Udder health outcomes in Irish herds participating in cellcheck dry cow consults.

The CellCheck Dry Cow Consult (DCC) was developed by the CellCheck Technical Working Group to enable farmers to engage with their nominated vet to develop farm-specific selective dry cow therapy (SDCT) plans, where appropriate. This study evaluated the effect of the DCC on farmer decision-making around dry cow therapy, and the udder health impact of implementing SDCT, in study herds over the 2019 and 2020 dry periods. The DCC was a 3-h consult, delivered and funded as part of the Targeted Advisory Service on Animal Health (TASAH). Herds that completed a DCC were invited to register for a Dry Cow Review the following year. The combined data set for analysis across both years comprised of 439 herds and 25,357 cows. Available herd size ranged from 25 to 800. The median SCC of cows dried off with teat sealant only was 47,000 cells/ml before drying off in 2019 and 48,000 cells/ml at first milk recording in 2020, and 43,000 cells/ml before drying off in 2020 and 39,000 cells/ml at first milking recording in 2021. Following both the 2019 and 2020 dry periods, cows tended to converge toward a similar median SCC early in the following lactation, irrespective of prior dry cow treatment strategy. The uptake of SDCT was greater in Review herds, with 21% of cows receiving teat sealant only in 2020, compared with 16.3% of cows in herds participating in a Consult for the first time in 2020. At an individual cow level, in both years dry period new infection rate (NIR) was approximately 2.7% higher for cows treated with teat sealant only, than for those treated with both dry cow antibiotic tubes and teat sealant, and 1.2% higher than cows treated with antibiotic only. Regardless of treatment, there was a significant association between increasing parity and the risk of a dry period new infection. Increasing herd size had a statistically significant effect on the risk of dry period new infection rates. At a herd level, there was no statistically significant increase in NIR when SDCT was used compared with herds where blanket dry cow therapy was used. While not without risk, SDCT can be successfully implemented in Irish herds; however, constant attention to hygiene and management is essential. Though there are challenges to face, facilitating continued farmer education and engagement with professional guidance will be important.

Increased detection of mastitis pathogens by real-time PCR compared to bacterial culture.

Rapid and accurate identification of mastitis pathogens is important for disease control. Bacterial culture and isolate identification is considered the gold standard in mastitis diagnosis but is time consuming and results in many culture-negative samples. Identification of mastitis pathogens by PCR has been proposed as a fast and sensitive alternative to bacterial culture. The results of bacterial culture and PCR for the identification of the aetiological agent of clinical mastitis were compared. The pathogen identified by traditional culture methods was also detected by PCR in 98 per cent of cases indicating good agreement between the positive results of bacterial culture and PCR. A mastitis pathogen could not be recovered from approximately 30 per cent of samples by bacterial culture, however, an aetiological agent was identified by PCR in 79 per cent of these samples. Therefore, a mastitis pathogen was detected in significantly more milk samples by PCR than by bacterial culture (92 per cent and 70 per cent, respectively) although the clinical relevance of PCR-positive culture-negative results remains controversial. A mixed infection of two or more mastitis pathogens was also detected more commonly by PCR. Culture-negative samples due to undetected Staphylococcus aureus infections were rare. The use of PCR technology may assist in rapid mastitis diagnosis, however, accurate interpretation of PCR results in the absence of bacterial culture remains problematic.

Pathogen profile of clinical mastitis in Irish milk-recording herds reveals a complex aetiology.

Effective mastitis control requires knowledge of the predominant pathogen challenges on the farm. In order to quantify this challenge, the aetiological agents associated with clinical mastitis in 30 milk-recording dairy herds in Ireland over a complete lactation were investigated. Standard bacteriology was performed on 630 pretreatment quarter milk samples, of which 56 per cent were culture-positive, 42 per cent culture-negative and 2 per cent contaminated. Two micro-organisms were isolated from almost 5 per cent of the culture-positive samples. The bacteria isolated were Staphylococcus aureus (23 per cent), Streptococcus uberis (17 per cent), Escherichia coli (9 per cent), Streptococcus species (6 per cent), coagulase-negative Staphylococci (4 per cent) and other species (1 per cent). A wide variety of bacterial species were associated with clinical mastitis, with S aureus the most prevalent pathogen overall, followed by S uberis. However, the bacterial challenges varied widely from farm to farm. In comparison with previous reports, in the present study, the contagious pathogens S aureus and Streptococcus agalactiae were less commonly associated with clinical mastitis, whereas, the environmental pathogens S uberis and E coli were found more commonly associated with clinical mastitis. While S aureus remains the pathogen most commonly associated with intramammary infection in these herds, environmental pathogens, such as S uberis and E coli also present a considerable challenge.

Opportunities and constraints to improving milk quality in Ireland: enabling change through collective action.

Ireland plays a key role in contributing to the global supply of dairy produce, and increasing international demand, as well as the abolition of milk quotas in the European Union in 2015, present opportunities for the Irish milk industry. Improving milk quality is required to maximize these opportunities. National action on milk quality is spearheaded by Animal Health Ireland, yet the potential for collective action at an industry level is undermined by the inability of individual stakeholders to accept responsibility for action. In-depth qualitative interviews were conducted with n=12 stakeholder representatives. The theoretical concepts of collective action (i.e., when a group of people with a shared interest undertake some kind of voluntary common action in pursuit of that shared interest) is applied to understanding the results and identifying a collective way forward. Though consensus is apparent on the need to improve milk quality, differences exist about individual responsibility and the best way to achieve higher quality standards. The propensity for collective action is undermined by shifting responsibility to other stakeholders, stakeholder positions, trust concerns, and concerns over the commitment of other stakeholders to cooperate. Understanding how collective action works provides Animal Health Ireland with a knowledge framework in which to build stakeholder consensus. The paper concludes with practical examples of how Animal Health Ireland continues to apply this understanding by bringing individual stakeholders together to achieve milk quality improvement.

Acquired differential regulation of caspase-8 in cisplatin-resistant non-small-cell lung cancer.

Failure to efficiently induce apoptosis contributes to cisplatin resistance in non-small-cell lung cancer (NSCLC). Although BCL-2-associated X protein (BAX) and BCL-2 antagonist killer (BAK) are critical regulators of the mitochondrial apoptosis pathway, their requirement has not been robustly established in relation to cisplatin. Here, we show that cisplatin can efficiently bypass mitochondrial apoptosis block caused by loss of BAX and BAK, via activation of the extrinsic death receptor pathway in some model cell lines. Apoptosis resistance following cisplatin can only be observed when both extrinsic and intrinsic pathways are blocked, consistent with redundancy between mitochondrial and death receptor pathways in cisplatin-induced apoptosis. In H460 NSCLC cells, caspase-8 cleavage was shown to be induced by cisplatin and is dependent on death receptor 4, death receptor 5, Fas-associated protein with death domain, acid sphingomyelinase and ceramide synthesis. In contrast, cisplatin-resistant cells fail to activate caspase-8 via this pathway despite conserving sensitivity to death ligand-driven activation. Accordingly, caspase-8 activation block acquired during cisplatin resistance, can be bypassed by death receptor agonism.

Estimating the effect of mastitis on the profitability of Irish dairy farms.

The objective of this paper was to estimate the effect of the costs of mastitis on the profitability of Irish dairy farms as indicated by various ranges of bulk milk somatic cell count (BMSCC). Data were collected from 4 sources and included milk production losses, cases treated, and on-farm practices around mastitis management. The Moorepark Dairy Systems Model, which simulates dairying systems inside the farm gate, was used to carry out the analysis. The cost components of mastitis that affect farm profitability and that were included in the model were milk losses, culling, diagnostic testing, treatment, veterinary attention, discarded milk, and penalties. Farms were grouped by 5 BMSCC thresholds of ≤ 100,000, 100,001-200,000, 200,001-300,000, 300,001-400,000, and > 400,000 cells/mL. The ≤ 100,000 cells/mL threshold was taken as the baseline and the other 4 thresholds were compared relative to this baseline. For a 40-ha farm, the analysis found that as BMSCC increased, milk receipts decreased from €148,843 at a BMSCC <100,000 cells/mL to €138,573 at a BMSCC > 400,000 cells/mL. In addition, as BMSCC increased, livestock receipts increased by 17%, from €43,304 at a BMSCC <100,000 cells/mL to €50,519 at a BMSCC > 400,000 cells/mL. This reflected the higher replacement rates as BMSCC increased and the associated cull cow value. Total farm receipts decreased from €192,147 at the baseline (< 100,000 cells/mL) to €189,091 at a BMSCC > 400,000 cells/mL. Total farm costs increased as BMSCC increased, reflecting treatment, veterinary, diagnostic testing, and replacement heifer costs. At the baseline, total farm costs were €161,085, increasing to €177,343 at a BMSCC > 400,000 cells/mL. Net farm profit decreased as BMSCC increased, from €31,252/yr at the baseline to €11,748/yr at a BMSCC > 400,000 cells/mL. This analysis highlights the impact that mastitis has on the profitability of Irish dairy farms. The analysis presented here can be used to develop a "cost of mastitis" tool for use on Irish dairy farms to motivate farmers to acknowledge the scale of the problem, realize the value of improving mastitis control, and implement effective mastitis control practices.

Obatoclax induces Atg7-dependent autophagy independent of beclin-1 and BAX/BAK.

Direct pharmacological targeting of the anti-apoptotic B-cell lymphoma-2 (BCL-2) family is an attractive therapeutic strategy for treating cancer. Obatoclax is a pan-BCL-2 family inhibitor currently in clinical development. Here we show that, although obatoclax can induce mitochondrial apoptosis dependent on BCL-2 associated x protein/BCL-2 antagonist killer (BAX/BAK) consistent with its on-target pharmacodynamics, simultaneous silencing of both BAX and BAK did not abolish acute toxicity or loss of clonogenicity. This is despite complete inhibition of apoptosis. Obatoclax dramatically reduced viability without inducing loss of plasma membrane integrity. This was associated with rapid processing of light chain-3 (LC3) and reduction of S6 kinase phosphorylation, consistent with autophagy. Dramatic ultrastructural vacuolation, not typical of autophagy, was also induced. Silencing of beclin-1 failed to prevent LC3 processing, whereas knockout of autophagy-related (Atg)7 abolished LC3 processing but failed to prevent obatoclax-induced loss of clonogenicity or ultrastructural changes. siRNA silencing of Atg7 in BAX/BAK knockout mouse embryonic fibroblasts did not prevent obatoclax-induced loss of viability. Cells selected for obatoclax resistance evaded apoptosis independent of changes in BCL-2 family expression and displayed reduced LC3 processing. In summary, obatoclax exhibits BAX- and BAK-dependent and -independent mechanisms of toxicity and activation of autophagy. Mechanisms other than autophagy and apoptosis are blocked in obatoclax resistant cells and contribute significantly to obatoclax's anticancer efficacy.

Osseous expansion of the cranial vault by craniotasis.

A study of cranial vault lengthening using a custom expandable fixation-distraction (craniotatic) appliance was performed in the young-adult rabbit model. Ten 24-week-old rabbits underwent circumferential suturectomy plus expansion (expanded group), 10 underwent circumferential suturectomy without expansion (sham control group), and 10 served as normal controls. The appliance was lengthened at a rate of 2.5 mm per week for 5 weeks. Serial lateral cephalometry, comparative dry-skull anthropometric measurements, and histologic examinations were performed. The expanded group demonstrated a significantly longer skull, cranial vault, anterior cranial base, posterior face, and orbit as compared with the control groups (p less than 0.05). Callus bone filled the distracted suturectomy and united the frontofacial complex to the posterior cranium. In conclusion, skull lengthening by distraction osteogenesis is possible in the rabbit model and offers a new technique for future investigation in the treatment of coronal synostosis.

A technique for placement of interosseous wires.

A technique for passing interosseous wires is described. By using an intravenous cathether, it is possible to pass an interosseous wire through the drill hole without difficulty.

A multi-chemical death involving caffeine, nicotine and malathion.

Death of a 21-year-old man who was found in a shower stall in his residence is described in the study. At the scene, a 3/4 filled blue glass bottle labeled "Black Leaf 40" (an insecticide containing nicotine), a white plastic pitcher 1/3 full of thick white fluid, a beer mug 1/4 full of thick white fluid, and an empty carton of milk were found. In addition, a can of malathion and an empty bottle labeled caffeine also were found in the vicinity. Autopsy was performed, and the gross examinations of organs revealed no specific findings to account for the death. However, marked congestion in lung, liver, spleen and kidney were noted at microscopic level. Autolytic degenerative changes were also observed in stomach, small bowel and colon. Toxicological analyses of the autopsy samples (blood, urine, liver and gastric contents) revealed the presence of caffeine and nicotine in each sample. Malathion was found to be present only in gastric content. Caffeine and nicotine were analyzed by utilizing gas liquid chromatography-nitrogen phosphorus detector, while malathion was by gas liquid chromatography-flame photometric detector. Analyses of the fluids from the bottle, pitcher and mug disclosed the presence of nicotine in the concentrations of 17.8%, 3.7% and 5.7% (w/w), respectively. The fluids from the pitcher and mug also contained 2.7-2.9% malathion. Results conclude the death was associated with caffeine, nicotine and malathion.

Glomerulonephritis associated with male pseudohermaphroditism and nephroblastoma.

A child with male pseudohermaphroditism, Wilms' tumor, and glomerulonephritis (Drash syndrome) was found to have a proliferative glomerular lesion, extensive renal cortical interstitial and glomerular scarring, and marked renal tubular foam cell change. By electron microscopy, dense deposits were seen in mesangial areas with focal extension into the subendothelial space. Segmental deposits of immunoglobulin and complement were found in the glomeruli by immunofluorescence microscopy. A consistent karyotypic abnormality consisting of isochromosomes of the long arms of 1 and 17, and an interstitial deletion of the long arm of 5 was found in cultures of tumor cells, but no karyotypic abnormalities were found in peripheral blood lymphocytes or non-neoplastic kidney. Renal failure in this case has progressed despite the surgical removal of the tumor. These findings are similar to those reported previously in patients with this syndrome and suggest a common pathophysiological abnormality in all of the patients reported so far.

Pigmentary macular degeneration with multifocal necrotizing encephalopathy.

A previously healthy 10-year-old girl suffered sudden, binocular visual deterioration. During the next few years her neurologic and visual condition progressively worsened and she developed hypertension, seizures, ataxia, and lactic acidemia, leading to death at the age of 16 years. Bilateral optic disk pallor was followed by the loss of the foveal reflex and pigmentary maculopathy, manifested as disorganization of the retinal layers, loss of ganglion cells, degeneration of the photoreceptors and nuclei, and irregular infiltration of the retina by pigment epithelial cells. The optic nerves and tracts showed central axonal loss. Bilateral, multifocal symmetric areas of cerebral atrophy and necrosis of the neuropil and neurons in the cerebral cortex, basal ganglia, and thalamus were observed; neurons persisted in the dorsal medulla, despite neuropil degeneration.

Transmural adenosine with increased cardiac work.

In hearts with five different levels of myocardial performance there was an inverse correlation between myocardial adenosine content and coronary vascular resistance. Higher levels of oxygen consumption were associated with higher myocardial adenosine content and lower coronary vascular resistance. Adenosine was uniformly distributed across the myocardial wall under all conditions, except those involving increased oxygen consumption with concomitant decreased coronary input pressure, as was observed with isoproterenol infusion. Under these conditions the adenosine content of the inner wall was significantly higher than the outer wall.

Myocardial adenosine and coronary resistance during increased cardiac performance.

The relation between myocardial adenosine content and coronary vascular resistance was studied in the open-chest dog. Cardiac performance was increased by aortic constriction or by intravenous infusion of isoproterenol. Coronary blood flow was measured by the microsphere tracer technique. In control animals, adenosine content and coronary vascular resistance were 0.22 +/- 0.03 nmol/g and 1.9 +/- 0.11 mmHg . ml-1 . min . 100 g, respectively. A range of myocardial oxygen consumptions of 5.3-24 ml O2 . min-1 . 100 g-1 was elicited. This was associated with a range of coronary blood flows of 33-166 ml . min-1 . 100 g-1. There was a significant negative correlation between coronary vascular resistance and the log of the myocardial adenosine content (r = 0.77). There was no transmural gradient in adenosine content in the control and aortic-constricted groups, but there was a significant adenosine gradient in the isoproterenol-infused group in which coronary input pressure was decreased. The hearts were not ischemic, as indicated by low myocardial lactate contents and a stable coronary sinus blood pH. These results provide support for a role of adenosine in the local control of the coronary circulation during increased cardiac performance.

A behavioral version of catecholamine involvement in new learning rewarded by brain stimulation.

Numerous studies in the rat indicate that catecholamines (CA) mediate rewarding properties of self-administered electrical stimulation to the brain. One such property is the learning of new response-reinforcement relationships. In the present experiment, amphetamine which potentiates CA at the synapse produces stereotypical responding but does not interfere with the learning of new response-reinforcement relationships. Apomorphine, which mimics dopamine (DA) at DA receptors, also produces stereotypy and interferes with learning. The results suggest that DA released by stimulation mediates the stereotyped responding seen in intracranial self-stimulation (ICS) but norepinephrine mediates reward of newly learned responses.

The crocodile tear syndrome.

Gusto-lacrimation, or "crocodile tear syndrome," is a rare complication, with 95 cases reported in the literature. Two patients are presented here, one after a facial fracture which apparently extended into the temporal bone proximal to the optic ganglion, and one after a Bell's palsy. The mechanism appears to be a misdirection of regenerating gustatory fibers destined for the salivary glands, so that they become secretory fibers to the lacrimal gland and cause homolateral tearing while the patient is eating. A simple procedure, involving subtotal resection of the palpebral lobe of the involved lacrimal gland, proved to be an effective corrective measure in these cases. Although it was not done in these cases, it would perhaps be advisable to do a Schirmer's test to assist in determining the amount of gland to be removed.

beta-Endorphin induces nonconvulsive limbic seizures.

The endogenous opioid peptide, beta-endorphin, induces nonconvulsive limbic epileptiform activity when administered intraventricularly to rats. Epileptiform activity is elicited by beta-endorphin in doses that are devoid of analgesic or behavioral signs. Equimolar intraventricular doses of morphine or of the enkephalin analog [DAIa2,Met5]enkephalin-NH2 fail to elicit this limbic epileptiform activity. These observations, together with the recent immunohistochemical localization of beta-endorphin to midline limbic structures, suggest that beta-endorphin may have an important role in the regulation of limbic excitability.

Ferris Smith.

Important events and renowned persons are seen and remembered differently by those who live the happening or know the person. In As I Remember Ferris Smith, four of his trainees provide a kaleidoscopic view of the doyen.

Volume increase by Z-plasty to the finger skin: its application in electrical ring burns.

Arc welder finger ring burns are an illustration of traumatic annular contractures. The potential for these and similar circumferential injuries to produce digital edema has led us to utilize Z-plasty in the early wound healing phase. Early Z-plasty in selected cases can prevent this loss of function from edema.