patients developed foot ulcers, of which 1461 developed toe ulcers; in 790 patients these were neuropathic, in 551 they were neuro-ischemic and in 120 they were critically ischemic. One-year healing rates increased in the period 2001-2011 from 75% to 91% for neuropathic toe ulcers and from 72% to 80% for neuro-ischemic toe ulcers, while no changes was observed for ischemic toe ulcers. Adjusted for changes in the patient population, the overall rate of healing for neuropathic and neuro-ischemic toe ulcers almost doubled (HR=1.95 [95% CI: 1.36-2.80])., Conclusion: The results show that the healing of toe ulcers improved. This outcome could not be explained by changes in the patient characteristics, but coincided with a number of improvements in organization and therapy., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: To map the usage of out-of-office hours acute telephone counselling (ATC) provided by diabetes specialist nurses (n=18) for diabetes patients to explore potentials for improvement., Methods: A mixed methods study involved mapping of ATC-usage during 6 months and a retrospective audit of frequent users., Results: Altogether, 3197 calls were registered that were related to 592 individual patients, corresponding to 10% of the population. Proportionally more users suffered from type 1 diabetes (p<0.001). ATC-users' mean HbA1c was 8.8% (73 mmol/mol) compared to 8.1% (65 mmol/mol) for all patients attending the clinic (p<0.001). Hyperglycaemia was the most frequent reason for calling. The use of ATC likely prevented 15 admissions. More than half of the calls came from general nurses based in the community (n=619) and general nurses and nursing assistants based in care homes (n=1018). The majority (75%) of patients called less than five times. However, 8% called 16 times or more accounting for 52% of all calls. A retrospective audit identified them as physically and/or psychologically fragile patients., Conclusion: Hyperglycaemia was the most frequent reason for calling, and insulin dose adjustment the most frequent advice given., Practice Implications: Frequent users identified need additional support., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We studied the glycaemic threshold and prevalence of diabetic retinopathy in screen-detected diabetes in Saudi Arabia, Algeria and Portugal. The prevalence of diabetes-specific retinopathy started to increase at an HbA1c level of 6-6.4% (42-47 mmol/mol) and in individuals with HbA(1c) >7.0% the prevalence was 6.0%., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Erica tetralix is the key species on NW European wet heathlands, where it is often found to be the dominating plant species. Consequently, it is of considerable concern that the species has decreased significantly in cover from 28% to 18% over a six-year period. In order to understand the underlying causes, a structural equation modeling (SEM) approach was applied on ecological data from 1130 wet heathland plots. Both atmospheric N deposition and soil acidification were included in the SEM. The most important causal effect revealed by the SEM was a significant negative effect of N deposition on the cover of E. tetralix, whereas soil acidity tended to have a negative effect of relatively less importance. There was no significant effect of N deposition on soil pH, which indicates that there are no major indirect effects of N deposition on the cover of E. tetralix mediated by soil acidification., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A syndrome involving acute urinary retention in combination with sacral radiculitis and cerebrospinal fluid pleocytosis was first described by the American neurosurgeon Charles Elsberg in 1931. In many instances the aetiology is herpes simplex virus type 2 (HSV-2) reactivation from sensory neurons. In this case report we present a 34-year-old pregnant woman with previous undiagnosed sensory lumbosacral symptoms. She was hospitalized with HSV-2 meningitis and lumbosacral radiculitis but no genital rash. A week after the onset of symptoms she developed acute urinary retention, thus indicating Elsberg syndrome.

We report observations of disappearance of Erica tetralix in wet heathland, which is unlikely to be caused by competition, as E. tetralix is dying before its place is taken up by other species. To investigate the causes, we used both old and new data. Results showed that presence of Molinia caerulea and Calluna vulgaris were substantial in the former E. tetralix dominated areas. Measurements of the C/N ratio in the morlayer were between 21 and 26 under the E. tetralix stands. As the expected C/N ratio in a healthy nutrient poor ecosystem like the E. tetralix wet heathland is around 30, this indicates that the ratio is probably decreasing and, correspondingly, the probability of nitrogen leaching from the ecosystem is increasing. The morlayer pH was extremely low-between 3.03 and 3.78. This represents a pH decline since the 1960s, where pH values generally were above 4. This supports the hypothesis that the decrease in morlayer pH is the major factor explaining the disappearance of E. tetralix and that measures to increase pH should be considered as part of the recommendations for relevant future management.

A new species has recently invaded coastal dune ecosystems in North West Europe. The native and expansive inland grass, Deschampsia flexuosa, progressively dominating inland heaths, has recently invaded coastal dunes in Denmark, occasionally even as a dominant species. A total of 222 coastal locations with 5,000 random sample plots have been investigated. These findings are in contrast to historical records, and D. flexuosa has never been considered belonging to coastal dune ecosystems. The occurrence of the typical inland grass in the coastal dunes is a strong indication of increase in nutrient level and that human influences may cause a native species to be invasive in new ecosystems. This could be a radical example of change in species composition due to a long lasting exceedance of critical load of nitrogen. The investigation also showed a general increase in cover of the most dominant species.

The effect of atmospheric nitrogen deposition on the species richness of acid grasslands was investigated by combining data from a large Danish monitoring program with a large European data set, where a significant non-linear negative effect of nitrogen deposition had been demonstrated (Stevens et al., 2010). The nitrogen deposition range in Denmark is relatively small and when only considering the Danish data a non-significant decrease in the species richness with nitrogen deposition was observed. However, when both data sets were combined, then the conclusion of the European survey was further corroborated by the results of the Danish monitoring. Furthermore, by combining the two data sets a more comprehensive picture of the threats to the biodiversity of acid grasslands emerge; i.e., species richness in remnant patches of acid grassland in intensively cultivated agricultural landscapes is under influence not only from nitrogen deposition, but also from current and historical land use., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

We report the synthesis of two C4'-modified DNA analogues and characterize their structural impact on dsDNA duplexes. The 4'-C-piperazinomethyl modification stabilizes dsDNA by up to 5°C per incorporation. Extension of the modification with a butanoyl-linked pyrene increases the dsDNA stabilization to a maximum of 9°C per incorporation. Using fluorescence, ultraviolet and nuclear magnetic resonance (NMR) spectroscopy, we show that the stabilization is achieved by pyrene intercalation in the dsDNA duplex. The pyrene moiety is not restricted to one intercalation site but rather switches between multiple sites in intermediate exchange on the NMR timescale, resulting in broad lines in NMR spectra. We identified two intercalation sites with NOE data showing that the pyrene prefers to intercalate one base pair away from the modified nucleotide with its linker curled up in the minor groove. Both modifications are tolerated in DNA:RNA hybrids but leave their melting temperatures virtually unaffected. Fluorescence data indicate that the pyrene moiety is residing outside the helix. The available data suggest that the DNA discrimination is due to (i) the positive charge of the piperazino ring having a greater impact in the narrow and deep minor groove of a B-type dsDNA duplex than in the wide and shallow minor groove of an A-type DNA:RNA hybrid and (ii) the B-type dsDNA duplex allowing the pyrene to intercalate and bury its apolar surface.

Phenylketonuria (PKU) is an inherited metabolic disease characterized by phenylalanine (Phe) accumulation due to defects in the enzyme phenylalanine hydroxylase (PAH). Phe accumulation can lead to cognitive impairment. Some individuals with PKU respond to tetrahydrobiopterin (BH4) treatment, the natural cofactor of PAH, by a reduction in blood Phe concentrations.We tested 12 patients with PKU, 8-29 years of age, all carrying the common Y414C mutation in the PAH gene. Three were homozygous and nine were compound heterozygous, with the second mutation being a putative null mutation. During the study period, genuine protein was increased to approximately 1 g/kg. The patients were treated with 20, 10, and 5 mg BH4/kg/day for 1 week on each dose, starting with 20 mg/kg. A positive response was defined as a decline in blood Phe>30%. Blood Phe was measured four times a week. Nonresponding children were excluded from the study. Eleven of 12 patients had a positive response with 20 mg/kg, 5/10 responded on 10 mg/kg, and 1/9 on 5 mg/kg. Two were late responders, with a response on 20 mg/kg after >48 h. We could confirm the previously reported inconsistent responsiveness of Y414C in the nine heterozygous patients, whereas the three homozygous patients had early median Phe declines of 73%, 51%, and 27%, respectively, on the three different doses. The varying responses despite uniform trial conditions and genotypes may be due to individual differences in BH4 absorption or metabolism. No side effects were observed.

A 5'-C-allylthymidine derivative was prepared from thymidine by the application of a stereoselective allylation procedure and its 5'(S)-configuration was confirmed. From this nucleoside derivative, appropriately protected building blocks were prepared and coupled using standard phosphoramidite chemistry to afford a dinucleotide with two 5'-C-allylgroups. This molecule was used as a substrate for a ring-closing metathesis (RCM) reaction and after deprotection, a 1 : 1 mixture of E- and Z-isomers of a cyclic dinucleotide with an unsaturated 5'-C-to-5'-C connection was obtained. Alternatively, a hydrogenation of the double bond and deprotection afforded a saturated cyclic dinucleotide. An advanced NMR-examination confirmed the constitution of this molecule and indicated a restriction in its overall conformational freedom. After variation of the protecting group strategy, a phosphoramidite building block of the saturated cyclic dinucleotide with the 5'-O-position protected as a pixyl ether and the phosphate protected as a methyl phosphotriester was obtained. This building block was used in the preparation of two 14-mer oligonucleotides with a central artificial bend due to the cyclic dinucleotide moiety. These were found to destabilise duplexes, slightly destabilise bulged duplexes but, to some extent, stabilise a three-way junction in high Mg(2+)-concentrations.

Using UV melting and CD spectroscopy, we show that alpha-l-LNA-modified oligonucleotides possess the ability to form triplexes at pH 6.8 with significantly increased thermostability relative to DNA triplexes.

A study of the internal dynamics of an LNA/DNA:RNA duplex has been performed to further characterize the conformational changes associated with the incorporation of locked nucleic acid (LNA) nucleotides in a DNA:RNA duplex. In general, it was demonstrated that the LNA/DNA:RNA duplex has a very high degree of order compared to dsDNA and dsRNA duplexes. The order parameters of the aromatic carbon atoms in the LNA/DNA strand are uniformly high, whereas a sharp drop in the degree of order was seen in the RNA strand in the beginning of the AUAU stretch in the middle of the strand. This can be related to a return to normal dsRNA dynamics for the central A:U base pair. The high order of the heteroduplex is consistent with preorganization of the chimera strand for an A-form duplex conformation. These results partly explain the dramatic increase in T(m) of the chimeric heteroduplex over dsDNA and DNA:RNA hybrids of the same sequence.

A cyclic dinucleotide with a butylene linker between the upper 2'-C position and the 3'-O-phosphate linkage was synthesised from simple nucleoside building blocks via a tandem ring-closing metathesis and hydrogenation procedure. The major of two phosphorus epimers was incorporated into an oligodeoxynucleotide, as well as into an LNA-DNA mixmer oligonucleotide. These were evaluated as parts in three different secondary structures, a duplex, a bulged duplex and a three-way junction, with both DNA and RNA complements. In the DNA:RNA hybrid molecule, the oligodeoxynucleotide containing this single 2'-C to 3'-O-phosphate butylene linkage was found to stabilise a three-way junction.

LNA is a bicyclic nucleic acid analogue that contains one or more 2'-O,4'-C methylene linkage(s), which effectively locks the furanose ring in a C3'-endo conformation. We report here the NMR solution structure of a nonamer LNA:RNA hybrid and a structural characterization of a nonamer LNA:DNA hybrid, where the LNA strands are composed entirely of LNA nucleotides. This is the first structural characterization of fully modified LNA oligonucleotides. The high-resolution structure reveals that the LNA:RNA hybrid adopts an almost canonical A-type duplex morphology. The helix axis is almost straight and the duplex geometry is regular. This shows that fully modified LNA oligomers can hybridize with complementary RNA and form duplexes within the Watson-Crick framework. The LNA:DNA hybrid structurally resembles an RNA:DNA hybrid as shown by determination of deoxyribose sugar puckers and analysis of NOESY NMR spectra.

Many studies have shown that correlation between clinical asthma status and asthma-specific quality of life is only weak to moderate. However, this relationship has never been explored to determine whether the weakness is due to noise of measurement or whether quality of life is a distinct component of asthma health status. With a database from three clinical trials (n = 763), factor analysis was used to explore the relationships between quality of life, measured by the Asthma Quality of Life Questionnaire (AQLQ), and conventional measures of asthma clinical status (symptoms, airway calibre and rescue beta2-agonist use). The analysis revealed that although patients with severe, poorly controlled asthma tend to have worse quality of life than milder, well-controlled patients, overall asthma health status has four components (factors): asthma-specific quality of life; airway calibre; daytime symptoms and daytime beta2-agonist use, and night-time symptoms and night-time beta2-agonist use. The clean loading of all 21 outcomes onto four distinct and clinically identifiable factors suggests that, although some weakness of correlation between clinical indices and quality of life may be due to noise of measurement, it is mainly attributable to asthma health status being composed of distinct components.

Objectives: Certain milk factors may help to promote the growth of a host-friendly colonic microflora (e.g. bifidobacteria, lactobacilli) and explain why breast-fed infants experience fewer and milder intestinal infections than those who are formula-fed. The effects of supplementation of formula with two such milk factors was investigated in this study., Materials and Methods: Infant rhesus macaques were breast-fed, fed control formula, or formula supplemented with glycomacropeptide (GMP) or alpha-lactalbumin (alpha-LA) from birth to 5 months of age. Blood was drawn monthly and rectal swabs were collected weekly. At 4.5 months of age, 10(8) colony-forming units of enteropathogenic E.coli O127, strain 2349/68 (EPEC) was given orally and the response to infection assessed. The bacteriology of rectal swabs pre- and post-infection was determined by culture independent fluorescence in situ hybridization., Results: Post-challenge, breast-fed infants and infants fed alpha-LA-supplemented formula had no diarrhea, whilst those infants fed GMP-supplemented formula had intermittent diarrhea. In infants fed control formula the diarrhea was acute., Conclusions: Supplementation of infant formula with appropriate milk proteins may be useful for improving the infant's ability to resist acute infection caused by E.coli.

The remarkable binding properties of LNA (Locked Nucleic Acid) and alpha-L-LNA (the alpha-L-ribo configured diastereoisomer of LNA) are summarized, and hybridization results for LNA/2'-O-Me-RNA chimera and LNAs with a "dangling" nucleotide are introduced. In addition, results from NMR investigations on the furanose conformations of the individual nucleotide monomers in different duplexes are presented. All these data are discussed with focus on the importance of conformational steering of unmodified nucleotides in partly modified LNA and alpha-L-LNA sequences in relation to the unprecedented binding properties of LNA and alpha-L-LNA.

We have used two-dimensional (1)H NMR spectroscopy at 750 MHz to determine a high-resolution solution structure of an oligonucleotide containing restricted nucleotides with a 2'-O, 4'-C-methylene bridge (LNA) hybridized to the complementary DNA strand. The LNA:DNA duplex examined contained four thymidine LNA modifications (T(L), d(C1T(L)2G3C4T(L)5T(L)6C7T(L)8G9C10):d( G11C12A13G14A15A16G17C 18A19G20). A total relaxation matrix approach was used to obtain interproton distance bounds from NOESY cross-peak intensities. These distance bounds were used as restraints in molecular dynamics (rMD) calculations. Forty final structures were generated for the duplex from A-form and B-form DNA starting structures. The root-mean-square deviation (RMSD) of the coordinates for the 40 structures of the complex was 0.6 A. The sugar puckerings are averaged values of a dynamic interchange between N- and S-type conformation except in case of the locked nucleotides that were found to be fixed in the C3'-endo conformation. Among the other nucleotides in the modified strand, the furanose ring of C7 and G9 is predominantly in the N-type conformation whereas that of G3 is in a mixed conformation. The furanose rings of the nucleotides in the unmodified complementary strand are almost exclusively in the S-type conformation. Due to these different conformations of the sugars in the two strands, there is a structural strain between the A-type modified strand and the B-type unmodified complementary strand. This strain is relaxed by decreasing the value of rise and compensating with tip, buckle, and propeller twist. The values of twist vary along the strand but for a majority of the base pairs a value even lower than that of A-DNA is observed. The average twist over the sequence is 32+/-1 degrees. On the basis of the structure, we conclude that the high stability of LNA:DNA duplexes is caused by a local change of the phosphate backbone geometry that favors a higher degree of stacking.

We have used 2D NMR spectroscopy to study the sugar conformations of oligonucleotides containing a conformationally restricted nucleotide (LNA) with a 2'-O, 4'-C-methylene bridge. We have investigated a modified 9-mer single stranded oligonucleotide as well as three 9- and 10-mer modified oligonucleotides hybridized to unmodified DNA. The single-stranded LNA contained three modifications whereas the duplexes contained one, three and four modifications, respectively. The LNA:DNA duplexes have normal Watson-Crick base-pairing with all the nucleotides in anti-conformation. By use of selective DQF-COSY spectra we determined the ratio between the N-type (C3'-endo) and S-type (C2'-endo) sugar conformations of the nucleotides. In contrast to the corresponding single-stranded DNA (ssDNA), we found that the sugar conformations of the single-stranded LNA oligonucleotide (ssLNA) cannot be described by a major S-type conformer of all the nucleotides. The nucleotides flanking an LNA nucleotide have sugar conformations with a significant population of the N-type conformer. Similarly, the sugar conformations of the nucleotides in the LNA:DNA duplexes flanking a modification were also shown to have significant contributions from the N-type conformation. In all cases, the sugar conformations of the nucleotides in the complementary DNA strand in the duplex remain in the S-type conformation. We found that the locked conformation of the LNA nucleotides both in ssLNA and in the duplexes organize the phosphate backbone in such a way as to introduce higher population of the N-type conformation. These conformational changes are associated with an improved stacking of the nucleobases. Based on the results reported herein, we propose that the exceptional stability of the LNA modified duplexes is caused by a quenching of concerted local backbone motions (preorganization) by the LNA nucleotides in ssLNA so as to decrease the entropy loss on duplex formation combined with a more efficient stacking of the nucleobases., (Copyright 2000 John Wiley & Sons, Ltd.)

We examined bisection of lines viewed in only one hemifield by normal subjects. Subjects first performed a traditional version of line bisection, by indicating the perceived midpoint of a line on paper with a penmark. Bisection was accurate when they were allowed to shift their gaze over the stimulus, but it was biased towards the central visual field (centripetally) when gaze was fixed so that the line was seen in only one hemifield. In a second experiment, lines with transectors at various locations were presented briefly on a screen and subjects had to indicate on which side of the perceived midpoint the transector was located. A centripetal bias was still found, indicating that it has a perceptual origin. The interaction between bias and effects of tangent line presentation suggested that subjects were performing an angle bisection rather than a line bisection. Also, there was bias in not only right and left hemifields but also upper and lower hemifields. In a third experiment, increasing the width of the stimulus bars peripherally did not eliminate this bias. Bias was size-invariant along the horizontal meridian. This spatial version of Weber's law was modeled by a magnification function using an exponential equation. The slope of this function is much shallower than those currently known for V1, V4 and V5. We conclude that a centripetal bias exists for hemifield line bisection and that this bias likely contributes to the contralateral bias of line bisection by hemianopic patients found in other studies.

We have used one and two dimensional exchange 1H NMR spectroscopy to characterize the dynamics of the binding of a homodimeric thiazole orange dye, 1,1'-(4,4,8,8-tetramethyl-4,8-diaza-undecamethylene)-bis- 4-(3-methyl-2,3-dihydro-(benzo-1,3-thiazole)-2-methylidene)-quinol inium tetraiodide (TOTO), to double stranded DNA (dsDNA). The double stranded oligonucleotides used were d-(CGCTAGCG)2 (1) and d(CGCTAGCTAGCG)2 (2). TOTO binds preferentially to the (5'-CTAG-3')2 sites and forms mixtures of 1:1 and 1:2 dsDNA-TOTO complexes with 2 in ratios dependent on the relative amount of TOTO and the oligonucleotide in the sample. The dynamic exchange between preferential binding sites in the case of a 2:1 1-TOTO mixture is an intermolecular exchange process between two binding sites on different oligonucleotides. In the case of the 1:1 2-TOTO complex an intramolecular exchange process occur between two different binding sites on the same strand. Both processes were studied. The results demonstrate the ability of TOTO to migrate along a dsDNA strand in an intramolecular exchange process. The migration process ("creeping") along the DNA strand is 6 times faster than the rate of intermolecular exchange between sites in two different oligonucleotides.