Brain volume, energy balance, and cardiovascular health in two nonindustrial South American populations.

Little is known about brain aging or dementia in nonindustrialized environments that are similar to how humans lived throughout evolutionary history. This paper examines brain volume (BV) in middle and old age among two indigenous South American populations, the Tsimane and Moseten, whose lifestyles and environments diverge from those in high-income nations. With a sample of 1,165 individuals aged 40 to 94, we analyze population differences in cross-sectional rates of decline in BV with age. We also assess the relationships of BV with energy biomarkers and arterial disease and compare them against findings in industrialized contexts. The analyses test three hypotheses derived from an evolutionary model of brain health, which we call the embarrassment of riches (EOR). The model hypothesizes that food energy was positively associated with late life BV in the physically active, food-limited past, but excess body mass and adiposity are now associated with reduced BV in industrialized societies in middle and older ages. We find that the relationship of BV with both non-HDL cholesterol and body mass index is curvilinear, positive from the lowest values to 1.4 to 1.6 SDs above the mean, and negative from that value to the highest values. The more acculturated Moseten exhibit a steeper decrease in BV with age than Tsimane, but still shallower than US and European populations. Lastly, aortic arteriosclerosis is associated with lower BV. Complemented by findings from the United States and Europe, our results are consistent with the EOR model, with implications for interventions to improve brain health.

Preservation of the heart in ancient Egyptian mummies: A computed tomography investigation with focus on the myocardium.

The ancient Egyptians considered the heart to be the most important organ. The belief that the heart remained in the body is widespread in the archeological and paleopathological literature. The purpose of this study was to perform an overview of the preserved intrathoracic structures and thoracic and abdominal cavity filling, and to determine the prevalence and computed tomography (CT) characteristics of the myocardium in the preserved hearts of ancient Egyptian mummies. Whole-body CT examinations of 45 ancient Egyptian mummies (23 mummies from the Ägyptisches Museum und Papyrussammlung, Berlin, Germany, and 22 mummies from the Museo Egizio, Turin, Italy) were systematically assessed for preserved intrathoracic soft tissues including various anatomical components of the heart (pericardium, interventricular septum, four chambers, myocardium, valves). Additionally, evidence of evisceration and cavity filling was documented. In cases with identifiable myocardium, quantitative (measurements of thickness and density) and qualitative (description of the structure) assessment of the myocardial tissue was carried out. Heart structure was identified in 28 mummies (62%). In 33 mummies, CT findings demonstrated evisceration, with subsequent cavity filling in all but one case. Preserved myocardium was identified in nine mummies (five male, four female) as a mostly homogeneous, shrunken structure. The posterior wall of the myocardium had a mean maximum thickness of 3.6 mm (range 1.4-6.6 mm) and a mean minimum thickness of 1.0 mm (range 0.5-1.7 mm). The mean Hounsfield units (HU) of the myocardium at the posterior wall was 61 (range, 185-305). There was a strong correlation between the HU of the posterior wall of the myocardium and the mean HU of the muscles at the dorsal humerus (R = 0.77; p = 0.02). In two cases, there were postmortem changes in the myocardium, most probably due to insect infestation. To our knowledge, this is the first study to investigate the myocardium systematically on CT scans of ancient Egyptian mummies. Strong correlations between the densities of the myocardium and skeletal muscle indicated similar postmortem changes of the respective musculature during the mummification process within individual mummies. The distinct postmortem shrinking of the myocardium and the collapse of the left ventriclular cavity in several cases did not allow for paleopathological diagnoses such as myocardial scarring.

Prevalence of dementia and mild cognitive impairment in indigenous Bolivian forager-horticulturalists.

INTRODUCTION: We evaluated the prevalence of dementia and mild cognitive impairment (MCI) in indigenous Tsimane and Moseten, who lead a subsistence lifestyle. METHODS: Participants from population-based samples ≥ 60 years of age (n = 623) were assessed using adapted versions of the Modified Mini-Mental State Examination, informant interview, longitudinal cognitive testing and brain computed tomography (CT) scans. RESULTS: Tsimane exhibited five cases of dementia (among n = 435; crude prevalence = 1.2%, 95% confidence interval [CI]: 0.4, 2.7); Moseten exhibited one case (among n = 169; crude prevalence = 0.6%, 95% CI: 0.0, 3.2), all age ≥ 80 years. Age-standardized MCI prevalence was 7.7% (95% CI: 5.2, 10.3) in Tsimane and 9.8% (95% CI: 4.9, 14.6) in Moseten. Cognitive impairment was associated with visuospatial impairments, parkinsonian symptoms, and vascular calcification in the basal ganglia. DISCUSSION: The prevalence of dementia in this cohort is among the lowest in the world. Widespread intracranial medial arterial calcifications suggest a previously unrecognized, non-Alzheimer's disease (AD) dementia phenotype.

Effects of provision of drinking water on the behavior and growth rate of group-housed calves with different milk allowances.

Despite the clear importance of drinking water, calves are not always provided water on farm for the first few weeks of life. The main objective of this study was to investigate the effects of water provision (access or no access) and milk allowance (high or low) on the behavior and growth rate of calves. Fifty mixed-breed calves were each assigned to 1 of 4 treatments: (1) water and high (10 L/d) milk allowance (n = 13), (2) no water and high milk allowance (n = 12), (3) water and low (5 L/d) milk allowance (n = 12), or (4) no water and low milk allowance (n = 13). Visits to the water trough, water intake, milk drinking behavior (visits and drinking speed), proportion of observations eating hay and calf starter, and lying behavior were recorded from when the calves were, on average, 5 d of age (standard deviation: 2 d) for 4 consecutive weeks. Calves were weighed weekly. Some calves began to visit the water trough from the start of the recording period, as early as 4 d of age, and water intake increased with age for all calves that had access to it. This increase was greater for calves provided a high milk allowance. Water intake increased with ambient temperature, which highlights the importance of providing drinking water in warm conditions. Overall, calves spent a greater proportion of observations eating hay and calf starter with age. The provision of drinking water was associated with a greater proportion of observations eating hay but less eating calf starter. The increase in the proportion of observations eating calf starter with age was greater for calves on a low milk allowance than of those provided a high milk allowance; this is likely due to calves on a low milk allowance searching for nutrients and energy. Calves on a high milk allowance grew faster and spent more time lying compared with calves with a low milk allowance, thus suggesting greater satiety of well-fed calves. Our results suggest that calves should have free access to drinking water from birth and that access to drinking water may aid in hay (fiber) intake and possibly rumen development.

Lower limb cellulitis: low diagnostic accuracy and underdiagnosis of risk factors.

Accurate diagnosis and recognition of predisposing factors has been shown to be challenging in lower limb cellulitis (LLC). Assessment of 1746 consecutive patients with cellulitis presenting to a UK university hospital showed increasing overdiagnosis, with only 31.9% of patients referred during the period 2015-2018 having the diagnosis of LLC confirmed. Recognition of at least one predisposing factor increased from 61% to 89% following introduction of more specific screening questions. This identified a need for better primary care dermatology education and the benefit of a proforma with specific screening questions for reversible predisposing factors for LLC.

Short communication: Evaluation of the efficacy of novel disbudding methods for dairy calves.

The objectives of this study were to (1) evaluate whether cryoablation or the administration of clove oil was as efficacious as cautery disbudding at preventing horn growth, and (2) evaluate whether the efficacy of cautery disbudding is affected by removing or leaving the horn bud tissue intact after disbudding of dairy calves. At approximately 4 d of age (4.0 ± 0.88 d of age, mean ± SD), 265 dairy heifer calves from 3 dairy farms (farm 1: n = 129 calves; farm 2: n = 109 calves; farm 3: n = 27 calves) were disbudded. Each calf had 1 of 4 treatments randomly assigned to each horn bud: (1) clove oil (0.5 mL) administered subcutaneously under the horn bud (CLOV, n = 135 buds); (2) a liquid nitrogen-filled probe applied to the horn bud area for 30 s (CRYO, n = 134 buds); (3) cautery disbudding using an electric hot-iron and the horn bud removed (BUDOFF, n = 130); or (4) cautery disbudding and the horn bud tissue left intact (BUDON, n = 131). Calves were assessed for signs of infection at the disbudding site frequently within the first month after disbudding. At approximately 6 mo of age (6 ± 2.2 mo, mean ± SD) calves were assessed for scur or horn growth. The disbudding procedures were considered successful if no scur or horn development was observed. Within the first month, 12% of disbudding wounds showed some indication of infection, such as pus, exudate, or swelling; of the infected buds, 52% were associated with the BUDON treatment, 27% with CLOV, 25% with BUDOFF, and 2% with CRYO treatments. At 6 mo of age, BUDOFF was the most effective method of preventing horn growth and CRYO was the least efficacious [mean percentage of success: BUDOFF: 100% (95% CI: 97.7-100.0); CRYO: 1% (95% CI: 0.2-5.3)]. Injecting clove oil under the horn bud was 87% (95% CI: 80.6-92.5) successful. Not removing the horn bud tissue after cautery disbudding reduced the efficacy of this method by 9% [91% success (95% CI: 83.8-95.7)]; moreover, this method was associated with more infection at the site of disbudding. It appears as though the clove oil treatment could be used as an alternative to cautery disbudding of dairy calves; however, further research is needed to evaluate the tissue damage and associated pain caused by clove oil and to refine this technique (i.e., administration methods to improve efficacy) before it could be considered an alternative to cautery.

Physiological and behavioral responses as indicators for early disease detection in dairy calves.

This study investigated physiological and behavioral responses associated with the onset of neonatal calf diarrhea (NCD) in calves experimentally infected with rotavirus and assessed the suitability of these responses as early disease indicators. The suitability of infrared thermography (IRT) as a noninvasive, automated method for early disease detection was also assessed. Forty-three calves either (1) were experimentally infected with rotavirus (n = 20) or (2) acted as uninfected controls (n = 23). Health checks were conducted on a daily basis to identify when calves presented overt clinical signs of disease. In addition, fecal samples were collected to verify NCD as the cause of illness. Feeding behavior was recorded continuously as calves fed from an automated calf feeder, and IRT temperatures were recorded once per day across 5 anatomical locations using a hand-held IRT camera. Lying behavior was recorded continuously using accelerometers. Drinking behavior at the water trough was filmed continuously to determine the number and duration of visits. Respiration rate was recorded once per day by observing flank movements. The effectiveness of inoculating calves with rotavirus was limited because not all calves in the infected group contracted the virus; further, an unexpected outbreak of Salmonella during the trial led to all calves developing NCD, including those in the healthy control group. Therefore, treatment was ignored and instead each calf was analyzed as its own control, with data analyzed with respect to when each calf displayed clinical signs of disease regardless of the causative pathogen. Milk consumption decreased before clinical signs of disease appeared. The IRT temperatures were also found to change before clinical signs of disease appeared, with a decrease in shoulder temperature and an increase in side temperature. There were no changes in respiration rate or lying time before clinical signs of disease appeared. However, the number of lying bouts decreased and lying bout duration increased before and following clinical signs of disease. There was no change in the number of visits to the water trough, but visit duration increased before clinical signs of disease appeared. Results indicate that milk consumption, IRT temperatures of the side and shoulder, number and duration of lying bouts, and duration of time spent at the water trough show potential as suitable early indicators of disease.

A new method of administering local anesthesia for calf disbudding: Findings from a comparative on-farm study in New Zealand.

Anesthesia of the horn bud for calf disbudding commonly is attained by injection of local anesthetic over branches of the cornual nerve, with anesthesia achieved in 3 to 20 min. With experienced and trained staff, this method is effective in 88 to 100% of calves. Variability in response and time of onset can compromise calf welfare if calves are disbudded before anesthesia is attained. Proposed legislative reliance on effective local anesthetic as the minimal method of pain relief for calves at disbudding means that administration of local anesthetic must achieve a repeatable level and rapid onset of analgesia. We describe an alternative method of local anesthesia administration that uses local site infiltration of anesthetic over the horn bud. However, this method has not yet been scientifically validated. This study assessed differences between disbudding using the cornual nerve block and disbudding with local anesthesia administered by local site infiltration. Efficacy of local anesthesia was assessed at 30-s intervals after administration by absence of reaction to 3 consecutive needle pricks over the horn buds. Behavior indicating pain was assessed during disbudding and scored from 0 to 3. Calf behavior was also recorded for 3 h after disbudding. Accelerometer data loggers were fitted to each calf for 24 h before and after disbudding to assess lying and standing times. Median time to cutaneous desensitization for local infiltration was 60 s compared with 225 s for cornual nerve block, and the variance in time to desensitization was less with local infiltration. Calves disbudded under cornual block had a larger behavioral response (indicated by a graded aversive body reaction) than calves disbudded under local infiltration. A multivariable model predicted that the mean body reaction score would be 0.6 for calves disbudded under local infiltration and 1.2 for calves disbudded under cornual block. There was no difference in any behaviors between the treatment groups in the 3 h after disbudding. Method of analgesia had no effect on lying time over the 24 h after disbudding. In this study, local infiltration was at least as effective in providing analgesia for disbudding as the cornual nerve block. Our results suggest that a more consistent, effective level of analgesia during disbudding was achieved using local infiltration and that there was no difference in postoperative expressions of pain.

Coronary atherosclerosis in indigenous South American Tsimane: a cross-sectional cohort study.

BACKGROUND: Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. METHODS: We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. FINDINGS: Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1-100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0·0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2·35 mmol/L (91 mg/dL) and 1·0 mmol/L (39·5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High-sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3·0 mg/dL in 360 (51%) Tsimane participants. INTERPRETATION: Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined. FUNDING: National Institute on Aging, National Institutes of Health; St Luke's Hospital of Kansas City; and Paleocardiology Foundation.

Working while unwell: Workplace impairment in people with severe asthma.

BACKGROUND: Severe asthma affects quality of life; however, its impact on workplace productivity is poorly understood. OBJECTIVE: To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. METHODS: The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years; 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. RESULTS: At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). CONCLUSION AND CLINICAL RELEVANCE: Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.

Is coronary calcium scoring too late? Total body arterial calcium burden in patients without known CAD and normal MPI.

BACKGROUND: Patients with normal myocardial perfusion imaging (MPI) have a good prognosis. However, pre-clinical coronary and extracoronary atherosclerosis may exist in the absence of myocardial ischemia. METHODS: 154 Egyptian patients (mean age 53 years) underwent whole-body non-contrast CT following normal MPI. RESULTS: Atherosclerosis in the form of calcification was observed in ≥1 vascular bed in 115 of 154 (75%) patients. This included the iliofemoral (62%), abdominal aorta (53%), thoracic aorta (47%), coronary (47%), and carotid (25%) vascular beds. Mean total body calcium score was 3172 ± 530 AU. Extracoronary atherosclerosis in patients with a zero coronary artery calcium (CAC) score was common, occurring in the above-listed beds 42%, 36%, 29%, and 7% of the time, respectively. CAC was rarely present without iliofemoral or abdominal aortic calcification. CONCLUSION: Quantitative assessment of calcification in different vascular beds demonstrates that extracoronary atherosclerosis is common in patients who have normal MPI. Atherosclerotic calcifications are most common in the iliofemoral arteries and abdominal aorta, which typically predate coronary calcifications. An imaging strategy to detect extracoronary atherosclerosis could lead to greater understanding of the natural history of atherosclerosis in its long pre-clinical phase and possibly to earlier preventive strategies.

Measurement of dairy calf behavior prior to onset of clinical disease and in response to disbudding using automated calf feeders and accelerometers.

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. At 4 d of age, 112 calves had accelerometers attached to their hind leg and were housed in pens with ACFS. Calves were examined daily for signs of illness or injury. Of the 112 calves monitored, 18 were diagnosed with NCD; activities of calves with NCD were then compared with those of 18 healthy controls (calves that had no symptoms of NCD, other illnesses, or injury). 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. Calves with NCD performed fewer unrewarded visits and consumed less milk than healthy calves during the 2- and 4-d periods before diagnosis with NCD, respectively. Calves with NCD tended to perform fewer lying bouts than healthy calves over the 5-d period before diagnosis with NCD. At 3 wk of age, a subset of 51 healthy calves were allocated to 1 of 5 treatment groups: (1) sham handling (SHAM, n = 10), (2) cautery disbudding (DB, n = 11), (3) administration of local anesthetic (LA) and DB (LA+DB, n = 11), 4) administration of a nonsteroidal anti-inflammatory drug (NSAID) and DB (NSAID+DB, n = 9), and (5) administration of LA, NSAID and DB (LA+NSAID+DB, n = 10). Feeding and lying behavior were recorded continuously for 24 h pre- and postdisbudding. We found no effect of treatment on the number of rewarded or unrewarded visits to the feeder and milk volume consumed 24 h before administration of treatments. During the 24-h postdisbudding period, SHAM calves performed more unrewarded visits than DB, LA+DB, and NSAID+DB calves, but the number of unrewarded visits did not differ between SHAM and LA+NSAID+DB calves. During the first hour of the posttreatment period we noted a difference in lying times among treatments, with DB and NSAID+DB calves spending less time lying than SHAM calves and lying times being similar between SHAM, LA+DB, and LA+NSAID+DB calves. The ACFS and accelerometers have the potential to automatically gather valuable information regarding health status and pain in calves. Therefore, it may be advantageous to combine both of these measures (ACFS and accelerometers) when evaluating NCD on farm or pain in calves in future research.

An Improved Detached-Leaf Assay for Phenotyping Net Blotch of Barley Caused by Pyrenophora teres.

Net blotch, caused by Pyrenophora teres, is a major barley (Hordeum vulgare) leaf disease worldwide. P. teres occurs as two forms-P. teres f. teres, and P. teres f. maculata-inducing net and spot-like symptoms, respectively. An intact-seedling assay, where entire seedlings are inoculated by spraying with a conidial suspension, is frequently used for phenotyping net blotch. However, this presents a biosecurity risk in the glasshouse when nonlocal isolates are being screened. Alternatively, a detached-leaf assay (DLA-droplet method) can be used in which leaf segments laid out in a covered tray are inoculated with droplets of a conidial suspension, confining the inoculum. However, using this method, net and spot form symptoms cannot be distinguished from each other. We have developed an improved DLA (DLA-spray method) in which detached whole leaves are sprayed with the inoculum to produce distinct lesions. We compare the results for the three phenotyping methods above using four isolates from both net and spot forms of the disease to inoculate a standard set of eight barley genotypes. Results indicate that the DLA-spray method is a functional, informative and rapid test that readily differentiates the two forms of the pathogen in a biosecure environment.

The use of infrared thermography and accelerometers for remote monitoring of dairy cow health and welfare.

Increasing reliance on automated systems on-farm has led to a need for remote monitoring of health and welfare. We aimed to validate 2 methods that could be integrated into automated systems currently in use: infrared thermography (IRT) to measure respiration rate (RR), and accelerometers to measure the flinch, step, kick (FSK) response and assessing stress and discomfort. We monitored 22 multiparous, nonlactating, Friesian and Friesian × Jersey cows (average 5.1 yr of age) during a baseline period (2 min), a restraint in a crush (2 min), and then a recovery period after exposure to a startle (2 min). We measured RR with continuous IRT imaging of airflow through the nostrils and by counting flank movements from video and live recordings. We recorded heart rate (HR) and HR variability using HR monitors, and we recorded FSK from continuous video analysis of leg movements and indirectly using accelerometers attached to both hind legs. The FSK response was scored between 1 and 4 based on the height and direction of each leg movement. We observed no change in RR, HR variability, or FSK in response to the startle; however, HR increased briefly by 10 bpm. Bland-Altman plots indicated good agreement between the different methods of measuring RR, with average differences of -0.01 ± 0.87, 0.83 ± 0.57, and 0.37 ± 1.02 breaths/min for video versus live, IRT versus live and IRT versus video, respectively. Acceleration was also highly correlated with FSK scores of ≤3 (R2 = 0.96) and ≤2 (R2 = 0.89) and moderately correlated with FSK scores of 1 (R2 = 0.66) over the 4-min sampling period. The results show that accelerometers can provide an indirect measure of the FSK response, and IRT can be used reliably to measure RR. With further development, both technologies could be integrated into existing systems for remote monitoring of dairy cows' health and welfare on-farm.

Health, physiology, and behavior of dairy calves reared on 4 different substrates.

The objective of this study was to compare the health, physiology, and behavior of group-housed calves reared on wood shavings with those reared on alternative surfaces. At 1 wk of age, 80 calves were moved into 1 of 20 experimental pens (n = 4 calves/pen) where they remained until 6 wk of age. Pens had floors covered with pea gravel (PG), rubber chip (RC), sand (SA), or wood shavings (WS; n = 5 pens/substrate). Body weight, cleanliness, health, and skin surface and vaginal temperature were recorded at 1, 3, and 6 wk of age. Escherichia coli numbers were assessed on the skin surface of the shoulder and in the feces of calves at 3 and 6 wk of age. Blood samples were taken at 1, 3, and 6 wk of age to measure hematological values and cortisol, IgG, and lactate concentrations. Behaviors (lying, running, and self-grooming) were recorded in the home pen at 1, 3, and 6 wk of age using video recorders and accelerometer data loggers. At 6 wk of age, calves were tested individually in an arena test and behavior was recorded continuously for 20 min. Body weight did not differ among calves reared on PG, RC, SA, or WS, regardless of age. All calves were clean and no calves displayed any signs of lameness, leg lesions, or injuries at wk 1, 3, or 6, regardless of substrate. The number of E. coli recovered from a surface area of 100 cm2 on the shoulder of each calf was affected by rearing substrate, with more E. coli recovered from calves reared on WS than PG, RC, or SA at 3 and 6 wk of age. Fecal E. coli counts were not affected by rearing substrate at 3 or 6 wk of age. Over the entire study period, calves reared on PG and SA had lower skin temperatures than calves reared on RC or WS, but skin temperature was similar between calves reared on PG and SA. However, vaginal temperature did not differ among calves reared on different substrates at 1, 3, or 6 wk of age. Hematology values and cortisol, IgG, and lactate concentrations of calves were similar among rearing substrates over the 6-wk study period. In the home pen, rearing substrate did not influence time spent lying; however, calves reared on WS performed more lying bouts than calves reared on PG or SA. In addition, rearing substrate did not influence the time calves spent running; however, calves reared on WS spent more time self-grooming than calves reared on PG, RC, and SA. During a 20-min arena test, running, bucks, jumps, and kicks performed by calves was not affected by rearing substrate. In conclusion, the physiology and behavior of calves reared on PG, RC, and SA was similar to WS, which is considered the preferred rearing substrate to use when rearing calves. Therefore, PG, RC, and SA may be acceptable substrate options when rearing group-housed dairy calves.

Electroencephalographic assessment of oral meloxicam, topical anaesthetic cream and cautery iron for mitigating acute pain in pigs (Sus scrofa) undergoing tail docking.

OBJECTIVE: To evaluate the efficacy of oral meloxicam, topical anaesthetic cream and cautery iron in mitigating acute nociceptive responses of pigs to tail docking. STUDY DESIGN: A prospective, randomized, controlled experimental study. ANIMALS: A total of 40 healthy Large WhitexLandrace pigs aged 21±1 days, weighing 6.1±0.9 kg. METHODS: Pigs were randomly assigned to one of four treatments (n=10 per treatment): CONTROL: docked using clippers without analgesia; MEL: docked using clippers after administration of oral meloxicam; EMLA: docked using clippers after application of topical anaesthetic cream; and CAUT: docked using a cautery iron without analgesia. Anaesthesia was induced and maintained with halothane in oxygen. Following induction, end-tidal halothane was stabilized at 0.95-1.05% and electroencephalograph (EEG) recording commenced. After 5 minutes of baseline data collection, tail docking was performed and recording continued for a further 10 minutes. The EEG summary variables median frequency (F50), 95% spectral edge frequency (F95) and total power (PTOT) were calculated for the baseline period and for consecutive 30-second intervals following docking. RESULTS: Following docking, F50 increased and PTOT decreased significantly in CONTROL and MEL pigs. EMLA pigs exhibited no change in any variable, whilst CAUT pigs exhibited a reduction in PTOT but no change in F50. F50 was higher in control pigs than in EMLA pigs 30-60 seconds after docking (p≤0.01). PTOT was lower in CONTROL than in EMLA pigs 30-90 seconds after docking (p<0.03) and in CAUT pigs 60 seconds after docking (p=0.01). CONCLUSIONS AND CLINICAL RELEVANCE: Prior application of EMLA cream abolished EEG indicators of nociception in pigs docked using clippers. Docking using a cautery iron without analgesia ameliorated EEG indicators of nociception, relative to using clippers without analgesia. Prior administration of EMLA cream or the use of cautery instead of clippers may reduce the acute pain experienced by pigs undergoing tail docking.

Paleoimaging of a modern mummy from Lithuania (circa 19th-20th century).

An anthropogenic human mummy curated in the Museum of the History of Medicine, Vilnius University, was recently examined by means of computed tomography. Although the mummy lacked data regarding its specific context and historical information on its identity and chronology, the investigation focused on the embalming method adopted to preserve it. Some pathological alterations were also recorded. This research appears to suggest that this body was prepared for educational and/or scientific purposes rather than funerary purposes. Hence, the case could be categorized as a "medical mummy" prepared between the mid-19th and the mid-20th centuries.

Real-life effectiveness of omalizumab in severe allergic asthma above the recommended dosing range criteria.

BACKGROUND: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). OBJECTIVES: To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. METHODS: Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). RESULTS: Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria; other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV1 ) improved among above-range participants. There was no difference in response between above-range and within-range participants. Above-range participants due to either IgE alone or IgE and weight had similar improvements in ACQ-5, AQLQ and FEV1 . CONCLUSIONS AND CLINICAL RELEVANCE: Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg.

In vitro comparison of the effect of two factor XI (FXI) concentrates on thrombin generation in major FXI deficiency.

INTRODUCTION: Bleeding risk in factor XI (FXI) deficiency following surgery may be reduced by treatment with either of two FXI concentrates, but indications for their use are unclear and treatment has been associated with thrombosis. AIM: To quantify and compare the effects of two different FXI concentrates on thrombin generation (TG) in major FXI deficiency (FXI:C < 15 IU dL(-1) ). METHODS: Thrombin generation was measured in controls (n = 50), FXI-deficient individuals pre and post in vitro spiking with FXI concentrates (n = 10), and in ex vivo samples following treatment with FXI concentrate (n = 3). RESULTS: Thrombin generation was significantly impaired in FXI deficiency but improved following FXI replacement in vitro and in vivo. LFB Hemoleven(®) had greater effect on TG than BPL FXI concentrate in vitro (equivalent in vivo doses 10, 20 and 30 U kg(-1) ): higher endogenous thrombin potential (ETP) (P < 0.0001), peak height (P < 0.01) velocity (P < 0.0002) and shorter lag time and time to peak (both P < 0.003). Some measurements with LFB Hemoleven(®) exceeded the reference range. At lower dose (5 U kg(-1) ), BPL FXI concentrate normalized all TG parameters and LFB Hemoleven(®) normalized the ETP but exceeded the reference range with other parameters. CONCLUSION: Both FXI concentrates improve TG in vitro in major FXI deficiency but differ in dose response, and for both products, doses lower than previously recommended normalized TG in vitro. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement.