Effect of season on weaned piglet mortality during transport greater than 8 h under Canadian conditions.

North American swine producers commonly transport piglets away from sow farms at weaning. However, limited information on factors associated with piglet mortality during these transports is available. The objectives of this study were to identify transport characteristics that were associated with the occurrence of in-transit mortality (≥1 piglet found dead on arrival) and/or associated with increased rates of in-transit mortality using records of weaned piglet transport voluntarily provided by Canadian swine companies. Following cleaning and validation, records of 810 long duration (>8 h to <28 h) weaned piglet (min.: 4.2, max.: 7.7 kg) transports conducted between 2016 and 2017 by four companies were available to investigate risk factors for the occurrence of in-transit mortality. Transports originated in Ontario, Saskatchewan, or Alberta and 30% of transports had one or more mortality events recorded. Season of transport was significant in the final logistic regression model; the odds of a transport having mortality occur was greater during the winter (December, January, February) compared to the spring (March, April, May) (OR=1.8; 95% CI: 1.13-2.96; P = 0.013), summer (June, July, August) (OR= 2.1; 95% CI: 1.28-3.34; P = 0.003) and fall (September, October, November) (OR=2.2; 95% CI: 1.36-3.62; P = 0.001), with no differences observed between the other seasons. Additionally, records from 755 long duration weaned piglet (min.: 4.2, max.: 7.9 kg) transports conducted between 2014 and 2017 by a single company was used to identify risk factors for increased rates of in-transit mortality. Transports originated in Saskatchewan or Alberta and 44.9% of transports had one or more mortality events recorded with in-transit mortality rates ranging from 0.00% to 6.16%. Season of transport was again significant in the final negative binomial regression model. The rate of piglet death in-transit was increased in all seasons compared to the summer with winter transport having the highest predicted rate of in-transit mortality. Transports conducted during the winter had a rate of in-transit mortality nearly five times greater compared to transports conducted during the summer (IRR= 4.94; 95% CI: 3.11-7.87; P = 0.000) and approximately three times greater compared to transports conducted during the fall (IRR=2.7; 95% CI: 1.73-4.30; P = 0.000) and spring (IRR=3.1; 95% CI: 1.96-4.99; P = 0.000). These results suggest that winter transport in Western Canada is an area of opportunity to reduce in-transit mortality during long duration weaned piglet transport. Research investigating transport practices that may mitigate the effects of extreme cold (e.g., space allowance, bedding provision) would be useful for informing specific recommendations for this age group.

A descriptive study of weaned piglet transport practices in Alberta, Ontario, and Saskatchewan, Canada between 2014 and 2018.

Canadian transport practices for shipments of newly weaned piglets are not well-described despite documentation requirements for those conducting the movement of these animals. The objective of this study was to describe the characteristics of weaned piglet transport events that occurred between 2014 and 2018 using records provided by five Canadian swine companies. Following cleaning and validation, the dataset included records from 6203 transport events involving the transport of approximately 6.9 million piglets (5.7 kg, 4.1-7.9 kg) from 62 origin sites in Alberta, Ontario, or Saskatchewan, Canada. This represents approximately 4.7% of the piglets estimated to have been weaned in Canada between 2014 and 2018, and 1.7% of sow farms in Canada according to 2016 National census data. Most transport events ended at farms in Canada (71.3%), while the remaining delivered piglets to one of eight American states. The predominant trailer types used were Straightdeck (51.4%) and Potbelly (36.6%), but this did not reflect the number of piglets transported as Potbelly trailers have greater load capacity. Transport events most frequently involved loading piglets from one origin barn and delivering them to a single destination barn (78.1%). Only transport events involving export to the United States picked up piglets from, or delivered them to, more than one farm site. Most transport events had very short trip distances (median distance: 48.0 km; IQR: 497.0), but a marked range was observed (1.8-2931.2 km). Average daily temperature data matched to the transport records by origin and destination location demonstrated ambient environmental conditions during these transport events ranged from - 30.3-28.7 °C. Overall, less than 10% of transport events had mortality occur. Comparable with other observational studies documenting weaned piglet mortality, the average in-transit mortality rate observed over the multiple seasons, companies, trip distances, and other characteristics in this dataset was 0.027%. However, instances of mortality over 1% did sporadically occur and could translate to considerable losses given the large load sizes common for piglets of this age and size (median load size: 1105 piglets; IQR: 1036 piglets). These data provide a better understanding of the interconnectedness of the Canadian swine industry as well as common transport practices which may inform future research on disease transmission in swine transport networks, or piglet welfare during transport. Additionally, variables that were not present in this dataset that would further strengthen these types of investigations are highlighted (e.g., space allowance).

The 40Ar(d,p)41Ar cross section between 3-7 MeV.

To determine the safety of using argon as a deuteron beam stopping material, the  40Ar(d,p)41Ar cross section was measured at average deuteron energies of 3.6 MeV, 5.5 MeV, and 7.0 MeV using an activation method. A 16-MeV deuteron beam produced by Lawrence Berkeley National Laboratory's 88-Inch Cyclotron was degraded to each energy by nickel foils and the front wall of an aluminum gas chamber. The reduced-energy deuterons were used to activate a sample of natAr gas. After each irradiation, the gas chamber's  41Ar activation was measured with a high-purity germanium detector. The cross sections measured were larger than a previous measurement by ∼40%.

Physically fit with a higher cancer risk? Influences of cervical cancer screening among a sample of physically active women ages 21-49 living in the United States.

To achieve the lowest risk level for various cancers, individuals would engage in several healthy lifestyle behaviors and age-eligible cancer screenings as recommended. Nonetheless, research has largely omitted exploration of concurrent primary and secondary prevention behaviors. This study was designed to explore influences of cervical cancer screening among physically active women who reported participation in recreational sports. U.S. based women between the ages of 21-49, who had never been diagnosed with cancer, were eligible to complete a web-based survey. Logistic regression analyses were conducted using SAS 9.4. On average, women were 31 years of age (N = 394) and self-identified as Black (51.3 %). Although low overall (30.7 %), higher odds of cervical cancer screening were associated with age (OR = 1.06, 95 % CI = 1.03-1.10), employment (OR = 2.43, 95 % CI = 1.14-5.18), knowledge of cancer-related risk behaviors (OR = 4.04, 95 % CI = 1.33-12.28), routine doctor's visit (OR = 4.25, 95 % CI = 1.56-11.54), and team-based vs individual-based sport participation (OR = 1.95, 95 % CI = 1.13-3.34). Our study provides insight into the health profile of physically active women, ages 21-49, as it relates to risks for cervical cancer. Screening uptake among this diverse sample was much lower than the general population and national goals set by Healthy People 2030. Interventions should be tailored to increase knowledge of cancer-related risk behaviors, access to healthcare, and recommended cervical cancer screenings among even assumed-to-be healthy populations.

Danger and distress: Parabrachial-extended amygdala circuits.

Our understanding of the role of the parabrachial nucleus (PBN) has evolved as technology has advanced, in part due to cell-specific studies and complex behavioral assays. This is reflected in the heterogeneous neuronal populations within the PBN to the extended amygdala (EA) circuits which encompass the bed nucleus of the stria terminalis (BNST) and central amygdala (CeA) circuitry, as they differentially modulate aspects of behavior in response to diverse threat-like contexts necessary for survival. Here we review how the PBN→CeA and PBN→BNST pathways differentially modulate fear-like behavior, innate and conditioned, through unique changes in neurotransmission in response to stress-inducing contexts. Furthermore, we hypothesize how in specific instances the PBN→CeA and PBN→BNST circuits are redundant and in part intertwined with their respective reciprocal projections. By deconstructing the interoceptive and exteroceptive components of affect- and stress related behavioral paradigms, evidence suggests that the PBN→CeA circuit modulates innate response to physical stimuli and fear conditioning. Conversely, the PBN→BNST circuit modulates distress-like stress in unpredictable contexts. Thereby, the PBN provides a pathway for alarming interoceptive and exteroceptive stimuli to be processed and relayed to the EA to induce stress-relevant affect. Additionally, we provide a framework for future studies to detail the cell-type specific intricacies of PBN→EA circuits in mediating behavioral responses to threats, and the relevance of the PBN in drug-use as it relates to threat and negative reinforcement. This article is part of the special Issue on 'Neurocircuitry Modulating Drug and Alcohol Abuse'.

Species-specific thermal classification schemes can improve climate related marine resource decisions.

Global climate change increasingly contributes to large changes in ecosystem structure. Timely management of rapidly changing marine ecosystems must be matched with methods to rapidly quantify and assess climate driven impacts to ecological communities. Here we create a species-specific, classification system for fish thermal affinities, using three quantifiable datasets and expert opinion. Multiple sources of information limit potential data bias and avoid misclassification. Using a temperate kelp forest fish community in California, USA as a test case for this new methodology, we found the majority of species had high classification agreement across all four data sources (n = 78) but also a number of low agreement species (2 sources disagree from the others, n = 47). For species with low agreement, use of just one dataset to classify species, as is commonly done, would lead to high risk of misclassification. Differences in species classification between individual datasets and our composite classification were apparent. Applying different thermal classifications, lead to different conclusions when quantifying 'warm' and 'cool' species density responses to a marine heatwave. Managers can use this classification approach as a tool to generate accurate, timely and simple information for resource management.

Marine protected areas do not prevent marine heatwave-induced fish community structure changes in a temperate transition zone.

Acute climate events like marine heatwaves have the potential to temporarily or permanently alter community structure with effects on biodiversity and ecosystem services. We aimed to quantify the magnitude and consistency of climate driven community shifts inside and outside Marine Protected Areas before and after a marine heatwave using a kelp forest fish community dataset in southern California, USA. Abundance, biomass, diversity and recruitment of warm-water affinity species during the marine heatwave were significantly greater compared with prior years yet cool-water affinity species did not show commensurate declines. Fish communities inside MPAs were not buffered from these community shifts. This result is likely because the particular species most responsible for the community response to environmental drivers, were not fisheries targets. Resource managers working to preserve biodiversity in a changing climate will need to consider additional management tools and strategies in combination with protected areas to mitigate the effect of warming on marine communities.

Which animals are at risk? Predicting species susceptibility to Covid-19.

In only a few months, the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, leaving physicians, scientists, and public health officials racing to understand, treat, and contain this zoonotic disease. SARS-CoV-2 has made the leap from animals to humans, but little is known about variations in species susceptibility that could identify potential reservoir species, animal models, and the risk to pets, wildlife, and livestock. While there is evidence that certain species, such as cats, are susceptible, the vast majority of animal species, including those in close contact with humans, have unknown susceptibility. Hence, methods to predict their infection risk are urgently needed. SARS-CoV-2 spike protein binding to angiotensin converting enzyme 2 (ACE2) is critical for viral cell entry and infection. Here we identified key ACE2 residues that distinguish susceptible from resistant species using in-depth sequence and structural analyses of ACE2 and its binding to SARS-CoV-2. Our findings have important implications for identification of ACE2 and SARS-CoV-2 residues for therapeutic targeting and identification of animal species with increased susceptibility for infection on which to focus research and protection measures for environmental and public health.

Quantifying Argonaute 2 (Ago2) expression to stratify breast cancer.

BACKGROUND: Argonaute-2 (Ago2) is an essential component of microRNA biogenesis implicated in tumourigenesis. However Ago2 expression and localisation in breast cancer remains undetermined. The aim was to define Ago2 expression (mRNA and protein) and localisation in breast cancer, and investigate associations with clinicopathological details. METHODS: Ago2 protein was stained in breast cancer cell lines and tissue microarrays (TMAs), with intensity and localization assessed. Staining intensity was correlated with clinicopathological details. Using independent databases, Ago2 mRNA expression and gene alterations in breast cancer were investigated. RESULTS: In the breast cancer TMAs, 4 distinct staining intensities were observed (Negative, Weak, Moderate, Strong), with 64.2% of samples stained weak or negatively for Ago2 protein. An association was found between strong Ago2 staining and, the Her2 positive or basal subtypes, and between Ago2 intensity and receptor status (Estrogen or Progesterone). In tumours Ago2 mRNA expression correlated with reduced relapse free survival. Conversely, Ago2 mRNA was expressed significantly lower in SK-BR-3 (HER2 positive) and BT-20 (Basal/Triple negative) cell lines. Interestingly, high levels of Ago2 gene amplification (10-27%) were observed in breast cancer across multiple patient datasets. Importantly, knowledge of Ago2 expression improves predictions of breast cancer subtype by 20%, ER status by 15.7% and PR status by 17.5%. CONCLUSIONS: Quantification of Ago2 improves the stratification of breast cancer and suggests a differential role for Ago2 in breast cancer subtypes, based on levels and cellular localisation. Further investigation of the mechanisms affecting Ago2 dysregulation will reveal insights into the molecular differences underpinning breast cancer subtypes.

Dopamine receptor D4 (DRD4) polymorphisms with reduced functional potency intensify atrophy in syndrome-specific sites of frontotemporal dementia.

OBJECTIVE: We aimed to understand the impact of dopamine receptor D4 (DRD4) polymorphisms on neurodegeneration in patients with dementia. We hypothesized that DRD4dampened-variants with reduced functional potency would be associated with greater atrophy in regions with higher receptor density. Given that DRD4 is concentrated in anterior regions of the limbic and cortical forebrain we anticipated genotype effects in patients with a more rostral pattern of neurodegeneration. METHODS: 337 subjects, including healthy controls, patients with Alzheimer's disease (AD) and frontotemporal dementia (FTD) underwent genotyping, structural MRI, and cognitive/behavioral testing. We conducted whole-brain voxel-based morphometry to examine the relationship between DRD4 genotypes and brain atrophy patterns within and across groups. General linear modeling was used to evaluate relationships between genotype and cognitive/behavioral measures. RESULTS: DRD4 dampened-variants predicted gray matter atrophy in disease-specific regions of FTD in anterior cingulate, ventromedial prefrontal, orbitofrontal and insular cortices on the right greater than the left. Genotype predicted greater apathy and repetitive motor disturbance in patients with FTD. These results covaried with frontoinsular cortical atrophy. Peak atrophy patterned along regions of neuroanatomic vulnerability in FTD-spectrum disorders. In AD subjects and controls, genotype did not impact gray matter intensity. CONCLUSIONS: We conclude that DRD4 polymorphisms with reduced functional potency exacerbate neuronal injury in sites of higher receptor density, which intersect with syndrome-specific regions undergoing neurodegeneration in FTD.

Quantifying Tip60 (Kat5) stratifies breast cancer.

Breast cancer is stratified into four distinct clinical subtypes, using three key biomarkers (Her2/Neu gene status, Estrogen and Progesterone receptor status). However, each subtype is a heterogeneous group, displaying significant variation in survival rates and treatment response. New biomarkers are required to provide more precise stratification of breast cancer cohorts to inform personalised treatment options/predict outcomes. Tip60 is a member of the MYST sub-family of histone acetyltransferases (HATs), and is directly involved in genome maintenance, gene regulation and DNA damage response/repair pathways (key chemotherapeutic influencing mechanisms). We aimed to determine if quantifying Tip60 staining patterns improved breast cancer stratification. We defined Tip60 protein in vivo, quantifying location (cytoplasmic, nuclear), percent of cells and staining intensity in a breast cancer tissue microarray (n = 337). A significant association of specific Tip60 staining patterns with breast cancer subtype, ER or PR status and Tumour grade was found. Importantly, low Tip60 mRNA expression correlated with poor overall survival and relapse free survival. We found Tip60 is a biomarker able to stratify breast cancer patients, and low Tip60 expression is a significant risk factor indicating a higher chance of disease reoccurrence. This work highlights Tip60 regulation as a key factor influencing the development of breast cancer.

Short-term outcome and risk factors for post-operative complications following umbilical resection in 82 foals (2004-2016).

BACKGROUND: Umbilical remnant infection and patent urachus are an important cause of morbidity for the equine neonate. Left untreated, fatal complications can develop. Identifying risk factors for post-operative complications after surgery are important for estimating prognosis. OBJECTIVES: To identify risk factors associated with post-operative complications in foals undergoing umbilical remnant resection due to patent and/or infected umbilical remnants. STUDY DESIGN: Retrospective case series. METHODS: Foals undergoing umbilical remnant resection due to patent urachus or infected remnants at the Marion duPont Scott Equine Medical Center from 2004 to 2016 were included in the study. Data were obtained from medical records and associations between outcomes and post-operative complications, and pre or intraoperative clinical variables were assessed using bivariable and multivariable analyses. RESULTS: Eighty-two foals underwent umbilical remnant resection of which 73 (89.0%) survived to discharge. The urachus was the most commonly affected structure being patent and/or infected in 84.1% of cases. Concurrent diseases were present in 60.6% of foals prior to surgery, with diarrhoea and septic arthritis being most common. The presence of preoperative septic arthritis and/or physitis were significantly associated with nonsurvival (OR 33; 95% confidence interval 1.1-985.2; P = 0.04). Longer anaesthesia time (OR 1.4; 95% confidence interval 1.1-1.7; P = 0.02) and failure of passive transfer of immunoglobulins (OR 5.9; 95% confidence interval 1.2-29.04; P = 0.03) were associated with increased odds for post-operative complications. MAIN LIMITATIONS: It is not known if medical treatment alone would have been successful in foals that did not receive preoperative medical treatment. CONCLUSIONS: Overall survival is high after surgical excision of umbilical remnants. The presence of preoperative septic arthritis and/or physitis was associated with decreased survival and failure of passive transfer of immunoglobulins and longer anaesthesia times were associated with increased odds for post-operative complications.

Desvenlafaxine overdose and the occurrence of serotonin toxicity, seizures and cardiovascular effects.

CONTEXT: Desvenlafaxine is used to treat major depression. Desvenlafaxine is also the active metabolite of venlafaxine. Venlafaxine overdose can cause serotonin toxicity, seizures and cardiovascular effects, but there is limited information on desvenlafaxine overdose. OBJECTIVE: We aimed at investigating the clinical effects and complications from desvenlafaxine overdose. MATERIALS AND METHODS: This was a retrospective observational study of desvenlafaxine overdoses over a six-year period. Demographic details, dose and timing of the overdose, together with clinical effects, treatment and complications were extracted from a local hospital network database or the medical records of patients following hospital admission with a desvenlafaxine overdose. RESULTS: There were 182 cases of desvenlafaxine overdose included in the study. From the 182 cases, 75 were desvenlafaxine (± alcohol) only ingestions and 107 included one or more co-ingested drugs. In single-agent desvenlafaxine ingestions, median age was 25 years (range: 13-68 years) with a median ingested dose of 800 mg (range: 250-3500 mg; interquartile range (IQR): 600-1400 mg), and 54/75 (72%) were female. The Glasgow Coma Score (GCS) was 15 in 68/74 (92%) patients, 13-14 in 5/74 (7%), and was seven in one patient following aspiration. Mild hypertension (systolic blood pressure [BP] > 140-180 mmHg) occurred in 23/71 patients (32%), and tachycardia occurred in 29/74 (39%) patients. There were no abnormal QT intervals and no QRS >120 m s. Serotonin toxicity was diagnosed by the treating physician in 7/75 (9%) patients, but only one of these met the Hunter Serotonin Toxicity Criteria. None of the 75 patients who took desvenlafaxine only (± alcohol) had seizures, were admitted to intensive care or died. In comparison, the 107 patients taking desvenlafaxine in overdose with other medications developed more pronounced toxicity. Generalised seizures occurred in 5/107 (5%), but in three of these cases co-ingestants were possible proconvulsants. Fifteen patients had a GCS ≤9 and none had an abnormal QT or QRS. Severe effects appeared to be associated with coingestants. CONCLUSION: Desvenlafaxine overdose causes minor effects with mild hypertension and tachycardia. The risk of seizures or serotonin toxicity is low.

Identifying the barriers and enablers in the implementation of the New Zealand and Australian Antenatal Corticosteroid Clinical Practice Guidelines.

BACKGROUND: The ineffective implementation of evidence based practice guidelines can mean that the best health outcomes are not achieved. This study examined the barriers and enablers to the uptake and implementation of the new bi-national (Australia and New Zealand) antenatal corticosteroid clinical practice guidelines among health professionals, using the Theoretical Domains Framework. METHODS: Semi-structured interviews or online questionnaires were conducted across four health professional groups and three district health boards in Auckland, New Zealand. The questions were constructed to reflect the 14 behavioural domains from the Theoretical Domains Framework. Relevant domains were identified by the presence of conflicting beliefs within a domain; the frequency of beliefs; and the likely strength of the impact of a belief on the behaviour using thematic analysis. The influence of health professional group and organisation on the different barriers and enablers identified were explored. RESULTS: Seventy-three health professionals completed either a semi-structured interview (n = 35) or on-line questionnaire (n = 38). Seven behavioural domains were identified as overarching enablers: belief about consequences; knowledge; social influences; environmental context and resource; belief about capabilities; social professional role and identity; and behavioural regulation. Five behavioural domains were identified as overarching barriers: environmental context and resources; knowledge; social influences; belief about consequences; and social professional role and identity. Differences in beliefs between individual health professional groups were identified within the domains: belief about consequences; social professional role and identity; and emotion. Organisational differences were identified within the domains: belief about consequences; social influences; and belief about capabilities. CONCLUSION: This study has identified some of the enablers and barriers to implementation of the New Zealand and Australian Antenatal Corticosteroid Clinical Practice Guidelines using the validated Theoretical Domains Framework, as perceived by health professionals. We have identified differences between individual health professional groups and organisations. The identification of these behavioural determinants can be used to enhance an implementation strategy, assist in the design of interventions to achieve improved implementation and facilitate process evaluations to understand why or how change interventions are effective.

Consumers attitudes and beliefs towards the receipt of antenatal corticosteroids and use of clinical practice guidelines.

BACKGROUND: Active participation of consumers in health care decision making, policy and clinical research is increasingly encouraged by governments, influential bodies and funders. Identifying the best way to achieve this is difficult due to the paucity of evidence. Consumers have mixed feelings towards clinical practice guidelines (CPG) demonstrating scepticism towards their purpose and applicability to their needs. There is no information pertaining to consumers' views and attitudes on the receipt of antenatal corticosteroids (ACS). The aim of this study was to examine the barriers and enablers to receiving ACS and use of CPG amongst consumers. METHODS: Consumers were recruited from neonatal units across three district health boards (DHBs) in Auckland, New Zealand. Participants completed a semi-structured interview or questionnaire. The questions posed and analyses were informed by the Theoretical Domains Framework (TDF). Barriers and enablers were identified by the presence of conflicting beliefs within a domain; the frequency of beliefs; and the likely strength of the impact of a belief on use of CPG and receipt of ACS. RESULTS: Twenty four consumers participated in the study. Six domains were identified as barriers to receipt of ACS and use of CPG. Key barriers to receipt of ACS included: difficulty retaining information conveyed, requiring further information in a variety of formats, and time constraints faced by consumers and health professionals in the provision and understanding of information to facilitate decision making. Barriers to use of CPG included: uncertainty about applicability of guideline use among consumers and scepticism about health professionals adhering too rigidly to guidelines. Enablers to receipt of ACS included: optimism toward ACS use, a strong knowledge of why ACS were administered, improved resilience in their pregnancy and confidence in their decision making following receipt of information about ACS. Enablers to use of CPG included: validation and standardisation of decision making among health professionals providing care and facilitating the best care for women and their babies. CONCLUSIONS: Key barriers and enablers exist among consumers regarding receipt of ACS and use of CPG. These need to be addressed or modified in any intervention strategy to facilitate implementation of the ACS CPG.

Disconnection and hyper-connectivity underlie reorganization after TBI: A rodent functional connectomic analysis.

While past neuroimaging methods have contributed greatly to our understanding of brain function after traumatic brain injury (TBI), resting state functional MRI (rsfMRI) connectivity methods have more recently provided a far more unbiased approach with which to monitor brain circuitry compared to task-based approaches. However, current knowledge on the physiologic underpinnings of the correlated blood oxygen level dependent signal, and how changes in functional connectivity relate to reorganizational processes that occur following injury is limited. The degree and extent of this relationship remain to be determined in order that rsfMRI methods can be fully adapted for determining the optimal timing and type of rehabilitative interventions that can be used post-TBI to achieve the best outcome. Very few rsfMRI studies exist after experimental TBI and therefore we chose to acquire rsfMRI data before and at 7, 14 and 28 days after experimental TBI using a well-known, clinically-relevant, unilateral controlled cortical impact injury (CCI) adult rat model of TBI. This model was chosen since it has widespread axonal injury, a well-defined time-course of reorganization including spine, dendrite, axonal and cortical map changes, as well as spontaneous recovery of sensorimotor function by 28 d post-injury from which to interpret alterations in functional connectivity. Data were co-registered to a parcellated rat template to generate adjacency matrices for network analysis by graph theory. Making no assumptions about direction of change, we used two-tailed statistical analysis over multiple brain regions in a data-driven approach to access global and regional changes in network topology in order to assess brain connectivity in an unbiased way. Our main hypothesis was that deficits in functional connectivity would become apparent in regions known to be structurally altered or deficient in axonal connectivity in this model. The data show the loss of functional connectivity predicted by the structural deficits, not only within the primary sensorimotor injury site and pericontused regions, but the normally connected homotopic cortex, as well as subcortical regions, all of which persisted chronically. Especially novel in this study is the unanticipated finding of widespread increases in connection strength that dwarf both the degree and extent of the functional disconnections, and which persist chronically in some sensorimotor and subcortically connected regions. Exploratory global network analysis showed changes in network parameters indicative of possible acutely increased random connectivity and temporary reductions in modularity that were matched by local increases in connectedness and increased efficiency among more weakly connected regions. The global network parameters: shortest path-length, clustering coefficient and modularity that were most affected by trauma also scaled with the severity of injury, so that the corresponding regional measures were correlated to the injury severity most notably at 7 and 14 days and especially within, but not limited to, the contralateral cortex. These changes in functional network parameters are discussed in relation to the known time-course of physiologic and anatomic data that underlie structural and functional reorganization in this experiment model of TBI.

Evidence of a molecular clock in the ovine ovary and the influence of photoperiod.

The influence of the central circadian clock on reproductive timing is well established. Much less is known about the role of peripheral oscillators such as those in the ovary. We investigated the influence of photoperiod and timing of the LH surge on expression of circadian clock genes and genes involved in steroidogenesis in ovine ovarian stroma. Seventy-two Suffolk cross ewes were divided into two groups, and their estrous cycles were synchronized. Progestagen sponge removal was staggered by 12 hours between the groups such that expected LH peak would occur midway through either the light or dark phase of the photoperiodic cycle. Four animals from each group were killed, and their ovaries were harvested beginning 36 hours after sponge removal, at 6-hour intervals for 48 hours. Blood was sampled every 3 hours for the period 24 to 48 hours after sponge removal to detect the LH surge. The interval to peak LH did not differ between the groups (36.2 ± 1.2 and 35.6 ± 1.1 hours, respectively). There was an interaction between group and the time of sponge removal on the expression of the core clock genes ARNTL, PER1, CRY1, CLOCK, and DBP (P < 0.01, P < 0.05, P < 0.01, P < 0.01, and P < 0.01, respectively). As no significant interaction between group and time of day was detected, the datasets were combined. Statistically significant rhythmic oscillation was observed for ARNTL, CLOCK, CRY1 (P < 0.01, respectively), PTGS2, DBP, PTGER2, and CYP17A1 (P < 0.05, respectively), confirming the existence of a time-sensitive functionality within the ovary, which may influence steroidogenesis and is independent of the ovulatory cycle.

Inhibition of parvalbumin-expressing interneurons results in complex behavioral changes.

Reduced expression of the Gad1 gene-encoded 67-kDa protein isoform of glutamic acid decarboxylase (GAD67) is a hallmark of schizophrenia. GAD67 downregulation occurs in multiple interneuronal sub-populations, including the parvalbumin-positive (PVALB+) cells. To investigate the role of the PV-positive GABAergic interneurons in behavioral and molecular processes, we knocked down the Gad1 transcript using a microRNA engineered to target specifically Gad1 mRNA under the control of Pvalb bacterial artificial chromosome. Verification of construct expression was performed by immunohistochemistry. Follow-up electrophysiological studies revealed a significant reduction in γ-aminobutyric acid (GABA) release probability without alterations in postsynaptic membrane properties or changes in glutamatergic release probability in the prefrontal cortex pyramidal neurons. Behavioral characterization of our transgenic (Tg) mice uncovered that the Pvalb/Gad1 Tg mice have pronounced sensorimotor gating deficits, increased novelty-seeking and reduced fear extinction. Furthermore, NMDA (N-methyl-d-aspartate) receptor antagonism by ketamine had an opposing dose-dependent effect, suggesting that the differential dosage of ketamine might have divergent effects on behavioral processes. All behavioral studies were validated using a second cohort of animals. Our results suggest that reduction of GABAergic transmission from PVALB+ interneurons primarily impacts behavioral domains related to fear and novelty seeking and that these alterations might be related to the behavioral phenotype observed in schizophrenia.

Effect of rest duration on recovery from repeated exercise in near-market-weight pigs.

The process of transportation can be seen as a succession of stressors, from which pigs may not have time to recover before slaughter. The aim of this study was to determine the extent to which the duration of the rest time given to near-market-weight pigs after an initial exposure to exercise affected their recovery from subsequent exercise. Eighteen groups of 3 gilts were exercised (Ex1) through a standard handling course, including two 19° ramps, and then were held in a holding pen for either 35 (RT35), 75 (RT75), or 150 (RT150) min (Rest Period 1, RP1). Afterward, pigs were exercised a second time (Ex2) and left to rest for 150 min. Recovery from Ex2 (Rest Period 2, RP2) was assessed using measures of heart rate (HR), respiratory rate (RR), skin temperature (ST), and posture. Repeated measures and regression analysis were used to analyze the data. For RT75 pigs, there were no detrimental effects of Ex2 on HR, RR, and handling time (P > 0.05, for all) during the exercise and recovery periods. Skin temperature during Ex2 was greater than ST during Ex1 (P < 0.001), whereas ST during RP1 did not differ from ST during RP2 (P > 0.05). Doubling the rest period did not provide any more beneficial effects in regard to RR and HR (P > 0.05 for both) during Ex2 and RP2 compared to RT75 pigs, as shown by the similar latencies to recover for these 2 variables. However, ST did not increase between exercises, and RT150 pigs required less time to complete the handling course during Ex2. The results show that a lack of rest after an initial exposure to exercise made pigs more susceptible to stress during Ex2 and RP2, as demonstrated by greater (P < 0.001 for all) HR, RR, and ST during RP2 compared to RP1 and Ex2 compared to Ex1. When given more than 35 min to rest during RP2, RT35 pigs eventually recovered. Latencies of recovery for HR, ST, RR, and posture were all greater (P < 0.05 for HR, ST, and RR and P < 0.001 for posture) than those obtained for RT75 and RT150 pigs. This study highlights that if pigs are not initially given enough rest to recover from exercise, a subsequent exposure to the same exercise will cause an increase in these physiological variables during exercise and recovery. Further research is needed to investigate factors contributing to the quality of rest, with a particular focus on conditions not allowing a proper rest on the truck or in lairage.