Reaction of Copper(II) Chloroacetate with Pyrazole. Synthesis of a One-Dimensional Coordination Polymer and Unexpected Dehydrochlorination Reaction

The reaction of copper(II) chloroacetate (1d) with pyrazole (Hpz) mainly yielded the mononuclear compound [Cu(μ-ClCH2COO)2(Hpz)2] (2m), which self-assembled generating a one-dimensional coordination polymer. Moreover, the concomitant isolation of the tetranuclear [{Cu2(μ-pz)(μ-OCH2COO)(Hpz)(MeOH)}2(μ-ClCH2COO)2] (3t) and hexanuclear [{Cu3(μ3-OH)(μ-pz)3(Hpz)2}2(μ-ClCH2COO)2](Cl)2 (4h) species evidenced the occurrence of a peculiar, previously unreported, dehydrochlorination reaction and the formation of the trinuclear triangular moiety [Cu3(μ3-OH)(μ-pz)3]. Theoretical calculations based on density functional theory including solvation effects indicate a possible pathway for the formation of 3t. Interestingly, besides the energy minimum corresponding to 3t, a further relative energy minimum is found for a species which can be considered a possible reaction intermediate.

A picture paints a thousand words: Heart drawings reflect acute distress and illness perception and predict posttraumatic stress symptoms after acute myocardial infarction

The aim of this study was to examine whether heart drawings of patients with acute myocardial infarction reflect acute distress symptoms and negative illness beliefs and predict posttraumatic stress symptoms 3 months post-myocardial infarction. In total, 84 patients aged over 18 years drew pictures of their heart. The larger the area drawn as damaged, the greater were the levels of acute distress (r = 0.36; p < 0.05), negative illness perceptions (r = 0.42, p < 0.05), and posttraumatic stress symptoms (r = 0.54, p < 0.01). Pain drawings may offer a tool to identify maladaptive cognitions and thus patients at risk of posttraumatic stress disorder.

Tracing reinforcement through asymmetrical partner preference in the European common vole Microtus arvalis

Background The mechanistic basis of speciation and in particular the contribution of behaviour to the completion of the speciation process is often contentious. Contact zones between related taxa provide a situation where selection against hybridization might reinforce separation by behavioural mechanisms, which could ultimately fully isolate the taxa. One of the most abundant European mammals, the common vole Microtus arvalis, forms multiple natural hybrid zones where rapidly diverging evolutionary lineages meet in secondary contact. Very narrow zones of hybridization spanning only a few kilometres and sex-specific gene flow patterns indicate reduced fitness of natural hybrids and incipient speciation between some of the evolutionary lineages. In this study, we examined the contribution of behavioural mechanisms to the speciation process in these rodents by fine-mapping allopatric and parapatric populations in the hybrid zone between the Western and Central lineages and experimental testing of the partner preferences of wild, pure-bred and hybrid female common voles. Results Genetic analysis based on microsatellite markers revealed the presence of multiple parapatric and largely non-admixed populations at distances of about 10 km at the edge of the area of natural hybridization between the Western and Central lineages. Wild females from Western parapatric populations and lab-born F1 hybrids preferred males from the Western lineage whereas wild females of Central parapatric origin showed no measurable preference. Furthermore, wild and lab-born females from allopatric populations of the Western or Central lineages showed no detectable preference for males from either lineage. Conclusions The detected partner preferences are consistent with asymmetrical reinforcement of pre-mating reproductive isolation mechanisms in the European common vole and with earlier results suggesting that hybridization is more detrimental to the Western lineage. As a consequence, these differences in behaviour might contribute to a further geographical stabilization of this moving hybrid zone. Such behavioural processes could also provide a mechanistic perspective for frequently-detected asymmetrical introgression patterns in the largely allopatrically diversifying Microtus genus and other rapidly speciating rodents.

Human impacts and aridity differentially alter soil N availability in drylands worldwide

Aims Climate and human impacts are changing the nitrogen (N) inputs and losses in terrestrial ecosystems. However, it is largely unknown how these two major drivers of global change will simultaneously influence the N cycle in drylands, the largest terrestrial biome on the planet. We conducted a global observational study to evaluate how aridity and human impacts, together with biotic and abiotic factors, affect key soil variables of the N cycle. Location Two hundred and twenty-four dryland sites from all continents except Antarctica widely differing in their environmental conditions and human influence. Methods Using a standardized field survey, we measured aridity, human impacts (i.e. proxies of land uses and air pollution), key biophysical variables (i.e. soil pH and texture and total plant cover) and six important variables related to N cycling in soils: total N, organic N, ammonium, nitrate, dissolved organic:inorganic N and N mineralization rates. We used structural equation modelling to assess the direct and indirect effects of aridity, human impacts and key biophysical variables on the N cycle. Results Human impacts increased the concentration of total N, while aridity reduced it. The effects of aridity and human impacts on the N cycle were spatially disconnected, which may favour scarcity of N in the most arid areas and promote its accumulation in the least arid areas. Main conclusions We found that increasing aridity and anthropogenic pressure are spatially disconnected in drylands. This implies that while places with low aridity and high human impact accumulate N, most arid sites with the lowest human impacts lose N. Our analyses also provide evidence that both increasing aridity and human impacts may enhance the relative dominance of inorganic N in dryland soils, having a negative impact on key functions and services provided by these ecosystems.

Impact of Clinical Presentation (Stable Angina Pectoris vs Unstable Angina Pectoris or Non-ST-Elevation Myocardial Infarction vs ST-Elevation Myocardial Infarction) on Long-Term Outcomes in Women Undergoing Percutaneous Coronary Intervention With Drug-Eluting Stents

The long-term risk associated with different coronary artery disease (CAD) presentations in women undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DES) is poorly characterized. We pooled patient-level data for women enrolled in 26 randomized clinical trials. Of 11,577 women included in the pooled database, 10,133 with known clinical presentation received a DES. Of them, 5,760 (57%) had stable angina pectoris (SAP), 3,594 (35%) had unstable angina pectoris (UAP) or non-ST-segment-elevation myocardial infarction (NSTEMI), and 779 (8%) had ST-segment-elevation myocardial infarction (STEMI) as clinical presentation. A stepwise increase in 3-year crude cumulative mortality was observed in the transition from SAP to STEMI (4.9% vs 6.1% vs 9.4%; p <0.01). Conversely, no differences in crude mortality rates were observed between 1 and 3 years across clinical presentations. After multivariable adjustment, STEMI was independently associated with greater risk of 3-year mortality (hazard ratio [HR] 3.45; 95% confidence interval [CI] 1.99 to 5.98; p <0.01), whereas no differences were observed between UAP or NSTEMI and SAP (HR 0.99; 95% CI 0.73 to 1.34; p = 0.94). In women with ACS, use of new-generation DES was associated with reduced risk of major adverse cardiac events (HR 0.58; 95% CI 0.34 to 0.98). The magnitude and direction of the effect with new-generation DES was uniform between women with or without ACS (pinteraction = 0.66). In conclusion, in women across the clinical spectrum of CAD, STEMI was associated with a greater risk of long-term mortality. Conversely, the adjusted risk of mortality between UAP or NSTEMI and SAP was similar. New-generation DESs provide improved long-term clinical outcomes irrespective of the clinical presentation in women.

Towards tailored radiopeptide therapy.

PURPOSE Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor. METHODS Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving (90)Y-DOTATOC, (177)Lu-DOTATOC or their combination. RESULTS (90)Y-DOTATOC plus (177)Lu-DOTATOC treatment was associated with longer survival than (90)Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or (177)Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). (177)Lu-DOTATOC was associated with longer survival than (90)Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). (90)Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5% vs. 4.0%, p = 0.005) or (177)Lu-DOTATOC (9.5 vs. 1.4%, p = 0.002). Renal toxicity was similar among the treatments. CONCLUSIONS Using (90)Y and (177)Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors.

Azacyclic FTY720 Analogues That Limit Nutrient Transporter Expression but Lack S1P Receptor Activity and Negative Chronotropic Effects Offer a Novel and Effective Strategy to Kill Cancer Cells in Vivo

FTY720 sequesters lymphocytes in secondary lymphoid organs through effects on sphingosine-1-phosphate (S1P) receptors. However, at higher doses than are required for immunosuppression, FTY720 also functions as an anticancer agent in multiple animal models. Our published work indicates that the anticancer effects of FTY720 do not depend on actions at S1P receptors but instead stem from FTY720s ability to restrict access to extracellular nutrients by down-regulating nutrient transporter proteins. This result was significant because S1P receptor activation is responsible for FTY720s dose-limiting toxicity, bradycardia, that prevents its use in cancer patients. Here, we describe diastereomeric and enantiomeric 3- and 4-C-aryl 2-hydroxymethyl pyrrolidines that are more active than the previously known analogues. Of importance is that these compounds fail to activate S1P1 or S1P3 receptors in vivo but retain inhibitory effects on nutrient transporter proteins and anticancer activity in solid tumor xenograft models. Our studies reaffirm that the anticancer activity of FTY720 does not depend upon S1P receptor activation and uphold the promise of using S1P receptor-inactive azacyclic FTY720 analogues in human cancer patients.

Resilience as a correlate of acute stress disorder symptoms in patients with acute myocardial infarction

OBJECTIVES Myocardial infarction (MI) may be experienced as a traumatic event causing acute stress disorder (ASD). This mental disorder has an impact on the daily life of patients and is associated with the development of post-traumatic stress disorder. Trait resilience has been shown to be a protective factor for post-traumatic stress disorder, but its association with ASD in patients with MI is elusive and was examined in this study. METHODS We investigated 71 consecutive patients with acute MI within 48 h of having stable haemodynamic conditions established and for 3 months thereafter. All patients completed the Acute Stress Disorder Scale and the Resilience Scale to self-rate the severity of ASD symptoms and trait resilience, respectively. RESULTS Hierarchical regression analysis showed that greater resilience was associated with lower symptoms of ASD independent of covariates (b=-0.22, p<0.05). Post hoc analysis revealed resilience level to be inversely associated with the ASD symptom clusters of re-experiencing (b=-0.05, p<0.05) and arousal (b=-0.09, p<0.05), but not with dissociation and avoidance. CONCLUSIONS The findings suggest that patients with acute MI with higher trait resilience experience relatively fewer symptoms of ASD during MI. Resilience was particularly associated with re-experiencing and arousal symptoms. Our findings contribute to a better understanding of resilience as a potentially important correlate of ASD in the context of traumatic situations such as acute MI. These results emphasise the importance of identifying patients with low resilience in medical settings and to offer them adequate support.

Association of Trait Resilience With Peritraumatic and Posttraumatic Stress in Patients With Myocardial Infarction.

OBJECTIVE Acute myocardial infarction (MI) is a life-threatening condition, leading to immediate fear and distress in many patients. Approximately 18% of patients develop posttraumatic stress disorder in the aftermath of MI. Trait resilience has shown to be a protective factor for the development of posttraumatic stress disorder. However, whether this buffering effect has already an impact on peritraumatic distress and applies to patients with MI is elusive. METHODS We investigated 98 consecutive patients with acute MI within 48 hours after having reached stable circulatory conditions and 3 months thereafter. Peritraumatic distress was assessed retrospectively with three single-item questions about pain, fear, and helplessness during MI. All patients completed the Posttraumatic Diagnostic Scale (PDS) and the Resilience Scale to self-rate posttraumatic stress and trait resilience. RESULTS Multivariate models adjusting for sociodemographic and medical factors showed that trait resilience was not associated with peritraumatic distress, but significantly so with posttraumatic stress. Patients with greater trait resilience showed lower PDS scores (b = -0.06, p < .001). There was no significant relationship between peritraumatic distress scores and PDS scores; resilience did not emerge as a moderator of this relationship. CONCLUSIONS The findings suggest that trait resilience does not buffer the perception of acute MI as stressful per se but may enhance better coping with the traumatic experience in the longer term, thus preventing the development of MI-associated posttraumatic stress. Trait resilience may play an important role in posttraumatic stress symptoms triggered by medical diseases such as acute MI.

Perception of a hectic hospital environment at admission relates to acute stress disorder symptoms in myocardial infarction patients.

OBJECTIVE Hospital crowding is a public health problem that may impact on the quality of medical treatment and increase the risk of developing traumatic stress, e.g., after myocardial infarction (MI). This study examines whether subjective appraisal of crowding at hospital admission due to MI is associated with acute stress disorder (ASD) symptoms. METHOD We investigated 102 consecutive patients with acute MI within 48h after having reached stable circulatory conditions. The appraisal of crowding was measured by the retrospective assessment of the perception of a hectic hospital environment at admission. Furthermore, patients completed the Acute Stress Disorder Scale to rate the psychological stress reaction. RESULTS The perception of a hectic hospital environment was associated with the development of ASD symptoms (r=0.254, P=.013) independently of demographic, peritraumatic and medical factors. Post hoc analysis revealed associations with dissociative (r=0.211, P=.041), reexperiencing (r=0.184, P=.074) and arousal (r=0.179, P=.083) symptoms. CONCLUSION The findings suggest that, besides objective circumstances, the way hospital admission due to MI is perceived by the patient may influence the development of MI-triggered ASD symptoms. The psychological and physiological long-term outcomes of the perception of a hectic hospital environment and the role of preventive interventions need further examination.

Predicting 5- and 10-year survival in older women with early-stage breast cancer: self-rated health and walking ability.

OBJECTIVES To determine life expectancy for older women with breast cancer. DESIGN Prospective longitudinal study with 10 years of follow-up data. SETTING Hospitals or collaborating tumor registries in four geographic regions (Los Angeles, California; Minnesota; North Carolina; Rhode Island). PARTICIPANTS Women aged 65 and older at time of breast cancer diagnosis with Stage I to IIIA disease with measures of self-rated health (SRH) and walking ability at baseline (N = 615; 17% aged ≥80, 52% Stage I, 58% with ≥2 comorbidities). MEASUREMENTS Baseline SRH, baseline self-reported walking ability, all-cause and breast cancer-specific estimated probability of 5- and 10-year survival. RESULTS At the time of breast cancer diagnosis, 39% of women reported poor SRH, and 28% reported limited ability to walk several blocks. The all-cause survival curves appear to separate after approximately 3 years, and the difference in survival probability between those with low SRH and limited walking ability and those with high SRH and no walking ability limitation was significant (0.708 vs 0.855 at 5 years, P ≤ .001; 0.300 vs 0.648 at 10 years, P < .001). There were no differences between the groups in breast cancer-specific survival at 5 and 10 years (P = .66 at 5 years, P = .16 at 10 years). CONCLUSION The combination of low SRH and limited ability to walk several blocks at diagnosis is an important predictor of worse all-cause survival at 5 and 10 years. These self-report measures easily assessed in clinical practice may be an effective strategy to improve treatment decision-making in older adults with cancer.

Association of nutritional risk and adverse medical outcomes across different medical inpatient populations

OBJECTIVE The aim of this study was to examine the prevalence of nutritional risk and its association with multiple adverse clinical outcomes in a large cohort of acutely ill medical inpatients from a Swiss tertiary care hospital. METHODS We prospectively followed consecutive adult medical inpatients for 30 d. Multivariate regression models were used to investigate the association of the initial Nutritional Risk Score (NRS 2002) with mortality, impairment in activities of daily living (Barthel Index <95 points), hospital length of stay, hospital readmission rates, and quality of life (QoL; adapted from EQ5 D); all parameters were measured at 30 d. RESULTS Of 3186 patients (mean age 71 y, 44.7% women), 887 (27.8%) were at risk for malnutrition with an NRS ≥3 points. We found strong associations (odds ratio/hazard ratio [OR/HR], 95% confidence interval [CI]) between nutritional risk and mortality (OR/HR, 7.82; 95% CI, 6.04-10.12), impaired Barthel Index (OR/HR, 2.56; 95% CI, 2.12-3.09), time to hospital discharge (OR/HR, 0.48; 95% CI, 0.43-0.52), hospital readmission (OR/HR, 1.46; 95% CI, 1.08-1.97), and all five dimensions of QoL measures. Associations remained significant after adjustment for sociodemographic characteristics, comorbidities, and medical diagnoses. Results were robust in subgroup analysis with evidence of effect modification (P for interaction < 0.05) based on age and main diagnosis groups. CONCLUSION Nutritional risk is significant in acutely ill medical inpatients and is associated with increased medical resource use, adverse clinical outcomes, and impairments in functional ability and QoL. Randomized trials are needed to evaluate evidence-based preventive and treatment strategies focusing on nutritional factors to improve outcomes in these high-risk patients.

Twenty years' experience with the Swiss data registry for assisted reproductive medicine: outcomes, key trends and recommendations for improved practice.

QUESTIONS UNDER STUDY The impact of assisted reproductive technology (ART) on Swiss demography was quantified. From 1993 to 2012 the number of deliveries, including multiples, generated by ART was compared with overall delivery numbers. Swiss experts in ART collaborated in a consensus to increase successful outcomes, to reduce the incidence of complications of ART and to validate recommendations through statistical review of available data. METHODS Data generated between 1993 and 2012 and published by the Federal Office of Statistics (BfS) were compared with the Swiss database on ART (FIVNAT-CH) as organised by the Swiss Society of Reproductive Medicine (SGRM). From these analyses a panel of Swiss experts in ART extracted recommendations to improve current practice, to prevent complications related to ART and to recommend changes in current Swiss legislation dealing with ART. RESULTS Since 1993 the age of women giving birth rose together with the number of women asking for ART. This demographic trend was reflected in a rise in the number of deliveries generated by ART (in 2012: 2.2%) and the proportion of multiple births (in 2012: 17.6%). The outcome of ART was most negatively influenced by the age of the treated patient. The number of retrieved oocytes decisively impacted the likelihood of delivery, the risk of multiple births and the incidence of ovarian hyperstimulation syndrome. CONCLUSIONS Optimal ovarian stimulation should be designed for the retrieval of 10 to 15 oocytes per treatment. Swiss legislation should enable and stimulate a policy of elective single embryo transfer to avoid multiple births.

Pelvic floor muscle electromyography during different running speeds: an exploratory and reliability study.

PURPOSE Stress urinary incontinence (SUI) affects women of all ages including young athletes, especially those involved in high-impact sports. To date, hardly any studies are available testing pelvic floor muscles (PFM) during sports activities. The aim of this study was the description and reliability test of six PFM electromyography (EMG) variables during three different running speeds. The secondary objective was to evaluate whether there was a speed-dependent difference between the PFM activity variables. METHODS This trial was designed as an exploratory and reliability study including ten young healthy female subjects to characterize PFM pre-activity and reflex activity during running at 7, 9 and 11 km/h. Six variables for each running speed, averaged over ten steps per subject, were presented descriptively, tested regarding their reliability (Friedman, ICC, SEM, MD) and speed difference (Friedman). RESULTS PFM EMG variables varied between 67.6 and 106.1 %EMG, showed no systematic error and were low for SEM and MD using the single value model. Applying the average model over ten steps, ICC (3,k) were >0.75 and SEM and MD about 50 % lower than for the single value model. Activity was found to be highest in 11 km/h. CONCLUSION EMG variables showed excellent ICC and very low SEM and MD. Further studies should investigate inter-session reliability and PFM reactivity patterns of SUI patients using the average over ten steps for each variable as it showed very high ICC and very low SEM and MD. Subsequently, longer running distances and other high-impact sports disciplines could be studied.