^1H{^(19)F} NOE NMR Structural Signatures of the Insulin R_6 Hexamer: Evidence of a Capped HisB10 Site in Aryl- and Arylacryloyl-carboxylate Complexes

New and improved insulin: ^1H{^(19)F} NOE NMR difference spectra for CF_3-substituted aromatic carboxylates bound at the HisB10 sites of the R_6 human insulin (HI) hexamer show strong NOEs between the CF_3 groups and the LeuB6, AsnB3, and PheB1 sidechains. The NOEs and structural modeling establish that these carboxylates form closed complexes with the HisB10 site capped by the PheB1 rings

Association between transfer of passive immunity, health, and performance of female dairy calves from birth to weaning

The objective of this observational study was to compare calf health, average daily weight gain, and calf mortality considering the proposed categories of transfer of passive immunity (TPI) by the consensus report of Lombard et al. (2020). The consensus report defines 4 categories of passive immunity (excellent, good, fair, and poor) of calves obtained after colostrum ingestion. The association between the 4 TPI categories was analyzed on calf health (i.e., hazards for morbidity and mortality), and average daily weight gain (ADG) of female Holstein Friesian calves during the first 90 d of age. A further aim of this study was to examine the effects of calving-related factors, such as dystocia or winter season, on TPI status. We hypothesized that calves with excellent TPI have greater ADG, lower risks for infectious diseases such as neonatal diarrhea, pneumonia, and omphalitis, and lower mortality rates. This observational study was conducted from December 2017 to March 2021. Blood was collected from 3,434 female Holstein Friesian dairy calves from 1 commercial dairy farm. All female calves aged 2 to 7 d were assessed for TPI status by determination of total solids (TS) in serum via Brix refractometry by the farm personnel once a week. Passive immunity was categorized according to Lombard et al. (2020) with excellent (≥9.4% Brix), good (8.9–9.3% Brix), fair (8.1–8.8% Brix), or poor TPI (<8.1% Brix). For the analysis of ADG and calving ease 492 or 35 calves had to be excluded due to missing data. The distribution of calves according to TPI categories was as follows: 4.8% poor (n = 166), 29.5% fair (n = 1,012), 28.3% good (n = 971), and 37.4% excellent (n = 1,285). From the calving-related factors, parity of the dam, calving ease, birth month, calving assistance by different farm personnel, and day of life for TPI assessment were significantly associated with TS concentration. Out of 3,434 calves, 216 (6.3%) had diarrhea, and 31 (0.9%) and 957 (27.9%) suffered from omphalitis and pneumonia during the first 90 d of life, respectively. Overall, the morbidity during the preweaning period was 32.6% (n = 1,118), and the mortality was 3.1% (n = 107). The ADG was 0.90 ± 0.15 kg with a range of 0.32 to 1.52 kg. The Cox regression model showed that calves suffering from poor TPI tended toward a greater hazard risk (HR) for diarrhea (HR = 1.57, 95% CI: 0.92–2.69) compared with calves with excellent TPI. Calves suffering from TPI had a greater HR for pneumonia (HR = 2.00, CI: 1.53–2-61), overall morbidity (HR = 1.99, CI: 1.56–2.55), and mortality (HR = 2.47, CI: 1.25–4.86) in contrast to excellent TPI. Furthermore, calves with good and fair TPI had significantly greater HR for pneumonia (good TPI: HR = 1.35, CI: 1.15–1.59; fair TPI: HR = 1.41, CI: 1.20–1.65) and overall morbidity (good TPI: HR = 1.26, CI: 1.09–1.47; fair TPI: HR = 1.32, CI: 1.14–1.53) compared with the excellent TPI category. Average daily weight gain during the first 60 d of life was associated with TPI categories. Calves with excellent and good TPI status had ADG of 0.90 ± 0.01 kg/d and 0.92 ± 0.01 kg/d (mean ± SE), respectively. The ADG of calves with fair TPI status was 0.89 ± 0.01 kg/d, and calves suffering from poor TPI had 0.86 ± 0.01 kg/d. Average daily weight gain differed in calves with poor TPI compared with the other categories. Fair and excellent TPI differed additionally from good TPI. We found no statistical difference between the TPI categories fair and excellent. In conclusion, poor TPI was associated with higher morbidity and mortality during the first 90 d of life. Furthermore, calves with fair, good or excellent TPI had greater ADG

Bouke Spoelstra: 'n blyk van waardering

Hiermee wil ons Bouke Spoelstra se aandeel aan die werksaamhede van die Kerkhistoriese Werkgemeenskap van Suider-Afrika in oënskou neem. Een van die voordele van die stigting van die Kerkhistoriese Werkgemeenskap op 1 Oktober 1970 was dat waar ons mekaar tevore uit geskrifte geken het, ons nou persoonlik kennisgemaak het. So het die naam Bouke Spoelstra, bekend uit sy geskrifte, veral sy proefskrif Die Doppers in Suid-Afrika (1760-1899) en sy aan­ deel aan die Handleiding by die Kerkorde, nou vir ons 'n gesig gekry en het hy vanweë ons jaarlikse kontak by die byeenkomste 'n gewaardeerde vriend geword

Effect of dose and frequency of prostaglandin F2α treatments during a 7-day Ovsynch protocol with an intravaginal progesterone releasing device on luteal regression and pregnancy outcomes in lactating Holstein cows

Our objective was to evaluate the effect of 3 different Ovsynch protocols on progesterone (P4) and pregnancies per artificial insemination (P/AI), where all cows received a P4 releasing intravaginal device (PRID) from d 0 until d 8. We hypothesized that (1) both modified PGF2α treatments lead to decreased P4 at the second GnRH treatment (G2), resulting in greater P/AI, (2) the treatment effect is influenced by the presence of a corpus luteum (CL) at the beginning of the protocol, and (3) potential vaginal discharge caused by the PRID does not have a negative influence on fertility. Lactating Holstein cows (n = 1,056) were randomly assigned to 1 of 3 treatment groups on a weekly basis (n = 356; control: d 0, 100 µg of GnRH + PRID; d 7, 25 mg of dinoprost; d 8, PRID removal; d 9, 100 µg of GnRH). Cows in the second group (n = 353) received an Ovsynch protocol with a double dose of PGF2α (DoubleDose: d 0, 100 µg of GnRH + PRID; d 7, 50 mg of dinoprost; d 8, PRID removal; d 9, 100 µg of GnRH). Cows in the third group (n = 347) received an Ovsynch protocol with a second PGF2α treatment 24 h after the first one (2PGF: d 0, 100 µg of GnRH + PRID; d 7, 25 of mg dinoprost; d 8, 25 mg of dinoprost and PRID removal; d 9, 100 µg of GnRH). All cows had their ovaries scanned to determine the presence of a CL at the beginning of the Ovsynch protocol. Vaginal discharge score (VS) was evaluated at PRID removal. All cows received timed artificial insemination approximately 16 h after G2. Pregnancy diagnosis was performed via transrectal ultrasonography (d 38 ± 3 after timed artificial insemination) and rechecked on d 80 ± 7 after timed artificial insemination. Blood samples were collected on d 0, 7, and 9 of the protocol to determine P4 concentrations. Treatment affected P4 at G2. Progesterone was lower for 2PGF and DoubleDose cows compared with cows in the control group (control 0.35 ± 0.02 ng/mL; DoubleDose 0.29 ± 0.02 ng/mL; 2PGF 0.30 ± 0.02 ng/mL). Overall, P/AI did not differ among treatments. We found, however, an interaction between treatment and CL at the first GnRH treatment. Cows lacking a CL at the first GnRH treatment in the 2PGF group had greater P/AI (47.9%) compared with the same type of cows in the DoubleDose group (32.7%). We observed an effect of VS on P4 concentration at d 7. We found an increase in P4 with greater VS. Vaginal discharge score at PRID removal tended to have a positive effect on P/AI at d 38 (VS0: 36.5%; VS1: 41.3%; VS2: 49.7%). In conclusion, the addition of a second PGF treatment on d 7 and 8 of a 7-d Ovsynch protocol increased luteal regression and decreased mean P4 at G2. Cows treated with PGF2α 2 times 24 h apart showed greater P/AI, compared with cows treated with an increased dose of PGF2α

Effect of a progesterone-releasing intravaginal device (PRID) for 8 days during a modified Ovsynch protocol on pregnancy outcomes in lactating Holstein cows

Our objective was to evaluate the effect of a progesterone-releasing intravaginal device (PRID) in a 7-d Ovsynch protocol on pregnancy per artificial insemination (P/AI) and pregnancy loss, compared with a standard 7-d Ovsynch protocol without progesterone supplementation. We hypothesized that progesterone supplementation during an Ovsynch protocol would increase P/AI and decrease pregnancy loss. Data were collected on lactating Holstein cows (n = 716) that either received a 7-d Ovsynch protocol (control: d 0, 100 µg of GnRH; d 7, 500 µg of cloprostenol; d 9, µg of GnRH; n = 360) or a modified Ovsynch protocol with addition of a PRID (PRIDsynch; d 0, 100 µg of GnRH + PRID; d 7, 25 mg of dinoprost; d 8, PRID removal; d 9, 100 µg of GnRH; n = 356). All cows received timed artificial insemination (TAI) approximately 16 h after the second GnRH treatment. Pregnancy diagnosis was performed via ultrasonography on d 38 ± 3 after TAI and rechecked on d 80 ± 7 after TAI. Reproductive performance differed between treatments, with PRIDsynch cows having greater (38.9%) P/AI compared with control cows (31.7%) at d 38 ± 3 and also at d 80 ± 7 (34.6% vs. 28.9%, for PRIDsynch and control cows, respectively). Pregnancy loss did not differ among treatments

Instabilities and turbulence in stellarators from the perspective of global codes

In this work, a comparison of the global gyrokinetic codes EUTERPE and GENE-3D in stellarator configurations of LHD and W7-X is carried out. In linear simulations with adiabatic electrons, excellent agreement is found in the mode numbers, growth rate and frequency, mode structure, and spatial localization of the most unstable mode in LHD. In W7-X, the dependence of the growth rate and frequency with the mode number is well reproduced by both codes. The codes are also compared in linear simulations with kinetic ions and electrons in W7-X using model profiles, and reasonable agreement is found in the wavenumber of the most unstable modes. A stabilization of small-scale modes in kinetic-electron simulations with respect to the adiabatic-electron case is consistently found in both codes. Nonlinear simulations using adiabatic electrons and model profiles are also studied and the heat fluxes are compared. Very good agreement is found in the turbulent ion heat fluxes in both LHD and W7-X. Two problems that cannot be properly accounted for in local flux tube codes are studied: the localization of instabilities and turbulence over the flux surface and the influence of a background long-wavelength electric field. Good agreement between codes is found with respect to the spatial localization of instabilities and turbulence over the flux surface. The localization of saturated turbulence is found in both codes to be much smaller than that of the linear instabilities and smaller than previously reported in full-surface radially-local simulations. The influence of the electric field on the localization is also found to be smaller in the developed turbulent state than in the linear phase, and smaller than in previous works. A stabilizing effect of a constant electric field on the linearly unstable modes is found in both codes. A moderate reduction of turbulent transport by the radial electric field..

Evaluation of the diagnostic accuracy of a point-of-care device to measure concentrations of nonesterified fatty acids in serum and whole blood

The objective of this study was to compare measurements of nonesterified fatty acids (NEFA) between the gold standard diagnostic laboratory method and a handheld NEFA meter (Qucare Pro meter, DFI Co. Ltd.). Three experiments were conducted to study the usability of the meter. In experiment 1 we compared results of the meter obtained from measurements in serum and whole blood with results of the gold standard method. Based on the results of experiment 1 we compared the results measured by the meter in whole blood with results obtained from the gold standard method on a larger scale, as we wanted to omit the step of centrifugation with the cow-side test. In experiment 3 we determined the influence of ambient temperature on measurements. Overall, blood samples of 231 cows were collected between 14 and 20 d in milk. The Spearman correlation coefficients (ρ) were calculated and Bland-Altman plots were created to compare the accuracy of the NEFA meter with the gold standard. In addition, in experiment 2 receiver operating characteristic (ROC) curve analyses were performed, to define thresholds for the NEFA meter to detect cows with a NEFA concentration above 0.3, 0.4, and 0.7 mEq/L. In experiment 1, there was a high correlation between NEFA concentrations in whole blood and serum determined by the NEFA meter and the gold standard (ρ = 0.90 for measurement in whole blood; ρ = 0.93 for measurement in serum). In experiment 2, the measurement in whole blood with the NEFA meter was compared with the gold standard. Despite a lower correlation (ρ = 0.79) the ROC curve analyses revealed a high specificity and a moderate sensitivity for lower cut-points (i.e., 0.3 and 0.4 mEq/L). The NEFA meter underestimated especially high concentration of >0.7 mEq/L. Considering thresholds of 0.3, 0.4, and 0.7 mEq/L measured by the gold standard test, sensitivity and specificity were 59.1% and 96.7%, 79.0% and 95.4%, and 86.4% and 95.6%, respectively, when using 0.3, 0.3, and 0.4 mEq/L as thresholds for the NEFA meter. Accuracy was 74.1%, 88.3%, and 93.8% for the 3 thresholds tested. Experiment 3 showed that measurements should be conducted at approximately 21°C (ρ = 0.73) as correlations were poor at 6.2°C and 15.1°C (ρ = 0.18 and 0.22, respectively)

Auf dem Wege zu einer integrierten Versorgung: Neue sozialrechtliche Rahmenbedingungen unter Berücksichtigung der Erfahrungen aus den USA und am Beispiel Berlins

Die vollzogene Gesundheitsreform eröffnet im Rahmen des Sozialgesetzbuches neue Möglichkeiten für Managed Care Lösungen. Bislang basierte das System auf Kollektivverträgen während Managed Care selektives Kontrahieren von Versicherungen mit Leistungsanbietern vorsieht. Im Ergebnis soll der Wettbewerb zwischen den Krankenversicherungen verstärkt werden. Die Einführung von zusätzlichen Wettbewerbselementen soll eine kostengünstigere und dennoch qualitativ hochwertige Versorgung sicherstellen. In den USA ist ein Grossteil der Bevölkerung in unterschiedlichen Formen von Managed Care Organisationen versichert, deshalb soll eine kritische Analyse der amerikanischen Erfahrungen beispielhaft in die Arbeit einfließen. Kosteneinsparungen konnten dort nur mit Hilfe eines durchgängigen Managed Care Systems erreicht werden. Im Rahmen der Arbeit soll untersucht werden, inwiefern eine Managed Care Organisation in Berlin implementiert werden könnte. Als Region soll dabei der innere S-Bahnring der Stadt Berlin dienen. Dort gibt es genügend Leistungserbringer, die zu einem Netzwerk verbunden werden könnten. Als Rechtsrahmen wird eine GmbH-Lösung empfohlen. -- The latest health care reform in German provides a new codification of the social law and framework that creates the base for a managed care. Up to now social security was characterised by collective agreements whereas managed care consists of a number of selective agreements between insurance companies and providers of medical services. As a result competition between the providers should be increased. The introduction of additional market elements should improve the co-ordination of the single providers. This is for the purpose to offer a high-grade health service at lower costs. In the United States a greater part of the population is enrolled in a Managed Care Organisation (MCO) and that is why it served as an example to be critically reviewed. A reduction of costs can only be realised when the Managed Care idea dominates all sectors of public health service and a consistent system can be founded. The present work examines the possibilities to implement a MCO in Berlin. The inner circle of the Berlin urban railway (S-Bahn) is an ideal location for the MCO. Favourable are a relatively low age of local population and a high level of education. Both criteria are correlated with a low demand of health services. Moreover in the mentioned area already exists a certain number of hospitals and medical service points that could be united to a network. The legal form of a GmbH (Ltd.) fits best for this purpose.

Evaluation of laboratory and on-farm tests to estimate colostrum quality for dairy cows

The objectives of this study were to evaluate different analytical methods to determine colostrum quality in dairy cattle, including one laboratory-based method (ELISA) and 4 on-farm tests. We hypothesized that the colostral IgG concentration using different analytical methods, such as ELISA (mg/mL), digital Brix refractometer (% Brix), colostrometer (specific gravity and mg/mL), an outflow funnel (seconds), and a lateral flow assay (mg/mL), were highly correlated with the reference method, radial immunodiffusion (RID; mg/mL) and would generate comparable results. Colostrum samples were collected from 209 Holstein Friesian cows on 2 commercial dairy farms in Germany. Colostrum weight and colostrum temperature were measured. Test characteristics, such as optimum thresholds, sensitivity, specificity, and area under the curve (AUC) were determined using a receiver operating characteristic curve analyses for each test. Out of 209 colostrum samples assessed by RID, 186 (89%) samples had high quality (≥50 mg IgG/mL), while 23 colostrum samples (11%) showed poor quality with IgG concentrations less than 50 mg/mL. The mean IgG concentration (±SD) was 101.3 ± 45.9 mg/mL and the range was 6.0 to 244.3 mg/mL. The Pearson correlation coefficient (r) between RID and ELISA was r = 0.78. In comparison to RID, Pearson correlation coefficients for the on-farm tests were: r = 0.79 (digital Brix refractometry), r = 0.58 (colostrometer: specific gravity), r = 0.61 (colostrometer: temperature corrected), r = 0.26 (outflow funnel) and r = 0.43 (lateral flow assay), respectively. The optimal threshold to identify high-quality colostrum using ELISA was 50.8 mg/mL with sensitivity 91.3%, specificity 92.3%, and AUC of 0.94. For the on-farm tests sensitivity ranged from 95.7% (Brix refractometry) to 60.9% (lateral flow assay). Specificity ranged from 88.6% (lateral flow assay) to 75.9% (colostrometer: temperature corrected). The AUC ranged from 0.93 (Brix refractometry) to 0.73 (outflow funnel). Based on the AUC, ELISA (0.94) and Brix refractometry (0.93) can be considered highly accurate. In conclusion, the ELISA is accurate to assess colostrum quality. Regarding the on-farm tests only the digital Brix refractometer and the colostrometer were adequate to determine colostrum quality

Effect of transition cow health and estrous expression detected by an automated activity monitoring system within 60 days in milk on reproductive performance of lactating Holstein cows

The objective of this observational study was to evaluate the association of transition cow health and estrous expression, detected by an automated activity monitoring system (Smarttag Neck, Nedap Livestock Management), with reproductive performance in lactating Holstein cows. A total of 3,750 lactating Holstein cows (1,563 primiparous cows and 2,187 multiparous cows) from a commercial dairy farm in Slovakia calving from January 2020 until July 2021 were enrolled on an ongoing basis. Activity data were recorded from d 7 until d 60 postpartum. Within this observational period, cows were classified into 3 categories: (1) no estrus event (Estrus0), (2) 1 estrus event (Estrus1), or (3) 2 or more estrus events (Estrus2+). Transition cow health was assessed by farm personnel within the first 30 d in milk (DIM) using standard operating procedures. Generalized linear mixed models were used to analyze continuous and categorical data. Cox proportional hazard models were used for time to event data. The overall prevalence of anestrus was 20.8%. Multiparous cows had a greater risk for anestrus compared with primiparous cows [odds ratio (OR) = 1.4]. Cows with stillbirth (OR = 1.76), retained placenta (OR = 2.19), puerperal metritis (OR = 1.48), or subclinical ketosis (OR = 1.51) had a greater risk for anestrus. In addition, cows calving in summer (OR = 0.82), autumn (OR = 0.38), or winter (OR = 0.56) had a higher incidence of anestrus than cows calving in spring. Estrous expression from d 7 until d 60 postpartum was associated with estrous duration (DU) and estrous intensity at first artificial insemination (AI). Cows in Estrus0 had the shortest DU at first postpartum AI (9.4 ± 0.18 h) compared with cows in Estrus1 (10.5 ± 0.13 h) and Estrus2+ (11.4 ± 0.12 h). Cows in Estrus2+ had a longer DU at first postpartum AI compared with cows in Estrus1. For Estrus0, Estrus1, and Estrus2+ cows, pregnancy per AI at first service was 42.5%, 50.9%, and 55.4%, respectively. Estrous expression from d 7 until d 60 postpartum was associated with time to first AI and time to pregnancy. Compared with Estrus0 cows, Estrus1 [hazard ratio (HR) = 1.43] and Estrus2+ cows (HR = 1.62) had an increased hazard of being inseminated within 100 DIM. Compared with Estrus2+, Estrus1 cows had a reduced hazard of being inseminated within 100 DIM (HR = 0.89). Compared with Estrus0 cows, Estrus1 (HR = 1.24) and Estrus2+ cows (HR = 1.46) had an increased hazard of becoming pregnant within 200 DIM. Median DIM to pregnancy were 121, 96, and 92 for Estrus0, Estrus1, and Estrus2+ cows, respectively. In conclusion, cows with transition cow disorders (i.e., stillbirth, retained placenta, puerperal metritis, or subclinical ketosis) had a greater chance for anestrus compared with healthy cows. Cows in Estrus0 had reduced estrous expression at first AI and inferior reproductive performance compared with cows that displayed estrous activity from d 7 until d 60