cord-003782-my6frz5s 2019 title: Exploratory cohort study to determine if dry cow vaccination with a Salmonella Newport bacterin can protect dairy calves against oral Salmonella challenge HYPOTHESIS/OBJECTIVE: To evaluate the protective effect on calves of colostrum from cows vaccinated with a commercially available Salmonella Newport bacterin against a Salmonella Typhimurium challenge. Colostral immunity stimulated by vaccinating dry cows for Escherichia coli, rotavirus, and coronavirus has been used extensively in the dairy and beef industries to protect calves against diarrhea challenge. 8 This finding suggests that dry cow vaccination and subsequent colostrum administration may be a viable method to provide immunity against Salmonella in neonatal calves, potentially decreasing the incidence, severity, and mortality of the infection. Secondary outcomes also were evaluated to determine if consumption of colostrum from vaccinated cows would impact the titers, clinical disease, or shedding of Salmonella in calves after experimental infection. Administration of the Salmonella Newport bacterin to dry cows did not provide protective immunity to calves in our study despite increased titers. cord-007180-pho3miid 1984 Clinically affected calves have atrophy of villi and hyperplasia of crypt epithelium (apparently as a result of the destruction of villous epithelium); those areas of the small intestine that are heavily infected with the parasite become inflamed [7, 9, 10] . On the other hand, if confirmed, the reported occurrence of diarrhea and intestinal lesions in gnotobiotic pigs infected with an inoculum treated in a manner that destroys infectious agents other than Cryptosporidium [18] provides strong evidence that the parasite can act as a primary enteropathogen in the absence of other enteric flora. Gnotobiotic calves inoculated with oocysts of Cryptosporidium that had been treated with potassium dichromate and peracetic acid became infected with Cryptosporidium and developed clinical signs and enteric lesions. cord-007442-13q74l4f 2017 The most important aspect in the treatment of the diarrheic calfis the administration of fluids to replace the extensive losses of water and electrolytes that occur and which are responsible for the clinical signs and potential death of the calf. Oral administration of fluids is always the route of choice in the treatment of the diarrheic calf, unless the condition is so acute that intestinal absorption is not rapid enough to keep up with losses of fluid or unless the animal is too severely dehydrated. The intravenous route of fluid therapy is the route of choice when the animal is more than 8 per cent dehydrated (Table 1) , when the loss of fluids from the body is so rapid that replacement fluids given by other routes may not be absorbed fast enough to compensate for the losses, when shock is present, or when the animal shows clinical signs of altered concentrations of plasma electrolyte or glucose. cord-007481-4mj5isyl 2002 Two of the four isolates were inoculated alone into 4-day-old gnotobiotic calves deprived of colostrum; neither calf developed dysentery but microscopic lesions identical to those produced by S102-9 were detected in the large intestines of both animals. An atypical strain of Escherichia coli (designated $102-9) was isolated from the faeces and intestinal contents of farm calves aged 8--21 days old during an outbreak of dysentery (Hall et al., 1985) and reproduced the disease after experimental infection of gnotobiotic calves . $102-9 was shown by an immunoperoxidase method to adhere to the mucosae of the large bowel in gnotobiotic and farm calves with dysentery, and microscopic lesions were seen in the colonic and rectal mucosae (Hall et al., 1985) . coli with atypical characteristics were an important cause of calf diarrhoea by examining a culture collection of 659 isolates from field outbreaks of diarrhoea, and thirdly, to investigate by experimental infection of gnotobiotic calves, the association between the atypical characteristics of these isolates and pathogenicity. cord-009694-e59kuwf1 2006 Prevention of typical calf diseases in the first 6 months of life such as diarrhoea and enzootic bronchopneumonia requires a systematic approach by improving management and housing conditions, specifically the preparation of the cow, hygiene of the calving environment, including dry clean bedding and high air quality, immediate supply with maternal antibodies, no mixing with older animals and careful attention and a rapid response to any sign indicating disease. -Space requirements -Health monitoring systems and the effect of such on clinical health in calves -Infection transmission (respiratory and digestive diseases) due to direct contact between calves in relation to social benefits of mixing -Pain relief when disbudding, dehorning and castrating calves -Design of appropriate ventilation systems for calves in confined rearing conditions -Health and environmental effects of feeding minerals as antimicrobial agents -For quantitative food safety risk categorization of farming systems individually, and/or their related ranking, further scientific information is needed. cord-017622-aqhyt7jg 2013 Cryptosporidiosis was first identified as a disease of veterinary, rather than human medical, importance, and infection of farmed animals with different species of Cryptosporidium continues to be of veterinary clinical concern. This chapter provides insights into Cryptosporidium infection in a range of farmed animals – cattle, sheep, goats, pigs, cervids, camelids, rabbits, water buffalo and poultry – presenting not only an updated overview of the infection in these animals, but also information on clinical disease, infection dynamics and zoonotic potential. Although extensive data have been accrued on, for example, Cryptosporidium parvum infection in calves, and calf cryptosporidiosis continues to be a major veterinary concern especially in temperate regions, there remains a paucity of data for other farmed animals, despite Cryptosporidium infection causing significant clinical disease and also, for some species, with the potential for transmission of infection to people, either directly or indirectly. cord-018404-jdu4h00e 2019 Passive immunity can be provided to animals by several sources of antibodies including from colostrum, avian eggs, and monoclonal sources. This provides a rationale for the observations that bovine colostrum from nonimmunized cows may also afford passive immune protection against human pathogens in both humans and animals (Li-Chan et al. The animal industry has recognized this issue and has developed methods to produce specific antibodies in high titer against specific diseases that can be delivered in colostrum products. Passive antibody therapy in the treatment of infectious diseases is a concept which dates back more than 120 years, to the 1890s, when the use of serum from immunized animals provided the first effective treatment options against infections with Clostridium tetani and Corynebacterium diphtheriae (Hey 2015) . Passive immunity provided by chicken egg antibodies will gain increasing use in production animals. cord-251994-ygd8xv5x 2018 parvum in the laboratory (Zintl et al., 2010) , and when hydrated lime disinfection of the calf pens was used as a complement to the standard cleaning procedures in two Swedish herds with long-lasting cryptosporidiosis problems, the farmers reported a lower incidence and less severe diarrhea in the calves (C. Before it was finally decided if a herd could be included, faecal samples were collected from five calves under three weeks of age and analysed for presence of Cryptosporidium spp., rotavirus and coronavirus. parvum-associated calf diarrhea problems, calves kept in the hydrated lime disinfected pens were older when diarrhea was first recorded and had a higher body condition score at six to eight weeks of age. oocysts in faecal samples collected from 5 to 21 day old calves in four dairy herds participating in a study on the effect of hydrated lime on cryptosporidiosis. cord-257418-cyul92w0 2008 This article focuses on the most important diseases of dairy calves and heifers and presents clinical approaches that can improve detection, diagnosis, and treatment of herd-based problems. As shown in Table 2 , fecal shedding results show evidence of increased exposure to C parvum and Salmonella newport in a herd with calf diarrhea problems in 9-day-old calves. For herd problems of enteric disease in calves, bedding materials from each environment that has housed calves are submitted both for bacterial counts (University of Minnesota Laboratory for Udder Health, Minnesota Veterinary Diagnostic Laboratory, St. Paul, MN) and Salmonella spp culture. In investigating a dairy calf or heifer pneumonia problem, the review of records to determine morbidity and mortality data, seasonal patterns, health, management, housing, number of calves at maximum occupancy, nutrition, vaccinations, procedures, case definition, and treatment protocols is important. cord-261338-gvlkc2r1 2009 Infectious diarrhea in calves is most commonly associated with enterotoxigenic Escherichia coli, Cryptosporidium parvum, rotavirus, coronavirus, or some combination of these pathogens. 63 Severity of diarrhea and incidence of clinical signs in calves shedding oocysts can be variable within and between farms, leading some to question the true importance of C parvum as a primary pathogen; 67 however, it has been repeatedly isolated independent of other known pathogens in clinical cases. 79 Specifically, research has shown that the activation and inhibition of apoptosis is Calf Diarrhea related to the life stage of C parvum, and that apoptosis is inhibited during the trophozoite stage when the organism is most dependent on the host, but then increases later during the infection. Epithelial cell loss, villous atrophy, and malabsorption cannot account for all the fluid loss seen in C parvum infections, and studies have documented a prostaglandin-mediated anion secretion (Cl Ã� or HCO 3 Ã� ) and inhibition of neutral NaCl absorption (Fig. 3) . cord-261614-3m72qwl4 2017 This study evaluated the impact of an algorithm targeting antimicrobial therapy of diarrhoeic calves on the incidence of diarrhoea, antimicrobial treatment rates, overall mortality, mortality of diarrhoeic calves and changes in the faecal microbiota. Therefore, the aims of the present study were to evaluate the impact of an antibiotic use algorithm on calf health (morbidity and mortality) and antimicrobial treatment rates, and to characterise the faecal microbiota of healthy calves before and after implementing the algorithm. Data for antimicrobial treatment rates, incidence of diarrhoea, and overall mortality and mortality of diarrhoeic calves, on both farms for each period are presented in Table 2 . The use of an algorithm for treatment of calf diarrhoea decreased the rates of antimicrobial treatment on two dairy farms without an adverse effect on the health of the calves. Management practices and reduction in antimicrobial treatment rates at the farm level could have an impact on the development and establishment of faecal microbiota of healthy calves. cord-262115-kdeynhzq 2020 Our objective was to determine the dose response to fish and flaxseed oil when supplemented in colostrum on concentrations of plasma fatty acid (FA), FA metabolites, and index of oxidative stress during the critical first week of life in calves to understand how supplementing n-3 FA may decrease oxidative stress. In conclusion, supplementing colostrum with 30, 60, and 120 mL of a 1:1 mixture of fish and flaxseed oil linearly increased plasma concentrations of n-3 FA and metabolites and decreased biomarkers of oxidative stress, but did not alter oxidant status or affect health or growth. Increasing doses of 30, 60, and 120 mL of 1:1 fish: flaxseed oil blend supplemented in colostrum did not affect health or growth in calves, decreased phospholipid n-6 FA: n -3 FA profile, increased free and phospholipid n-3 FA concentrations, and increased several oxylipids deriving from n-3 FA during the first week of life. cord-264227-eym33p51 2017 The objective of this study was to evaluate under field conditions, whether daily administration of oregano essential oil is effective in preventing and/or diminishing the severity of neonatal diarrhea syndrome in calves aged less than 15 days. The objective of the present study was to evaluate under field conditions whether daily administration of oregano essential oil is effective in preventing and/or diminishing the severity of neonatal diarrhea syndrome in calves aged < 15 days. In a former experiment Table 3 Incidence of diarrhea, percentages of calves with adequate passive immunity transfer and percentages of positive calves to Cryptosporidium spp., Rotavirus A (RVA), Bovine coronavirus (BCoV) and enterotoxic Escherichia coli K99/F5 (ETEC) in the three farms of the experiment (Farm 1, 2 and 3) and in calves drenched with oregano essential oil (Eco) or left untreated as controls (Conts). cord-264391-7fse4h3f 2009 While a few studies have provided some insight to more intensive livestock production units such as hog farms (Dunlop et al., 1998; Rajic et al., 2006) , there is no information about antimicrobial drug use (AMU) in western Canadian cow-calf herds. A better understanding of AMU patterns in this population is essential to develop a baseline and determine Investigators examined antimicrobial drug use practices and reason for treatment as part of a large on-farm observational study of cow-calf herds from western Canada. The objectives of this study were to describe the frequency of treatment with any antimicrobial drug in beef calves and cows, common reasons for AMU, the types of antimicrobial drugs used, and risk factors for treatment in western Canadian cow-calf herds during the calving season. The investigation of antimicrobial drug use practices was undertaken to maximize the industry benefit from this unique opportunity for on-farm access to individual animal data from a large number of cow-calf herds. cord-264469-a71vxxzh 2007 The authors propose that increased morbidity and mortality in our study was caused by administration of refused calf milk replacer (CMR) by esophageal feeder. They wrote "we suggest that the increased incidence of illness observed in the calves fed the higher levels of milk replacer was due to sick calves being force-fed." They further suggested that feed refusals were a manifestation of anorexia caused by expression of proinflammatory cytokines. The authors criticized our paper for including the use of fecal scoring in calves fed varying amounts of CMR and wrote "Although this system has been widely used to evaluate diarrhea in limit-fed calves, the authors provide no evidence that this measure was repeatable or a valid indicator of any underlying pathology." The authors further suggested that ". Growth and body composition of dairy calves fed milk replacers containing different amounts of protein at two feeding rates cord-266153-c1w1pf5t 2015 coli using standard sugar fermentation tests and identify risk factors associated with its isolation from diarrheic calf feces in the area. Animals included in this study were calves under 4 months of age that were clinically affected with diarrhea and exhibiting signs of systemic disease (e.g., poor appetite, fever, dehydration, decreased mentation, and reduced suckle reflex) and had pasty-watery feces with different colors. coli isolation associated with host and management factors Among the 201 diarrheic fecal samples, six types of diarrhea, namely, yellowish, blood-tinged, pure bloody, greenish, watery, and mucoid, were observed at different proportions. coli in the present study might be attributed to the variations in age groups examined as well as environmental and management conditions of the farms such as insufficient and/or poor-quality colostrum intake by the calves as stated by Charles et al. cord-266424-wchxkdtj 2008 12, 16 No single laboratory test has emerged as being completely reliable for the early diagnosis of septicemia in farm animal neonates, 12, 17 therefore, various scoring systems and predictive models using easily obtainable historical, clinical, and clinicopathologic data have been developed for this purpose. For a period of time, routine blood cultures were performed on all diarrheic calves presented to the Atlantic Veterinary College Teaching Hospital regardless of whether the clinical or clinicopathologic findings indicated a diagnosis of septicemia. The prevalence of septicemia in this study was identical to that reported for calves with diarrhea, depression, and/or weakness on a veal raising facility, 14 which suggests that the predictive values of the models developed herein may be relevant to other calf populations. cord-267659-9iy8l55f 2020 ABSTRACT Objective This research study aimed to determine whether preweaning plane of milk-replacer nutrition influences health, standing and oral behaviors, and performance of high-risk calves. The HPN calves had greater performance over the preweaning period including final BW, ADG, and feed:gain (total kg of milk replacer + calf starter, kg of DM/kg of BW gain), but weaning was more stressful for HPN calves. Determining the effects of an increased plane of nutrition (PON) on the health, behavior, and performance of high-risk dairy calves can help establish recommendations for feeding calves more milk solids to increase measures of gain and animal health without compromising normal calf behavior. Potential issues with high-risk calves being fed a HPN may be reduced with increased feeding times per day, a gradual step-up method, or other nutritional strategies that improve gastrointestinal development and function. cord-268382-94hlbf98 2020 title: Colostrum-supplemented transition milk positively affects serum biochemical parameters, humoral immunity indicators and the growth performance of calves It can be concluded that additional five days of colostrum feeding positively influences non-specific humoral immunity indicators and serum biochemical parameters in dairy calves. Additionally, the effect of colostrum-supplemented transition milk on the growth performance of calves was determined based on changes in body weight (BW) and average daily gain (ADG). The effect of colostrum-supplemented transition milk on selected serum biochemical variables (ALT, AST, AP, LDH, gluc, chol, TAG, urea, crea and TP) is presented in Table 2 . The effect of colostrum-supplemented transition milk on the serum concentrations of gluc, chol, TAG and TP at different time points is presented in Fig. 3a -d. TRT calves had higher average concentrations of chol and TP compared with CR calves (by 28% and 8%, respectively; P < 0.05) at each time point, but colostrum-supplemented transition milk had a significant effect only on chol levels. cord-269730-a8h7irel 2018 From the calves that were fattened during the study period, observations of 1.1 million calves originated from the Netherlands and were available to study risk factors for veal calf mortality associated with the herd of origin. The risk factors that were significantly associated with a higher mortality rate during the fattening period were a higher use of antimicrobials, hair colour as proxy for breed, country of origin, not having an all-in/all-out system, and the answer ''not applicable'' at the critical control point "Medicines are stored in a closed cabinet or room separated from animals and feed" (Table 3 ). The significant association between veal calf mortality and number of calves in the specific production cycle that was found in this study was incoherent as both the smallest and largest veal herds were protective factors, whereas the size groups in between had a higher risk. cord-274450-mukc7mxi 2014 A blinded, randomized, controlled, multi-centric field study was conducted on French dairy farms (n = 9) to evaluate the long term efficacy of metaphylactic, single oral treatments with either 1 mg/kg body weight (BW) of diclazuril (Vecoxan(®)), or 15 mg/kg BW of toltrazuril (Baycox(®)) against natural infections with Eimeria zuernii and/or Eimeria bovis, compared to untreated control animals. This study demonstrates that, over an extended observation period of 78 days, metaphylactic treatment with both diclazuril and toltrazuril reduces the impact of coccidiosis, but greater performance benefits based on average daily weight gains, were achieved following the use of diclazuril. Using a multiple linear regression model with mixed effect (data normally distributed, Shapiro-Wilk normality test, p-value = 0.5379), the diclazuril treated calves had an average daily gain (ADG) of 0.057 kg/day, significantly (p = 0.01) higher compared to calves in the toltrazuril group over the 11 weeks post-treatment observation period. cord-276186-fgvu1wcx 2009 Neither prophylactic nor therapeutic use of NTZ improved the clinical appearance and calves of the therapeutic showed a longer diarrheic episode (p < 0.05) with strong altered faecal consistence compared to the untreated control group. Neither prophylactic nor therapeutic use of NTZ improved the clinical appearance and calves of the therapeutic showed a longer diarrheic episode (p < 0.05) with strong altered faecal consistence compared to the untreated control group. In conclusion, these preliminary results about the first prophylactic and therapeutic use of NTZ in calves did not show the expected positive effect on the course of the Cryptosporidium-infection, neither on reducing the clinical severity, nor on oocyst excretion. In conclusion, these preliminary results about the first prophylactic and therapeutic use of NTZ in calves did not show the expected positive effect on the course of the Cryptosporidium-infection, neither on reducing the clinical severity, nor on oocyst excretion. cord-277545-xyhh7uky 2020 The etiological agents involved in a bovine respiratory disease (BRD) outbreak were investigated in a dairy heifer calf rearing unit from southern Brazil. A battery of PCR assays was performed to detect the most common viruses and bacteria associated with BRD, such as bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), bovine alphaherpesvirus 1 (BoHV-1), bovine coronavirus (BCoV), bovine parainfluenza virus 3 (BPIV-3), Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. The present study reports a molecular diagnostic survey for multiple etiological agents during an outbreak of BRD in heifer calves in a Brazilian dairy calf rearing unit. In this study, the findings of 85.7% positive BALF samples for at least one of the pathogens associated with BRD highlight the importance of this disease in the calf rearing unit, especially of the mixed infections that were more frequent (72.2%) than single infections (27.7%). cord-280036-ev82fzly 2013 We performed a randomized controlled field trial of the efficacy of HL for the prevention of natural calf cryptosporidiosis, in the presence of co-infection with rotavirus and Salmonella Typhimurium. Motivated by the need of more data on the utility HL in the presence of co-infections with other pathogens, we performed a randomized controlled field trial of the anti-Cryptosporidium preventive efficacy of the compound in calves on a New Zealand farm enzootically infected with C. In addition to the analysis for Cryptosporidium, 23 fecal specimens taken haphazardly from the three treatment groups were analyzed for the presence of rotavirus, coronavirus, enterotoxigenic K99 + Escherichia coli (K99) and Salmonella spp. The calves in Group 3 (control Group) showed an oocyst shedding curve which was typical for natural cryptosporidiosis, with the majority of the animals becoming parasitologically positive by Day 8 and again negative by Day 20 (Tables 1 and 2) . cord-281229-s9s7awtn 2018 Based on our previous findings in dairy cows, the objective of this study was to determine if feeding Se-replete beef cows Se-enriched alfalfa (Medicago sativa) hay during the last trimester of gestation delays turnover and replacement of fetal intestinal epithelial cells in their calves, thus extending the period of time during which large proteins can be transferred from intestinal lumen to neonatal blood. In this paper, to test the hypothesis that passive transfer is enhanced in calves born to cows fed Se-biofortified alfalfa hay in the last trimester of pregnancy compared to calves born to Control cows fed the USDA-approved upper limit of Na-selenite in salt [21] , we administered 25 g oral ovalbumin (OVA) to calves at 12, 24, or 36 h after birth, and measured serum OVA concentrations to estimate the time of gut closure. cord-281635-a6ia8kxf 1989 title: Efficacy of an inactivated oil-adjuvanted rotavirus vaccine in the control of calf diarrhoea in beef herds in Argentina In a small-scale experimental trial, involving 21 pregnant cows (13 vaccinated and eight unvaccinated controls), a significant increase in neutralizing antibody titres against different serotypes of bovine rotaviruses was found in both the colostrum and serum of vaccinated cows compared with that of unvaccinated controls. For that reason, after several years of epidemiological studies, it was decided to develop and test an inactivated oil-adjuvanted vaccine with the aim of controlling diarrhoea in beef and dairy herds in Argentina. The results showed that the oil-adjuvanted rotavirus vaccine tested was effective in the control of calf neonatal diarrhoea in Argentina. As shown in Figure 1 , compared with controls, vaccinated cows showed significantly higher neutralizing antibody levels against rotavirus in serum, colostrum and milk until at least 30 days after calving. cord-287778-ewowkq8o 2013 Serum chemistry determinations and measurement of the sodium content of milk replacer and water used on the farm identified salt poisoning as the cause of the clinical signs. 1, 3 The current report describes acute and chronic salt toxicity in neonatal dairy calves on a Wisconsin dairy from November 2010 to February 2011 in which abnormally high concentrations of sodium were detected in sera collected from these animals and in the water in which a commercial milk replacer powder was being mixed. Two milk replacer samples from the first and last calves fed for each of 6 successive feedings after the farm visit were analyzed for total solids and sodium concentration. Additional sodium from the milk replacer powder (approximately 60 mEq/L), electrolyte powder (3% sodium), and 2 times the recommended lasalocid concentration fed to calves with no access to free-choice water likely contributed to the early onset of clinical signs and death. cord-289728-s6xmdmpf 2011 In neonatal calf diarrhoea, oral rehydration therapy is the single most important therapeutic measure to be carried out by the farmer and is usually successful if instigated immediately after diarrhoea has developed. Eimeriosis has a high economic impact on the farming industries due to direct cost of treatment and calf losses, but especially due to decreased performance of clinically as well as sub-clinically affected animals. Calfhood diseases have a major impact on the economic viability of cattle operations, due to the direct costs of calf losses and treatment and the long term effects on performance [1] . Enterotoxic Escherichia coli, Cryptosporidium parvum, rotavirus and coronavirus are usually seen as the most common infectious causes of neonatal calf diarrhoea [7] . Oral rehydration therapy, continued milk feeding and prudent use of antibiotics are each important in the successful management of neonatal calf diarrhoea. The comparative effectiveness of three commercial oral solutions in correcting fluid, electrolyte and acid-base disturbances caused by calf diarrhoea cord-290783-ipoelk4h 1985 This article examines methods currently used to enhance the titre and duration of specific antibody in the mammary secretions of cows and pigs with particular reference to rotavirus and coronavirus infections. The situation in neonatal piglets is less clear, rotavirus infections are apparently common 6.t4-tt, w.hilst transmissible gastroenteritis virus (TGEV), the prototype enteric coronavirus in swine, is an example of a seasonal cold-weather disease, probably related to both the thermal sensitivity of the virus ~ and the effect of cold-stress on converting subclinical to clinical infections ~8. It is apparent that the enhancement of lactogenic immunity through the vaccination of the dam provides a suitable mechanism by which neonatal pigs and calves can be protected against rotavirus and coronavirus infections. Passive immunity in calf rotavirus infections: Maternal vaccination increases and prolongs immunoglobulin G 1 antibody secretion in milk Antibody responses in serum, colostrum and milk of swine after infection or vaccination with transmissible gastroenteritis virus cord-293079-z7dx6ey9 2012 The animals were monitored for BRD using conventional biometric signs for clinical scores, core temperatures, haematology, serum cortisol and infrared thermal values over 3weeks. The data collected demonstrated that true positive animals for BRD based on a gold standard including core temperature, clinical score, white blood cell number and neutrophil/lymphocyte ratio displayed higher peak infrared thermal values of 35.7±0.35°C compared to true negative animals 34.9±0.22°C (P <0.01). Many of the aforementioned technologies including clinical scores, haematology, acute phase proteins, cytokines, antibody response and core temperature monitoring are useful aids to the diagnosis of BRD particularly when its prevalence is high in a population and once the clinical signs of respiratory disease are present. The objective of the present study was to investigate the use of infrared thermography to non-invasively identify animals with BRD in a population with a low prevalence of respiratory disease. The use of infrared thermography in the non-invasive, automated detection of calves displaying bovine respiratory disease cord-294463-rtepmxt2 2017 Common causes of infectious enteritis in neonate and juvenile ruminants include viral, bacterial, and protozoal pathogens. Clinical signs generally occur in calves 2 days to 4 weeks of age; however adult cattle may have subclinical disease and serve as a source of infection. Persistently infected calves may have severe enteritis as part of mucosal disease syndrome or may be more susceptible to diarrhea caused by other diarrheal agents because of their immunocompromised status. Diarrheal diseases also causing blood loss in neonates include salmonellosis, enterohemorrhagic E coli, and clostridial enteritis. Infectious enteritis causes diarrhea and associated fluid and electrolyte losses. This concentration should be decreased proportionally when increasing fluid rate to more than Table 4 Recommendations for electrolyte, carbohydrate, buffering capacity, and osmolality of oral electrolyte replacement fluids used to treat enteritis and diarrhea in neonatal ruminants maintenance, or if blood glucose measurements are greater than the normal range (6.5 AE 1.2 mmol/L, 117 AE 21.6 mg/dL). cord-295193-uf3eryoy 2017 The aim of the present work was to study if maternal IgG1 antibodies (Abs) to BCoV acquired by colostrum intake modulate the development of BCoV infection in calves reared in a dairy farm in Argentina. Thus, the aim of the present study was to determine if IgG1 passive maternal Abs to BCoV acquired by colostrum intake modulate the development of BCoV natural infection and disease in calves reared in a dairy farm in Argentina. In order to evaluate the presence of neonatal diarrhea in calves with varying titers of colostrum-derived Abs, and to understand the BCoV infection dynamics under field conditions, feces were collected daily from each calf and a diarrhea score was recorded (0 = normal, 1 = pasty, 2 = semi liquid, 3 = liquid, 4 = hemorrhagic; a fecal score of 2 or higher was considered diarrhea). cord-297597-tqc1usry 2008 Unfortunately, a significant proportion of North American dairy calves suffer from failure of passive transfer of antibodies from colostrum, contributing to excessively high preweaning mortality rates and other shortand long-term losses associated with animal health, welfare, and productivity. In addition to reduced risk for preweaning morbidity and mortality, additional long-term benefits associated with successful passive transfer include reduced mortality in the postweaning period, improved rate of gain and feed efficiency, reduced age at first calving, improved first and second lactation milk production, and reduced tendency for culling during the first lactation [7] [8] [9] [10] . In a study feeding beef cows either 100% (CO) or 57% (RS) of National Research Council (NRC) (1984) [38] protein and energy requirements, maternal nutrition did not affect either colostrum IgG concentration (43.0 versus 39.5 g/L for RS and CO, respectively) or the calves'' serum IgG concentration at 24 hours (19.1 versus 20.2 mg/mL for RS and CO, respectively) [39] . cord-299310-ukn6hm5x 2018 ABSTRACT We determined if feeding and lying behavior, recorded by automatic calf feeding systems (ACFS) and accelerometers, could be used to detect changes in behavior before onset of neonatal calf diarrhea (NCD) or in response to disbudding pain in dairy calves. Feeding (milk consumption and the number of rewarded and unrewarded visits to the feeder) and lying behavior during the 5 d leading up to calves displaying clinical signs of NCD were analyzed. Information on feeding and lying behavior collected from ACFS and accelerometers could potentially be measured remotely on-farm and used by producers as a tool to help detect NCD early so that strategies could be promptly implemented to reduce the negative effects of this disease on calf health and production. Therefore, the objectives of our study were to determine if behav-ioral data collected from ACFS and accelerometer data loggers could be used to detect changes in behavior before the onset of NCD or in response to disbudding pain in dairy calves. cord-306194-2vraae5h 2017 The objectives of our study were to profile the fecal microbiota and predict the functional potential of microbial communities in healthy calves and calves with diarrhea from 2 large dairy farms with dissimilar management practices. Linear discriminant analysis effect size (LEfSe) 22 was used to identify bacterial taxa and predicted functional genes (PICRUSt) that were enriched in feces of healthy and diarrheic calves, based on a P < .05 and LDA score >2.0. [31] [32] [33] We identified significant differences in the fecal microbiota and its predicted functional metabolic pathways in healthy and diarrheic calves from 2 large dairy farms with different management practices. Significant differences in microbiota structure and membership between healthy and diarrheic calves suggest that dysbiosis occurred in diarrheic calves and was associated with changes in the predictive metagenomic function of the bacterial communities. Median relative abundance of the main metabolic pathways genes identified in feces of healthy and diarrheic calves from 2 different farms (n = 15 per group). cord-306297-bt35kaix 1995 Abstract Ninety-six Jersey calves were used to evaluate the effects of housing and method of colostrum feeding on serum Ig concentrations, incidence and severity of scours, intake, and BW changes from birth to 35 d of age. Therefore, our objectives were to determine the effects of housing and method of colostrum feeding on the incidence and severity of scours, intake, BW gain, and feed efficiency for neonatal Jersey calves. Calves were allowed to nurse the dam for 3 d or were separated from the dam and fed 1 L of colostrum in nipple-bottles at 0 and 12 h after birth and housed in individual fiberglass hutches or individual pens in an unheated calf barn. Weekly mean fecal scores, number of days of scouring per week, BW gain, feed efficiency, and days x fecal score were analyzed as a randomized complete block design in a repeated measures analysis of covariance using a general linear mixed models algorithm (5) . cord-308343-crjjhpl1 2018 FINDINGS: Calves in confinement had no significant differences in mean log oocysts enumerated per gram of fecal dry matter between CFC and IC samples (P = 0.6), nor were there diurnal variations in oocyst shedding (P = 0.1). Confinement housed calves shed significantly more oocysts (P = 0.05), had higher plasma cortisol (P = 0.001), and required more supportive care (P = 0.0009) than calves in box stalls. With neonatal calves collection of CFC is a formidable challenge requiring use of confinement housing that severely restricts calf movement and their ability to engage in natural behaviors, such as grooming. The Wilcoxon Rank Sum test was also used to evaluate the differences in plasma cortisol, daily weight gain, daily milk replacer consumption, volume of fluid therapy, and frequency of non-fluid therapy treatments in confinement housing and box stall calves. Plasma cortisol was elevated at 4-5 days post-infection (62 ng/ml) in confinement housing calves, coinciding with the observed peak in fecal oocyst shedding. cord-308816-nux087gc 2000 Cryptosporidium parvum is considered to be an important agent in the aetiology of the neonatal diarrhoea syndrome of calves, lambs and goat kids, causing considerable direct and indirect economic losses. In the following years methods to free the infective oocysts from other contaminating pathogens became available, which permitted the experimental demonstration that Cryptosporidium was capable of causing clinical diarrhoea in calves [27, 28] . Since then, Cryptosporidium has been attributed an increasingly important role in neonatal diarrhoea syndrome in this domestic species and is currently associated with high morbidity rates and, depending on environmental conditions and the presence of other intestinal pathogens, mortality [46, 75, 76] . Cryptosporidium parvum is the most commonly found enteropathogen during the ®rst weeks of the life of calves, lambs and goat kids and is considered to be an important agent in the aetiology of the neonatal diarrhoea syndrome. cord-310009-yha2o28l 2015 title: Cryptosporidium parvum infection and associated risk factors in dairy calves in western France This study was conducted to determine the prevalence and risk factors for Cryptosporidium infection in calf neonates on dairy farms in Normandy. This study was conducted to determine the prevalence and risk factors for Cryptosporidium infection in calf neonates on dairy farms in Normandy. The aim of this study was to determine the prevalence and risk factors for Cryptosporidium infection in bovine neonates in an area of intensive dairy farming in western France. The aim of this study was to determine the prevalence and risk factors for Cryptosporidium infection in bovine neonates in an area of intensive dairy farming in western France. Evaluation of factors associated with the risk of infection with Cryptosporidium parvum in dairy calves Calf-level risk factors for neonatal diarrhea and shedding of Cryptosporidium parvum in Ontario dairy calves cord-310366-da1hsuj4 1996 A previous study indicated that feeding pasteurized colostrum and pasteurized waste milk to calves during the preweaning period resulted in reduced morbidity and improved weight gain compared with those fed nonpasteurized colostrum and nonpasteurized milk (Jamaludldin, 1995) . The objective of this observational study on a Californian dairy was to evaluate the effect of feeding pasteurized colostrum and pasteurized waste milk (versus unpasteurized colostrum and waste milk) during the preweaning period on postweaning weight gain of dairy heifers, controlling for demographic and morbidity variables simultaneously. Postweaning weights of calves were compared between the treatment groups, simultaneously controlling for age, birth weight, and number of days calves experienced diarrhea and pneumonia during the preweaning period using a time series cross section regression (PROC TSCSREG) (Statistical Analysis Systems Institute Inc., 1993). Results of the present study indicated that calves fed pasteurized colostrum and pasteurized waste milk during the preweaning period continued to perform better after weaning than those fed nonpasteurized colostrum and nonpasteurized milk. cord-310792-1brqzyn6 2014 title: Comparison of serum immunoglobulin G half-life in dairy calves fed colostrum, colostrum replacer or administered with intravenous bovine plasma To date studies evaluating half-life of colostrum replacer or plasma derived IgG are lacking. To the best of authors'' knowledge, no studies have evaluated the half-life of colostrum replacer or plasma derived IgG in dairy calves. The objective of this study was to compare the serum half-life of IgG derived from colostrum, colostrum replacer and plasma in dairy calves reared up to 35 days of age. The objective of this study was to compare the serum half-life of IgG derived from colostrum, colostrum replacer and plasma in dairy calves reared up to 35 days of age. The aim of this study was to compare serum half-life of IgG derived from colostrum or colostrum replacer and plasma. cord-313273-ajj4qy7c 2019 Given the lack of improvement in BRD incidence in US dairy cattle, despite the availability of numerous vaccines and antimicrobial drugs labeled for BRD, novel approaches that target prevention in addition to control Management factors associated with bovine respiratory disease in preweaned calves on California dairies: The BRD 100 study 7289 should be evaluated. Briefly, the questionnaire collected information about demographics (location, herd size, and organic or conventional production), maternity pen management (density and individual or group pens), colostrum management (source, heat treatment, storage, quality, volume fed, and testing of calves for failure of transfer of passive immunity), calf management (housing, time of weaning, treatment of sick calves, criteria for treatment, and type and volume of milk fed), vaccinations (type, timing, and frequency of administration to adult cattle and calves), and dust abatement (whether perceived as a problem and type of abatement). cord-313849-lh2ixof2 1990 In order to develop a calf model for studying the syndrome of ruminal drinking (RD) in veal calves, three dual-fistulated calves were used to test the effect of intraruminal administration of milk replacer on the jejunal mucosa. Means of villus length and brush border enzyme activities decreased during the period of intraruminal administration of milk. Clinical recovery from the signs of RD occurred rapidly after intraruminal administration of milk ceased and was followed by restoration of villus length and brush border enzyme activities 3–4 weeks later. A reduced lactase activity compared to the initial values was found in all three experimental calves in week 12, at the end of the induction period. A reduced lactase activity was reported in diarrhoeic calves between 10 and 30 days of age, which also showed villus atrophy and crypt hyperplasia in the proximal jejunum (Landsverk, 1981) . cord-316839-wckqscvm 2009 Mycoplasma bovis is an important cause of pneumonia, otitis media and arthritis in young dairy calves, and there is a critical need for improved preventative strategies for this pathogen. bovis-associated disease; for calves in the remaining 2 herds, the incidence risk for respiratory disease, otitis media and arthritis from 3 to 90 days of age was 0.64, 0.28 and 0.02, respectively. bovis has emerged as an increasingly important cause of respiratory disease, otitis media and arthritis in young calves less than 3 months of age [1, 2, 6, 7, 9] . bovis-associated disease (respiratory disease, otitis media, arthritis) and mortality in dairy calves up to 90 days of age. bovis bacterin in proprietary oil-based adjuvant that had a conditional license for the prevention of respiratory disease in U.S. feeder and stocker calves at the time of the study (Texas Vet. Labs, Inc., San Angelo, TX), while the other group received a placebo (all vaccine components except antigen; control group). cord-321958-ci4onndm 2010 The use of halofuginone lactate in combination with good hygienic measures, such as rearing animals in clean individual pens, was the most effective method to reduce the risk of cryptosporidiosis amongst 7-13 days old calves. The use of halofuginone lactate in combination with good hygienic measures, such as rearing animals in clean individual pens, was the most effective method to reduce the risk of cryptosporidiosis amongst 7-13 days old calves. The consistency of the faeces was recorded at the time of collection using the following scoring system: 0 for solid or pasty sample, 1 for liquid sample and 2 for watery Table 1 Cumulative geometric mean and range of the oocysts per gram (OPG) of faeces excreted by untreated control calves and calves treated with halofuginone lactate during their first 4 weeks and reared in either individual or group pens. cord-323467-ifwjvvjj 2019 A limiting factor in many of the cross-sectional studies presented in this review is the absence of a temporal relationship between Johne''s diagnosis and the impleListed for each study are country, breed of cattle, study design, groups compared (in reference to length of cow-calf contact), total number of calves sampled, the number of herds included (and groups within herds where applicable), the type of herd, the diagnostic(s) used, and the authors'' conclusion and direction of effect (with + signifying a beneficial effect of suckling or cow-calf contact, − signifying a negative effect, and = representing no difference. Official Johne''s disease control programs frequently describe the risks associated with allowing the calf to suckle and remain within the maternity area, or directly recommend immediate separation of cow and calf following parturition; such programs include the Three Step Calf Rearing Plan of Australia (Animal Health Australia, 2016), the Voluntary Bovine Johne''s Disease Control Program of the United States (USDA, 2010), and several regionspecific Canadian programs [such as the Atlantic Veterinary College (2015) Johne''s Disease Initiative, which deems calf nursing to be a risky practice, even within test-negative herds]. cord-324365-546cu3ly 2008 No obvious differences with respect to the extent of these clinical signs were observed between calves of study I (NaCl) and study II (NaHCO 3 ); however, during application of HBS, the respiratory rate increased more profoundly up to roughly 60 breaths per minute compared with the calves treated with hypertonic saline. Age, body weight (BW), clinical variables, and results of blood analysis before initial IV treatment of diarrheic calves with saline (5.85%; 5 mL/kg BW over 4 minutes; study I) and sodium bicarbonate (8.4%; 10 mL/ kg BW over 8 minutes; study II), respectively, followed by administration of 3 L of oral rehydration solution. General condition, rectal temperature, enophthalmus, heart rate, respiratory rate, and fecal dry matter before and after initial IV treatment of diarrheic calves with saline (5.85%; 5 mL/kg BW over 4 minutes; study I) and sodium bicarbonate (8.4%; 10 mL/kg BW over 8 minutes; study II), respectively, followed by administration of 3 L of oral rehydration solution. cord-325148-oe3yv69y 2015 Greater attention must be paid to animal and environmental biosecurity to prevent introduction of diseases into the herd and to digestive disorders such as diarrhea, internal parasites and appropriate vaccination programs for the calves. Continual video monitoring of the herd, modern thermal infrared imaging of the dry cows and calves body parts to identify early symptoms, and overall animal health and biosecurity risk analysis could achieve a sustainable and efficient replacement management practice in cattle industry. Focusing on improving health management of replacements will yield tremendous returns through decreased losses of animals with the greatest genetic potential on the dairy, decreased costs of medication, improved growth rates, improved feed efficiency and earlier entry into the milking herd. Focusing on improving health management of replacements will yield tremendous returns through decreased losses of animals with the greatest genetic potential on the dairy, decreased costs of medication, improved growth rates, improved feed efficiency and earlier entry into the milking herd. cord-329648-ixzymz8a 2002 In this study, the possibility of transmission of BVDV from calves simultaneously subjected to acute BVDV and bovine coronavirus (BCV) infection was investigated. Following infection, BCV was detected in nasal secretions and in faeces of the calves and, after three weeks in the study, all had seroconverted to this virus. All calves, including the controls, showed at least one of the following clinical signs during days 3–15 after the trial started: fever (≥40°C), depressed general condition, diarrhoea, and cough. Furthermore, BCV was introduced which should, in theory, facilitate the transmission of BVDV by causing increased nasal secretions, cough and diarrhoea, clinical signs that were indeed shown by the dually infected calves. All calves infected exclusively with BCV became diseased, which was regarded clinically as a sign of alimentary and respiratory tract involvement, i.e. diarrhoea, nasal and conjunctival discharge and coughing. Lack of virus transmission from primarily bovine viral diarrhoea virus (BVDV) infected calves to susceptible peers cord-331809-1d0c0zc2 2006 Faeces of 230 calves with and without diarrhoea collected during the winter period 2004/2005 in 100 Austrian farms (Styria and Lower Austria) were examined for viral, bacterial and parasitic enteropathogens. In addition, the following agents were detected in bovine faecal samples: Bovine coronavirus, 25.7%; Escherichia coli, 17%; Cryptosporidium spp., 11.7%; Eimeria spp., 10.4%; Rotavirus, 9.1%; Clostridium perfringens, 9.1% and Giardia spp., 6.1%. Furthermore, the faecal prevalences of the most important viral, bacterial and parasitic enteropathogens as co-infecting agents to BoTV on the one hand and on the other as causative pathogens in neonatal calf diarrhoea were determined. Single infection with BoTV was only found in two calves, both suffering from diarrhoea at the time of sampling. On clinical examination, the majority of BoTV-positive calves showed signs of dehydration, and faecal consistency was abnormal in seven animals ranging from watery to mushy. cord-333522-zsdymkjd 2016 Blood samples were taken repeatedly to measure plasma concentrations of flavonols, glucose, lactate, total protein, albumin, urea, non-esterified fatty acids, triglycerides, cholesterol, insulin, glucagon, cortisol, immunoglobulins, fibrinogen, haptoglobin and serum amyloid A. Basal blood samples were taken before the morning feeding on days 1, 2, 4 and 7 from the jugular vein using evacuated tubes containing either potassium-EDTA (1.2-2 mg/mL EDTA) for analyses of plasma metabolites, insulin, glucagon, immunoglobulins and acute-phase proteins or Li-heparin (12-30 IU heparin) for the determination of the cortisol and flavonol concentrations and the antioxidative status in the plasma. Feed intake, body temperature, heart and respiratory rate and plasma concentrations of metabolites, hormones, flavonols and markers of antioxidative status were analyzed by repeated measurement ANOVA using the MIXED procedure of SAS/STAT software and a model with the fixed factors diet, quercetin and day of life (repeated variable) and all interactions between the fixed factors. cord-333535-pzjj2wxc 2015 Despite the limited number of enteric diseases in adult cattle that would benefit from antimicrobial therapy, surveys indicate that diarrhea is a relatively common reason for the use of antibiotics. If Salmonella are the main target of antimicrobial therapy in adult cattle with diarrhea, drug selection should ideally be based on the results of susceptibility testing using bacterial strains recovered from that particular dairy or feedlot. Despite this importance, the United States Department of Agriculture Dairy 2007 study shows a preweaned Antimicrobial Decision Making heifer calf mortality rate of 8.7% and reports that only 40% of farms can supply an adequate number of replacements from their own herd. The investigators concluded that amoxicillin had a significant effect on disease by decreasing mortality and number of scouring days; however, treatment success could not be predicted by whether the E coli cultured from rectal swabs was susceptible or resistant to the antimicrobial being used. cord-335215-h9p4kmss 2011 These studies on dairy calves reported a within herd prevalence of Cryptosporidium without identifying species or the relation to the host''s age. parvum at the age of 5 weeks were excluded because Cryptosporidium species could not be identified in all of the following samples collected in these animals. The present study based on 18S rDNA and gp60 gene analysis is the first in France to include molecular characterization to describe the prevalence and the host age related susceptibility to different Cryptosporidium species after a follow up of the same animal. This observation shows that prevalence of Cryptosporidium infection decreases with increasing age of the cattle in France as in many other countries [17, 19, [33] [34] [35] [36] [37] [38] . parvum, a prevalent zoonotic species, in 5-week-old calves was in agreement with the report of Atwill et al., who considered that the contribution of cattle to human cryptosporidiosis is limited to calves under 2 months of age [53] . cord-337329-a9l8e5z6 1991 Faecal samples from 434 calves under 1 year of age (307 diarrhoeal and 127 normal) were collected from three dairy farms and one village in selected areas of Bangladesh. More than 80% of rotavirus-positive samples from diarrhoeic calves exhibited a titre of 128 or more (geometric mean 345±4.5), whereas non-diarrhoeal calves had titres less than or equal to 128 (geometric mean=29±1.9), suggesting that rotavirus infection in calves in Bangladesh was mostly associated with diarrhoea. This study was undertaken to determine the prevalence of rotavirus infection in selected dairy farms and in conventionally reared village calves in Bangladesh, and to study the prevalence of rotavirus in diarrhoeic and age matched non-diarrhoeic calves. The study, however, suggests that the rotavirus infection in young calves also exists in different locations of the country outside the Dhaka region and is the first report of the existence of the virus in high concentration in association with diarrhoea in young dairy calves in that country. cord-337354-ky8mq4y0 2019 The objective of this study was to evaluate the effect of prebiotic supplementation with stabilized rice bran (SRB) in milk on health, immunity, and performance of pre-weaned organic dairy calves. CONCLUSIONS: These results indicated that the dietary addition of SRB in milk did not have an effect in health, immunity or performance of pre-weaned dairy calves. We hypothesized that the addition of SRB in milk of pre-weaned calves would reduce the presentation and severity of neonatal diarrhea, improving the immune response and consequently the overall calf performance. The addition of prebiotics via SRB into milk starting at 6-7 days of age was assessed for effects on health and performance of pre-weaned organic dairy calves over a 28 days period. The major finding from this study was that the addition of SRB in the milk of newborn calves for 28 days did not enhance performance, health, or immunity during the first month of life, a period characterized for the presentation of digestive diseases. cord-349484-rp1a8lj8 2017 Reports of rotavirus excretion in calves usually result from cross-sectional studies, and in face of the conflicting results regarding protection of calves born to vaccinated dams against diarrhea, the aim of the present study was to evaluate rotavirus excretion in dairy calves born to vaccinated or unvaccinated dams, to identify the genotypes of bovine rotavirus group A (RVA) strains isolated from these animals as well as to investigate characteristics of the disease in naturally occurring circumstances throughout the first month of life. The aim of this study was to evaluate rotavirus excretion and to identify the genotypes of RVA strains isolated from a vaccinated and an unvaccinated dairy herd from São Paulo state, Brazil. A recent report of longitudinal evaluation of diarrhea occurrence in a dairy herd in Brazil stated that the excretion of rotavirus in feces lasted for 1-3 days, which agrees with the results of the present study (Coura et al. cord-350023-7wx5v9b8 2020 A cross-sectional study was conducted on fifty German dairy farms to identify risk factors for high mortality and poor growth in calves. In the model "Risk factors associated with median ADG from birth to weaning", average daily weight gain (ADG) of calves from birth until twelve weeks of life was the dependent variable at herd level. For the investigation of associations between potential risk factors with calf mortality and ADG from birth to weaning a multivariable model each was built. The results of the present field study indicate that high calf mortality (> 5%), FPT in the neonate (serum protein < 55 g/l) and low ADG from birth to weaning (< 700 g/day) are still a problem on dairy farms under livestock production conditions in northeast Germany. cord-351920-igmb2yfe 2016 The aims of the study were to investigate the duration and quantity of BCoV shedding in feces and nasal secretions related to clinical signs, the presence of virus in blood and tissues and to test the hypothesis that seropositive calves are not infectious to naïve in-contact calves three weeks after BCoV infection. In two experimental studies, infected calves were not protected against reinfection with a different BCoV strain three weeks after the first challenge, but did not develop clinical signs [19, 20] . The majority of experimental studies have used BCoV inoculation as challenge procedure, which may influence clinical signs and viral shedding, and thereby the transmission potential compared to natural infection. The present study showed that calves infected with BCoV shed viral RNA for five weeks, and harbored viral RNA in intestinal tissues and lymph nodes even longer. cord-355735-515n7knt 1998 To examine the possibility of a mycotic involvement in neonatal calf diarrhea (NCD) the presence of fungi was assessed in (a) the intestinal contents of dead calves and fecal samples submitted for routine laboratory examination, (b) fecal specimens, sampled once in winter and once in summer, of calves raised on 2 farms with different management systems, and (c) mucosal scrapings of various segments of the digestive tract of a diarrheic calf, massively shedding Candida glabrata. C. glabrata colonized the abomasum (the functional equivalent of the monogastric stomach) but not the other segments of the digestive tract of the euthanized calf Based on the findings of this study it seems that while some yeast species may be considered as commensals of the digestive tract of calves, and consequently their isolation from intestinal contents or fecal samples has no clinical significance, others, such as C.