Validation of Standing and Locomotion Scoring, Behavioral Assessments, and Mechanical Nociceptive Threshold Testing on Naturally Occurring Sow Lameness.

The objective of this study was to validate standing and locomotion lameness scoring, mechanical nociceptive threshold testing, and behavioral profile tools for the diagnosis of naturally occurring lameness etiologies in pigs. A total of 55 crossbred gilts and sows obtained from a commercial farm were enrolled in the study; with sound pigs classified as controls (8) and the remainder as lame due to integumentary (20), musculoskeletal (15), and combinations of integumentary and musculoskeletal (12) etiologies. Standing and locomotion lameness, mechanical nociceptive threshold (MNT) test, pig-human interventions, and latency to complete an obstacle course were evaluated. Standing and locomotion lameness scoring systems, MNT, and pig behavior (latency) were capable of discriminating between animals with mild organic lameness and animals that were sound and may have utility on the farm for staff to use to identify and manage lame animals. In rare instances, the tools used here were able to discriminate between broad categories of lameness etiology.

Tralesinidase Alfa Enzyme Replacement Therapy Prevents Disease Manifestations in a Canine Model of Mucopolysaccharidosis Type IIIB.

Mucopolysaccharidosis type IIIB (MPS IIIB; Sanfilippo syndrome B; OMIM #252920) is a lethal, pediatric, neuropathic, autosomal recessive, and lysosomal storage disease with no approved therapy. Patients are deficient in the activity of N-acetyl-alpha-glucosaminidase (NAGLU; EC 3.2.150), necessary for normal lysosomal degradation of the glycosaminoglycan heparan sulfate (HS). Tralesinidase alfa (TA), a fusion protein comprised of recombinant human NAGLU and a modified human insulin-like growth factor 2, is in development as an enzyme replacement therapy that is administered via intracerebroventricular (ICV) infusion, thus circumventing the blood brain barrier. Previous studies have confirmed ICV infusion results in widespread distribution of TA throughout the brains of mice and nonhuman primates. We assessed the long-term tolerability, pharmacology, and clinical efficacy of TA in a canine model of MPS IIIB over a 20-month study. Long-term administration of TA was well tolerated as compared with administration of vehicle. TA was widely distributed across brain regions, which was confirmed in a follow-up 8-week pharmacokinetic/pharmacodynamic study. MPS IIIB dogs treated for up to 20 months had near-normal levels of HS and nonreducing ends of HS in cerebrospinal fluid and central nervous system (CNS) tissues. TA-treated MPS IIIB dogs performed better on cognitive tests and had improved CNS pathology and decreased cerebellar volume loss relative to vehicle-treated MPS IIIB dogs. These findings demonstrate the ability of TA to prevent or limit the biochemical, pathologic, and cognitive manifestations of canine MPS IIIB disease, thus providing support of its potential long-term tolerability and efficacy in MPS IIIB subjects. SIGNIFICANCE STATEMENT: This work illustrates the efficacy and tolerability of tralesinidase alfa as a potential therapeutic for patients with mucopolysaccharidosis type IIIB (MPS IIIB) by documenting that administration to the central nervous system of MPS IIIB dogs prevents the accumulation of disease-associated glycosaminoglycans in lysosomes, hepatomegaly, cerebellar atrophy, and cognitive decline.

Effects of Waiting Room and Feline Facial Pheromone Experience on Blood Pressure in Cats.

Obtaining accurate blood pressure measurements in cats is challenging due to the stressful nature of clinic visits. The objective of this study was to evaluate the effects of veterinary clinic waiting experiences and a feline pheromone spray on blood pressure in the cat. We hypothesized that reduced stress associated with bypassing the waiting room and use of synthetic feline facial pheromone (FFP) spray would result in lower blood pressure. A 2 × 2 factorial design involved two rooms and two FFP treatments. Thirty-nine healthy adult cats were recruited and were systematically assigned to four treatment combinations administered over four visits in 2016 and 2017. Cats were kept in the hospital waiting room or were taken directly to the exam room, with or without FFP treatment. All cats were then acclimated to the exam room for an additional 10 min, where vocalizations were recorded manually, before blood pressure measurements were collected using Doppler ultrasonography. Data were analyzed using generalized linear mixed models, with room × FFP interaction, visit, sex, and trial year in the model. There was no significant effect of waiting room by FFP interaction on blood pressure (n = 0.95). Mean blood pressure was significantly higher at visit 1 than visits 2 and 4 (P < 0.01), but higher at visit 3 than visit 2 (n = 0.02). Mean blood pressure was higher in males (n = 0.01), and males were more likely to be categorized as borderline hypertensive/hypertensive or severely hypertensive (n = 0.01). Number of vocalizations was significantly associated with waiting room by FFP interactions (P < 0.01), with fewer vocalizations associated with bypassing the waiting room and when FFP was provided. In conclusion, although we found some behavioral evidence supporting stress reduction when feline patients bypass the waiting room and are provided with FFP, these interventions did not result in lower blood pressure in a clinical setting.

Characterization of Efficacy and Animal Safety across Four Caprine Disbudding Methodologies.

There is a strong industry demand for technically simple and highly efficacious alternatives to heat cautery disbudding in goat kids that can be performed as a stand-alone procedure without adjunct anesthesia, and that result in improved overall welfare through reduced acute pain, reduced tissues healing interval, and a consistent safety record. The objective of this study was to consider the net effect of disbudding techniques on goat welfare by examining vocalization frequency, long-term efficacy and animal safety associated with four alternative caprine disbudding methods against sham-disbudded and heat-cautery controls. Sixty-five commercial male dairy kids were disbudded at 3-10 days of age with one of six disbudding treatments (clove oil injection, caustic paste, two cryosurgical methods, heat-cautery, and sham procedure). Heat cautery was 91% effective, caustic paste was 55% effective, and the other treatments were ineffective. Heat cautery and sham procedures resulted in similar vocalization efforts; freezing with a liquid-nitrogen cooled iron resulted in significantly greater vocalization numbers. No unintended paste transfer injuries were observed with short-term application of the caustic paste. Heat cautery resulted in numerous superficial infections but no permanent injury. Clove oil injection was associated with several unexpected and severe complications including unintended tissue necrosis, temporary paresis, skull defects, meningitis, and death. Collectively, we did not find that any of the alternative methods of disbudding provided a feasible option over heat cautery to improve welfare.

Assessing the Socio-Environmental Risk of Onsite Wastewater Treatment Systems to Inform Management Decisions.

Quantifying the risk that failing onsite waste treatment systems (OWTS), such as septic systems, present to human health and the environment is a key component in natural resource management. We integrated environmental and socio-demographic data to assess the potential environmental risk and environmental justice concerns related to septic infrastructure. We used this process to develop a framework that can be applied in other jurisdictions. We found only 8% of the registered OWTS presented potential environmental risk due to the topographic, hydrologic, or edaphic characteristics of their placement. In contrast, almost 70% of the OWTS presented potential environmental risk due to their age (25 years or older). Approximately 60% of the OWTS we estimated to be at risk from age or placement were found in census blocks with more than 30% of the population living below the poverty line, had a population that was more than 50% nonwhite, or was predominantly nonwhite and impoverished. Our work suggests that jurisdictions with limited information about septic infrastructure may be able to use geospatial data that they do have to predict the parcel-level locations of OWTS. These locations can then be used to inform environmental monitoring to proactively address environmental justice concerns.

Incidence, Severity, and Welfare Implications of Lesions Observed Postmortem in Laying Hens from Commercial Noncage Farms in California and Iowa.

The egg industry is moving away from the use of conventional cages to enriched cage and noncage laying hen housing systems because of animal welfare concerns. In this study, the prevalence and severity of lesions in noncage laying hens from commercial farms in two of the largest egg-producing states, California and Iowa, were evaluated by postmortem examination. Hens that died or were culled were collected during early, mid, and late stages of the laying cycle from 16 houses on three farms. Of the 25 gross lesions identified for study, 22 were observed, with an average of four lesions per hen. Vent cannibalism, reduced feather cover, keel bone deformation, and beak abnormalities were the most frequent lesions, observed in ≥40% of hens. Other common lesions were cloacal prolapse (30.5%), footpad dermatitis (24.3%), and septicemia (23.1%). Beak abnormality and enteric disease had the highest proportion of severe lesions. Pearson chi-square analysis revealed a number of stage-of-lay effects (P ≤ 0.05), some of which differed by state. For both states combined, the lesions observed more frequently during early lay were beak abnormalities, northern fowl mite infestation, and cage layer fatigue, whereas during mid lay, they were poor feather cover, vent cannibalism, footpad dermatitis, keel bone deformation, respiratory disease and roundworms. Feather pecking and cloacal prolapse were most common during late lay. Although differences in hen genetics, farm management practices, and environmental factors could all have affected the results of this study, the information provides a better understanding of hen health in noncage housing systems and could help to identify potential interventions to reduce hen welfare problems.

Pain and sickness behavior associated with corneal lesions in dairy calves.

Infectious bovine keratoconjunctivitis (IBK) is a common corneal disease of calves that adversely affects animal welfare by causing pain and weight loss. Identifying behavioral indicators of pain and sickness in calves with IBK is necessary for designing studies that aim to identify effective means of pain mitigation. Consistent with principles of the 3Rs for animal use in research, data from a randomized blinded challenge study was used to identify and describe variation of behaviors that could serve as reliable indicators of pain and sickness in calves with corneal injuries. Behavioral observations were collected from 29 Holstein calves 8 to 12 weeks of age randomly allocated to one of three treatments: (1) corneal scarification only, (2) corneal scarification with inoculation with Moraxella bovoculi and (3) corneal scarification with inoculation with Moraxella bovis. Behavior was continuously observed between time 1230 - 1730 h on day -1 (baseline time period) and day 0 (scarification time period). Corneal scarification and inoculation occurred between 0800 - 1000 h on day 0. Frequency of head-directed behaviors (head shaking, head rubbing, head scratching) and durations of head rubbing, feeding, standing with head lifted, lying with head lifted and sleeping were compared between study days and groups. Following scarification, the frequency of head-directed behavior significantly increased (p = 0.0001), as did duration of head rubbing (p=0.02). There was no significant effect of trial, trial day, treatment or treatment-day interaction on other behaviors studied. Our study demonstrated that head-directed behavior, such as head shaking, rubbing and scratching, was associated with scarification of eyes using an IBK challenge model, but sickness behavior was not observed.

Critical role of apoptotic speck protein containing a caspase recruitment domain (ASC) and NLRP3 in causing necrosis and ASC speck formation induced by Porphyromonas gingivalis in human cells.

Periodontal disease is a chronic inflammatory disorder that leads to the destruction of tooth-supporting tissue and affects 10-20 million people in the U.S. alone. The oral pathogen Porphyromonas gingivalis causes inflammatory host response leading to periodontal and other secondary inflammatory diseases. To identify molecular components that control host response to P. gingivalis in humans, roles for the NLR (NBD-LRR) protein, NLRP3 (cryopyrin, NALP3), and its adaptor apoptotic speck protein containing a C-terminal caspase recruitment domain (ASC) were studied. P. gingivalis strain A7436 induces cell death in THP1 monocytic cells and in human primary peripheral blood macrophages. This process is ASC and NLRP3 dependent and can be replicated by P. gingivalis LPS and Escherichia coli. P. gingivalis-induced cell death is caspase and IL-1 independent and exhibits morphological features consistent with necrosis including loss of membrane integrity and release of cellular content. Intriguingly, P. gingivalis-induced cell death is accompanied by the formation of ASC aggregation specks, a process not previously described during microbial infection. ASC specks are observed in P. gingivalis-infected primary human mononuclear cells and are dependent on NLRP3. This work shows that P. gingivalis causes ASC- and NLRP3-dependent necrosis, accompanied by ASC speck formation.

Videoconferencing for delivery of breast cancer support groups to women living in rural communities: a pilot study.

Women with breast cancer in rural areas are likely to exhaust their usual sources of psychosocial support while still facing challenges posed by breast cancer, but are unlikely to have access to professionally led support groups. In this community-based project, we assessed the feasibility and acceptability of providing support groups to women with breast cancer in a large rural area using videoconferencing and a workbook journal, and we assessed the intervention's potential to reduce distress and increase emotional expression and self-efficacy for coping with cancer. Twenty-seven women in the Intermountain Region of northeastern California participated in eight-session support groups led by an oncology social worker by going to nearby videoconferencing sites. Feasibility and acceptability were demonstrated. Older as well as younger women were comfortable using videoconferencing and said the groups were valuable because they promoted information sharing and emotional bonds with other women with breast cancer. They emphasized the importance of a professional facilitator and identified advantages of using videoconferencing for support groups. Pretest and posttest comparisons showed significant decreases in depression and posttraumatic stress disorder symptoms. The results suggest that the intervention has the potential to provide a valuable service that is not readily available in rural communities.

Perpetrators of homicide with schizophrenia: a national clinical survey in England and Wales.

OBJECTIVE: Few studies have described rates of schizophrenia in a national sample of homicide perpetrators. This study aimed to describe this group's social and clinical characteristics, mental state features, offense details, and outcome in court. METHOD: Analyses used a national clinical survey that collected data on people convicted of homicide in England and Wales (1996-1999). Data were collected for those with schizophrenia or other delusional disorders from psychiatric reports and questionnaires. RESULTS: Of the 1,594 people convicted of homicide, 85 (5 percent) had schizophrenia. Of the 57 people with schizophrenia for whom data were available, 32 (56 percent) had been ill for less than 12 months, and in the month before the offense, 32 (56 percent) had shown a change in the quality, intensity, or conviction of or emotional response to their delusional beliefs. Twenty-four (28 percent) had no previous contact with psychiatric services. CONCLUSIONS: Regular assessment of delusions may help to detect an increased risk of violence, including homicide. More intensive care should be available for patients with a history of schizophrenia and previous violence.

The role of alcohol and drugs in homicides in England and Wales.

BACKGROUND: The annual number of homicide convictions in England and Wales is increasing. Previous studies have highlighted the aetiological role of alcohol and drugs in homicide. AIMS: To examine rates of alcohol and drug misuse and dependence in people convicted of homicide; the role of alcohol and drugs in the offence; the social and clinical characteristics of alcohol- and drug-related homicides; and the social and clinical characteristics of patients with dual diagnosis who commit homicide. METHODS: A national clinical survey based on a 3-year (1996-9) consecutive sample of people convicted of homicide in England and Wales. Information on rates of alcohol and drug misuse/dependence, the role of alcohol and drugs in the offence and social and clinical characteristics of perpetrators were collected from psychiatric reports prepared for the court in homicide convictions. Detailed clinical information was gathered from questionnaires completed by mental health teams for those in contact with mental health services. RESULTS: Of the 1594 homicide perpetrators, more than one-third (42%) occurred in people with a history of alcohol misuse or dependence and 40% in people with a history of drug misuse or dependence. Alcohol or drug misuse played a contributory role in two-fifths of homicides. Alcohol played a major role in 52 (6%) and a minor role in 364 (39%) homicides. Drugs played a major role in six (1%) and a minor role in 138 (14%) homicides. Forty-two homicides (17%) were committed by patients with severe mental illness and substance misuse. Alcohol- and drug-related homicides were generally associated with male perpetrators who had a history of violence, personality disorders, mental health service contact and with stranger victims. CONCLUSIONS: Substance misuse contributes to the majority of homicides in England and Wales. A public health approach to homicide would highlight alcohol and drugs before severe mental illness.

Suicide in the homeless within 12 months of contact with mental health services : a national clinical survey in the UK.

BACKGROUND: Suicide prevention is a health service priority. Homeless mental health patients present a challenge to services because of their complex health and social needs. AIMS: To establish the numbers of homeless patients in contact with services who die by suicide; to describe their suicide methods and their social and clinical characteristics including aspects of clinical care. METHOD: A national clinical survey based on a 4-year (1996-2000) sample of people in England and Wales who died by suicide. Detailed data were collected on those who had been in contact with mental health services in the year before death. RESULTS: A total of 131 individuals who died by suicide were reported to have been homeless at the time of death--3% of all suicides by psychiatric patients, over 30 per year. Hanging was the most common cause of death. The most frequent diagnosis was schizophrenia. Around half were in-patients at the time of death. Social and clinical risk factors for suicide were common, including drug and alcohol misuse, and recent suicidal ideas and behaviour. Despite this, their clinical care was characterised by disengagement from services as a result of missed contacts, self-discharge, lack of follow-up and lack of key worker. CONCLUSIONS: In order to reduce the number of deaths by suicide in those who are homeless and mentally ill, improvements in in-patient safety and engagement in the community are needed. This may be achieved through assertive community treatment, dual diagnosis services, and dedicated community mental health teams.

Suicide in schizophrenia: findings from a national clinical survey.

BACKGROUND: A reduction in suicide among individuals with mental illness is an international public-health priority. Approximately 10% of patients with schizophrenia will die by suicide. OBJECTIVE: The goal of this study was to describe social and clinical characteristics of people with schizophrenia who completed suicide, including aspects of the clinical care they received. METHOD: A national clinical survey was conducted based on a 4-year (1996-2000) sample of people in England and Wales who had died by suicide and had been in contact with mental health services in the previous 12 months. RESULTS: Of 20,927 individuals who committed suicide, 5,099 (24%) were known to have been in contact with mental health services in the year prior to death. Completed questionnaires were returned on 4,859 cases of suicide. Of these, 960 (20%) were diagnosed with schizophrenia. These suicides were characterized by more violent modes of death, with over a quarter (27%) jumping from a height or in front of a moving vehicle compared to 10% of the remaining sample. They were more likely than the other individuals in the sample to be young, male, unmarried, and from an ethnic minority with high rates of unemployment. Rates of previous violence and drug abuse were high and they were proportionally more likely to be inpatients at the time of death and to have been noncompliant with medication. Patients with schizophrenia and comorbid substance abuse showed particularly complex social and clinical morbidity. CONCLUSIONS: Measures that may prevent suicide among patients with schizophrenia include improved ward safety, closer supervision in both inpatient and community settings, particularly for those with poor medication compliance, and effective treatment of substance abuse.

Emotional self-efficacy, stressful life events, and satisfaction with social support in relation to mood disturbance among women living with breast cancer in rural communities.

This study evaluated the relationships of emotional self-efficacy, stressful life events, and social support with mood disturbance among women diagnosed with breast cancer who live in rural communities. Eighty-two women completed measures of demographic characteristics, medical status, and psychosocial variables. Using multiple regression analysis, we found that greater mood disturbance was related to having less emotional self-efficacy (p < 0.001) and to having experienced more stressful life events (p = 0.02), while satisfaction with social support was not significantly related to mood disturbance (adjusted R2 = 0.39). Women living with breast cancer in rural communities who have experienced multiple stressful life events may have an increased risk for mood disturbance, whereas having greater emotional self-efficacy may provide resilience against mood disturbance.

Suicide in mental health in-patients and within 3 months of discharge. National clinical survey.

BACKGROUND: Suicide prevention is a health service priority. Suicide risk may be greatest during psychiatric in-patient admission and following discharge. AIMS: To describe the social and clinical characteristics of a comprehensive sample of in-patient and post-discharge cases of suicide. METHOD: A national clinical survey based on a 4-year (1996-2000) sample of cases of suicide in England and Wales who had been in recent contact with mental health services (n=4859). RESULTS: There were 754 (16%) current in-patients and a further 1100 (23%) had been discharged from psychiatric in-patient care less than 3 months before death. Nearly a quarter of the in-patient deaths occurred within the first 7 days of admission; 236 (31%) occurred on the ward, the majority by hanging. Post-discharge suicide was most frequent in the first 2 weeks after leaving hospital; the highest number occurred on the first day. CONCLUSIONS: Suicide might be prevented among in-patients by improving ward design and removing fixtures that can be used in hanging. Prevention of suicide after discharge requires early community follow-up and closer supervision of high-risk patients.

Suicide within 12 months of mental health service contact in different age and diagnostic groups: National clinical survey.

BACKGROUND: Suicide prevention is a health service priority but the most effective approaches to prevention may differ between different patient groups. AIMS: To describe social and clinical characteristics in cases of suicide from different age and diagnostic groups. METHOD: A national clinical survey of a 4-year (1996-2000) sample of cases of suicide in England and Wales where there had been recent (<1 year) contact with mental health services (n=4859). RESULTS: Deaths of young patients were characterised by jumping from a height or in front of a vehicle, schizophrenia, personality disorder, unemployment and substance misuse. In older patients, drowning, depression, living alone, physical illness, recent bereavement and suicide pacts were more common. People with schizophrenia were often in-patients and died by violent means. About a third of people with depressive disorder died within a year of illness onset. Those with substance dependence or personality disorder had high rates of disengagement from services. CONCLUSIONS: Prevention measures likely to benefit young people include targeting schizophrenia, dual diagnosis and loss of service contact; those aimed at depression, isolation and physical ill-health should have more effect on elderly people.

Rates of mental disorder in people convicted of homicide. National clinical survey.

BACKGROUND: Previous studies of people convicted of homicide have used different definitions of mental disorder. AIMS: To estimate the rate of mental disorder in people convicted of homicide; to examine the relationship between definitions, verdict and outcome in court. METHOD: A national clinical survey of people convicted of homicide (n=1594) in England and Wales (1996-1999). Rates of mental disorder were estimated based on: lifetime diagnosis, mental illness at the time of the offence, contact with psychiatric services, diminished responsibility verdict and hospital disposal. RESULTS: Of the 1594,545 (34%) had a mental disorder: most had not attended psychiatric services; 85 (5%) had schizophrenia (lifetime); 164 (10%) had symptoms of mental illness at the time of the offence; 149 (9%) received a diminished responsibility verdict and 111 (7%) a hospital disposal - both were associated with severe mental illness and symptoms of psychosis. CONCLUSIONS: The findings suggest an association between schizophrenia and conviction for homicide. Most perpetrators with a history of mental disorder were not acutely ill or under mental healthcare at the time of the offence. Some perpetrators receive prison sentences despite having severe mental illness.

Clustering of suicides among people with mental illness.

BACKGROUND: Most previous investigations of imitative suicide have reported suicide clustering in the general population, either temporal clustering following media reporting of suicide or case studies of geographically localised clusters. AIMS: To determine whether space - time and space-time-method clustering occur in a national case register of those who had recent contact with mental health services and had died by suicide and to estimate the suicide imitation rate in this population. METHOD: Knox tests were used for space-time and space-time-method clustering. Model simulations were used to estimate effect size. RESULTS: Highly significant space-time and space-time-method clustering was found in a sample of 2741 people who died by suicide over 4 years who had had recent contact with one of 105 mental health trusts. Model simulations with an imitation rate of 10.1% (CI 4-17) reproduced the observed space-time-method clustering. CONCLUSIONS: This study provides indirect evidence that imitative suicide occurs among people with mental illnesses and may account for about 10% of suicides by current and recent patients.