Comparing gradual debonding strategies after prolonged cow-calf contact: Stress responses, performance, and health of dairy cow and calf

We assessed effects of two-step debonding strategies in calf rearing systems with different types of prolonged cow-calf contact (CCC) on stress responses, health and performance of dairy cows and calves. Forty-eight Holstein Friesian cow-calf pairs had either: 1) full contact including suckling, where contact was reduced before weaning via fence-line separation at day 49 (FC-FS) (n = 10); 2) full contact, where contact was reduced at day 56 by fitting calves with a nose-flap (FC-NF) (n = 10); 3) partial contact (calves were housed in a pen adjacent to the cow area allowing physical contact on initiative of the dam but no suckling), where contact was reduced before weaning by moving the calf box from the wall to prevent physical contact at day 49 (PC-BW) (n = 6); 4) partial contact, where contact was reduced the week after weaning by moving the calf box away from the wall at day 63 (PC-AW) (n = 12); 5) no contact (calves were removed from dam directly after birth and housed in a calf barn), calves were weaned at day 56 (NC) (n = 10). Between weeks 7–10, we assessed physiological stress parameters, weight gain, and the health status of calves, plus general activity patterns based on accelerometer sensor data of cow-calf pairs before, during and after the debonding interventions. Additionally, calves were subjected to four consecutive behavioural tests (i.e. open field, novel object, voluntary human approach and involuntary human approach test) prior to permanent separation at day 70 and their behavioural responses were assessed via video recordings to assess fearfulness. Machine-harvested milk yields of cows were evaluated during weeks 6–12. Data were analyzed with (generalized) linear mixed models. Throughout the debonding period, FC-NF calves had an impaired growth rate (P = 0.02). In weeks 6–9, FC-FS and FC-NF cows had lower machine-harvested milk yields than PC-BW, PC-AW, and NC cows (P ≤ 0.01). We found no differences in responsiveness of calves to behavioural tests, except that NC calves exhibited more solitary play events compared to PC and FC calves in the novel object test (P = 0.002). Overall, our results imply that calves with partial CCC showed low stress responses to debonding, whereas abrupt weaning with a nose-flap during full contact seemed most stressful. Machine-harvested milk yield of FC cows seemed to recover once calves were weaned. More research into strategies to improve the process of debonding is warranted

Effect of Type of Cow-Calf Contact on Health, Blood Parameters, and Performance of Dairy Cows and Calves

Prolonged cow-calf contact (CCC) could potentially improve dairy calf welfare. However, it is currently unknown how different types of CCC affect animals' biological functions. We evaluated health and performance parameters of dairy calves and their dams, where calves: (i) had no contact with their dam (NC), in which the calf was removed from the dam directly after birth (n = 10); (ii) were allowed to have partial contact (PC) with their dam, in which the calf was housed in a calf pen adjacent to the cow area allowing physical contact on the initiative of the dam but no suckling (n = 18); (iii) were allowed to have full contact (FC) with their dam, including suckling, in which calves were housed together with their dams in a free-stall barn (n = 20). Throughout the first 7 weeks postpartum, data were collected on the health status, fecal microbiota, hematological profile, immune and hormonal parameters, and growth rates of calves, and on the health status, metabolic responses, and performance of dams. Overall, FC calves had more health issues (P = 0.02) and a tendency for higher antibiotic usage (P = 0.07) than NC calves. Additionally, FC calves showed elevated levels of erythrocytes, hematocrit, hemoglobin, and leukocytes on day 49 compared to NC calves (P < 0.001). Calf fecal microbiota changed over time, and we found preliminary evidence that fecal microbiota is affected by the type of CCC, as reflected by differences in relative abundances of taxa including Lactobacillus in FC calves compared to NC and PC calves except on days 7 and 66. The FC calves had a greater average daily gain in body weight than NC and PC calves (P = 0.002). Cow health was not affected by the type of CCC, although in the first 7 weeks of lactation FC cows had a lower machine-gained milk yield accompanied by a lower fat percentage than NC and PC cows (P < 0.001). These results indicate that full contact posed a challenge for calf health, presumably because the housing conditions of FC calves in this experimental context were suboptimal. Secondly, ad libitum suckling leads to higher weight gains and negatively affected milk fat content besides machine-gained yields. More research into strategies to improve cow-calf housing and management in CCC systems is warranted

Comparing gradual debonding strategies after prolonged cow-calf contact: Stress responses, performance, and health of dairy cow and calf

We assessed effects of two-step debonding strategies in calf rearing systems with different types of prolonged cow-calf contact (CCC) on stress responses, health and performance of dairy cows and calves. Forty-eight Holstein Friesian cow-calf pairs had either: 1) full contact including suckling, where contact was reduced before weaning via fence-line separation at day 49 (FC-FS) (n = 10); 2) full contact, where contact was reduced at day 56 by fitting calves with a nose-flap (FC-NF) (n = 10); 3) partial contact (calves were housed in a pen adjacent to the cow area allowing physical contact on initiative of the dam but no suckling), where contact was reduced before weaning by moving the calf box from the wall to prevent physical contact at day 49 (PC-BW) (n = 6); 4) partial contact, where contact was reduced the week after weaning by moving the calf box away from the wall at day 63 (PC-AW) (n = 12); 5) no contact (calves were removed from dam directly after birth and housed in a calf barn), calves were weaned at day 56 (NC) (n = 10). Between weeks 7-10, we assessed physiological stress parameters, weight gain, and the health status of calves, plus general activity patterns based on accelerometer sensor data of cow-calf pairs before, during and after the debonding interventions. Additionally, calves were subjected to four consecutive behavioural tests (i.e. open field, novel object, voluntary human approach and involuntary human approach test) prior to permanent separation at day 70 and their behavioural responses were assessed via video recordings to assess fearfulness. Machine-harvested milk yields of cows were evaluated during weeks 6-12. Data were analyzed with (generalized) linear mixed models. Throughout the debonding period, FCNF calves had an impaired growth rate (P = 0.02). In weeks 6-9, FC-FS and FC-NF cows had lower machineharvested milk yields than PC-BW, PC-AW, and NC cows (P <= 0.01). We found no differences in responsiveness of calves to behavioural tests, except that NC calves exhibited more solitary play events compared to PC and FC calves in the novel object test (P = 0.002). Overall, our results imply that calves with partial CCC showed low stress responses to debonding, whereas abrupt weaning with a nose-flap during full contact seemed most stressful. Machine-harvested milk yield of FC cows seemed to recover once calves were weaned. More research into strategies to improve the process of debonding is warranted

Effect of Type of Cow-Calf Contact on Health, Blood Parameters, and Performance of Dairy Cows and Calves

Prolonged cow-calf contact (CCC) could potentially improve dairy calf welfare. However, it is currently unknown how different types of CCC affect animals' biological functions. We evaluated health and performance parameters of dairy calves and their dams, where calves: (i) had no contact with their dam (NC), in which the calf was removed from the dam directly after birth (n = 10); (ii) were allowed to have partial contact (PC) with their dam, in which the calf was housed in a calf pen adjacent to the cow area allowing physical contact on the initiative of the dam but no suckling (n = 18); (iii) were allowed to have full contact (FC) with their dam, including suckling, in which calves were housed together with their dams in a free-stall barn (n = 20). Throughout the first 7 weeks postpartum, data were collected on the health status, fecal microbiota, hematological profile, immune and hormonal parameters, and growth rates of calves, and on the health status, metabolic responses, and performance of dams. Overall, FC calves had more health issues (P = 0.02) and a tendency for higher antibiotic usage (P = 0.07) than NC calves. Additionally, FC calves showed elevated levels of erythrocytes, hematocrit, hemoglobin, and leukocytes on day 49 compared to NC calves (P < 0.001). Calf fecal microbiota changed over time, and we found preliminary evidence that fecal microbiota is affected by the type of CCC, as reflected by differences in relative abundances of taxa including Lactobacillus in FC calves compared to NC and PC calves except on days 7 and 66. The FC calves had a greater average daily gain in body weight than NC and PC calves (P = 0.002). Cow health was not affected by the type of CCC, although in the first 7 weeks of lactation FC cows had a lower machine-gained milk yield accompanied by a lower fat percentage than NC and PC cows (P < 0.001). These results indicate that full contact posed a challenge for calf health, presumably because the housing conditions of FC calves in this experimental context were suboptimal. Secondly, ad libitum suckling leads to higher weight gains and negatively affected milk fat content besides machine-gained yields. More research into strategies to improve cow-calf housing and management in CCC systems is warranted

Biologicals as theranostic vehicles in paediatric oncology

Biologicals, such as antibodies or antibody-fragments e.g. nanobodies, have changed the landscape of cancer therapy and can be used in combination with traditional cancer treatments. They have been demonstrated to be excellent vehicles for molecular imaging. Several biologicals for nuclear imaging of adult cancer may be used in combination with (nuclear) therapy. Though it's great potential, molecular imaging using biologicals is rarely applied in paediatric oncology. This paper describes the current status of biologicals as radiopharmaceuticals for childhood cancer. Furthermore, the importance and potential for developing additional biological theranostics as opportunity to image and treat childhood cancer is discussed

Epidemiology of heart failure in diabetes: a disease in disguise

Left ventricular diastolic dysfunction (LVDD) without symptoms, and heart failure (HF) with preserved ejection fraction (HFpEF) represent the most common phenotypes of HF in individuals with type 2 diabetes mellitus, and are more common than HF with reduced ejection fraction (HFrEF), HF with mildly reduced ejection fraction (HFmrEF) and left ventricular systolic dysfunction (LVSD) in these individuals. However, diagnostic criteria for HF have changed over the years, resulting in heterogeneity in the prevalence/incidence rates reported in different studies. We aimed to give an overview of the diagnosis and epidemiology of HF in type 2 diabetes, using both a narrative and systematic review approach; we focus narratively on diagnosing (using the 2021 European Society of Cardiology [ESC] guidelines) and screening for HF in type 2 diabetes. We performed an updated (2016–October 2022) systematic review and meta-analysis of studies reporting the prevalence and incidence of HF subtypes in adults ≥18 years with type 2 diabetes, using echocardiographic data. Embase and MEDLINE databases were searched and data were assessed using random-effects meta-analyses, with findings presented as forest plots. From the 5015 studies found, 209 were screened using the full-text article. In total, 57 studies were included, together with 29 studies that were identified in a prior meta-analysis; these studies reported on the prevalence of LVSD (n=25 studies, 24,460 individuals), LVDD (n=65 studies, 25,729 individuals), HFrEF (n=4 studies, 4090 individuals), HFmrEF (n=2 studies, 2442 individuals) and/or HFpEF (n=8 studies, 5292 individuals), and on HF incidence (n=7 studies, 17,935 individuals). Using Hoy et al’s risk-of-bias tool, we found that the studies included generally had a high risk of bias. They showed a prevalence of 43% (95% CI 37%, 50%) for LVDD, 17% (95% CI 7%, 35%) for HFpEF, 6% (95% CI 3%, 10%) for LVSD, 7% (95% CI 3%, 15%) for HFrEF, and 12% (95% CI 7%, 22%) for HFmrEF. For LVDD, grade I was found to be most prevalent. Additionally, we reported a higher incidence rate of HFpEF (7% [95% CI 4%, 11%]) than HFrEF 4% [95% CI 3%, 7%]). The evidence is limited by the heterogeneity of the diagnostic criteria over the years. The systematic section of this review provides new insights on the prevalence/incidence of HF in type 2 diabetes, unveiling a large pre-clinical target group with LVDD/HFpEF in which disease progression could be halted by early recognition and treatment. Registration PROSPERO ID CRD42022368035. Graphical Abstract: (Figure presented.)

Respiratory responses to hypercapnia and hypoxia in mice with genetic ablation of Kir5.1 (Kcnj16)

Inward rectifier (Kir) potassium channels contribute to the control of electrical activity in excitable tissues and their activity is modulated by many biochemical factors, including protons. Heteromeric Kir4.1–Kir5.1 channels are highly pH sensitive within the physiological range of pH changes and are strongly expressed by the peripheral chemosensors as well as in the brainstem pH-sensitive areas which mediate respiratory responses to changes in blood and brain levels of /[H+]. In the present study, Kir5.1 knockout mice (Kir5.1−/−) were used to determine the role of these channels in the chemosensory control of breathing. We found that Kir5.1−/− mice presented with persistent metabolic acidosis and a clear respiratory phenotype. Despite metabolic acidosis, ventilation at rest and in hyperoxic hypercapnia were similar in wild-type and Kir5.1−/− mice. Ventilatory responses to hypoxia and normoxic hypercapnia were significantly reduced in Kir5.1−/− mice; however, carotid body chemoafferent responses to hypoxia and CO2 were not affected. In the in situ brainstem–spinal cord preparations with denervated peripheral chemoreceptors, resting phrenic nerve activity and phrenic nerve responses to respiratory acidosis or isohydric hypercapnia were also similar in Kir5.1−/− and wild-type mice. In in situ preparations of Kir5.1−/− mice with intact peripheral chemoreceptors, application of CN− resulted in a significantly reduced phrenic nerve response, suggesting that the relay of peripheral chemosensory information to the CNS is compromised. We suggest that this compensatory modulation of the peripheral chemosensory inputs develops in Kir5.1−/− mice in order to counteract the effect of continuing metabolic acidosis on the activity of the peripheral chemoreceptors. These results therefore suggest that despite their intrinsic pH sensitivity, Kir4.1–Kir5.1 channels are dispensable for functional central and peripheral respiratory chemosensitivity

A Mathematical model for Astrocytes mediated LTP at Single Hippocampal Synapses

Many contemporary studies have shown that astrocytes play a significant role in modulating both short and long form of synaptic plasticity. There are very few experimental models which elucidate the role of astrocyte over Long-term Potentiation (LTP). Recently, Perea & Araque (2007) demonstrated a role of astrocytes in induction of LTP at single hippocampal synapses. They suggested a purely pre-synaptic basis for induction of this N-methyl-D- Aspartate (NMDA) Receptor-independent LTP. Also, the mechanisms underlying this pre-synaptic induction were not investigated. Here, in this article, we propose a mathematical model for astrocyte modulated LTP which successfully emulates the experimental findings of Perea & Araque (2007). Our study suggests the role of retrograde messengers, possibly Nitric Oxide (NO), for this pre-synaptically modulated LTP.Comment: 51 pages, 15 figures, Journal of Computational Neuroscience (to appear

The effect of preprandial versus postprandial physical activity on glycaemia: Meta-analysis of human intervention studies

This meta-analysis aims to investigate the effect of preprandial physical activity (PA) versus postprandial PA on glycaemia in human intervention studies. Medline and Embase.com were searched until February 2023 for intervention studies in adults, directly comparing preprandial PA versus postprandial PA on glycaemia. Studies were screened using ASReview (34,837) and full texts were read by two independent reviewers (42 full text, 28 included). Results were analysed using pooled mean differences in random-effects models. Studies were either acute response studies (n = 21) or Randomized Controlled Trials (RCTs) over multiple weeks (n = 7). In acute response studies, postprandial outcomes followed the expected physiological patterns, and outcomes measured over 24 h showed no significant differences. For the RCTs, glucose area under the curve during a glucose tolerance test was slightly, but not significantly lower in preprandial PA vs postprandial PA (-0.29 [95 %CI:-0.66, 0.08] mmol/L, I2 = 64.36 %). Subgroup analyses (quality, health status, etc.) did not significantly change the outcomes. In conclusion, we found no differences between preprandial PA versus postprandial PA on glycaemia both after one PA bout as well as after multiple weeks of PA. The studies were of low to moderate quality of evidence as assessed by GRADE, showed contradictive results, included no long-term studies and used various designs and populations