Anaesthesia & Intensive Care Medicine

Lower limb nerve blocks Publication date: Available online 14 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Calum R.K. Grant Abstract The proliferation of ultrasound use is changing the approach to regional anaesthesia of the lower limb. Techniques are being developed that provide high-quality postoperative analgesia while minimizing associated motor block that may impair mobilization. Regional anaesthetic techniques also provide significant opioid-sparing benefits (e.g. less sedation, nausea and urinary retention) that are key principles of current enhanced recovery protocols. Ultrasound-guided nerve localization offers several potential advantages when performing femoral, adductor canal, sciatic and ankle blocks; however, neurostimulation remains a useful and widely used aid to lower limb regional anaesthesia practice.

Complications of regional anaesthesia Publication date: Available online 14 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Alasdair Taylor, Calum R.K. Grant Abstract Complications of regional anaesthesia can be divided into those specific to central neuraxial blockade, those specific to peripheral nerve blockade, and those that pertain to both. Fortunately, severe complications, namely spinal cord damage, vertebral cord haematoma and epidural abscess are rare. Here we have given an overview of these complications, with reference to incidences available following the 3rd National Audit Project of the Royal College of Anaesthetists. A thorough knowledge of anatomy and pharmacology, and a meticulous, unhurried technique are key to reducing the risk of such complications. When considering the use of a regional anaesthetic technique, the risks and benefits for the individual patient should be assessed on a case-by-case basis, and set against the risks and benefits of alternatives.

Systemic toxic effects of local anaesthetics Publication date: Available online 13 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Heather N. Sheppard, Ravi Anandampillai Abstract Local anaesthetics are widely used in the provision of local/regional anaesthesia and the management of acute and chronic pain. Their mechanism of action temporarily inhibits voltage gated sodium channels in neuronal plasma membranes. Local anaesthetic systemic toxicity (LAST) is a serious yet largely preventable complication that can occur by any of the multiple routes of administration. LAST predominantly affects the central nervous and cardiovascular systems. Awareness of LAST and vigilance during administration of local anaesthetics may help in early recognition and successful management of the toxicity. Intralipid emulsion (ILE) infusions have been successfully used in reversing local anaesthetic-induced cardiotoxicity. Since 2007 in the UK, ILE infusion has been incorporated into the safety guidelines for management of LAST.

Practical aspects of ultrasound-guided regional anaesthesia Publication date: Available online 8 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Pavan Kumar BC. Raju, Calum RK. Grant Abstract Ultrasound-guided regional anaesthesia is increasingly popular, offering the user a number of advantages over alternative methods of nerve localization (neurostimulation or paraesthesia). These include a more accurate understanding of individual patient anatomy, identification of needle tip position and the ability to assess local anaesthetic spread in relation to a target nerve. An understanding of the basic principles and commonly used terminologies of ultrasound scanning is a fundamental requirement when using this technology. The aim of this article is to outline these basic principles and explain the practical aspects of performing nerve blocks, using ultrasound, in order to achieve quick, safe and effective block performance with minimal procedural discomfort for the patient.

Omics and anaesthesia: pharmacogenomics, proteomics and metabolomics Publication date: Available online 8 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Thomas E.F. Walton, Jonathan N. Rajan Abstract The inter-individual response to medications and the presence of genetic polymorphisms which impact the safe conduct of anaesthesia and analgesia are of paramount importance to the anaesthetist, intensivist and pain physician. The frequency of these phenomena is not reflected in the attention afforded them in undergraduate or postgraduate curricula. In order to appreciate how these issues may affect our clinical practice, it is crucial to have a working understanding of the concepts that underpin the relevant fields within the collection of disciplines we term the 'omics'.

Upper limb nerve blocks Publication date: Available online 8 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Pavan Kumar B.C. Raju, James S. Bowness Abstract Brachial plexus blockade is used for a variety of upper limb surgical procedures. Ultrasound guidance is generally considered to be the gold-standard technique, although large-scale studies examining efficacy and complications of ultrasound-guided techniques compared with nerve stimulation are still needed. Interscalene block remains the approach of choice for shoulder surgery, although phrenic nerve blockade is common even using low volumes of local anaesthetic. Of the currently available studies comparing the other approaches, there seems to be little difference in efficacy between axillary, supraclavicular and infraclavicular approaches for elbow, forearm and hand surgery when equivalent levels of expertise are used. The major features influencing block choice and performance are discussed.

Action potential: generation and propagation Publication date: Available online 8 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Allan Fletcher Abstract In the normal resting state, the plasma membrane of nerve and muscle cells generates a transmembrane electrical potential difference – the intracellular surface of the membrane being approximately 70–80 mV negative to the extracellular surface. This is a result of markedly different concentrations of ions inside and outside the cell, together with different membrane permeabilities to different ions that permits K+ to flow down their concentration gradient from inside to outside the cell. Nerve and muscle cells are 'excitable' because they can react to external stimuli by generating an extremely rapid change in transmembrane electrical potential difference known as the action potential. This comprises an initial explosive increase in membrane Na+ permeability that allows these ions to flood down their concentration gradient into the cell, thereby depolarizing the membrane such that the potential difference is transiently reversed to a positive value. However, in nerve and skeletal muscle this lasts for only a millisecond, at which time the membrane potential is just as rapidly restored to its resting negative value (repolarization). These events are controlled by the brief opening and closing of voltage-activated sodium and potassium channels in the membrane. The key features of the action potential are that it is: (i) an all-or-none event, rather than a graded response; (ii) it is self-propagating, such that the wave of depolarization travels rapidly along the plasma membrane; and (iii) it is transient, such that membrane excitability is quickly restored. These features of the action potential allow rapid transfer of information along nerve axons in the nervous system.

Nerve cell function and synaptic mechanisms Publication date: Available online 7 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Allan Fletcher Abstract Nerve cells (neurones) are 'excitable' cells that can transduce a variety of stimuli into electrical signals, continuously sending information about the external and internal environment (in the form of sequences of action potentials) to the central nervous system (CNS). Interneurones in the CNS integrate this information and send signals along output (efferent) neurones to various parts of the body for the appropriate actions to be taken in response to environmental changes. Networks of neurones have been arbitrarily classified into various nervous systems that gather and transmit sensory information and control skeletal muscle function and autonomic function, etc. The junctions between neurones (synapses) are either electrical or chemical. The former permit the direct transfer of electrical current between cells, whereas the latter utilize chemical signalling molecules (neurotransmitters) to transfer information between cells. Neurotransmitters are mainly amino acids, amines or peptides (although other molecules such as purines and nitric oxide are utilized by some cells), and can be excitatory or inhibitory. Individual neurones within the CNS may receive synaptic inputs from thousands of other neurones. Therefore, each neurone 'integrates' this vast complexity of inputs and responds accordingly (either by remaining silent or firing action potentials to other neurones). Adaptations in the function and structure of chemical synapses in particular (synaptic plasticity) are thought to underlie the mechanisms mediating cognitive functions (learning and memory).

Peripheral nerve catheter techniques Publication date: Available online 7 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Ayman H.M. Mustafa Abstract Peripheral nerve catheters (PNC) or perineural catheters are used synonymously to describe placing a catheter in close proximity to nerve plexuses or individual nerves for the provision of continuous pain relief. The indications of PNCs extend beyond upper and lower extremity orthopaedic surgery to perioperative analgesia in patients undergoing a wide range of surgical procedures (e.g. abdominal, vascular, thoracic, breast and trauma surgeries). PNC use can facilitate early mobilization after surgery by providing high quality analgesia that in turn leads to reduced opioid consumption and associated opioid related side effects. Perioperative PNC analgesia can result in reduced length of in-hospital stay and improved rates of patient satisfaction. Insertion of peripheral nerve catheters can be done by either anaesthetist or surgeon. Long term benefits are still to be ascertained. Risks are similar to peripheral nerve block although catheter dislodgement remains a specific problem.

Intravenous regional anaesthesia Publication date: Available online 7 March 2019 Source: Anaesthesia & Intensive Care Medicine Author(s): Alastair J.M. Baird, Colin B. Donald Abstract Intravenous regional anaesthesia, or Bier's block, is a useful and safe technique for anaesthetizing distal limbs for short surgical procedures. It is most commonly used for reduction of forearm fractures within the emergency department and can be a useful method of providing anaesthesia in patients who may be unsuitable for a general anaesthetic, or when skills or equipment for other forms of regional anaesthesia are unavailable. When performed as recommended it has a proven safety record.

NeuroImage

Benchmarking functional connectome-based predictive models for resting-state fMRI Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Kamalaker Dadi, Mehdi Rahim, Alexandre Abraham, Darya Chyzhyk, Michael Milham, Bertrand Thirion, Gaël Varoquaux, for the Alzheimer's Disease Neuroimaging Initiative Abstract Functional connectomes reveal biomarkers of individual psychological or clinical traits. However, there is great variability in the analytic pipelines typically used to derive them from rest-fMRI cohorts. Here, we consider a specific type of studies, using predictive models on the edge weights of functional connectomes, for which we highlight the best modeling choices. We systematically study the prediction performances of models in 6 different cohorts and a total of 2000 individuals, encompassing neuro-degenerative (Alzheimer's, Post-traumatic stress disorder), neuro-psychiatric (Schizophrenia, Autism), drug impact (Cannabis use) clinical settings and psychological trait (fluid intelligence). The typical prediction procedure from rest-fMRI consists of three main steps: defining brain regions, representing the interactions, and supervised learning. For each step we benchmark typical choices: 8 different ways of defining regions –either pre-defined or generated from the rest-fMRI data– 3 measures to build functional connectomes from the extracted time-series, and 10 classification models to compare functional interactions across subjects. Our benchmarks summarize more than 240 different pipelines and outline modeling choices that show consistent prediction performances in spite of variations in the populations and sites. We find that regions defined from functional data work best; that it is beneficial to capture between-region interactions with tangent-based parametrization of covariances, a midway between correlations and partial correlation; and that simple linear predictors such as a logistic regression give the best predictions. Our work is a step forward to establishing reproducible imaging-based biomarkers for clinical settings. Graphical abstract

Frequency and power of human alpha oscillations drift systematically with time-on-task Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Christopher S.Y. Benwell, Raquel E. London, Chiara F. Tagliabue, Domenica Veniero, Joachim Gross, Christian Keitel, Gregor Thut Abstract Oscillatory neural activity is a fundamental characteristic of the mammalian brain spanning multiple levels of spatial and temporal scale. Current theories of neural oscillations and analysis techniques employed to investigate their functional significance are based on an often implicit assumption: In the absence of experimental manipulation, the spectral content of any given EEG- or MEG-recorded neural oscillator remains approximately stationary over the course of a typical experimental session (∼1 h), spontaneously fluctuating only around its dominant frequency. Here, we examined this assumption for ongoing neural oscillations in the alpha-band (8–13 Hz). We found that alpha peak frequency systematically decreased over time, while alpha-power increased. Intriguingly, these systematic changes showed partial independence of each other: Statistical source separation (independent component analysis) revealed that while some alpha components displayed concomitant power increases and peak frequency decreases, other components showed either unique power increases or frequency decreases. Interestingly, we also found these components to differ in frequency. Components that showed mixed frequency/power changes oscillated primarily in the lower alpha-band (∼8–10 Hz), while components with unique changes oscillated primarily in the higher alpha-band (∼9–13 Hz). Our findings provide novel clues on the time-varying intrinsic properties of large-scale neural networks as measured by M/EEG, with implications for the analysis and interpretation of studies that aim at identifying functionally relevant oscillatory networks or at driving them through external stimulation.

Speech processing and plasticity in the right hemisphere predict variation in adult foreign language learning Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Zhenghan Qi, Michelle Han, Yunxin Wang, Carlo de los Angeles, Qi Liu, Keri Garel, Ee San Chen, Susan Whitfield-Gabrieli, John D.E. Gabrieli, Tyler K. Perrachione Abstract Foreign language learning in adulthood often takes place in classrooms where learning outcomes vary widely among students, for both initial learning and long-term retention. Despite the fundamental role of speech perception in first language acquisition, its role in foreign language learning outcomes remains unknown. Using a speech discrimination functional magnetic resonance imaging (fMRI) task and resting-state fMRI before and after an intensive, classroom-based, Mandarin Chinese course, we examined how variations in pre-training organization and pre-to-post reorganization of brain functions predicted successful language learning in male and female native English-speakers. Greater pre-training activation in right inferior frontal gyrus (IFG) to Mandarin speech was associated with better Mandarin attainment at the end of the course. After four weeks of class, learners showed overall increased activation in left IFG and left superior parietal lobule (SPL) to Mandarin speech, but in neither region was variation related to learning outcomes. Immediate attainment was associated with greater pre-to-post reduction of right IFG activation to Mandarin speech but also greater enhancement of resting-state connectivity between this region and both left IFG and left SPL. Long-term retention of Mandarin skills measured three months later was more accurately predicted by models using features of neural preparedness (pre-training activation) and neural plasticity (pre-to-post activation change) than models using behavior preparedness and plasticity features (pre-training speech discrimination accuracy and Mandarin attainment, respectively). These findings suggest that successful holistic foreign language acquisition in human adulthood requires right IFG engagement during initial learning but right IFG disengagement for long-term retention of language skills.

Auditory and language contributions to neural encoding of speech features in noisy environments Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Jiajie Zou, Jun Feng, Tianyong Xu, Peiqing Jin, Cheng Luo, Jianfeng Zhang, Xunyi Pan, Feiyan Chen, Jing Zheng, Nai Ding Abstract Recognizing speech in noisy environments is a challenging task that involves both auditory and language mechanisms. Previous studies have demonstrated human auditory cortex can reliably track the temporal envelope of speech in noisy environments, which provides a plausible neural basis for noise-robust speech recognition. The current study aimed at teasing apart auditory and language contributions to noise-robust envelope tracking by comparing the neural responses of 2 groups of listeners, i.e., native listeners and foreign listeners who did not understand the testing language. In the experiment, speech signals were mixed with spectrally matched stationary noise at 4 intensity levels and listeners' neural responses were recorded using electroencephalography (EEG). When the noise intensity increased, the neural response gain increased in both groups of listeners, demonstrating auditory gain control. Language comprehension generally reduced the response gain and envelope-tracking precision, and modulated the spatial and temporal profile of envelope-tracking activity. Based on the spatio-temporal dynamics of envelope-tracking activity, a linear classifier can jointly decode the 2 listener groups and 4 levels of noise intensity. Altogether, the results showed that without feedback from language processing, auditory mechanisms such as gain control can lead to a noise-robust speech representation. High-level language processing modulated the spatio-temporal profile of the neural representation of speech envelope, instead of generally enhancing the envelope representation.

Brain regions preferentially responding to transient and iso-intense painful or tactile stimuli Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Q. Su, W. Qin, Q.Q. Yang, C.S. Yu, T.Y. Qian, A. Mouraux, G.D. Iannetti, M. Liang Abstract How pain emerges from cortical activities remains an unresolved question in pain neuroscience. A first step toward addressing this question consists in identifying brain activities that occur preferentially in response to painful stimuli in comparison to non-painful stimuli. A key confound that has affected this important comparison in many previous studies is the intensity of the stimuli generating painful and non-painful sensations. Here, we compared the brain activity during iso-intense painful and tactile sensations sampled by functional MRI in 51 healthy participants. Specifically, the perceived intensity was recorded for every stimulus and only the stimuli with rigorously matched perceived intensity were selected and compared between painful and tactile conditions. We found that all brain areas activated by painful stimuli were also activated by tactile stimuli, and vice versa. Neural responses in these areas were correlated with the perceived stimulus intensity, regardless of stimulus modality. More importantly, among these activated areas, we further identified a number of brain regions showing stronger responses to painful stimuli than to tactile stimuli when perceived intensity was carefully matched, including the bilateral opercular cortex, the left supplementary motor area and the right frontal middle and inferior areas. Among these areas, the right frontal middle area still responded more strongly to painful stimuli even when painful stimuli were perceived less intense than tactile stimuli, whereas in this condition other regions showed stronger responses to tactile stimuli. In contrast, the left postcentral gyrus, the visual cortex, the right parietal inferior gyrus, the left parietal superior gyrus and the right cerebellum had stronger responses to tactile stimuli than to painful stimuli when perceived intensity was matched. When tactile stimuli were perceived less intense than painful stimuli, the left postcentral gyrus and the right parietal inferior gyrus still responded more strongly to tactile stimuli while other regions now showed similar responses to painful and tactile stimuli. These results suggest that different brain areas may be engaged differentially when processing painful and tactile information, although their neural activities are not exclusively dedicated to encoding information of only one modality but are strongly determined by perceived stimulus intensity regardless of stimulus modality.

Differences in functional connectivity along the anterior-posterior axis of human hippocampal subfields Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Marshall A. Dalton, Cornelia McCormick, Eleanor A. Maguire Abstract There is a paucity of information about how human hippocampal subfields are functionally connected to each other and to neighbouring extra-hippocampal cortices. In particular, little is known about whether patterns of functional connectivity (FC) differ down the anterior-posterior axis of each subfield. Here, using high resolution structural MRI we delineated the hippocampal subfields in healthy young adults. This included the CA fields, separating DG/CA4 from CA3, separating the pre/parasubiculum from the subiculum, and also segmenting the uncus. We then used high resolution resting state functional MRI to interrogate FC. We first analysed the FC of each hippocampal subfield in its entirety, in terms of FC with other subfields and with the neighbouring regions, namely entorhinal, perirhinal, posterior parahippocampal and retrosplenial cortices. Next, we analysed FC for different portions of each hippocampal subfield along its anterior-posterior axis, in terms of FC between different parts of a subfield, FC with other subfield portions, and FC of each subfield portion with the neighbouring cortical regions of interest. We found that intrinsic functional connectivity between the subfields aligned generally with the tri-synaptic circuit but also extended beyond it. Our findings also revealed that patterns of functional connectivity between the subfields and neighbouring cortical areas differed markedly along the anterior-posterior axis of each hippocampal subfield. Overall, these results contribute to ongoing efforts to characterise human hippocampal subfield connectivity, with implications for understanding hippocampal function.

A dual architecture for the cognitive control of language: Evidence from functional imaging and language production Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Nicolas J. Bourguignon, Vincent L. Gracco Abstract The relation between language processing and the cognitive control of thought and action is a widely debated issue in cognitive neuroscience. While recent research suggests a modular separation between a 'language system' for meaningful linguistic processing and a 'multiple-demand system' for cognitive control, other findings point to more integrated perspectives in which controlled language processing emerges from a division of labor between (parts of) the language system and (parts of) the multiple-demand system. We test here a dual approach to the cognitive control of language predicated on the notion of cognitive control as the combined contribution of a semantic control network (SCN) and a working memory network (WMN) supporting top-down manipulation of (lexico-)semantic information and the monitoring of information in verbal working memory, respectively. We reveal these networks in a large-scale coordinate-based meta-analysis contrasting functional imaging studies of verbal working memory vs. active judgments on (lexico-)semantic information and show the extent of their overlap with the multiple-demand system and the language system. Testing these networks' involvement in a functional imaging study of object naming and verb generation, we then show that SCN specializes in top-down retrieval and selection of (lexico-)semantic representations amongst competing alternatives, while WMN intervenes at a more general level of control modulated in part by the amount of competing responses available for selection. These results have implications in conceptualizing the neurocognitive architecture of language and cognitive control.

The disentanglement of the neural and experiential complexity of self-generated thoughts: A users guide to combining experience sampling with neuroimaging data Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Léa M. Martinon, Jonathan Smallwood, Deborah McGann, Colin Hamilton, Leigh M. Riby Abstract Human cognition is not limited to the processing of events in the external environment, and the covert nature of certain aspects of the stream of consciousness (e.g. experiences such as mind-wandering) provides a methodological challenge. Although research has shown that we spend a substantial amount of time focused on thoughts and feelings that are intrinsically generated, evaluating such internal states, purely on psychological grounds can be restrictive. In this review of the different methods used to examine patterns of ongoing thought, we emphasise how the process of triangulation between neuroimaging techniques, with self-reported information, is important for the development of a more empirically grounded account of ongoing thought. Specifically, we show how imaging techniques have provided critical information regarding the presence of covert states and can help in the attempt to identify different aspects of experience.

Neural variability quenching during decision-making: Neural individuality and its prestimulus complexity Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Annemarie Wolff, Lin Yao, Javier Gomez-Pilar, Mahsa Shoaran, Ning Jiang, Georg Northoff Abstract The spontaneous activity of the brain interacts with stimulus-induced activity which is manifested in event-related amplitude and its trial-to-trial variability (TTV). TTV describes the variability in the amplitude of the stimulus-evoked response across trials, and it is generally observed to be reduced, or quenched. While such TTV quenching has been observed on both the cellular and regional levels, its exact behavioral relevance and neuronal basis remains unclear. Applying a novel paradigm for testing neural markers of individuality in internally-guided decision-making, we here investigated whether TTV (i) represents an individually specific response by comparing individualized vs shared stimuli; and (ii) is mediated by the complexity of prestimulus activity as measured by the Lempel-Ziv Complexity index (LZC). We observed that TTV - and other electrophysiological markers such as ERP, ERSP, and ITC – showed first significant differences between individualized and shared stimuli (while controlling for task-related effects) specifically in the alpha and beta frequency bands, and secondly that TTV in the beta band correlated significantly with reaction time and eLORETA activity. Moreover, we demonstrate that the complexity (LZC) of neuronal activity is higher in the prestimulus period while it decreases during the poststimulus period, with the former also correlating specifically with poststimulus individualized TTV in alpha (but not with shared TTV). Together, our results show that the TTV represents a marker of 'neural individualization' which, being related to internal processes on both neural and psychological levels, is mediated by the information complexity of prestimulus activity. More generally, our results inform the pre-post-stimulus dynamics of rest-stimulus interaction, which is a basic and ubiquitous neural phenomenon in the brain and highly relevant for mental features including their individuality.

Probing cortical and sub-cortical contributions to instruction-based learning: Regional specialisation and global network dynamics Publication date: 15 May 2019 Source: NeuroImage, Volume 192 Author(s): Adam Hampshire, Richard E. Daws, Ines Das Neves, Eyal Soreq, Stefano Sandrone, Ines R. Violante Abstract Diverse cortical networks and striatal brain regions are implicated in instruction-based learning (IBL); however, their distinct contributions remain unclear. We use a modified fMRI paradigm to test two hypotheses regarding the brain mechanisms that underlie IBL. One hypothesis proposes that anterior caudate and frontoparietal regions transiently co-activate when new rules are being bound in working memory. The other proposes that they mediate the application of the rules at different stages of the consolidation process. In accordance with the former hypothesis, we report strong activation peaks within and increased connectivity between anterior caudate and frontoparietal regions when rule-instruction slides are presented. However, similar effects occur throughout a broader set of cortical and sub-cortical regions, indicating a metabolically costly reconfiguration of the global brain state. The distinct functional roles of cingulo-opercular, frontoparietal and default-mode networks are apparent from their activation throughout, early and late in the practice phase respectively. Furthermore, there is tentative evidence of a peak in anterior caudate activity mid-way through the practice stage. These results demonstrate how performance of the same simple task involves a steadily shifting balance of brain systems as learning progresses. They also highlight the importance of distinguishing between regional specialisation and global dynamics when studying the network mechanisms that underlie cognition and learning.

Addiction Medicine

Screening, Brief Intervention, and Referral to Treatment in a Retail Pharmacy Setting: The Pharmacist's Role in Identifying and Addressing Risk of Substance Use Disorder Objective: This study determined the feasibility of interviewing and screening patients presenting to a retail pharmacy using Screening, Brief Intervention, and Referral to Treatment (SBIRT) interview protocols, and to compare SBIRT results to a risk score calculated from Prescription Drug Monitoring Program (PDMP) data. Methods: Using the NIDA Quick Screen and NIDA Modified-ASSIST (NM-ASSIST) and the Alcohol Use Disorder Identification Test (AUDIT), retail pharmacy customers were screened for substance and alcohol use disorder and tobacco use. PDMP reports were collected on subjects and a PDMP-risk score was calculated based on the numbers of Schedule II-V prescriptions and prescribers over the previous 12 months. Results: A total of 24 patients were included in this study (67% response rate). SBIRT screening revealed that 20.8% were at-risk for substance use disorder (SUD), 16.7% for alcohol use disorder, and 37.5% used tobacco. Overall, 33.3% of subjects were at-risk for SUD or alcohol use disorder. Fifty percent of subjects required education and/or brief intervention based on their responses, 37.5% of all subjects were deemed at-risk based on their PDMP-risk score, and 60% of patients who were risk-positive by SBIRT screening were also PDMP-risk positive. Conclusions: This study demonstrates the feasibility of performing SBIRT-based screenings in a retail pharmacy setting and combining these with PDMP-risk analysis to screen patients for prescription and illicit drug misuse. Findings from this study will inform the design of larger multisite studies, which should validate these findings and include follow-up analysis to assess the efficacy of intervention on this patient population. Send correspondence to Richard M. Gustin, PhD, The Recovery Research Network Foundation, Atlantis, FL 33462. E-mail: Richard.Gustin@trrn.org Received 17 September, 2018 Accepted 22 February, 2019 Funding Sources: The Recovery Research Network Foundation, B.C.S. was supported by NIMH Grant K01-MH107765. The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

A Pilot Crossover Trial of Sleep Medications for Sleep-disturbed Methadone Maintenance Patients Objectives: Problems with sleep are a common and detrimental occurrence among individuals who receive methadone maintenance for opioid use disorder (OUD). Methods: We enrolled ten methadone-maintained persons with insomnia (60% female, mean age 40) in a double-blind trial using actigraphy to confirm daily sleep reports. After a no-medication week to establish baseline sleep patterns, each participant received 1 week each of mirtazapine (30 mg), zolpidem (sustained-release 12.5 mg), mirtazapine (30 mg IR) plus zolpidem (10 mg), and placebo, with a washout week between each medication week. Study medication order was randomized so that the order of each 1-week medication treatment was different for each participant, but all participants received all 4 regimens. Results: We found that mirtazapine alone improved total sleep (mean 23 minutes), sleep latency (mean 23 minutes), and sleep efficiency (mean 3%), surpassing the other regiments. Conclusions: This pilot work suggests that mirtazapine is worthy of further testing as a sleep aid for persons with OUD receiving methadone maintenance. Send correspondence to Claire E. Blevins, PhD, 345 Blackstone Blvd., Providence, RI 02906. E-mail: Claire_Blevins@Brown.edu Received 10 October, 2018 Revised 12 December, 2018 Accepted 26 December, 2018 Dr Blevins is a recipient of an Institutional Development Award (U54GM115677) from the National Institute of General Medical Sciences of the National Institutes of Health, which funds Advance Clinical and Translational Research (Advance-CTR). The other authors declare no conflicts of interest. © 2019 American Society of Addiction Medicine

Psychotropics in Your Medicine Cabinet: A Case Study of Dimenhydrinate Use Reporting of intoxication and withdrawal from aberrant use of over-the-counter medication has been sparse and inconsistent in literature. Attributed to their anticholinergic properties, medications such as dimenhydrinate (Gravol) taken in supratherapeutic doses have been associated with euphoria, anxiolysis, and hallucinations. We present a case of a woman in her forties, with a psychiatric history of bipolar disorder, and complex concurrent medical history including familial Mediterranean fever (FMF), and fibromyalgia, admitted for withdrawal management of her intravenous dimenhydrinate use. As a result of her FMF, there were numerous hospital admissions and treatment which required intravenous access. Hence, a physician-inserted intravenous access port was placed on her chest. The port was maintained monthly with the help of a community agency. In this port, she was injecting 100 to 200 mg of dimenhydrinate hourly for its euphoric and calming effects, consuming upwards of 2400 mg/d. Comprehensive laboratory work-up and urine drug screening were unremarkable. Vital signs were stable. Her mental status at time of admission was lethargic, unfocused, but calm. Her withdrawal symptoms included severe nausea, vomiting, sedation, headaches, dizziness, anxiety, and muscle stiffness. Her detoxification was managed with benztropine and lorazepam, and was well tolerated. The patient was discharged to a community inpatient rehabilitation center. Urine drug testing before discharge was negative. This case draws attention to the addictive potential of dimenhydrinate and offers a regime for its medical withdrawal management. Additionally, this case highlights that screening and management of over-the-counter medications warrants further clinical consideration and investigation. Send correspondence to Nitin Chopra, MD, Centre for Addiction and Mental Health, Toronto, ON, Canada. E-mail: nitin.chopra@camh.ca Received 25 November, 2018 Accepted 26 January, 2019 No commercial organizations had any role in the completion or publication of this article. The authors declare no competing interest during the past 36 months. © 2019 American Society of Addiction Medicine

Prescribing of Opioids and Benzodiazepines Among Patients With History of Overdose Objectives: Addiction and overdose related to prescription drugs continues to be a leading cause of morbidity and mortality in the United States. We aimed to characterize the prescribing of opioids and benzodiazepines to patients who had previously presented with an opioid or benzodiazepine overdose. Methods: This was a retrospective chart review of patients who were prescribed an opioid or benzodiazepine in a 1-month time-period in 2015 (May) and had a previous presentation for opioid or benzodiazepine overdose at a large healthcare system. Results: We identified 60,129 prescribing encounters for opioids and/or benzodiazepines, 543 of which involved a patient with a previous opioid or benzodiazepine overdose. There were 404 unique patients in this cohort, with 97 having more than 1 visit including a prescription opioid and/or benzodiazepine. A majority of prescriptions (54.1%) were to patients with an overdose within the 2 years of the documented prescribing encounter. Prescribing in the outpatient clinical setting represented half (49.9%) of encounters, whereas emergency department prescribing was responsible for nearly a third (31.5%). Conclusions: In conclusion, prescribing of opioids and benzodiazepines occurs across multiple locations in a large health care system to patients with a previous overdose. Risk factors, such as previous overdose should be highlighted through clinical decision support tools in the medical record to help prescribers identify patients at higher risk and to mobilize resources for this patient population. Prescribers need further education on factors that place their patients at risk for opioid use disorder and on alternative therapies to opioids and benzodiazepines. Send correspondence to Christopher Griggs, MD, MPH, Department of Emergency Medicine, Carolinas Trauma Network Research Center of Excellence, Atrium Health, Carolinas Medical Center, 1000 Blythe Blvd, Charlotte, NC 28203. E-mail: Christopher.Griggs@atriumhealth.org. Received 23 August, 2018 Accepted 26 January, 2019 Supported by Centers for Disease Control and Prevention grant (CE14-004 Award Number CE002520). Presented as a poster at American College of Emergency Physician in Las Vegas, NV, October 2016 and at American Public Health Association in Denver, CO, October 2016. The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

Genetic Variant in the CRH-binding Protein Gene (CRHBP) is Associated With Cessation of Cocaine Use in Methadone Maintenance Patients With Opioid Addiction Objectives: We have previously shown associations between 4 genetic variants in opioid and stress-related genes (OPRM1, NPYR1/NPYR5, NR3C1, and CRHBP) and prolonged abstinence from heroin without methadone maintenance treatment (MMT). We currently assessed the associations between these variants and MMT patients' characteristics. Methods: A non-selective group of 351 patients who stayed at least 1 year in their first admission to MMT were genotyped and their characteristics and substance in urine on admission and after 1 year were studied. Results: The proportions of patients with both cocaine and benzodiazepine abuse were reduced significantly after 1 year in MMT; however, cocaine abuse cessation was significantly associated with the non-carriers of the CRHBP (corticotrophin releasing hormone binding protein) SNP rs1500 minor C allele (GG genotype) (P = 0.0009, PBonferroni = 0.0221). More carriers of the 2 C alleles (CC genotype) than carriers of the GC and GG genotypes abused cocaine on admission (32.3% vs 19.7%, respectively, P = 0.0414, recessive model), and more of the C allele carriers (GC and CC genotypes) than non-carriers (GG genotype) abused cocaine after 1 year in MMT (25.7% vs 15.8%, respectively, P = 0.0334, dominant model). Abusers of benzodiazepine were more prevalent among carriers of the C allele compared with non-carriers on admission (60.6% vs 45.9%, respectively, P = 0.0080, dominant model), as well as after 1 year in MMT (50.9% vs 39.1%, respectively, P = 0.0362). Conclusions: Reduction in cocaine abuse among MMT patients may be mediated by a genetic effect in a stress-related gene (CRHBP SNP rs1500 minor C allele). Evaluations of larger samples, additional SNPs, and different populations are needed to support these findings. Send correspondence to Einat Peles, PhD, Adelson Clinic, Tel Aviv Medical Center, 1 Henrietta Szold St., Tel Aviv 64924, Israel. E-mail: einatp@tlvmc.gov.il Received 31 October, 2018 Accepted 14 December, 2018 The authors report no conflicts of interest. The study was funded by The Dr. Miriam and Sheldon G. Adelson Family Foundation. Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.journaladdictionmedicine.com). © 2019 American Society of Addiction Medicine

Patient-centered Outcomes in Participants of a Buprenorphine Monthly Depot (BUP-XR) Double-blind, Placebo-controlled, Multicenter, Phase 3 Study Objective: Opioid use disorder (OUD) is associated with physical, social, psychological, and economic burden. This analysis assessed the effects of RBP-6000, referred to as BUP-XR (extended-release buprenorphine), a subcutaneously injected, monthly buprenorphine treatment for OUD compared with placebo on patient-centered outcomes measuring meaningful life changes. Methods: Patient-centered outcomes were collected in a 24-week, phase 3, placebo-controlled study assessing the efficacy, safety, and tolerability of BUP-XR 300/300 mg (6 × 300 mg) and 300/100 mg (2 × 300 mg followed by 4 × 100 mg) injections in treatment-seeking participants with moderate-to-severe OUD. Measures included the EQ-5D-5L, SF-36v2, Medication Satisfaction Questionnaire, employment/insurance status, and healthcare resource utilization (HCRU). Changes from baseline to end of study were compared across treatment arms, using mixed models for repeated measures. Results: Participants receiving BUP-XR (n = 389) versus placebo (n = 98) had significantly greater changes from baseline on the EQ-5D-5L index (300/300 mg: difference = 0.0636, P  = 0.003), EQ-5D-5L visual analog scale (300/300 mg: difference = 5.9, P  = 0.017; 300/100 mg: difference = 7.7, P  = 0.002), and SF-36v2 physical component summary score (300/300 mg: difference = 3.8, P  < 0.001; 300/100 mg: difference = 3.2, P  = 0.002). Satisfaction was significantly higher for participants receiving BUP-XR 300/300 mg (88%, P < 0.001) and 300/100 mg (88%, P < 0.001) than placebo (46%). Employment and percentage of insured participants increased by 10.8% and 4.1% with BUP-XR 300/300 mg and 10.0% and 4.7% with 300/100 mg but decreased by 12.6% and 8.4% with placebo. Participants receiving BUP-XR compared with placebo had significantly fewer hospital days per person-year observed. Conclusions: These results show the feasibility of measuring patient-centered life changes in substance use disorder clinical studies. Participants receiving up to 6 monthly injections of BUP-XR, compared with placebo, reported better health, increased medication satisfaction, increased employment, and decreased healthcare utilization. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Send correspondence to Caitlyn T. Solem, PhD, Pharmerit International, 4350 East-West Highway, Suite 1100, Bethesda, MD 20814. E-mail: csolem@pharmerit.com Received 25 October, 2018 Accepted 4 February, 2019 Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.journaladdictionmedicine.com). This study was funded by Indivior Inc. W.L. is a consultant for Indivior Inc, Alkermes, Camurus/Braeburn, Opiant and Titan Pharmaceuticals. V.R.N., S.M.L., and C.H. are employees of Indivior Inc. N.A.R. was an employee of Indivior Inc. at the time of study conduct. C.T.S. and Y.-C.Y. are employees of Pharmerit International and are consultants for Indivior Inc. V.M. was a clinical investigator for the RBP-6000 clinical trials and consultant for Indivior Inc. The authors report no conflicts of interest © 2019 American Society of Addiction Medicine

Disparities Between US Opioid Overdose Deaths and Treatment Capacity: A Geospatial and Descriptive Analysis Introduction: With opioid-related deaths reaching epidemic levels, gaining a better understanding of access to treatment for opioid use disorder (OUD) is critical. Most studies have focused on 1 side of the equation—either provider capacity or patients' need for care, as measured by overdose deaths. This study examines the overlay between treatment program availability and opioid mortality, comparing accessibility by region. Methods: Geospatial and statistical analyses were used to model OUD treatment programs relative to population density and opioid overdose death incidence at the state and county level. We computed a ratio between program capacity and mortality called the programs-per-death (PPD) ratio. Results: There were 40 274 opioid deaths in 2016 and 12 572 treatment programs across the contiguous 48 states, yielding a ratio of 1 program for every 3.2 deaths. Texas had the lowest number of treatment programs per 100 000 persons (1.4) and Maine the highest (13.2). West Virginia ranked highest in opioid deaths (39.09 per 100 000). Ohio, the District of Columbia, and West Virginia had the greatest mismatch between providers and deaths, with an average of 1 program for every 8.5 deaths. Over 32% of US counties had no treatment programs and among those with >10 deaths, nearly 2.5% had no programs. Over 19% of all counties had a ratio ≤1 provider facility per 10 deaths. Conclusion: Assessing the overlay between treatment capacity and need demonstrated that regional imbalances exist. These data can aid in strategic planning to correct the mismatch and potentially reduce mortality in the most challenged geographic regions. Send correspondence to James R. Langabeer, PhD, University of Texas Health Science Center at Houston, Houston, TX 77030. E-mail: James.R.Langabeer@uth.tmc.edu Received 4 December, 2018 Accepted 9 February, 2019 © 2019 American Society of Addiction Medicine

Adverse Events During Treatment Induction With Injectable Diacetylmorphine and Hydromorphone for Opioid Use Disorder Objectives: The present study aims to describe a 3-day induction protocol for injectable hydromorphone (HDM) and diacetylmorphine (DAM) used in 3 Canadian studies and examine rates of opioid-related overdose and somnolence during this induction phase. Methods: The induction protocol and associated data on opioid-related overdose and somnolence are derived from 2 clinical trials and one cohort study conducted in Vancouver and Montreal (2005–2008; 2011–2014; 2014–2018). In this analysis, using the Medical Dictionary for Regulatory Activities coding system we report somnolence (ie, drowsiness, sleepiness, grogginess) and opioid overdose as adverse events. Overdoses requiring intervention with naloxone are coded as severe adverse events. Results: Data from the 3 studies provides a total of 1175 induction injections days, with 700 induction injection days for DAM, and 475 induction injection days for HDM. There were 34 related somnolence and adverse event (AE) overdoses (4.899 per 100 injection days) in DAM and 6 (1.467 per 100 days) in HDM. Four opioid overdoses requiring naloxone (0.571 per 100 injection days) were registered in DAM and 1 in HDM (0.211 per 100 injection days), all safely mitigated onsite. The first week maximum daily dose patients received were on average 433.62 mg [standard deviation (SD) = 137.92] and 223.26 mg (SD = 68.06) for DAM and HDM, respectively. Conclusions: A 3-day induction protocol allowed patients to safely reach high doses of injectable hydromorphone and diacetylmorphine in a timely manner. These findings suggest that safety is not an evidence-based barrier to the implementation of treatment with injectable hydromorphone and diacetylmorphine. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0 Send correspondence to Eugenia Oviedo-Joekes, PhD, St. Paul's Hospital, 575-1081 Burrard St., Vancouver, BC, Canada V6Z 1Y6. E-mail: eugenia@cheos.ubc.ca Received 27 July, 2018 Accepted 8 January, 2019 The RUTH Study was funded by a Canadian Institutes of Health Research Project Grant. The SALOME trial was funded through an operating grant from the Canadian Institutes of Health Research in partnership with Providence Health Care with additional financial support from the InnerChange Foundation, Providence Health Care Research Institute, St. Paul's Hospital Foundation and Vancouver Coastal Health. The NAOMI study was supported by grants from the Canadian Institutes of Health Research, the Canada Foundation for Innovation, the Canada Research Chairs Program, the University of British Columbia, Providence Health Care, the University of Montreal, Centre de Recherche et Aide aux Narcomanes, the Government of Quebec, Vancouver Coastal Health, and the BC Centre for Disease Control. Further financial support was provided by the Michael Smith Foundation for Health Research Career Award and the Canada Institutes of Health Research New Investigator Award (EOJ) and the Canada Research Chairs Program (MTS). The funding sources had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; and preparation, review or approval of the manuscript. The authors have no competing interests to declare. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (www.journaladdictionmedicine.com). © 2019 American Society of Addiction Medicine

Evaluation of the Brief Alcohol Withdrawal Scale Protocol at an Academic Medical Center Objectives: The standard of care for treatment of alcohol withdrawal is symptom-triggered dosing of benzodiazepines using a withdrawal scale. Abbreviated scales are desired for clinician efficiency. The objective of this study was to evaluate the use of the 5-item Brief Alcohol Withdrawal Scale (BAWS) protocol. Methods: This single-center, retrospective, observational, cohort study assessed patients ordered the BAWS protocol between August 1, 2016 and July 31, 2017. Data were collected on benzodiazepine exposure, duration of treatment, withdrawal severity, agitation, over-sedation, and delirium while being treated for alcohol withdrawal. Comparisons were made to analyze predetermined patient subgroups. Results: Seven hundred ninety-nine patients were initiated on the BAWS protocol. Patients received a median (IQR) of 0 (0–4) lorazepam equivalents (LEs) and were on the BAWS protocol for a median (IQR) of 44.9 (22.4–77.2) hours. Of the patients that received benzodiazepines while on the BAWS protocol, a median (IQR) of 4 (2–11) LEs were given. Seventeen (2.1%) patients had severe withdrawal. Days of agitation, over-sedation, and delirium were minimal, with the median (IQR) of 0 (0–0). Few patients received adjunctive medications for symptom management. Intensive care unit (ICU) patients had more severe withdrawal than non-ICU patients, but received the same cumulative benzodiazepine dose. Conclusions: Most patients on the BAWS protocol received little-to-no benzodiazepines; severe withdrawal, agitation, delirium, or over-sedation were uncommon. This is the first evaluation of the BAWS protocol on a diverse population of hospitalized patients. Send correspondence to Brian K. Lindner, PharmD, Department of Pharmacy, The Johns Hopkins Hospital, 600 North Wolfe Street, Carnegie 180, Baltimore, MD 21287-6180. E-mail: blindne1@jhmi.edu Received 4 September, 2018 Accepted 8 January, 2019 Supplemental digital content is available for this article. Direct URL citation appears in the printed text and is provided in the HTML and PDF versions of this article on the journal's Web site (www.journaladdictionmedicine.com). The authors declare no conflicts of interest. © 2019 American Society of Addiction Medicine

Initiation and Rapid Titration of Methadone in an Acute Care Setting for the Treatment of Opioid Use Disorder: A Case Report Background: Although methadone is an effective treatment for opioid use disorder, its initiation requires prescribing at a subtherapeutic dose with subsequent titration to a therapeutic dose over many weeks. Accordingly, the methadone induction period can be a challenging one for individuals and can be associated with an increased risk for ongoing illicit drug use and consequently overdose. Given its capacity for regular clinical assessments, acute care settings may offer a unique opportunity to reduce the duration of the induction period for methadone maintenance therapy. Case summary: We report a case of an individual who successfully completed initiation and rapid methadone titration for treatment of opioid use disorder in an acute care setting. Discussion: Utilizing divided dosing intervals and regular monitoring for toxicity, the patient received a cumulative methadone dose of 130 mg total within the first 48 hours of admission with continuation of a similar dose subsequently. No adverse events occurred over a 9-day follow-up period. The case report described here highlights the potential acute care settings may offer for the successful initiation and rapid titration of methadone for the treatment of opioid use disorder. Such an approach could significantly reduce the induction period associated with methadone maintenance therapy and its associated negative outcomes including ongoing illicit substance use and risk for overdose. Send correspondence to Seonaid Nolan, MD, FRCPC, Assistant Professor, University of British Columbia, Clinician Scientist, British Columbia Centre on Substance Use, 553B–1081 Burrard St. Vancouver, BC V6Z 1Y6. E-mail: seonaid.nolan@bccsu.ubc.ca Received 23 October, 2018 Accepted 12 January, 2019 The authors report no conflicts of interest. © 2019 American Society of Addiction Medicine

Pediatric Surgery

Distal ureteric stump empyema managed with doxycycline instillation Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Kathryn M. O'Shea, Supul Hennayake

Wilms tumor of a horseshoe kidney in an 18 year old with an unusual metastasis Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Allison Couillard, Erika B. Lindholm, Sean Ciullo Abstract Wilms tumor is the most common malignant renal tumor in the pediatric population. Children usually present with an abdominal swelling and are frequently diagnosed at Stage I or Stage II disease. The most common sites of metastasis are the lungs. The presence of metastatic disease and age at diagnosis has an important impact on prognosis. Less is known about Wilms tumor in adults, but the treatment is the same as it is for pediatric patients. Here, we present an 18-year-old male with a horseshoe kidney diagnosed with Wilms tumor and metastasis to the rectum.

Gastric perforation in a newborn Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Euitae Kim Abstract Gastric perforation is a rare surgical emergency and a life-threatening disorder in a neonate. However, the exact mechanisms still remain unclear. Case presentation: A three-day-old male newborn was transferred our hospital with recurrent vomiting. The baby did not have any abnormal sign on prenatal examination. He was diagnosed with peritonitis after we performed an ultrasonogram and simple X-ray. We found a gastric perforation during an emergency laparotomy. The best way to saving neonatal gastric perforation patient is early diagnosis and performing the operation without delay.

Partial urorectal septum malformation sequence with prune belly syndrome and oesophageal atresia with a tracheoesophageal fistula Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): N.Z. Mashavave, D.S. Harrison, A.D. Grieve Abstract The concurrence of Urorectal Septum Malformation (URSM) Sequence and Prune Belly Syndrome are extremely uncommon, with increased rarity with the coexistence of an oesophageal atresia with tracheoesophageal fistula. The URSM is denoted by an absence of perineal/anal orifices together with ambiguous genitalia, urogenital, colorectal and lumbosacral anomalies. A persistent cloaca or a partial URSMS entails a single anal/perineal opening that drains the urethra, vagina and rectum. Prune belly syndrome (PBS) encompasses the triad of urological connective tissue anomalies, absence or weakened abdominal walls, and cryptorchidism. In patients that do not fulfil the complete criteria a term pseudo-prune belly syndrome (PPBS) is used. The Prune belly spectrum is associated with poor prognosis due to pulmonary and renal complications. We discuss a rare case of a neonate with pseudo-prune belly syndrome, partial urorectal septum malformation and oesophageal atresia with tracheoesophageal fistula.

Hydatid cyst of the parietal peritoneum Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Ayad Ahmad Mohammed, Sardar Hassan Arif Abstract Introduction Hydatid disease is a type of zoonosis that is caused by Echinococcus granulosus which is transmitted by the fecal-oral route. The disease is endemic in certain areas like the Mediterranean region, South America, and some parts of the central Europe. It commonly affects the liver, the lungs and the brain. But all organs could be affected. Multiple organs could be affected simultaneously. The presentation depends on the site and the size of the cyst. It may cause pain or pressure effect. Emergency presentations occurs when the cyst rupture. The disease is usually diagnosed by CT scan or MRI. Medical treatment may be effective in the uni-vesicular cyst or used after surgery to decrease the recurrence rate. Surgery is still the main treatment option. Case presentation An 11-year-old boy presented with left lower quadrant abdominal pain for 4 months. The pain was dragging like pain that was aggravated by movement and standing position and relieved with rest and analgesics. There was no any associated symptom. Examination of the abdomen showed a palpable oval shaped mass in the left iliac fossa. The mass was about 10 cm by 5 cm and disappeared with abdominal wall contraction. The complete blood count was normal and the ultrasound examination showed a cystic lesion that arises from the abdominal wall, the position of the mass was constant by changing the position of the patient. During laparotomy there was a cystic lesion that arises from the parietal layer of the of the peritoneum behind the posterior rectus sheath on the left side. Complete excision of the cyst done. The cyst was a solitary hydatid cyst that affects this rare location. The patients discharged home after 4 days with good medical condition. Conclusion The presence of any cystic lesion in any organ in a patient from an endemic area for hydatid disease should raise the suspicion to this possibility. Treatment options should be chosen by a multidisciplinary team; certain group of patients may benefit from medical treatment. Surgery is still the main treatment modality.

Intussusception in preterm neonate Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Mostafa Kotb, Mostafa Abdelatty, Omar Fawzy, Hayssam Rashwan Abstract Introduction While necrotizing enterocolitis (NEC) is more commonly encountered in premature infants in the neonatal intensive care unit, intussusception is extremely rare and usually forgotten in differential diagnosis. This is because both diseases share common clinical findings including abdominal distension, bilious gastric residuals and bloody stool. Presentation of case A 33-gestational week-male baby was referred on 23rd postnatal day with bleeding per rectum, intolerance to feed and absolute constipation 2 days earlier. He was misdiagnosed as necrotizing enterocolitis and received conservative treatment. Later, because of deterioration of general condition, he was explored and an intussusception was found. Resection and anastamosis were done and the child was discharged on the 11th day postoperative. Conclusion Although extremely rare, intussusception should be included in the differential diagnosis of neonatal intestinal obstruction, even in the preterms as delayed diagnosis will further result in gangrene and perforation as well as deterioration of the baby's general condition.

Traumatic buccal fat pad herniation in an infant Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Giulia De Giorgi, Rossella Angotti, Giulia Fusi, Lorenzo Salerni, Mario Messina, Francesco Molinaro Abstract Traumatic herniation of buccal fat pad (BFP) is very rare, usually seen in young children, from 5 months to 12 years of age. A minor injury or perforation of the buccinator muscle and buccal mucosa can cause the extrusion of the buccal fat pad into the oral cavity. A differential diagnosis is very important but a history of trauma, an absence of masses before the accident, anatomical site and fatty appearance should suggest the correct diagnosis. The treatment options are usually excision or repositioning of the herniated fat. For the present case report, a 7 month-old boy, diagnosed with traumatic buccal fat pad herniation, was successfully treated with surgical excision.

Internal surgical drainage for bile lakes following hepatoportoenterostomy for biliary atresia Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Edward C. Dee, Benjamin Zendejas, Rima Fawaz, Heung Bae Kim Abstract Bile lakes may be present at time of diagnosis or develop later following hepatoportoenterostomy (HPE) in patients with biliary atresia (BA). We report a patient with recurrent cholangitis following HPE who developed multiple large biliary cystic lesions. Percutaneous drainage resulted in resolution of jaundice and cholangitis but capping of drains resulted in recurrence of symptoms. Therefore, internal drainage of the bile lakes was accomplished using cystjejunostomy to the roux limb of the previous portoenterostomy. At 18 months of follow-up, the patient has remained jaundice free with only one recurrent cholangitis episode which occurred after stopping her antibiotic prophylaxis. Although this patient will likely require liver transplantation in the next few years, this case suggests that cystjejunostomy may be a viable surgical option to improve bile flow and prevent cholangitis in patients who develop bile lakes following HPE.

Cervical bronchogenic cyst diagnosed prenatally Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Takuro Kazama, Masaki Nio, Motoshi Wada, Hideyuki Sasaki, Hiromu Tanaka, Hironori Kudo, Megumi Nakamura, Taichi Fukuzawa, Satoshi Yamaki Abstract Bronchogenic cysts are congenital malformations caused by abnormal lung buds. Almost all bronchogenic cysts are found in the thoracic cavity but rarely in the neck. We report a rare case of a cervical bronchogenic cyst diagnosed in the fetal stage. A male baby with a cervical cyst detected at 20 weeks of gestation was suspected of having a 4-cm cystic lymphatic malformation and was subsequently delivered via normal vaginal delivery at 37 weeks. At birth, no symptoms, apart from the palpable elastic tumor mass (3 cm in diameter) on the left side of the neck, were observed. He was followed-up for observation. The cyst contracted at 4 months of age. However, at one year and 4 months of age, the cyst started to grow again without symptomatic manifestations. Cystectomy was performed at 1 year and 11 months of age, and the cyst was diagnosed histologically as a bronchogenic cyst. The postoperative course was uneventful, except for transient recurrent nerve paralysis, which improved 4 months after surgery. No signs of cyst recurrence were observed at the 1-year follow-up. Our case shows that bronchogenic cysts should be considered as a differential diagnosis of cervical cystic disease found before birth.

Pathological fracture due to prolonged steroid use in a child with transverse myelitis Publication date: April 2019 Source: Journal of Pediatric Surgery Case Reports, Volume 43 Author(s): Ahmad Jabir Rahyussalim, Ronald Henry Tendean, Rizky Priambodo Wisnubaroto, Tri Kurniawati Abstract Introduction Transverse myelitis (TM), a rare inflammatory disease of the spinal cord, is treated with corticosteroids that could result in other complications. Case report We present the case of a 4-year-old boy with a closed left femoral fracture after he hit the floor. He was diagnosed with TM 1 year ago and was treated with oral methylprednisolone for 8 months. Discussion In children, the prolonged use of corticosteroid enhances the osteoclast activity but reduces the osteoblast activity; this imbalance bone turnover causes osteoporosis that increases the fracture risk, which depends on the corticosteroid dose and treatment duration. Of note, the risk of fracture might last for years. Conclusion The increased risk of fracture because of the prolonged use of corticosteroids might not impede the corticosteroid treatment if indicated. Hence, bone health status and nutritional monitoring must be performed at the beginning of treatment in children who need corticosteroid therapy with a cumulative dose >1 g/year.

Dairy Science

Effect of heat treatment on activity of staphylococcal enterotoxins of type A, B, and C in milk Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): L Necidová, Š. Bursová, D. Haruštiaková, K. Bogdanovičová, I. Lačanin ABSTRACT Intoxication by staphylococcal enterotoxins (SE) is among the most common causes of food-poisoning outbreaks resulting from the consumption of raw milk or products made thereof. The aim of our study was to analyze the thermal stability of SE and evaluate the inactivation of SE types A, B, and C (SEA, SEB, SEC) by autoclaving at 100°C, 110°C, and 121°C. Milk samples were inoculated with 38 Staphylococcus aureus strains that possessed the ability to produce SEA, SEB, or SEC and incubated at 37°C for 24 h. This incubation was followed by heat treatment at 100°C, 110°C, or 121°C for 3 min. Samples were analyzed by Staph. aureus plate count method on Baird-Parker agar and specifically for the presence of SE. An enzyme-linked immunofluorescent assay (ELFA) on a MiniVIDAS analyzer (bioMérieux, Marcy l'Étoile, France) was used to detect SE, which were determined semi-quantitatively based on test values. The obtained results were analyzed by means of nonparametric statistical methods. All samples (100%; 38/38) were SE-positive before heat treatment, and the positivity rates decreased after heat treatment at 100°C, 110°C, and 121°C to 36.8% (14/38), 34.2% (13/38), and 31.6% (12/38), respectively. The rates of positive samples differed between SEA, SEB, and SEC producers: SEA was detected in the highest amounts both before and after heat treatment. The amount of SE (expressed as test values) decreased significantly after heat treatment. Comparing amounts of SE in positive and negative samples before and after heat treatment, we can conclude that the success of SE inactivation depends on the amount present before heat treatment. The highest amount of SE and the highest rate of SE-positive samples after all heat treatments were found in samples with strains producing SEA. For SEB and SEC, lower amounts of enterotoxin were present and were inactivated at 100°C. Although temperatures of 100°C, 110°C, and 121°C may inactivate SE in milk, the key measures in prevention of staphylococcal enterotoxicosis are avoiding initial contamination of milk by Staph. aureus, promoting consumption of heat-treated milk, and preventing disruption of the cold chain during milk production and processing.

Proposed dairy calf birth certificate data and death loss categorization scheme Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): J.E. Lombard, F.B. Garry, N.J. Urie, S.M. McGuirk, S.M. Godden, K. Sterner, T.J. Earleywine, D. Catherman, J. Maas ABSTRACT The majority of dairy heifer calves in the United States are destined to be dairy replacements. However, many dairy heifer and bull calves die before 6 mo of age. Of these calves, about 6% (more than 500,000 calves) die at birth or shortly after (i.e., currently termed "stillbirth"). An additional 6% of dairy heifers die during the preweaning period. Death loss in dairy calves is primarily due to stillbirths, failure to adapt to extrauterine life, and infectious disease processes. The reasons for preweaning heifer calf deaths caused by infectious diseases are generally categorized based on easily recognizable clinical signs such as digestive disease/scours or respiratory disease. Most causes of calf death can be mitigated by appropriate preventive care or well-tailored treatments, meaning that the typical death loss percentage could be decreased with better management. Producers could gather information on the circumstances near birth and at death if they had appropriate guidance on what details to record and monitor. This paper provides recommendations on data to collect at the time of birth (i.e., calf birth certificate data). The recording of these critical pieces of information is valuable in evaluating trends over time in morbidity and mortality events in dairy calves. Ideally, necropsy examination would substantially improve the identification of cause of death, but even without necropsy, attribution of cause of death can be improved by more carefully defining death loss categories in on-farm record systems. We propose a death loss categorization scheme that more clearly delineates causes of death. Recommendations are provided for additional data to be collected at the time of death. Recording and analyzing birth certificate and death loss data will allow producers and veterinarians to better evaluate associations between calf risk factors and death, with the goal of reducing dairy calf mortality.

Factors associated with dairy farmers' satisfaction and preparedness to adopt recommendations after veterinary herd health visits Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): Caroline Ritter, Cindy L. Adams, David F. Kelton, Herman W. Barkema ABSTRACT Herd health and production consultancy are important aspects of the modern dairy veterinary practice; therefore, veterinary farm visits will likely be more successful if veterinary practitioners communicate effectively and meet farmers' expectations. Objectives were to assess dairy farmers' satisfaction with veterinary advisors and their perceived preparedness to adopt veterinary advice. Furthermore, we assessed whether farmers' satisfaction and preparedness to adopt advice were associated with specific predictor variables; that is, general (demographic) factors of veterinarians or farmers, communication tools used by veterinarians, and veterinarians' affective attributes during the farm visit. Audio-video recordings of 14 dairy veterinarians during 70 herd health and production management farm visits were analyzed using the Roter interaction analysis system. Demographic data, farmers' satisfaction, and farmers' preparedness to adopt advice were obtained by using questionnaires. Overall, farmers were satisfied with their veterinarian's communication during farm visits and 58% of farmers felt "absolutely" prepared to follow veterinary recommendations. Based on multivariable regression analysis, farmers' satisfaction was positively associated with their level of education and the amount of talk the veterinarian dedicated to counseling the farmer. However, satisfaction was negatively association with the ratio between veterinarian talk and farmer talk. In addition to various demographic variables, farmers' preparedness to adopt veterinary advice was positively associated with their satisfaction. Other predictor variables for farmers' preparedness to follow recommendations included increased veterinary counseling and frequent herd data discussions, whereas there was a negative relationship between number of farmer questions and dominance of the veterinarian during the farm visit. Identification of factors influencing farmers' satisfaction and preparedness to adopt advice will make veterinary communication more effective and could inform training of veterinarians in communication.

Olive oil polyphenol extract inhibits vegetative cells of Bacillus cereus isolated from raw milk Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): Peng Fei, Yunfeng Xu, Shengjuan Zhao, Shaoying Gong, Ling Guo ABSTRACT This study was conducted to analyze the antibacterial effect of olive oil polyphenol extract (OOPE) against vegetative cells of Bacillus cereus isolated from raw milk and reveal the possible antibacterial mechanism. The diameter of inhibition zone, minimum inhibitory concentration, minimum bactericidal concentration, and survival counts of bacterial cells in sterile normal saline and pasteurized milk were used to evaluate the antibacterial activity of OOPE against B. cereus vegetative cells. The changes in intracellular ATP concentration, cell membrane potential, content of bacterial protein, and cell morphology were analyzed to reveal possible mechanisms of action. Our results showed the diameter of inhibition zone, minimum inhibitory concentration, and minimum bactericidal concentration of OOPE against B. cereus vegetative cells were 18.44 ± 0.55 mm, 0.625 mg/mL, and 1.25 mg/mL, respectively. Bacillus cereus GF-1 vegetative cells were decreased to undetectable levels from about 8 log cfu/mL after treatments with 0.625 mg/mL of OOPE in normal saline at 30°C for 3 h and in pasteurized milk at 30°C for 10 h. The antibacterial mechanisms of OOPE against B. cereus GF-1 vegetative cells may be due to the reduction of intracellular ATP concentrations, cell membrane depolarization, decrease of bacterial protein content, and leakage from cytoplasm. These findings illustrated that OOPE could be used to prevent the growth of contaminating B. cereus cells in dairy products.

Effect of energy source in calf milk replacer on performance, digestibility, and gut permeability in rearing calves Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): L. Amado, H. Berends, L.N. Leal, J. Wilms, H. Van Laar, W.J.J. Gerrits, J. Martín-Tereso ABSTRACT Current calf milk replacer (CMR) compositions significantly differ from whole milk in their levels of energy, protein, and minerals. Energy source is one of the major differences, as CMR contains high levels of lactose, whereas whole milk contains higher levels of fat. The aim of this study was to determine the effect of partially exchanging lactose for fat on performance, digestibility, and gut permeability in calves fed twice daily on a high feeding plane. Lactose and fat were exchanged in the CMR formulation on a weight–weight basis. The CMR were isonitrogenous but not isoenergetic. A total of 60 male Holstein-Friesian calves were assigned to 1 of 30 blocks based on serum IgG, body weight, and date of collection after birth. Within each block, calves were randomly assigned to 1 of 2 treatments: high fat and high lactose. The CMR was provided twice daily until 49 d of age, followed by a gradual weaning period of 14 d. Starter, straw, and water were available ad libitum throughout the complete study. Exchanging lactose for fat did not affect growth; intakes of starter, straw, water, crude protein, or total energy; or apparent total-tract digestibility of nutrients. Gastrointestinal permeability was assessed by measuring the recovery of lactulose and Cr in 24-h urine and the Cr concentration and lactulose:d-mannitol ratio in serum following an oral pulse dose. Urinary recoveries of Cr and lactulose were generally low in both treatments but were higher in calves fed the high-fat CMR. Accordingly, the serum lactulose:d-mannitol ratio and serum Cr concentrations were higher in calves fed the high-fat CMR. In wk 1 and during the weaning transition, calves fed the high-fat CMR had significantly fewer abnormal fecal scores. In conclusion, exchanging lactose for fat in the CMR did not affect growth performance, total feed intake, or nutrient digestibility. The high-fat CMR was associated with an increase in permeability markers but positively influenced fecal scores in calves.

Short communication: Global transcriptome analysis of Lactococcus lactis ssp. lactis in response to gradient freezing Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): Jike Lu, Lianming Cui, Songyang Lin, Limin Hao, Nana Cao, Juanjuan Yi, Xin Liu, Laizheng Lu, Qiaozhen Kang ABSTRACT Lactic acid bacteria are often preserved as starter cultures by freezing to extend shelf stability as well as maintain cell viability and acidification activity. Previous studies showed that the endocyte extracted from gradient-freezing pretreated cells could act as lyoprotectant in the lyophilization process of Lactococcus lactis ssp. lactis. In this study, the molecular mechanisms of L. lactis in response to gradient freezing exposure are described using high-throughput sequencing. Nineteen of 56 genes were upregulated after gradient freezing, whereas 37 genes were downregulated. Further validation results of quantitative real-time PCR experiments were consistent with the RNA sequencing. Gene Ontology (http://www.geneontology.org/) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG; https://www.genome.jp/kegg/) pathway were used to analyze the differentially expressed genes. Several pathways, such as glutathione metabolism, ATP-binding cassette transport, metabolism of cell wall and cell membrane components, and stress response-related pathways, were affected by gradient freezing. Six genes relevant to freezing stress response were selected for quantitative real-time PCR, including 3 upregulated genes (hisK, eutD, dukA) and 3 downregulated genes (als, yedF, pepN). The Gene Ontology enrichment and KEGG pathway analyses showed these genes may influence stress response-related pathways, improving the survival of the L. lactis under freezing stress. The identification of these genes deepened an understanding about their response under freezing stress, helping us find potential genes or pathways related to gradient freezing for further research on lyoprotectants.

Farm-level risk factors for bovine mastitis in Dutch automatic milking dairy herds Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): Z. Deng, G. Koop, T.J.G.M. Lam, I.A. van der Lans, J.C.M. Vernooij, H. Hogeveen ABSTRACT Automatic milking systems (AMS) are installed on a growing number of dairy farms worldwide. Management to support good udder health might be different on farms with an AMS compared with farms milking with a conventional milking system, as risk factors for mastitis on farms using an AMS may differ. The aim of this study was to identify farm level factors associated with mastitis on Dutch dairy farms using an AMS. In 2008, risk factor data were collected using a questionnaire combined with on-farm recordings of cow, stall, and AMS hygiene on 135 farms. These risk factor data were linked to 4 udder-health-associated dependent variables: average herd somatic cell count (HeSCCav), variance of the average herd somatic cell count (SCC) on test days (HeSCCvar), the average proportion of new high SCC cases (NHiSCC), and the farmer-reported annual incidence rate of clinical mastitis (IRCM). We employed regression models using multiple imputation to deal with missing values. Due to the high dimensionality of the risk factor data, we also performed nonlinear principal component analysis (NLPCA) and regressed the dependent variables on the principal components (PC). Good hygiene of cows and of AMS were found to be related to a lower HeSCCav and less NHiSCC. Effective postmilking teat disinfection was associated with a lower NHiSCC. A higher bulk tank milk SCC threshold for farmers' action was related to more NHiSCC. Larger farm size was related to lower HeSCCvar but higher NHiSCC. Negative attitude of farmers to animal health, higher frequency of checking AMS, and more time spent on viewing computer data were all positively related to higher IRCM. An NLPCA with 3 PC explained 16.3% of the variance in the risk factor variables. Only the first 2 PC were associated with mastitis. The first PC reflected older and larger farms with poor cow hygiene and AMS hygiene, and was related to higher HeSCCav and NHiSCC, whereas the second PC reflected newly built smaller farms with poor cow hygiene and low milk production, and was associated with higher HeSCCvar and NHiSCC, but lower IRCM. Our study suggests that many of the risk factors on conventional milking system farms are applicable to AMS farms, specifically concerning hygiene of the cows and the milking machine, but on large AMS farms, udder health may need more attention than on smaller AMS farms. Multiple imputation is instrumental to deal with missing values and NLPCA is a useful technique to process high dimensional data in our study.

Space allowance influences individually housed Holstein male calves' age at feed consumption, standing behaviors, and measures of immune resilience before and after step-down weaning Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): L.E. Hulbert, M.S. Calvo-Lorenzo, M.A. Ballou, K.C. Klasing, F.M. Mitloehner ABSTRACT Many dairy calves in the southwestern regions of the United States are raised in wooden hutches with 1.23 m2 of free space that house 3 calves individually. Producers claim that calves in hutch systems are not ready to wean and be placed in groups at the country-average age of 6 wk. Calves may remain in this individual housing system until as late as 10 wk of age. The objective of this study was to modify space allowance of hutches and evaluate weaning readiness using age at solid feed consumption, standing behaviors, and measures of immunity. Calves were randomly assigned at 4 d of age to conventional (CONV; 1.23 m2 of space; n = 18), moderate (MOD; 1.85 m2 of space; n = 17), or maximized (MAX; 3.71 m2 of space; n = 19) space allowance in hutches. These modifications also changed the number of calves housed per hutch from 3 (CONV) to 2 (MOD) and 1 (MAX). Calves were fed milk replacer via bottle twice daily until weaning and offered ad libitum feed throughout the experiment. Step-down weaning was initiated (Wi) at age 53 or 54 d by withdrawal of the p.m. bottle and was completed (Wc) 11 d later by removal of the a.m. milk replacer. Accelerometer data for standing behaviors were collected relative to Wi (3 consecutive days to represent −4 wk, −3 d, 3 d, and 3 and 5 wk). Blood samples were collected in the a.m. just before Wi (d 0) and at d 3, 11, 14, and 18 after Wi. Calves provided with more space (MOD and MAX) compared with CONV calves consumed feed at an earlier age and had slightly healthier erythrocytes, greater circulating glucose, and fewer circulating eosinophils. The CONV calves had haptoglobin (Hp) responses to the stressors of both Wi and Wc and had more IFN-γ from whole blood stimulated with phytohemagglutinin-P. The MAX calves had the least active neutrophils (phagocytosis and oxidative burst), but MOD calves' leukocytes secreted the most TNF-α from whole blood stimulated with lipopolysaccharide. Just before and after weaning, MAX calves spent more time per day in the standing position than CONV and MOD calves and had an Hp response to Wc, but MOD calves did not have an Hp response to Wi or Wc. Based on these results, MOD calves were the most ready for weaning; therefore, they potentially can be moved to group housing at an earlier age than CONV calves, thus improving animal welfare concerns over space allowance and individual housing.

Effect of diet energy density and genomic residual feed intake on prebred dairy heifer feed efficiency, growth, and manure excretion Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): K.T. Williams, K.A. Weigel, W.K. Coblentz, N.M. Esser, H. Schlesser, P.C. Hoffman, H. Su, M.S. Akins ABSTRACT The objective of this study was to determine the growth, feed efficiency, and manure excretion of prebred dairy heifers with differing predicted genomic residual feed intakes (RFI) when offered diets differing in energy density. Prebred Holstein heifers (n = 128, ages 4 to 8 mo) were blocked by weight (low, medium-low, medium-high, or high) with 32 heifers per block. Heifers in each weight block were grouped by RFI and randomly assigned to obtain 2 pens of high (HRFI) and 2 pens of low RFI (LRFI) heifers within each block (8 heifers/pen). Heifers with LRFI were hypothesized to have greater feed efficiency than HRFI heifers. Dietary treatments were a high-energy diet (HE; 66.6% total digestible nutrients, 14.0% crude protein, and 36.3% neutral detergent fiber, dry matter basis) and a low-energy diet (LE; 63.8% total digestible nutrients, 13.5% crude protein, and 41.2% neutral detergent fiber, dry matter basis). Each pen of heifers was randomly assigned to a treatment to obtain a 2 × 2 factorial arrangement (2 RFI levels × 2 diet energy densities). Diets were offered in a 120-d trial. Dry matter intake was not affected by diet, RFI, or their interaction. Average daily gain (ADG) was affected by diet, with heifers fed HE having greater ADG than heifers fed LE. In addition, RFI affected ADG, with LRFI heifers having greater ADG than HRFI heifers, whereas the interaction of RFI and diet was not significant. Feed efficiency was improved for heifers fed the HE diet, but it was not affected by RFI or the interaction of RFI and diet. Overall, feed efficiency of prebred heifers was not dependent on predicted genomic RFI, because the greater ADG of LRFI heifers was accompanied by slightly higher dry matter intake. Feed efficiency of heifers was reduced when heifers were fed the LE diet, but this resulted in more optimal ADG compared with the HE diet fed for ad libitum intake.

Short communication: Production of antimicrobial peptide S100A8 in the goat mammary gland and effect of intramammary infusion of lipopolysaccharide on S100A8 concentration in milk Publication date: Available online 7 March 2019 Source: Journal of Dairy Science Author(s): F.Y. Purba, T. Nii, Y. Yoshimura, N. Isobe ABSTRACT This study aimed to determine the production site of antimicrobial peptide S100A8 in the goat mammary gland and changes in its concentration in milk after lipopolysaccharide (LPS) challenge. Sixteen Tokara goats were used in this study for mammary gland tissue, blood leukocyte, and milk somatic cell collection and LPS challenge. The mRNA expression and protein localization of S100A8 in the mammary gland parenchyma and teat, blood leukocytes, and milk somatic cells were examined by reverse-transcription PCR and immunohistochemistry. The S100A8 concentration in milk was measured at 0 to 144 h after intramammary challenge of LPS by enzyme immunoassay. The mRNA of S100A8 was expressed in the parenchyma and teat, leukocytes isolated from blood, and milk somatic cells. Antimicrobial peptide S100A8 was immunolocalized in the outermost layer of the teat skin of udders with and without LPS infusion, whereas in the mammary gland it was immunolocalized only in the leukocytes infiltrated in the alveoli after LPS infusion. Antimicrobial peptide S100A8 was also immunolocalized in the blood and milk leukocytes. The number of S100A8-positive cells in milk was higher than that in blood. The concentration of S100A8 in milk increased significantly at 72 h after intramammary infusion of LPS. These results suggest that S100A8 is produced in the leukocytes and that its secretion into milk is affected by LPS stimulation.