Genotypic and phenotypic spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency.

OBJECTIVES: Pathogenic biallelic variants in PCK1 coding for the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) cause PEPCK-C deficiency, a rare disorder of gluconeogenesis presenting with hypoglycemia, lactic acidosis, and hepatopathy. To date, there has been no systematic analysis of its phenotypic, biochemical, and genetic spectrum. METHODS: All currently published individuals and a novel patient with genetically confirmed PEPCK-C deficiency were included. Clinical, biochemical, and genetic findings were analyzed. Protein and in-silico prediction score modeling was applied to analyze potential variant effects. RESULTS: Thirty-two individuals from 25 families were found, including one previously unreported patient. The typical biochemical pattern was hypoglycemia triggered by catabolic situations, elevated urinary concentrations of tricarboxylic acid cycle metabolites, mildly elevated alanine and aspartate aminotransferase and elevated lactate concentrations in serum. Plasma glutamine concentrations were elevated in some patients and may be a suitable marker for newborn screening. With adequate treatment, biochemical abnormalities usually normalized following a hypoglycemic episode. Symptom onset usually occurred in infancy with a broad range from neonatal age to adulthood. Regardless of the genotype, different phenotypes with a broad clinical spectrum were found. To date, eight genotypes with nine different PCK1 variants were identified, of which alleles with the recurrent variant c.925G > A; p.(Gly309Arg) are predominant and appear to be endemic in the Finnish population. Protein modeling suggests altered manganese- and substrate-binding as superordinate pathomechanisms. CONCLUSIONS: Environmental factors appear to be the main determinant for the phenotype in patients with biallelic variants in PCK1. Based on the biochemical pattern, PEPCK-C deficiency is a recognizable cause of childhood hypoglycemia. It is a treatable disease and early diagnosis is important to prevent metabolic derailment and morbidity. Newborn screening can identify at least a sub-cohort of affected individuals through elevated glutamine concentrations in dry blood.

Cardiac phenotype in propionic acidemia - Results of an observational monocentric study.

BACKGROUND: Propionic acidemia (PA) is an organic aciduria caused by inherited deficiency of propionyl-CoA carboxylase. Left ventricular dysfunction and QT prolongation may lead to life-threatening complications. Systematic analyses of cardiac phenotypes, in particular effects of specific cardiac therapies, are scarce. METHODS: In this longitudinal observational monocentric study (data from 1989 to 2017) all PA patients treated at our center were included. Echocardiographic parameters (left ventricular end-diastolic diameter: LVEDD, left ventricular shortening fraction, mitral valve Doppler inflow pattern) and 12­lead electrocardiogram recordings (corrected QT interval: QTc) were analyzed. Symptomatic patients were dichotomized to the group "early-onset" (symptoms within 28 days of life) and "late-onset" (symptoms after 28 days). Associations between cardiac function, LVEDD, QTc and clinical parameters (age at onset, beta-blocker or Angiotensin-converting enzyme inhibitor = ACE-I therapy) were analyzed. RESULTS: 18 patients with PA were enrolled, 17 of them were symptomatic and one asymptomatic, with a median age at diagnosis of 6 days. 14/17 (82%) had early onset disease manifestation. Systolic left ventricular dysfunction (i.e. hypokinetic phenotype of cardiomyopathy) was diagnosed in 7/18 (39%) patients at a median age of 14.4 years, all had early onset. Two patients had a dilated left ventricle and systolic left ventricular dysfunction (i.e. dilated hypokinetic phenotype - dilated cardiomyopathy). Diastolic left ventricular dysfunction was found in 11/18 (61%) individuals, typically preceding systolic left ventricular dysfunction. ACE-I therapy did not improve systolic left ventricular function. Mean QTc was 445 ms (+/- 18.11 ms). Longer QTc was associated with larger LVEDD. CONCLUSIONS: Systolic left ventricular dysfunction was found in 39% of patients, reflecting high disease severity. Two thirds of all individuals showed signs of diastolic left ventricular dysfunction usually preceding systolic left ventricular dysfunction; it therefore may be considered as an indicator for early cardiac disease manifestation, possibly allowing earlier treatment modification. Unresponsiveness to routine cardiac therapy highlights the need to evaluate further strategies, such as liver transplantation.

Technical note: Development of a noninvasive respiration rate sensor for cattle.

The measurement of the respiration rate (RR) in cattle is a valuable tool for monitoring health status. Thus, an RR sensor can be essential for stress detection, especially heat stress. Heat stress leads to a deviation of the normal RR and results in a decrease of milk production and fertility. Therefore, continuous monitoring of the RR can help early detection of heat stress and, thus, initiate timely counteractive actions to minimize physical stress. The most common method to measure the RR in cattle is to count the flank movement visually; however, this method is time-consuming and labor-intensive. In addition, the continuous measurement of the RR is difficult to implement and can be physically strenuous. Therefore, a device based on a differential pressure sensor that can record RR automatically has been developed to make continuous long-term studies possible. The aim of this study was to validate the data measured by the device with the help of a reference method. The reference method used was counting the flank movements of a total of 6 cows (Holstein-Friesian). The rear flank movements of each cow were recorded by a camera and counted independently of the device by an observer. Eight videos of 1 min each were recorded per cow. The data analysis was done with cows in 3 different body positions: dozing, lying, and standing. A total of 48 RR measurements of the device were compared with the counted RR frequencies of the video recording. The results were highly correlated during dozing [correlation coefficient (r) = 0.92, n = 13], lying (r = 0.98, n = 15), and standing (r = 0.99, n = 20). The evaluation showed that the device is suitable for automated RR counting. Further development of a marketable device is planned.

BRCA1-like profile is not significantly associated with survival benefit of non-myeloablative intensified chemotherapy in the GAIN randomized controlled trial.

PURPOSE: The BRCA1-like profile identifies tumors with a defect in homologous recombination due to inactivation of BRCA1. This profile has been shown to predict which stage III breast cancer patients benefit from myeloablative, DNA double-strand-break-inducing chemotherapy. We tested the predictive potential of the BRCA1-like profile for adjuvant non-myeloablative, intensified dose-dense chemotherapy in the GAIN trial. METHODS: Lymph node positive breast cancer patients were randomized to 3 × 3 dose-dense cycles of intensified epirubicin, paclitaxel, and cyclophosphamide (ETC) or 4 cycles concurrent epirubicin and cyclophosphamide followed by 10 cycles of weekly paclitaxel combined with 4 cycles capecitabine (EC-TX). Only triple negative breast cancer patients (TNBC) for whom tissue was available were included in these planned analyses. BRCA1-like or non-BRCA1-like copy number profiles were derived from low coverage sequencing data. RESULTS: 119 out of 163 TNBC patients (73%) had a BRCA1-like profile. After median follow-up of 83 months, disease free survival (DFS) was not significantly different between BRCA1-like and non-BRCA1-like patients [adjusted hazard ratio (adj.HR) 1.02; 95% confidence interval (CI) 0.55-1.86], neither was overall survival (OS; adj.HR 1.26; 95% CI 0.58-2.71). When split by BRCA1-like status, DFS and OS were not significantly different between treatments. However, EC-TX seemed to result in a trend to an improvement in DFS in patients with a BRCA1-like tumor, while the reverse accounted for ETC treatment in patients with a non-BRCA1-like tumor (p for interaction = 0.094). CONCLUSIONS: The BRCA1-like profile is not associated with survival benefit for a non-myeloablative, intensified regimen in this study population. Considering the limited cohort size, capecitabine might have additional benefit for TNBC patients.

Reproductive biology of Haemulon plumierii in the south-western Atlantic Ocean's most extensive reefs: implications for fisheries management.

The reproductive biology of the white grunt Haemulon plumierii was studied from 360 individuals obtained from artisanal fisheries landings in the Abrolhos Bank, Brazil, between August 2010 and March 2012. The overall sex-ratio did not differ significantly from 1:1, although males predominated in larger size classes. ß-Binomial modelling of historical sex-ratio data indicated that the catch rate of females has increased in recent years. Females reached maturity at a smaller total length (LT ; 214 mm) than males (235 mm LT ) and the LT at which 50% of all individuals are mature (L50 ) was 220 mm, corresponding to 41·5% of the maximum recorded LT . Variation in the gonado-somatic index and in the relative frequency of reproductive stages indicates that reproduction occurs year round, with increased activity during the austral spring and summer. Fecundity was not size dependent. The reproductive parameters provided here can support management measures focussed on seasonal closures during spawning peaks (September to November and February to March) and minimum sizes (>L50 ) for the capture of this important artisanal fisheries resource in Abrolhos, the region with the largest and most biodiverse coralline reefs in the South Atlantic Ocean.

[Safe treatment of acute hyperkalemia : The 1:4 and other principles]. / Sichere Behandlung der akuten Hyperkaliämie : Das 1:4 und andere Prinzipien.

Acute hyperkalemia is a dangerous electrolyte disorder, which must be treated immediately. It can lead to cardiac arrhythmia and death due to alterations in cell membrane potentials. The resulting alterations in the electrocardiogram (ECG) are multifarious and need to be rapidly recognized. Treatment consists of various stages. In addition to membrane stabilization, which is always necessary, potassium must be displaced into the intracellular space and then eliminated from the body. A commonly applied method for displacement of potassium into the intracellular space involves the administration of insulin-glucose mixtures, which is associated with many complications. In the clinical routine many prescription variations are applied, which do not always appear to be ideal with respect to the individual risk-benefit ratio. A practically useful and easily memorized insulin-glucose mixture has a relationship of 1IU insulin to 4g glucose. The therapeutic elimination from the body is carried out using an enhanced diuresis or the utilization of renal replacement procedures. Special attention must be paid to the continous monitoring of potassium and blood sugar levels. After overcoming the acute situation, attention must be paid to treatment of the underlying disorder and if necessary to readjustment of the long-term medication of the patient.

Comparison of prognostic and predictive impact of genomic or central grade and immunohistochemical subtypes or IHC4 in HR+/HER2- early breast cancer: WSG-AGO EC-Doc Trial.

INTRODUCTION: Potential prognostic and predictive markers in early, intermediate-risk breast cancer (BC) include histological grade, Ki-67, genomic signatures, e.g. genomic grade index (GGI), and intrinsic subtypes. Their prognostic/predictive impact in hormone receptor (HR: ER and/or PR) positive/HER2- BC is controversial. WSG-AGO EC-Doc demonstrated superior event-free survival (EFS) in patients with 1-3 positive lymph node receiving epirubicin/cyclophosphamide-docetaxel (EC-Doc) versus 5-fluoruracil/epirubicin/cyclophosphamide (FEC). METHODS: In a representative trial subset, we quantify concordance among factors used for clinical chemotherapy indication. We investigate the impact of central histology (n = 772), immunohistochemistry for intrinsic subtyping and IHC4, and dichotomous (GG) or continuous (GGI) genomic grade (n = 472) on patient outcome and benefit from taxane chemotherapy, focusing on HR+/HER2- patients (n = 459). RESULTS: Concordance of local grade (LG) with central (CG) or genomic grade was modest. In HR+/HER2- patients, low (GG-1: 16%), equivocal (GG-EQ: 17%), and high (GG-3: 67%) GG were associated with respective 5-year EFS of 100%, 93%, and 85%. GGI was prognostic for EFS within all LG subgroups and within CG3, whereas IHC4 was prognostic only in CG3 tumors.In unselected and HR+/HER2- patients, CG3 and luminal-A-like subtype entered the multivariate EFS model, but not IHC4 or GG. In the whole population, continuous GGI entered the model [hazard ratio (H.R.) of 75th versus 25th = 2.79; P = 0.01], displacing luminal-A-like subtype; within HR+/HER2- (H.R. = 5.36; P < 0.001), GGI was the only remaining prognostic factor.In multivariate interaction analysis (including central and genomic grade), luminal-B-like subtype [HR+ and (Ki-67 ≥20% or HER2+)] was predictive for benefit of EC-Doc versus FEC in unselected but not in HR+/HER2- patients. CONCLUSION: In the WSG-AGO EC-Doc trial for intermediate-risk BC, CG, intrinsic subtype (by IHC), and GG provide prognostic information. Continuous GGI (but not IHC4) adds prognostic information even when IHC subtype and CG are available. Finally, the high interobserver variability for histological grade and the still missing validation of Ki-67 preclude indicating or omitting adjuvant chemotherapy based on these single factors alone. TRIAL REGISTRATION: The WSG-AGO/EC-Doc is registered at ClinicalTrials.gov, NCT02115204.

MRI and (1)H-MRS in adenosine kinase deficiency.

INTRODUCTION: Adenosine kinase deficiency (ADK deficiency) is a recently described disorder of methionine and adenosine metabolism resulting in a neurological phenotype with developmental delay, muscular hypotonia, and epilepsy as well as variable systemic manifestations. The underlying neuropathology is poorly understood. We have investigated MRI and (1)H-MRS changes in ADK deficiency in order to better understand the in vivo neuropathologic changes of ADK deficiency. METHODS: Systematic evaluation of 21 MRIs from eight patients (age range 9 days-14.6 years, mean 3.9 years, median 2.7 years) including diffusion-weighted imaging in six and (1)H-MRS in five patients. RESULTS: Brain maturation was delayed in the neonatal period and in infancy (6/6), but ultimately complete. White matter changes occurring in five of eight patients were discrete, periventricular, and unspecific (4/5), or diffuse with sparing of optic radiation, corona radiata, and pyramidal tracts (1/5). Choline was low in white matter spectra (3/3), while there was no indication of low creatine in white matter or basal ganglia (5/5), and diffusion was variably decreased or increased. Central tegmental tract hyperintensity was a common finding (6/8), as was supratentorial atrophy (6/8). CONCLUSIONS: MRI changes in ADK deficiency consist of delayed but ultimately completed brain maturation with later onset of mostly unspecific white matter changes and potentially transient central tegmental tract hyperintensity. Immaturity on neonatal MRI is consistent with prenatal onset of disease and reduced choline with lower membrane turnover resulting in delayed myelination and deficient myelin maintenance.

[Surface Cleaning and Disinfection in the Hospital. Improvement by Objective Monitoring and Intervention]. / Flächenreinigung und Desinfektion im Krankenhaus. Verbesserung durch objektive Überwachung und Intervention.

Background and Objective: An assessment of cleaning and disinfection in hospitals by the use of objective surveillance and review of mandatory corrective measures was undertaken. Methods: A prospective examination of the cleaning and disinfection of surfaces scheduled for daily cleaning in 5 general care hospitals by use of an ultraviolet fluorescence targeting method (UVM) was performed, followed by structured educational and procedural interventions. The survey was conducted in hospital wards, operating theatres and intensive care units. Cleaning performance was measured by complete removal of UVM. Training courses and reinforced self-monitoring were implemented after the first evaluation. 6 months later, we repeated the assessment for confirmation of success. Results: The average cleaning performance was 34% (31/90) at base-line with significant differences between the 5 hospitals (11-67%). The best results were achieved in intensive care units (61%) and operating theatres (58%), the worst results in hospital wards (22%). The intervention significantly improved cleaning performance up to an average of 69% (65/94; +34.7%; 95% confidence interval (CI): 21.2-48.3; p<0.05), with differences between the hospitals (20-95%). The largest increase was achieved in hospital wards (+45%; CI 29.2-60.8; p<0.05). Improvements in operating theatres (+22.9%; CI 10.9-56.7) and intensive care units (+5.6%; CI 25.8-36.9) were statistically not significant. Conclusions: The monitoring of cleaning and disinfection of surfaces by fluorescence targeting is appropriate for evaluating hygiene regulations. An intervention can lead to a significant improvement of cleaning performance. As part of a strategy to improve infection control in hospitals, fluorescence targeting enables a simple inexpensive and effective surveillance of the cleaning performance and corrective measures.

Species cross-amplification, identification and genetic variation of 17 species of deer (Cervidae) with microsatellite and mitochondrial DNA from antlers.

Strong anthropogenic impact has caused 28 of the currently recognized 55 species of deer (Cervidae) to be listed on the IUCN Red List. Particular threats to vulnerable species include habitat deterioration and hybridization with alien, introduced species. The scarcity of many species has severely hampered genetic analyses of their populations, including the detection of loci for cross-species amplification. Because deer antlers are shed and re-grown annually, antlers offer the possibility for non-invasive genetic sampling of large individual numbers, and may provide material for reference genotyping from historical samples stored in zoos, museums and trophy collections of rare and extinct species/populations. In this paper, we report cross-species amplification of 19 nuclear microsatellite loci and the amplification of 16S mtDNA for barcoding from nearly a third of all deer species worldwide based on high quality DNA extracted from antler bone up to 40 years old. Phylogenetic analysis based on mtDNA of seventeen species and five subspecies corroborate previously published phylogenetic data, thus confirming the specific resolution of the DNA extraction methodology.

Health-related quality of life in adolescents with inflammatory bowel disease depends on disease activity and psychiatric comorbidity.

Adolescent patients with inflammatory bowel disease (IBD) show an increased risk for behavioral and emotional dysfunction. Health-related quality of life (HRQoL) is influenced by medical illnesses, as well as by psychiatric disorders, but for adolescents with IBD, the extent to which HRQoL is influenced by these two factors is unclear. For 47 adolescent IBD patients, we analyzed disease activity, HRQoL and whether or not a psychiatric disorder was present. Disease activity was estimated using pediatric Ulcerative Colitis Activity Index and pediatric Crohn's Disease Activity Index. The IMPACT-III and the EQ-5D were used to measure HRQoL and QoL, respectively. In addition, patient and parent diagnostic interviews were performed. 55.3 % patients fulfilled DSM-IV criteria for one or more psychiatric disorders. In all patients, psychiatric comorbidity together with disease activity contributed to a reduction in quality of life. Adolescents with IBD are at a high risk for clinically relevant emotional or behavioral problems resulting in significantly lower HRQoL. We conclude that accessible, optimally structured psychotherapeutic and/or psychiatric help is needed in adolescent patients with IBD.

Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression.

BACKGROUND: Taxane-based adjuvant chemotherapy is standard in node-positive (N+) early breast cancer (BC). The magnitude of benefit in intermediate-risk N+ early BC is still unclear. WSG-AGO epiribicine and cyclophosphamide (EC)-Doc is a large trial evaluating modern taxane-based chemotherapy in patients with 1-3 positive lymph nodes (LNs) only. PATIENTS AND METHODS: A total of 2011 BC patients (18-65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel 100 q3w (n = 1008) with the current standard: 6 × F500E100C500 q3w (n = 828) or C600M40F600 d1, 8× q4w (n = 175). Primary end point was event-free survival (EFS); secondary end points were overall survival (OS), toxicity, translational research, and quality of life. Central tumor bank samples were evaluable in a representative collective (n = 772; 40%). Ki-67 was assessed centrally in hormone receptor-positive disease as a surrogate marker for the distinction of luminal A/B-like tumors. RESULTS: Baseline characteristics were well balanced between study arms in both main study and central tumor bank subset. At 59-month median follow-up, superior efficacy of EC-Doc [versus FEC (a combination of 5-fluorouracil, epirubicin, and cyclophosphamide)] was seen in EFS and OS: 5-year EFS: 89.8% versus 87.3% (P = 0.038); 5-year OS: 94.5% versus 92.8% (P = 0.034); both tests one-tailed. EC-Doc caused more toxicity. In hormone receptor-positive (HR)+ disease, only high-Ki-67 tumors (≥ 20%) derived significant benefit from taxane-based therapy: hazard ratio = 0.39 (95% CI 0.18-0.82) for EC-Doc versus FEC (test for interaction; P = 0.01). CONCLUSION: EC-Doc significantly improved EFS and OS versus FEC in intermediate-risk BC (1-3 LNs) within all subgroups as defined by local pathology. In HR+ disease, patients with luminal A-like tumors may be potentially over-treated by taxane-based chemotherapy. CLINICAL TRIAL NUMBER: ClinicalTrials.gov, NCT02115204.

Mediterranean dietary pattern, inflammation and endothelial function: a systematic review and meta-analysis of intervention trials.

BACKGROUND: High adherence to a Mediterranean diet (MD) is associated with reduced all-cause and cardiovascular mortality risk. To our knowledge, there is no systematic review and meta-analysis of randomized controlled trials that has compared the effects of an MD on outcomes of endothelial function and inflammation. METHODS AND RESULTS: Literature search was performed using the electronic databases MEDLINE, EMBASE, and the Cochrane Trial Register. Inclusion criteria were: randomized controlled trials, 19 + years of age, and minimum intervention period of 12 weeks. Study specific weighted mean differences (WMD) were pooled using a random effect model. Seventeen trials including 2300 subjects met the objectives. MD regimens resulted in a significantly more pronounced increase in flow mediated dilatation [WMD: 1.86%, 95% CI 0.23 to 3.48, p = 0.02; I(2) = 43%], and adiponectin [WMD: 1.69 µg/ml, 95% CI 0.27 to 3.11, p = 0.02; I(2) = 78%], while high-sensitive C reactive protein [WMD: -0.98 mg/l, 95% CI -1.48 to -0.49, p < 0.0001; I(2) = 91%], interleukin-6 [WMD: -0.42 pg/ml, 95% CI -0.73 to -0.11, p = 0.008; I(2) = 81%], and intracellular adhesion molecule-1 [WMD: -23.73 ng/ml, 95% CI -41.24 to -6.22 p = 0.008; I(2) = 34%] turned out to be significantly more decreased. CONCLUSION: The results of the present meta-analysis provide evidence that an MD decreases inflammation and improves endothelial function.

Drug handling in a paediatric intensive care unit--can errors be prevented by a three-step intervention?

BACKGROUND: Drug handling in paediatric intensive care units (PICU) is prone to medication errors. We aimed to identify type and prevalence of those errors and to assess preventative interventions. METHODS: Prospective intervention study investigating a 3-step intervention for preventing errors in drug handling in a 10-bed PICU of a university hospital. Nurses' drug handling was monitored in daily routine to identify the number of patients affected by errors and overall prevalence and types of errors in drug handling. We implemented a comprehensive intervention consisting of an information handout, a training course, and a 76-page reference book tailored to reduce the prevalence. RESULTS: The prevalence of errors in drug handling decreased from 83 % (555 errors/668 processes)to 63 % (554/883; p < 0.001) after the intervention. The number of affected patients remained unchanged (95 % vs. 89 %, p = 0.370).Peroral (PO) drugs (1.33 errors/process) were more error-prone than intravenous (IV) drugs(0.64), despite being used less frequently (27 % vs.73 % of all processes, p < 0.001). The interventions decreased the prevalence to 0.77 errors/process(p < 0.001) in PO and to 0.52 in IV drugs (p = 0.025). CONCLUSION: Errors in drug handling were alarmingly frequent. PO drugs were frequently subject to errors, even though being used less frequently. The implementation of a comprehensive intervention succeeded in reducing the prevalence of errors. Yet further refinements are necessary to decrease also the number of affected patients.

Evaluation of Mucin-1 protein and mRNA expression as prognostic and predictive markers after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Mucin-1 (MUC1) is a promising antigen for the development of tumor vaccines. We evaluated the frequency of MUC1 expression and its impact on therapy response and survival after neoadjuvant chemotherapy for breast cancer. PATIENTS AND METHODS: Pre-treatment core biopsies of patients from the GeparTrio neoadjuvant trial (NCT 00544765) were evaluated for MUC1 by immunohistochemistry (IHC; N = 691) and quantitative RT-PCR (qRT-PCR; N = 286) from formalin-fixed paraffin-embedded (FFPE) samples. RESULTS: MUC1 protein and mRNA was detectable in the majority of cases and was associated with hormone-receptor-positive status (P < 0.001). High MUC1 protein and mRNA expression were associated with lower probability of pathologic complete response (P = 0.017 and P < 0.001) and with longer patient survival (P = 0.03 and P < 0.001). In multivariable analysis, MUC1 protein and mRNA expression were independently predictive (P = 0.001 and P < 0.001). MUC1 protein and mRNA expression were independently prognostic for overall survival (P = 0.029 and P = 0.015). CONCLUSIONS: MUC1 is frequently expressed in breast cancer and detectable on mRNA and protein level from FFPE tissue. It provides independent predictive information for therapy response and survival after neoadjuvant chemotherapy. In clinical immunotherapy trials, MUC1 expression may serve as a predictive marker.

Long-term effects of low glycemic index/load vs. high glycemic index/load diets on parameters of obesity and obesity-associated risks: a systematic review and meta-analysis.

AIM: The aim of the present meta-analysis was to investigate the long-term effects of glycemic index-related diets in the management of obesity with a special emphasis on the potential benefits of low glycemic index/load (GI/GL) in the prevention of obesity-associated risks. DATA SYNTHESIS: Electronic searches for randomized controlled trials (RCTs) comparing low glycemic index/load versus high glycemic index/load diets were performed in MEDLINE, EMBASE and the Cochrane Library. Outcome of interest markers included anthropometric data as well as biomarkers of CVD and glycemic control. Study specific weighted mean differences were pooled using a random effect model. 14 studies were included in the primary meta-analysis. Weighted mean differences in change of C-reactive protein [WMD: -0.43 mg/dl, (95% CI -0.78 to -0.09), p = 0.01], and fasting insulin [WMD: -5.16 pmol/L, (95% CI -8.45 to -1.88), p = 0.002] were significantly more pronounced in benefit of low GI/GL diets. However decrease in fat free mass [WMD: -1.04 kg (95% CI -1.73 to -0.35), p = 0.003] was significantly more pronounced following low GI/GL diets as well. No significant changes were observed for blood lipids, anthropometric measures, HbA1c and fasting glucose. Sensitivity analysis was performed for RCTs excluding subjects with type 2 diabetes. Decreases in C-reactive protein and fasting insulin remained statistically significant in the low GI/GL subgroups. CONCLUSIONS: The present systematic review provides evidence for beneficial effects of long-term interventions administering a low glycemic index/load diet with respect to fasting insulin and pro-inflammatory markers such as C-reactive protein which might prove to be helpful in the primary prevention of obesity-associated diseases.

Unprotected left main coronary artery disease. Surgical therapy.

Coronary artery bypass grafting (CABG) has been established as a safe concept in the treatment of unprotected left main coronary artery (ULMCA) disease and is considered the first-line treatment in current interdisciplinary guidelines. Regardless of the complexity of the lesion and the concomitant diseases, CABG is associated with excellent long-term results. Randomized controlled trials investigating the role of percutaneous coronary intervention in the setting of ULMCA lesions are frequently underpowered and suggest that, when restricted to less complex lesions, percutaneous coronary intervention is associated with results comparable to surgery. Thus, there is an urgent need for further randomized controlled trials RCTs with all-comers design to supply precise data under real-life conditions representative of the left main stem anatomy. Until then, an interdisciplinary approach to patients with ULMCA lesions is mandatory in view of the existing guidelines.

Sensor-based monitoring of the prevalence and severity of foot pad dermatitis in broiler chickens.

1. The aim of this study was to assess the suitability of a dielectric measurement to evaluate the prevalence and severity of foot pad dermatitis (FPD) in broiler chickens. 2. The study focussed on surveying the occurrence of FPD during the growing period of one broiler chicken flock. A scoring system consisting of 5 categories was used to assess the prevalence and severity of FPD macroscopically. Additionally, the dielectric constant (DC) of both foot pads of 50 chickens was measured in a triple iteration with the MoistureMeter D (Delfin Technologies, Kuopio, Finland) on three different dates. 3. On all measurement days, DC and FPD score were negatively correlated. The severity of FPD increased during the growing period, and severe lesions occurred at an early stage. 4. Further research is necessary to develop an effective early warning system for FPD in poultry houses. However, the non-invasive measurement of DC provides a reliable method for the objective assessment of occurrence and severity of FPD.

How should the respiration rate be counted in cattle?

Respiration rate (RR) is a proficient indicator to measure the health status of cattle. The common method of measurement is to count the number of respiratory cycles each minute based on flank movements. However, there is no consistent method of execution. In previous studies, various methods have been described, including counting flank movements for 15 s, 30 s or 60 s as well as stopping the time for 5 or 10 breaths. We assume that the accuracy of the aforementioned methods differs. Therefore, we compared their precision with an RR sensor, which was used as the reference method in this study. Five scientists from the fields of agricultural science and veterinary medicine quantified the flank movement according to each of the five methods mentioned above. The results showed that with an average RR of 30 breaths per minute (bpm), all methods showed a high correlation to the values of the RR sensor. However, counting breaths for 60 s had the highest level of conformity with the RR sensor (Lin`s concordance correlation coefficient: 0.96) regardless of the level of RR. With rising RR, the inaccuracy increased significantly for the other four investigated methods, especially when counting 5 and 10 breaths. Therefore, we would recommend that counting for 60 s should be used as the standard method for future studies due to its high precision regardless of the level of RR.