Obstetric outcomes and uptake of care among 149 non-Swedish speaking migrant women attending a birth preparation visit during pregnancy - An observational study from Sweden.

Introduction: In Sweden almost one third of the population is born in another country and a large number of the women who do not speak Swedish are of reproductive age. Women migrating from low-income countries have higher risks for poor obstetric outcomes than receiving country-born citizens. INFOR (a Swedish word for "before" or "ahead of") is an intervention offering language-assisted, individual birth preparation for non-Swedish speaking pregnant women unfamiliar with the maternity care system. The aim of this study was to describe the uptake of care and obstetric outcomes among non-Swedish speaking migrant women attending INFOR. Methods: A descriptive study of the obstetric outcomes and uptake of care was conducted of the 149 non-Swedish speaking pregnant women who participated in INFOR between 2016 and 2020. The data were accessed retrospectively from the medical record system Obstetrix and the population-based Swedish Pregnancy Registry and analysed descriptively. Results: Women participating in INFOR originated from 44 countries and spoke 35 different languages. During late pregnancy, 20 percent of the women sought care for decreased fetal movements and 80 percent of the women attended the postpartum visit. While the majority of the participants were offered professional language support during pregnancy, almost none had a professional interpreter present during labour and birth. After birth, 80 percent of the primiparous women were asked to rate their birth experience, but only half of the multiparous women were asked. Further, only half of the primiparous women attending the postpartum visit were asked about their self-rated health. Conclusion: INFOR may increase uptake of some important aspects of care during pregnancy, birth and postpartum among migrants of diverse backgrounds. The findings raise concerns however about communication support for migrant women, especially during labour and birth. The offer of professional interpreting as part of standard maternity care for women who need it is essential and must be improved in order to provide equitable care for all.

Legal assessment of ingrown horns and other horn-related anomalies in cattle and sheep.

Cattle and sheep horns have the potential to grow in such a way that the horn bends toward the animal's head and, if left untreated, may penetrate the skin, causing pressure, pain, and suffering. According to the Swedish Animal Welfare Act, animals must be looked after in a way that prevents ingrown horns; otherwise, the person responsible for the animal may be prosecuted. Here, we present a review of 32 legal cases that occurred in Sweden between 2008 and 2022 for which the charge involved horn-related anomalies in cattle or sheep. The aim being to investigate the nature of these horn-related anomalies and the circumstances under which they occur. Of the legal cases, 53% were discovered during official animal welfare control on farms and 44% at an abattoir during pre-slaughter inspection. These include extreme injuries, e.g. both horns penetrating the periosteum into the skull bone, or a horn penetrating into the eye or oral cavity. The reasons offered by the accused for failing to detect animals with horn-related anomalies included that the animal appeared normal, that it was long-haired, shy, or hard to reach, or that the horns had not undergone gradual growth but had accidentally or suddenly penetrated the skin. Overall, 81% of the cases led to convictions; however, none of these resulted in imprisonment. Reasons for acquittals included insufficient crime description or evidence as to how the horn-related anomaly occurred or of the animal being exposed to suffering. A number of recommendations are provided that could help limit the occurrence of ingrown horns.

Bolus rheology of texture adjusted food-Effect of age.

Swallowing disorders, or dysphagia, affect a large part of the population due to factors such as degenerative diseases, medication side effects or simply age-related impairment of physiological oropharyngeal function. The management of dysphagia is mainly handles through texture-modified foods of progressively softer, smoother, moister textures, depending on the severity of the disorder. Rheological and physiological-related properties of boluses were determined for a group of five older persons (average age, 74) for a set of texture-modified foods: bread, cheese and tomato and the combination into a sandwich. The softest class was gel food, after which came a smooth timbale; both were compared to boluses of regular food. The subjects chewed until ready to swallow, at which point the bolus was expectorated and measured regarding saliva content, linear viscoelasticity and shear viscosity. The results were compared to those of a previously studied younger group (average age, 38). The general physiological status of the subjects was determined by hand and tongue strength, diadochokinesis and one-legged standing and showed that all subjects were as healthy and fit as the younger group. Age-related properties such as one-legged standing with closed eyes and salivary flow plus bolus saliva content were lower for the older group, but the average chews-until-swallow was surprisingly also lower. Consequently, bolus modulus and viscosity were higher than for the younger group. Overall, the intended texture modification was reflected in bolus rheological and physiological-related properties. Bolus modulus, viscosity, saliva content and chews-until-swallowed all decreased from regular food to timbale food to gel food.

Inter-Rater Agreement for Diagnosing Adenomyosis Using Magnetic Resonance Imaging and Transvaginal Ultrasonography.

Our aim was to compare the inter-rater agreement about transvaginal ultrasonography (TVS) with magnetic resonance imaging (MRI) with regard to diagnosing adenomyosis and for assessing various predefined imaging features of adenomyosis, in the same set of women. The study cohort included 51 women, prospectively, consecutively recruited based on a clinical suspicion of adenomyosis. MRIs and TVS videoclips and 3D volumes were retrospectively assessed by four experienced radiologists and five experienced sonographers, respectively. Each rater subjectively evaluated the presence or absence of adenomyosis, as well as imaging features suggestive of adenomyosis. Fleiss kappa (κ) was used to reflect inter-rater agreement for categorical data, and the intraclass correlation coefficient (ICC) was used to reflect the reliability of quantitative data. Agreement between raters for diagnosing adenomyosis was higher for TVS than for MRI (κ = 0.42 vs. 0.28). MRI had a higher inter-rater agreement in assessing wall asymmetry, irregular junctional zone (JZ), and the presence of myometrial cysts, while TVU had a better agreement for assessing globular shape. MRI showed a moderate to good reliability for measuring the JZ (ICC = 0.57-0.82). For TVS, the JZ was unmeasurable in >50% of cases, and the remaining cases had low reliability (ICC = -0.31-0.08). We found that inter-rater agreement for diagnosing adenomyosis was higher for TVS than for MRI, despite the fact that MRI showed a higher inter-rater agreement in most specific features. Measurements of JZ in the coronal plane with 3D TVS were unreliable and thus unlikely to be useful for diagnosing adenomyosis.

Bromocriptine inhibits proliferation in the endometrium from women with adenomyosis.

Objective: Bromocriptine treatment has been shown to reduce menstrual bleeding and pain in women with adenomyosis in a pilot clinical trial. The underlying mechanism contributing to the treatment effect is however unknown. The purpose of this study was to explore the effect of bromocriptine on the proliferation and migration properties of the endometrium in women with adenomyosis, by assessing cellular and molecular changes after six months of vaginal bromocriptine treatment. Methods: Endometrial specimens were collected during the proliferative phase from women with adenomyosis (n=6) before (baseline) and after six months of treatment with vaginal bromocriptine. Immunohistochemistry was used to determine changes in the protein expression of Ki67 in the endometrium of women with adenomyosis. Primary endometrial stromal cells isolated at baseline were expanded in vitro and exposed to different doses of bromocriptine to determine the optimal half-maximum inhibitory concentration (IC50) using CellTiter-Blue® Cell Viability Assay. Cell proliferation was assessed by bromodeoxyuridine ELISA assay and Ki67 gene expression was checked by real-time PCR. The migratory ability of endometrial stromal cells was determined by wound healing and transwell migration assays. Small RNA sequencing was applied on tissues collected from women with adenomyosis before and after bromocriptine treatment to identify differentially expressed microRNAs (miRNAs) after bromocriptine treatment. Bioinformatic methods were used for target gene prediction and the identification of biological pathways by enrichment procedures. Results: Vaginal bromocriptine treatment reduced the Ki67 protein expression in the endometrium of women with adenomyosis and did not change the prolactin mRNA expression and protein concentration of prolactin in endometrial tissues. Bromocriptine significantly inhibited the proliferative and migrative abilities of endometrial stromal cells derived from women with adenomyosis in vitro. Moreover, small RNA sequencing revealed 27 differentially expressed miRNAs between the endometrium of women with adenomyosis before and after six months of vaginal bromocriptine treatment. KEGG pathway analysis on targeted genes of 27 miRNAs showed that several signaling pathways associated with cell proliferation and apoptosis were enriched after bromocriptine treatment. Conclusion: Bromocriptine treatment exhibits an anti-proliferative effect in the endometrium of women with adenomyosis in vivo and in vitro. Bromocriptine might inhibit the proliferation of endometrial tissue in adenomyosis in part through the regulation of dysregulated microRNAs and proliferation-associated signaling pathways.

Longitudinal neuropsychological trajectories in idiopathic normal pressure hydrocephalus: a population-based study.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) is a progressive syndrome affecting gait, incontinence, and cognition in a significant number of older adults. Still, prospective studies on early development of symptoms are scarce. AIM: To investigate how neuropsychological functions develop before and in already diagnosed iNPH over a two-year period in a population-based material. METHOD: A sample of 104 participants (median [IQR] 75 [72-80] years old) from the general population underwent CT-imaging and clinical assessment at baseline and follow-up. We used the iNPH symptom scale covering four domains (Neuropsychology, Gait, Balance, Incontinence) and additional tests of executive functions. Morphological signs were rated with the iNPH Radscale. Non-parametric statistics with Bonferroni corrections and a significance-level of p < 0.05 were used. RESULTS: Median (IQR) time to follow-up was 25 (23-26) months. Effect size (ES) for individuals who developed iNPH (n = 8) showed a large (ES r = -0.55) decline in the Gait domain and on the Radscale (ES r = -0.60), with a medium deterioration in declarative memory (ES r = -0.37). Those having iNPH at baseline (n = 12) performed worse on one executive sub-function i.e., shifting (p = 0.045). CONCLUSION: Besides deterioration in gait and radiology, our results suggest that a neuropsychological trajectory for those developing iNPH includes a reduction in declarative memory. Executive dysfunction was limited to those already having iNPH at baseline. These findings could suggest that memory impairments are included in the early development of iNPH.

Sustained inhibitory transmission but dysfunctional dopamine D2 receptor signaling in dorsal striatal subregions following protracted abstinence from amphetamine.

Behavioral sensitization to amphetamine is a complex phenomenon that engages several neurotransmitter systems and brain regions. While dysregulated signaling in the mesolimbic dopamine system repeatedly has been linked to behavioral sensitization, later research has implicated dorsal striatal circuits and GABAergic neurotransmission in contributing to behavioral transformation elicited by amphetamine. The aim of this study was thus to determine if repeated amphetamine exposure followed by abstinence would alter inhibitory neurotransmission in dorsal striatal subregions. To this end, male Wistar rats received amphetamine (2.0 mg/kg) in an intermittent manner for a total of five days. Behavioral sensitization to amphetamine was measured in locomotor-activity boxes, while neuroadaptations were recorded in the dorsolateral (DLS) and dorsomedial striatum (DMS) using ex vivo electrophysiology at different timepoints of amphetamine abstinence (2 weeks, 4-5 weeks, 10-11 weeks). Data show that repeated drug-exposure produces behavioral sensitization to the locomotor-stimulatory properties of amphetamine, which sustains for at least ten weeks. Electrophysiological recordings demonstrated a long-lasting suppression of evoked population spikes in both striatal subregions. Furthermore, following ten weeks of abstinence, the responsiveness to a dopamine D2 receptor agonist was significantly impaired in brain slices from rats previously receiving amphetamine. However, neither the frequency nor the amplitude of spontaneous inhibitory currents was affected by treatment at any of the time points analyzed. In conclusion, passive administration of amphetamine initiates long-lasting neuroadaptations in brain regions associated with goal-directed behavior and habitual performance, but these transformations do not appear to be driven by changes in GABAergic neurotransmission.

Remote Sensing of the Nano-Rheological Properties of Soft Materials Using Magnetic Nanoparticles and Magnetic AC Susceptometry.

We have developed a nano-rheological characterization tool to extract the frequency- and scale-dependent rheological properties of soft materials during oral processing. Taking advantage of AC susceptometry, the dynamic magnetization of magnetic nanoparticles blended in the matrix material is measured. The magnetic AC susceptibility spectra of the particles are affected by the viscosity and mechanical modulus of the matrix material and provide the rheological properties of the matrix. Commercially available iron-oxide magnetic nanoparticles with 80 and 100 nm particle sizes are used as tracers in the frequency range of 1 Hz-10 kHz. The AC susceptibility is measured using two differentially connected coils, and the effects of the sample temperature and distance with respect to the detection coils are investigated. The developed measurement setup shows the feasibility of remote nano-rheological measurements up to 2 cm from the coil system, which can be used to, e.g., monitor the texture of matrix materials during oral processing.

Liver health literacy and social stigma of liver disease: A general population e-survey.

BACKGROUND: Health literacy is increasingly recognized as an essential determinant for the health of the population. Liver patients report perceived stigma to be a considerable problem. Little is however known about liver health literacy in the general population and to what extent liver disease is considered stigmatizing in comparison with other chronic diseases. We aimed to explore these knowledge gaps. METHODS: We performed an exploratory e-survey in a statistically representative sample of 500 Swedes from the general population. A questionnaire developed for this purpose investigated awareness, attention, knowledge and attitudes towards liver health and compared some aspects with other common health problems. FINDINGS: Few worry (23%), think (28%), discuss with their doctor (31%) or hear about liver health in the news (19%). Few (18%) had a liver test in the last year and knew (23%) what is considered a normal liver test. More knew what is considered normal blood pressure (89%), blood sugar (74%) and BMI (73%). Few (22%) talk about liver health, mainly (50%) because abuse is presumed. Many (36%) believe that cirrhosis is only caused by alcohol, 31% that the liver produces urine and 21% that you can survive without a liver. Only mental illness (78%) and obesity (74%) were considered more stigmatizing than liver cirrhosis (61%). INTERPRETATION: The study confirms often held views that liver health receives less attention than many other health areas. Knowledge about liver health is generally poor, and liver cirrhosis carries significant social stigma. Improving public awareness and knowledge about liver health, and thereby ameliorating stigma, should be essential parts of policy objectives and action plans to improve liver health in Europe. FUNDING: This research was supported by a general grant from the Bengt Ihre Foundation.

Vaginal bromocriptine for treatment of adenomyosis: Impact on magnetic resonance imaging and transvaginal ultrasound.

OBJECTIVE: Vaginal bromocriptine significantly reduces heavy menstrual bleeding and pain in women with diffuse adenomyosis. The aim of this pilot study was to evaluate whether imaging findings of adenomyosis, as assessed by transvaginal ultrasound (TVU) and magnetic resonance imaging (MRI) reflect changes induced by the bromocriptine treatment. STUDY DESIGN: Eighteen women, aged 35-50, with heavy menstrual bleeding reporting Pictorial Blood Loss Assessment Chart (PBLAC) scores >100 and diffuse adenomyosis according to both MRI and TVU were included. The subjects underwent treatment with vaginal bromocriptine for 6 months. MRI and TVU were performed at baseline and after 6 months of medication. RESULTS: Mean age of the participants was 44.8 years, 77.8 % reported PBLAC scores > 250 and 66.7 % reported moderate to severe pain during menstruation at baseline. As compared to baseline, TVU revealed a thinner maximal Junctional Zone (JZmax) (8.5 mm [5.2-14] vs 7.9 mm [5-11.2], p = 0.02) at 6 months. Asymmetric wall thickening was seen in 13 (72 %) at baseline, and in 6 (33 %) women at 6 months, p = 0.02. No significant changes were seen in irregular endometrial-myometrial border, presence of fan-shaped shadowing, cystic changes, striations, hyperechogenic islands or lesion extension. MRI showed no significant difference in JZmax (16.0 mm[12.1-27.7] vs 15.5 mm [9.5-25.8], p = 0.81), JZdifference (9.5 mm[4.8-21.6] vs 8.4[3.8-19.5], p = 1) or Ratio JZ/myometrium (0.6 [0.5-0.8] vs. 0.6[0.4-0.8], p = 0.9) at baseline vs 6 month. Cystic lesions in the JZ were found in 9 women (50 %) before, and in 5 women (28 %) at 6 months, p = 0.13. CONCLUSION: TVU showed a significant decrease in JZ max and a reduced number of women with asymmetric myometrial wall thickness. The changes seen in this small pilot study may indicate that vaginal bromocriptine have an impact on adenomyosis that is reflected in radiological appearance.

Prevalence of idiopathic normal pressure hydrocephalus: A prospective, population-based study.

BACKGROUND: Idiopathic normal pressure hydrocephalus (iNPH) causing gait impairment, dementia and urinary incontinence among the elderly, is probably under-diagnosed and under-treated. Despite being known since the 1960s, there is still a lack of prospective, population-based studies on the prevalence of iNPH. Such studies are warranted to minimize selection bias and estimate the true prevalence of the disease. METHODS: The prevalence of iNPH was determined in a randomly selected sample of residents, aged 65 years and older, in the Swedish county of Jämtland. Out of 1,000 individuals invited to participate, 673 (67.3%) completed a questionnaire with seven questions on iNPH symptoms. A subgroup, with and without self-reported symptoms, participated in clinical and radiological evaluations and were diagnosed according to international guidelines. Measurement of cerebrospinal fluid opening pressure was not performed as it was considered too invasive. RESULTS: Those who reported at least two symptoms in the questionnaire (n = 117) and 51 randomly selected individuals with 0-1 symptom participated in further examinations. Out of them, 25 individuals received the diagnosis probable iNPH according to American-European guidelines (except for the criterion of CSF opening pressure) corresponding to a prevalence of 3.7%. The prevalence of iNPH was four times higher among those aged 80 years and older (8.9%) than among those aged 65-79 years (2.1%) (p <0.001). The difference in prevalence between men (4.6%) and women (2.9%) was not significant (p = 0.24). When iNPH was diagnosed according to the Japanese guidelines the prevalence was 1.5. CONCLUSIONS: In this prospective, population-based study the prevalence of iNPH was 3.7% among individuals 65 years and older, and more common in the higher age group, 80 years and above. INPH should be increasingly recognized since it is a fairly common condition and an important cause of gait impairment and dementia among the elderly that can be effectively treated by shunt surgery.

Vaginal bromocriptine improves pain, menstrual bleeding and quality of life in women with adenomyosis: A pilot study.

INTRODUCTION: Adenomyosis is a benign uterine disease where endometrial glands and stroma are found within the myometrium surrounded by an area of hypertrophic myometrium. Symptomatology includes heavy menstrual bleeding and pelvic pain. The pathogenesis of adenomyosis is not known; however, animal models have shown increased uterine concentration of prolactin as a risk factor. Prolactin acts as a smooth muscle cell mitogen. If prolactin is central to adenomyosis pathogenesis, reducing uterine prolactin could be a possible medical treatment option. In this pilot study, we aim to evaluate the effect of bromocriptine, a prolactin inhibitor, on menstrual bleeding and pain in women with adenomyosis. MATERIAL AND METHODS: 23 women with diffuse adenomyosis were enrolled from a university hospital in Sweden and a tertiary care center in the USA. Nineteen patients completed 6 months of treatment with vaginal bromocriptine at a dose of 5 mg daily. Participants completed validated measures at baseline, 3 and 6 months of treatment, and at 9 months (3 months after cessation of bromocriptine). Validated measures utilized included Pictorial Blood Loss Assessment Chart (PBLAC), Aberdeen Menorrhagia Clinical Outcomes Questionnaire (AMCOQ), Visual Analog Scale for pain (VAS), McGill Pain Questionnaire (MPQ), Endometriosis Health Profile (EHP-30), Female Sexual Function Index (FSFI) and the Fibroid Symptom Quality of Life (UFS-QOL) symptom severity and health-related quality of life (HRQL) subscores. Scores were compared between baseline and 9 months using the Wilcoxon signed rank test. RESULTS: Mean age of participants was 44.8 years. About 77.8% reported PBLAC scores >250 and 68.4% reported moderate to severe pain at baseline. Compared with baseline, women had lower 9-month scores (median [interquartile range] for all) on PBLAC (baseline 349 [292-645] vs 9-month 233 [149-515], P = 0.003), VAS (5.0 [4-8.3] vs 2.5 [0-4.5], P < 0.001), EHP Core Pain (15.9 [9.1-50.0] vs 3.4 [2.3-34.1], P = 0.029), EHP Core Self-image (41.7 [16.7-58.3] vs 25 [0-5], P = 0.048) and Symptom Severity Score (60 [44-72] vs 44 [25-56], P < 0.001) and higher HRQL scores (57 [37-63] vs 72 [51-85], P < 0.001) following bromocriptine treatment. Other EHP core parameters and FSFI were not significantly different. CONCLUSIONS: Significant improvement in menstrual bleeding, pain and quality of life after vaginal bromocriptine treatment suggests a novel therapeutic agent for adenomyosis.

Stick-slip motion and controlled filling speed by the geometric design of soft micro-channels.

HYPOTHESIS: Liquid can move by capillary action through interconnected porous materials, as in fabric or paper towels. Today mass transport is controlled by chemical modification. It is, however, possible to direct mass transport by geometrical modifications. It is here proposed that it is possible to tailor capillary flow speed in a model system of micro-channels by the angle, size and position of attached side channels. EXPERIMENTS: A flexible, rapid, and cost-effective method is used to produce micro-channels in gels. It involves 3D-printed moulds in which gels are cast. Open channels of micrometre size with several side channels on either one or two sides are produced with tilting angles of 10-170°. On a horizontal plane the meniscus of water driven by surface tension is tracked in the main channel. FINDINGS: The presence of side channels on one side slowed down the speed of the meniscus in the main channel least. Channels having side channels on both sides with tilting angles of up to 30° indicated tremendously slower flow, and the liquid exhibited a stick-slip motion. Broader side channels decreased the speed more than thinner ones, as suggested by the hypothesis. Inertial forces are suggested to be important in branched channel systems studied here.

Dynamics of capillary transport in semi-solid channels.

Capillary action has been described by Lucas and Washburn and extensively studied experimentally in hard materials, but few studies have examined capillary action in soft materials such as hydrogels. In tissue engineering, cells or dispersions must be often distributed within a hydrogel via microporous paths. Capillary action is one way to disperse such substances. Here, we examine the dynamics of capillary action in a model system of straight capillaries in two hydrogels. The channels had a circular cross-section in the micrometer size range (180-630 µm). The distance travelled over time was recorded and compared with the predictions of Lucas and Washburn. Besides water, we used a sucrose solution and a hydroxyethyl cellulose solution, both with viscosities slightly higher than that of water. The results showed that the distance travelled is proportional to the square root of time, , and that larger capillaries and lower viscosities result, as expected, in faster speeds. However, the absolute experimental values display large discrepancies from the predictions. We demonstrate that several possible reasons for these discrepancies can be ruled out and we describe a novel hypothesis for the cause of the retarded meniscus movement.

Guanine Can Direct Binding Specificity of Ru-dipyridophenazine (dppz) Complexes to DNA through Steric Effects.

X-ray crystal structures of three Λ-[Ru(L)2 dppz]2+ complexes (dppz=dipyridophenazine; L=1,10-phenanthroline (phen), 2,2'-bipyridine (bpy)) bound to d((5BrC)GGC/GCCG) showed the compounds intercalated at a 5'-CG-3' step. The compounds bind through canted intercalation, with the binding angle determined by the guanine NH2 group, in contrast to symmetrical intercalation previously observed at 5'-TA-3' sites. This result suggests that canted intercalation is preferred at 5'-CG-3' sites even though the site itself is symmetrical, and we hypothesise that symmetrical intercalation in a 5'-CG-3' step could give rise to a longer luminescence lifetime than canted intercalation.

DNA intercalation optimized by two-step molecular lock mechanism.

The diverse properties of DNA intercalators, varying in affinity and kinetics over several orders of magnitude, provide a wide range of applications for DNA-ligand assemblies. Unconventional intercalation mechanisms may exhibit high affinity and slow kinetics, properties desired for potential therapeutics. We used single-molecule force spectroscopy to probe the free energy landscape for an unconventional intercalator that binds DNA through a novel two-step mechanism in which the intermediate and final states bind DNA through the same mono-intercalating moiety. During this process, DNA undergoes significant structural rearrangements, first lengthening before relaxing to a shorter DNA-ligand complex in the intermediate state to form a molecular lock. To reach the final bound state, the molecular length must increase again as the ligand threads between disrupted DNA base pairs. This unusual binding mechanism results in an unprecedented optimized combination of high DNA binding affinity and slow kinetics, suggesting a new paradigm for rational design of DNA intercalators.

Dissecting the Dynamic Pathways of Stereoselective DNA Threading Intercalation.

DNA intercalators that have high affinity and slow kinetics are developed for potential DNA-targeted therapeutics. Although many natural intercalators contain multiple chiral subunits, only intercalators with a single chiral unit have been quantitatively probed. Dumbbell-shaped DNA threading intercalators represent the next order of structural complexity relative to simple intercalators, and can provide significant insights into the stereoselectivity of DNA-ligand intercalation. We investigated DNA threading intercalation by binuclear ruthenium complex [µ-dppzip(phen)4Ru2](4+) (Piz). Four Piz stereoisomers are defined by the chirality of the intercalating subunit (Ru(phen)2dppz) and the distal subunit (Ru(phen)2ip), respectively, each of which can be either right-handed (Δ) or left-handed (Λ). We used optical tweezers to measure single DNA molecule elongation due to threading intercalation, revealing force-dependent DNA intercalation rates and equilibrium dissociation constants. The force spectroscopy analysis provided the zero-force DNA binding affinity, the equilibrium DNA-ligand elongation Δxeq, and the dynamic DNA structural deformations during ligand association xon and dissociation xoff. We found that Piz stereoisomers exhibit over 20-fold differences in DNA binding affinity, from a Kd of 27 ± 3 nM for (Δ,Λ)-Piz to a Kd of 622 ± 55 nM for (Λ,Δ)-Piz. The striking affinity decrease is correlated with increasing Δxeq from 0.30 ± 0.02 to 0.48 ± 0.02 nm and xon from 0.25 ± 0.01 to 0.46 ± 0.02 nm, but limited xoff changes. Notably, the affinity and threading kinetics is 10-fold enhanced for right-handed intercalating subunits, and 2- to 5-fold enhanced for left-handed distal subunits. These findings demonstrate sterically dispersed transition pathways and robust DNA structural recognition of chiral intercalators, which are critical for optimizing DNA binding affinity and kinetics.

Safer fluid prescribing at North Bristol Trust: Bringing practice in line with NICE Guidance with a redesign of the fluid prescription chart.

The National Institute of Clinical Excellence (NICE) released new fluid guidelines following data suggesting 20% of patients receiving fluids suffer adversely (2013). This quality improvement group assessed fluid prescribing in a tertiary teaching centre and introduced a new fluid- prescribing chart to align practice with NICE recommendations. Notes and corresponding fluid prescription charts were reviewed for evidence of (1) indication, (2) co-morbidities, and (3) further management as surrogate markers of safe prescribing in accordance with NICE. Overall, the data showed practice fell short and prompted a redesign of the Trust fluid prescription chart. Three different variations of the chart were issued consecutively using a PDSA method (plan, do, study, act) over a 6-month period. They all included indication, co-morbidities and further management plans as constant design features. Suggestions from interested parties were incorporated and an educational programme was implemented to promote awareness. Prior to our intervention, an indication for fluids was documented in 26% of notes, it took an average of 4.6 minutes to find co-morbidities, and further management plans were rarely documented. Following the new prescription chart, an indication was recorded in 72% of cases, co-morbidities noted on 63% of charts with 93.1% accuracy, and further management documented in 100% of cases. The new fluid prescription chart encourages prescribers to incorporate NICE recommendations when prescribing fluids. The new fluid prescription design has since been rolled out Trust wide.

Constructing accountability in inter-organisational collaboration: the implications of a narrow performance-based focus.

PURPOSE: The purpose of this paper is to analyse how accounts of collaboration practice were made and used to construct accountability in the empirical context of coordination associations, a Swedish form of collaboration between four authorities in health and social care. They feature pooled budgets, joint leadership and joint reporting systems, intended to facilitate both collaboration and (shared) accountability. DESIGN/METHODOLOGY/APPROACH: Empirical data were collected in field observations in local, regional and national settings. In addition, the study is based on analysis of local association documents such as evaluations and annual reports, and analysis of national agency reports. FINDINGS: Accountability is constructed hierarchically with a narrow focus on performance, and horizontal (shared) accountability as well as outcomes are de-emphasised. Through this narrow construction of accountability the coordination associations are re-created as hierarchical and accountability is delegated rather than shared. RESEARCH LIMITATIONS/IMPLICATIONS: Features such as pooled budgets, joint leadership and joint reporting systems can support collaboration but do not necessarily translate into shared accountability if accountability is interpreted and constructed hierarchically. PRACTICAL IMPLICATIONS: When practice conforms to what is counted and accounted for, using the hierarchical and narrow construction of accountability, the result may be that the associations become an additional authority. That would increase rather than decrease fragmentation in the field. ORIGINALITY/VALUE: This research derives from first-hand observations of actor-to-actor episodes complemented with the analysis of documents and reports. It provides critical analysis of the construction and evaluation of accounts and accountability related to practice and performance in collaboration. The main contribution is the finding that despite the conditions intended to facilitate inter-organisational collaboration and horizontal accountability, the hierarchical accountability persisted.

Bridging ligand length controls at selectivity and enantioselectivity of binuclear ruthenium threading intercalators.

The slow dissociation of DNA threading intercalators makes them interesting as model compounds in the search for new DNA targeting drugs, as there appears to be a correlation between slow dissociation and biological activity. Thus, it would be of great value to understand the mechanisms controlling threading intercalation, and for this purpose we have investigated how the length of the bridging ligand of binuclear ruthenium threading intercalators affects their DNA binding properties. We have synthesised a new binuclear ruthenium threading intercalator with slower dissociation kinetics from ct-DNA than has ever been observed for any ruthenium complex with any type of DNA, a property that we attribute to the increased distance between the ruthenium centres of the new complex. By comparison with previously studied ruthenium complexes, we further conclude that elongation of the bridging ligand reduces the sensitivity of the threading interaction to DNA flexibility, resulting in a decreased AT selectivity for the new complex. We also find that the length of the bridging ligand affects the enantioselectivity with increasing preference for the ΔΔ enantiomer as the bridging ligand becomes longer.