Lower shedding of strongylid eggs by Warmblood horses with recurrent airway obstruction compared to unrelated healthy horses

An association between equine recurrent airway obstruction (RAO) and increased resistance to intestinal parasites has been demonstrated in descendants of an RAO-affected stallion. It was hypothesised that members of another high-incidence RAO family (F) and unrelated RAO-affected Warmblood horses (UA) would shed fewer strongylid eggs than unrelated RAO-unaffected pasture mates (PM) under the same environmental conditions. Faecal worm egg counts were performed on faecal samples (63 F, 86 UA, 149 PM) and classified into three categories: 0, 1-100 and >100 eggs per gram. While results for F did not differ from PM, UA were 2.5-times less likely to shed strongylid eggs than PM. RAO-affected Warmblood horses may be more resistant to strongylid nematodes than unrelated unaffected pasture mates and a family history of RAO does not necessarily confer protection against helminth infections.

Resistance against strongylid nematodes in two high prevalence Equine Recurrent Airway Obstruction families has a genetic basis

A recent study showed increased resistance against strongylid nematodes in offspring of a stallion affected by recurrent airway obstruction (RAG) compared with unrelated pasture mates. Resistance against strongylid nematodes was associated with RAG affection. Hypothesis: Resistance against strongylid nematodes has a genetic basis. The genetic variants influencing strongylid resistance also influence RAG susceptibility. Faecal samples from the half-sibling offspring of two RAG-affected Warmblood stallions 98 offspring from the first family (family 1) and 79 from the second family (family 2) were analysed using a combined sedimentation-flotation method. The phenotype was defined as a binary trait - either positive or negative for egg shedding. The influence of non-genetic factors on egg shedding was analysed using SAS, the mode of inheritance was investigated using PAP and iBay, and the association between shedding of strongyle eggs and RAG was estimated by odds ratios. Previously established genotypes for 315 microsatellite markers were used for QTL analyses using GRID QTL. The inheritance of "strongylid egg shedding" is influenced by major genes on ECA15 and ECA20. Shedding of strongylid eggs is associated with RAG in family 1 but not in family 2. Conclusions: The status of "shedding of strongyle eggs" has a genetic background. The results were inconclusive as to whether "egg shedding" and RAG share common genetic components. Our results suggest that it may be possible to select for resistance against strongylid nematodes.

High NRBP1 expression in prostate cancer is linked with poor clinical outcomes and increased cancer cell growth

We recently established the rationale that NRBP1 (nuclear receptor binding protein 1) has a potential growth-promoting role in cell biology. NRBP1 interacts directly with TSC-22, a potential tumor suppressor gene that is differently expressed in prostate cancer. Consequently, we analyzed the role of NRBP1 expression in prostate cancer cell lines and its expression on prostate cancer tissue microarrays (TMA).

Spatial heterogeneity and lake morphology affect diffusive greenhouse gas emission estimates of lakes

Most estimates of diffusive flux (F) of methane (CH4) and carbon dioxide (CO2) from lakes are based on single-point flux chamber measurements or on piston velocity (k) modeled from wind speed and single-point measurements of surface water gas concentrations (C-aq). We analyzed spatial variability of F of CH4 and CO2, as well as C-aq and k in 22 European lakes during late summer. F and k were higher in the lake centers, leading to considerable bias when extrapolating single-point chamber measurements to whole-lake estimates. The ratio of our empirical k estimates to wind speed-modeled k was related to lake size and shape, suggesting a lake morphology effect on the relationship between wind speed and k. This indicates that the error inherent to established wind speed models can be reduced by determining k and C-aq at multiple sites on lakes to calibrate wind speed-modeled k to the local system.

Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease

AIM We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. MATERIALS AND METHODS The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA-DNA hybridization assays. RESULTS In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 10(5) A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00-3.35, p = 0.049), but its level or levels of other bacteria did not. CONCLUSIONS The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.

Modelling Lake Kivu water level variations over the last seven decades

This study aimed at analysing the hydrological changes in the Lake Kivu Basin over the last seven decades with focus on the response of the lake water level to meteorological factors and hydropower dam construction. Historical precipitation and lake water levels were acquired from literature, local agencies and from global databases in order to compile a coherent dataset. The net lake inflow was modelled using a soil water balance model and the water levels were reconstructed using a parsimonious lake water balance model. The soil water balance shows that 370 mm yr−1 (25%) of the precipitation in the catchment contributes to the runoff and baseflow whereas 1100 mm yr−1 (75%) contributes to the evapotranspiration. A review of the lake water balance resulted in the following estimates of hydrological contributions: 55%, 25%, and 20% of the overall inputs from precipitation, surface inflows, and subaquatic groundwater discharge, respectively. The overall losses were 58% and 42% for lake surface evaporation and outflow discharge, respectively. The hydrological model used indicated a remarkable sensitivity of the lake water levels to hydrometeorological variability up to 1977, when the outflow bed was artificially widened.

Multidisciplinary consensus on assessment of unruptured intracranial aneurysms: proposal of an international research group.

BACKGROUND AND PURPOSE To address the increasing need to counsel patients about treatment indications for unruptured intracranial aneurysms (UIA), we endeavored to develop a consensus on assessment of UIAs among a group of specialists from diverse fields involved in research and treatment of UIAs. METHODS After composition of the research group, a Delphi consensus was initiated to identify and rate all features, which may be relevant to assess UIAs and their treatment by using ranking scales and analysis of inter-rater agreement (IRA) for each factor. IRA was categorized as very high, high, moderate, or low. RESULTS Ultimately, 39 specialists from 4 specialties agreed (high or very high IRAs) on the following key factors for or against UIA treatment decisions: (1) patient age, life expectancy, and comorbid diseases; (2) previous subarachnoid hemorrhage from a different aneurysm, family history for UIA or subarachnoid hemorrhage, nicotine use; (3) UIA size, location, and lobulation; (4) UIA growth or de novo formation on serial imaging; (5) clinical symptoms (cranial nerve deficit, mass effect, and thromboembolic events from UIAs); and (6) risk factors for UIA treatment (patient age and life expectancy, UIA size, and estimated risk of treatment). However, IRAs for features rated with low relevance were also generally low, which underlined the existing controversy about the natural history of UIAs. CONCLUSIONS Our results highlight that neurovascular specialists currently consider many features as important when evaluating UIAs but also highlight that the appreciation of natural history of UIAs remains uncertain, even within a group of highly informed individuals.

The stable carbon isotopic composition of Daphnia ephippia in small, temperate lakes reflects in-lake methane availability

Daphnia can ingest methane-oxidizing bacteria and incorporate methanogenic carbon into their biomass, leading to low stable carbon isotope ratios (expressed as δ13C values) of their tissue. Therefore, δ13C analysis of Daphnia resting eggs (ephippia) in lake sediment records can potentially be used to reconstruct past in-lake availability of methane (CH4). However, detailed multilake studies demonstrating that δ13C values of recently deposited Daphnia ephippia (δ13Cephippia) are systematically related to in-lake CH4 concentrations (CH4aq) are still missing. We measured δ13Cephippia from surface sediments of 15 small lakes in Europe, and compared these values with late-summer CH4aq. δ13Cephippia ranged from −51.6‰ to −25.9‰, and was strongly correlated with CH4aq in the surface water and above the sediment (r −0.73 and −0.77, respectively), whereas a negative rather than the expected positive correlation was found with δ13C values of carbon dioxide (CO2) (r −0.54), and no correlation was observed with CO2aq. At eight sites, offsets between δ13 CCO2 and δ13Cephippia exceeded offsets between δ13 CCO2 and δ13Calgae reported in literature. δ13Cephippia was positively correlated with δ13C values of sedimentary organic matter (r 0.54), but up to 20.7‰ lower in all except one of the lakes (average −6.1‰). We conclude that incorporation of methanogenic carbon prior to ephippia formation must have been widespread by Daphnia in our study lakes, especially those with high CH4aq. Our results suggest a systematic relationship between δ13Cephippia values and CH4aq in small temperate lakes, and that δ13Cephippia analysis on sediment records may provide insights into past changes in in-lake CH4aq.

Genetics of recurrent airway obstruction (RAO)

Recurrent airway obstruction (RAO) is a multifactorial and polygenic disease. Affected horses are typically 7 years of age or older and show exercise intolerance, increased breathing effort, coughing, airway neutrophilia, mucus accumulation and hyperreactivity as well as cholinergic bronchospasm. The environmental factors responsible are predominantly allergens and irritants in haydust, but the immunological mechanisms underlying RAO are still unclear. Several studies have demonstrated a familiar predisposition for RAO and it is now proven that the disease has a genetic basis. In offspring, the risk of developing RAO is 3-fold increased when one parent is affected and increases to almost 5-fold when both parents have RAO. Segregation analysis in two high-prevalence families demonstrated a high heritability and a complex inheritance with several major genes. A whole genomescan showed chromosome-wide significant linkage of seven chromosomal regions with RAO. Of the microsatellites, which were located near atopy candidate genes, those in a region of chromosome 13 harboring the IL4R gene were strongly associated with the RAO phenotype in the offspring of one RAO-affected stallion. Furthermore, IgE-levels are influenced by hereditary factors in the horse, and we have evidence that RAO-affected offspring of the same stallion have increased levels of specific IgE against moldspore allergens. The identification of genetic markers and ultimately of the responsible genes will not only allow for an improved prophylaxis, i.e. early identification of susceptible individuals and avoidance of high-risk matings, but also improve our ability to find new therapeutic targets and to optimize existing treatments.

An inter-regional assessment of concentrations and δ13C values of methane and dissolved inorganic carbon in small European lakes

Methane (CH4) and carbon dioxide emissions from lakes are relevant for assessing the greenhouse gas output of wetlands. However, only few standardized datasets describe concentrations of these gases in lakes across different geographical regions. We studied concentrations and stable carbon isotopic composition (δ13C) of CH4 and dissolved inorganic carbon (DIC) in 32 small lakes from Finland, Sweden, Germany, the Netherlands, and Switzerland in late summer. Higher concentrations and δ13C values of DIC were observed in calcareous lakes than in lakes on non-calcareous areas. In stratified lakes, δ13C values of DIC were generally lower in the hypolimnion due to the degradation of organic matter (OM). Unexpectedly, increased δ13C values of DIC were registered above the sediment in several lakes. This may reflect carbonate dissolution in calcareous lakes or methanogenesis in deepwater layers or in the sediments. Surface water CH4 concentrations were generally higher in western and central European lakes than in Fennoscandian lakes, possibly due to higher CH4 production in the littoral sediments and lateral transport, whereas CH4 concentrations in the hypolimnion did not differ significantly between the regions. The δ13C values of CH4 in the sediment suggest that δ13C values of biogenic CH4 are not necessarily linked to δ13C values of sedimentary OM but may be strongly influenced by OM quality and methanogenic pathway. Our study suggests that CH4 and DIC cycling in small lakes differ between geographical regions and that this should be taken into account when regional studies on greenhouse gas emissions are upscaled to inter-regional scales.

The unruptured intracranial aneurysm treatment score: a multidisciplinary consensus.

OBJECTIVE We endeavored to develop an unruptured intracranial aneurysm (UIA) treatment score (UIATS) model that includes and quantifies key factors involved in clinical decision-making in the management of UIAs and to assess agreement for this model among specialists in UIA management and research. METHODS An international multidisciplinary (neurosurgery, neuroradiology, neurology, clinical epidemiology) group of 69 specialists was convened to develop and validate the UIATS model using a Delphi consensus. For internal (39 panel members involved in identification of relevant features) and external validation (30 independent external reviewers), 30 selected UIA cases were used to analyze agreement with UIATS management recommendations based on a 5-point Likert scale (5 indicating strong agreement). Interrater agreement (IRA) was assessed with standardized coefficients of dispersion (vr*) (vr* = 0 indicating excellent agreement and vr* = 1 indicating poor agreement). RESULTS The UIATS accounts for 29 key factors in UIA management. Agreement with UIATS (mean Likert scores) was 4.2 (95% confidence interval [CI] 4.1-4.3) per reviewer for both reviewer cohorts; agreement per case was 4.3 (95% CI 4.1-4.4) for panel members and 4.5 (95% CI 4.3-4.6) for external reviewers (p = 0.017). Mean Likert scores were 4.2 (95% CI 4.1-4.3) for interventional reviewers (n = 56) and 4.1 (95% CI 3.9-4.4) for noninterventional reviewers (n = 12) (p = 0.290). Overall IRA (vr*) for both cohorts was 0.026 (95% CI 0.019-0.033). CONCLUSIONS This novel UIA decision guidance study captures an excellent consensus among highly informed individuals on UIA management, irrespective of their underlying specialty. Clinicians can use the UIATS as a comprehensive mechanism for indicating how a large group of specialists might manage an individual patient with a UIA.

Urinary Biomarkers Indicative of Apoptosis and Acute Kidney Injury in the Critically Ill.

BACKGROUND Apoptosis is a key mechanism involved in ischemic acute kidney injury (AKI), but its role in septic AKI is controversial. Biomarkers indicative of apoptosis could potentially detect developing AKI prior to its clinical diagnosis. METHODS As a part of the multicenter, observational FINNAKI study, we performed a pilot study among critically ill patients who developed AKI (n = 30) matched to critically ill patients without AKI (n = 30). We explored the urine and plasma levels of cytokeratin-18 neoepitope M30 (CK-18 M30), cell-free DNA, and heat shock protein 70 (HSP70) at intensive care unit (ICU) admission and 24h thereafter, before the clinical diagnosis of AKI defined by the Kidney Disease: Improving Global Outcomes -creatinine and urine output criteria. Furthermore, we performed a validation study in 197 consecutive patients in the FINNAKI cohort and analyzed the urine sample at ICU admission for CK-18 M30 levels. RESULTS In the pilot study, the urine or plasma levels of measured biomarkers at ICU admission, at 24h, or their maximum value did not differ significantly between AKI and non-AKI patients. Among 20 AKI patients without severe sepsis, the urine CK-18 M30 levels were significantly higher at 24h (median 116.0, IQR [32.3-233.0] U/L) than among those 20 patients who did not develop AKI (46.0 [0.0-54.0] U/L), P = 0.020. Neither urine cell-free DNA nor HSP70 levels significantly differed between AKI and non-AKI patients regardless of the presence of severe sepsis. In the validation study, urine CK-18 M30 level at ICU admission was not significantly higher among patients developing AKI compared to non-AKI patients regardless of the presence of severe sepsis or CKD. CONCLUSIONS Our findings do not support that apoptosis detected with CK-18 M30 level would be useful in assessing the development of AKI in the critically ill. Urine HSP or cell-free DNA levels did not differ between AKI and non-AKI patients.

Plasma Heme Oxygenase-1 in Patients Resuscitated from out-of-Hospital Cardiac Arrest

Heme oxygenase-1 (HO-1) is an enzyme induced by hypoxia and reperfusion injury, and is associated with organ dysfunction in critically ill patients. Patients resuscitated from out-of-hospital cardiac arrest (OHCA) are subjected to hypoxemia, brain injury, and organ dysfunction. Accordingly, we studied HO-1 among these patients. A total of 143 OHCA patients resuscitated from a shockable initial rhythm and admitted to an ICU were included, with plasma HO-1 measured at ICU admission and at 24 h. We analyzed the associations between plasma HO-1 and time to return of spontaneous circulation (ROSC), 90-day mortality, and 12-month Cerebral Performance Category (CPC). HO-1 plasma concentrations were higher after OHCA compared with controls. HO-1 concentrations at admission and on day 1 associated with ROSC (P = 0.002 to P = 0.003). Admission and day 1 HO-1 plasma concentrations were higher in 90-day non-survivors than in survivors (P = 0.017, 0.026). In addition, poor neurological outcome (CPC 3-5) was associated with higher HO-1 plasma levels at admission (P = 0.024). Admission plasma HO-1 levels had an AUC of 0.623 to predict 90-day mortality and an AUC of 0.611 to predict CPC 3 to 5. In conclusion, we found that higher HO-1 plasma levels are associated with longer ROSC and poor long-term outcome.