Effects of improved early-life conditions on health, welfare, and performance of pigs raised on a conventional farm.

Nowadays, most pigs are raised indoors, on intensive farms providing a poor environment. In these conditions, the risk of the occurrence of damaging behaviours is high, with dramatic consequences for animal health and welfare as well as economic losses for farmers. Early-life conditions may predispose individuals to develop damaging behaviours later in life. In contrast, reinforcing affiliative behaviours between piglets before weaning might help to prevent tail-biting episodes. In this field study, we aimed at improving early-life conditions of piglets on a commercial farm by completely suppressing painful procedures and staggering their exposure to weaning stress factors. The alternative early-life management strategy combined housing in free-farrowing pens with temporary crating of the sow, socialisation during the lactation period with whole-life maintenance of the hierarchical groups, and delayed transfer to the postweaning room after sow removal. Control conditions included birth in farrowing crates, tail docking, absence of socialisation during the lactation period, abrupt weaning with immediate transfer to the postweaning room and mixing with non-littermates. We evaluated the health, welfare, and performance of alternatively raised pigs (n = 80) as compared to controls (n = 75). Visits were made throughout the lifespan of individuals to evaluate their growth and health status. Body and tail lesions were scored as proxy measures of aggressiveness and impaired welfare. Blood and bristle samples were periodically collected to evaluate stress, inflammation and immune competence. While the whole-life performance of pigs was similar among groups, the alternative early-life conditions prevented the growth slowdown usually observed after weaning. In addition, alternatively raised pigs displayed more neutrophils, eosinophils and monocytes the day after weaning, as well as higher C-Reactive Protein levels. One week later, their monocytes displayed greater phagocytic capacity. Altogether, these data suggest an enhanced innate immune competence for alternatively raised pigs around weaning. Piglets reared under alternative conditions also exhibited fewer and less severe body lesions than standard pigs, one week after weaning. In contrast, they showed more tail lesions on days 36 and 66 associated with greater levels of acute phase proteins (C-Reactive Protein and haptoglobin). To conclude, alternative early-life management better prepared piglets for weaning. However, the whole-life maintenance of early-established social groups was not sufficient to prevent the occurrence of damaging behaviours in undocked pigs.

Depression and exposure to violence among Venda and Northern Sotho adolescents in South Africa.

OBJECTIVE: Despite the high levels of violence in South Africa, a lacunae in research exists regarding the influence of violence exposure on children. This study investigated the correlation between children's exposure to violence and the development of psychological problems such as depression. METHOD: 186 Venda and 151 Northern Sotho adolescents were studied in a questionnaire survey to determine this relationship. Two measuring instruments were used: The Children's Depression Inventory and the Child Exposure to Violence Form. RESULTS: When comparing gender, no significant differences were found in terms of overall exposure to violence between males and females. For depression, the total group of girls had a remarkably higher prevalence of depression. Regarding ethnic comparison, no significant differences were found in terms of overall exposure to violence or for witnessed events. However, the Venda adolescents had been victims significantly more often. Venda and Northern Sotho females had a similar prevalence of depression, but Northern Sotho boys had a higher depression rate than Venda boys. The correlation between victimisation and total group depression was relatively low for the Northern Sotho group, and non-existent for the Venda group. A significant correlation was found between total exposure to violence and depression for the overall group. CONCLUSION: This study indicates that adolescents' exposure to violence and subsequent mental health is an area of concern. However, adolescents could be taught effective coping and problem-solving techniques in schools to help empower them against stressors they might encounter.

Fetal calf serum-primed dendritic cells induce a strong anti-fetal calf serum immune response and diabetes protection in the non-obese diabetic mouse.

In recent years, several investigators have shown that transfer of dendritic cells (DC) prevents diabetes development in non-obese diabetic (NOD) mice. Accumulating evidences showing that DC cultured in medium containing fetal calf serum (FCS) can induce a dominant unspecific immune response in tumor models after i.v. injection prompted us to investigate if the protecting effect of DC on diabetes development in NOD mice might be supported by the induction of an anti-FCS immune response in recipient mice. Five-week-old NOD mice were injected i.v. with FCS-cultured bone marrow-derived DC or PBS as control. Levels of anti-FCS and anti-bovine serum albumin (BSA) antibodies were measured in the serum of recipient mice. Anti-FCS cellular immune responses were also analysed after a single DC injection using in vitro proliferation of splenocytes either in RPMI supplemented with FCS, AIMV-BSA or RPMI containing autologous mouse serum or BSA as a read out. DC injection prevented diabetes development in NOD mice and high titers of anti-FCS and anti-BSA antibodies were detected in serum of all DC-injected mice. Besides, splenocytes isolated from DC-injected mice proliferated vigorously in the presence of bovine proteins in contrast to splenocytes isolated from control mice but removing bovine proteins abrogated the high level of proliferation of those splenocytes suggesting that lymphocytes have been primed against bovine proteins in vivo after DC injection. All together, our data show that DC transfer induced cellular and humoral anti-FCS immune responses in recipient NOD mice suggesting that the protective effect of DC relies on their unspecific immunostimulatory effects.

Lymphocytic insulitis in a juvenile dog with diabetes mellitus.

Autoimmune diabetes has never been described in a juvenile dog, whereas serological evidence has established its development in adult dogs. Diabetes mellitus was diagnosed in a 3-mo-old Donge de Bordeaux dog suffering from persistent hyperglycemia and concurrent insulinopenia. Histological analysis of the pancreas revealed inflammatory lesions in 40% of the islets of Langerhans, with infiltration predominantly by T lymphocytes (more than 90%), either at the edge (peri-insulitis: 10%) or in the islets (insulitis: 30%). The remaining 60% of the islets showed a marked atrophy due to massive beta cell loss with no loss of alpha cells. This pattern is quite similar to that observed in humans in which a characteristic insulitis containing high numbers of T lymphocytes is found in 20% of the islets at diabetes diagnosis. By contrast, in rodent models, nearly 70% of the islets of Langerhans show inflammation at diagnosis and macrophages and dendritic cells predominate in the inflammatory lesions. This is the first report of lymphocytic insulitis in a juvenile dog exhibiting diabetes mellitus. Our observations suggest an autoimmune origin for the disease in this dog that is similar to human type 1 diabetes mellitus, for which there is no accurate spontaneous large animal model.

Protection against Leptospira interrogans sensu lato challenge by DNA immunization with the gene encoding hemolysin-associated protein 1.

The use of DNA constructs encoding leptospiral proteins is a promising new approach for vaccination against leptospirosis. In previous work we determined that immunization with hemolysis-associated protein 1 (Hap1) (LipL32) expressed by adenovirus induced significant protection against a virulent Leptospira challenge in gerbils. To avoid the use of the adenovirus vector, we checked for clinical protection against lethal challenge by DNA vaccination. A DNA vaccine expressing Hap1 was designed to enhance the direct gene transfer of this protein into gerbils. A challenge was performed 3 weeks after the last immunization with a virulent strain of serovar canicola. Our results show that the cross-protective effect with pathogenic strains of Leptospira, shared by Hap1, could be mediated by the DNA plasmid vector. This finding should facilitate the design and development of a new generation of vaccines against bacteria, particularly Leptospira interrogans sensu lato.

Functional canine dendritic cells can be generated in vitro from peripheral blood mononuclear cells and contain a cytoplasmic ultrastructural marker.

For physiological and practical reasons the dog is a large animal model used increasingly to study the pathogenesis of human diseases and new therapeutic approaches, in particular for immune disorders. However, some immunological resources are lacking in this model, especially concerning dendritic cells. The aim of our study was to develop an efficient method to generate dendritic cells (DC) in vitro from dog peripheral blood mononuclear cells (PBMC) and to characterize their functional, structural and ultrastructural properties. PBMC were cultured in vitro with IL-4 and GM-CSF. After 1 week of culture, a great proportion of non-adherent cells displayed typical cytoplasmic processes, as evidenced both by optical and electron microscopy. Cytometric analysis revealed the presence of 41.7+/-24.6% CD14+ cells expressing both CD11c and MHC class II molecules. Allogeneic mixed lymphocyte reactions confirmed the ability of these cultures to stimulate the proliferation of allogeneic lymphocytes as already reported as a characteristic of DC in other species. In addition, we describe for the first time the presence in canine DC of cytoplasmic periodic microstructures (PMS) that could represent ultrastructural markers of canine DC. In conclusion, our study provides an easy method to generate DC from PBMC in sufficient numbers for immunological in vitro investigations in dogs, a pre-clinical model for many human diseases.

DNA vaccination encoding glutamic acid decarboxylase can enhance insulitis and diabetes in correlation with a specific Th2/3 CD4 T cell response in non-obese diabetic mice.

DNA vaccination encoding beta cell autoantigens has been shown very recently to prevent type I diabetes in non-obese diabetic (NOD) mice. However, DNA vaccination encoding microbial or reporter antigens is known to induce specific long-lasting CD4 Th1 and strong cytolytic CD8 T cell responses. As this immune phenotype is associated strongly with beta cell destruction leading to diabetes, we have chosen to study the effects of plasmids encoding glutamic acid decarboxylase (GAD), a crucial beta cell autoantigen, in female NOD mice that developed a 'moderate' diabetes incidence. In the present study, 3-week-old female NOD mice were vaccinated twice in tibialis muscles with plasmid-DNA encoding 65-kDa GAD or betagalactosidase. In GAD-DNA immunized mice, diabetes cumulative incidence (P < 3.10(-3)) and insulitis (P < 7.10(-3)) increased significantly. Simultaneously, DNA immunization induced GAD-specific CD4 T cells secreting interleukin (IL)-4 (P < 0.05) and transforming growth factor (TGF)-beta (P = 0.03). These cells were detected in spleen and in pancreatic lymph nodes. Furthermore, vaccination produced high amounts of Th2 cytokine-related IgG1 (P < 3.10(-3)) and TGF-beta-related IgG2b to GAD (P = 0.015). Surprisingly, diabetes onset was correlated positively with Th2-related GAD-specific IgG1 (P < 10(-4)) and TGF-beta-related IgG2b (P < 3.10(-3)). Moreover, pancreatic lesions resembled Th2-related allergic inflammation. These results indicate, for the first time, that GAD-DNA vaccination could increase insulitis and diabetes in NOD mice. In addition, our study suggests that Th2/3 cells may have potentiated beta cell injury.

Axial and rotational alignment of the leg.

The axial and rotational alignments of the lower extremity are commonly referenced independently, with minimal research on whether coexistent axial and rotational malalignment cause pathologies. The present study analyzed whether a correlation exists between the axial and rotational alignments of the leg. The methodology to measure both alignments was adapted for computer tomography. Fifty patients were analyzed at five reference images to determine axial and rotational alignment. The reference images included the femoral head, the femoral shaft (at the level of the lesser trochanter), the distal femur, the proximal tibia, and the ankle joint. Axial alignment was calculated by using horizontal and vertical measurements of the location of the femoral head, the distal femur, and the ankle joint. Rotational alignments of femur, knee, and tibia were calculated using four angles: proximal femoral, distal femoral, proximal tibial, and ankle joint angles defined relative to a fixed reference. Pearson correlation analysis between axial alignment and the three mentioned rotational alignments were calculated. The correlation coefficient values ranged between -0.15-0.07 when comparing axial to rotational alignment, indicating that a week correlation exists between the two alignments. Though these results were derived using highly reproducible methods, the hypothesis of an existing correlation between the axial and rotational alignments of the leg was rejected. These findings allow for an improved understanding of lower extremity mechanics, which merit importance when considering pathologies of the leg and the surgical techniques that could ultimately benefit patients suffering from these pathologies.

Flexor muscle incursion into the carpal tunnel: a mechanism for increased carpal tunnel pressure?

PURPOSE: To explore the hypothesis that the extrinsic finger flexor muscles have the potential to move into the proximal end of the carpal tunnel with wrist extension. METHODS: The most distal muscle fibres from the deep and superficial finger flexors were measured relative to the pisiform bone in 18 cadaveric specimens. Muscle excursions during wrist extension were calculated using regression equations previously reported in the literature. RESULTS: The mean distances from the pisiform were 9.3 and 4.9 mm for the deep and superficial flexors, respectively. Ten flexor muscle bellies were at the level of or distal to the pisiform bone in the anatomical position, while 17 of 36 were within 5 mm. DISCUSSION: The excursions expected with wrist extension indicate that many muscles have the potential to enter the carpal tunnel, especially those within 5 mm of the pisiform bone. Comparing the expected excursions to recent pressure data, corroborating support for the pressure increase is found. CONCLUSION: Although not directly measured, the results of this study indicate incursion of the flexor muscles into the carpal tunnel space, particularly with wrist extension, is a plausible mechanism for increased carpal tunnel pressure. RELEVANCE: Proposing a mechanism by which carpal tunnel pressure is elevated during wrist and finger extension is a stepping stone to determining the etiology of the disease itself. Finding that the flexor muscle bellies appear to enter the carpal tunnel with wrist extension indicates that use of the flexor muscles should be avoided when the wrist and fingers are extended.

An in vitro biomechanical investigation of an equine interlocking nail.

OBJECTIVE: To determine the mechanical properties of Equine Interlocking Nail (EIN; JD Wheat Veterinary Orthopedic Research Laboratory, University of California, Davis) stabilized osteotomized tibiae and compare these variables with estimated in vivo loads. STUDY DESIGN: In vitro biomechanical investigation. ANIMALS: Twelve adult equine cadaveric tibiae. SAMPLE POPULATION: EIN-stabilized tibiae were tested monotonically under compression, 3- and 4-point bending, and torsion. Mechanical properties were compared with estimated in vivo loads. RESULTS: EIN-tibial composite mean compressive yield load (11 kN) and bending moment (216 Nm) were greater than loads expected postoperatively in vivo; however, the mean torsional yield load (156 Nm) was less than that expected in vivo. CONCLUSIONS: EIN-stabilized tibiae had compressive and bending strengths greater than those expected to maintain stability during walking in adult horses. Torsional yield strength did not appear sufficient to provide stability during walking in vivo. CLINICAL RELEVANCE: The EIN is not a feasible method of fracture repair for adult equine tibial fractures at this time, because its mechanical properties appear inadequate to withstand the postoperative torsional loads encountered during walking. Because this method of fracture repair may offer biological advantages, further modification of an interlocking nail for adult horses appears warranted.

Effects of computer mouse design and task on carpal tunnel pressure.

Computer mouse use has become an integral part of office work in the past decade. Intensive mouse use has been associated with increased risk of upper extremity musculoskeletal disorders, including carpal tunnel syndrome. Sustained, elevated fluid pressure in the carpal tunnel may play a role in the pathophysiology of carpal tunnel syndrome. Carpal tunnel pressure was measured in 14 healthy individuals while they performed tasks using three different computer mice. Participants performed a multidirectional dragging ('drag and drop') task starting with the hand resting (static posture) on the mouse. With one mouse, an additional pointing ('point-and-click') task was performed. All mice were associated with similar wrist extension postures (p = 0.41) and carpal tunnel pressures (p = 0.48). Pressures were significantly greater during dragging and pointing tasks than when resting the hand (static posture) on the mouse (p = 0.003). The mean pressures during the dragging tasks were 28.8-33.1 mmHg, approximately 12 mmHg greater than the static postures. Pressures during the dragging task were higher than the pointing task (33.1 versus 28.0 mmHg), although the difference was borderline non-significant (p = 0.06). In many participants the carpal tunnel pressures measured during mouse use were greater than pressures known to alter nerve function and structure, indicating that jobs with long periods of intensive mouse use may be at an increased risk of median mononeuropathy. A recommendation is made to minimize wrist extension, minimize prolonged dragging tasks and frequently perform other tasks with the mousing hand.

Analysis of major repetitive DNA sequences in the dog (Canis familiaris) genome.

A systematic screening and analysis of repeated DNA sequences from a dog genomic library composed of small DNA inserts enabled us to characterize abundant canine repetitive DNA families. Four main families were identified: i) a group of highly repeated tRNA-derived short interspersed repetitive DNA elements (tRNA-SINEs); ii) another type of SINE-like element that was mainly found inserted into long interspersed repetitive elements (LINEs); iii) LINEs of the L1 type; and iv) satellite or satellite-like DNA. Surprisingly, no SINEs derived from 7SL RNA were found in the dog genome. These data should help in the analysis of canine DNA sequences and in the design of canine genome mapping reagents.

Effects of finger posture on carpal tunnel pressure during wrist motion.

Persistent elevations in carpal tunnel pressure may aggravate carpal tunnel syndrome. This study examined the effects of finger posture on carpal tunnel pressure during wrist motion. Carpal tunnel hydrostatic pressure was measured using a saline-filled catheter inserted into the nondominant wrists of 14 healthy individuals. Range of motion tasks of wrist flexion-extension and radioulnar deviation were repeated with metacarpophalangeal (MCP) joint angles of 0 degrees, 45 degrees, and 90 degrees flexion. Pressures were significantly greater with the fingers straight (MCP = 0 degrees) than when the MCP joints were flexed to 45 degrees for all radioulnar deviation angles and from 10 degrees of wrist flexion to all angles of wrist extension tested. Pressures were also significantly higher with MCP joints at 0 degrees than at 90 degrees for wrist extension angles from 10 degrees to 40 degrees. Pressures increased to over 30 mm Hg (4.0 kPa) in some wrist extension and ulnar and radially deviated postures. Finger and wrist postures should be considered when designing splints or evaluating tasks for patients with carpal tunnel syndrome.

Identification of mimicry peptides based on sequential motifs of epitopes derived from 65-kDa glutamic acid decarboxylase.

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease with a predominantly non-hereditary etiology that results in a destruction of pancreatic beta cells by autoaggressive T lymphocytes. Neither the mechanism of initial stimulation of these T cells nor the nature of the environmental factors implicated in the disease have so far been identified. However, both issues are taken into account by the hypothesis of initial T cell activation by viral or bacterial mimicry peptides with sequence similarities to pancreatic self antigens. We determined sequential epitope motifs to search for mimicry peptides stimulating T cell lines specific for two epitopes derived from the IDDM autoantigen 65-kDa glutamic acid decarboxylase (GAD65). These were GAD65 (88-99), presented by HLA-DRB1*0101, and GAD65 (248-257), presented by HLA-DRB5*0101. T cell stimulation by peptides with substitutions in HLA anchor or T cell contact positions was analyzed to establish degenerate epitope motifs for database searching. Out of 28 tested candidate mimicry peptides derived from bacterial, viral and human proteins, 3 stimulated T cell lines and a T cell clone specific for epitope GAD65 (248-257). Our results demonstrate that mono- and polyclonal GAD65-specific T cells from IDDM patients can be stimulated by viral and bacterial peptides with little apparent sequence homology with autoantigenic epitopes. Moreover, in a synopsis with related published studies, our findings suggest that simple degenerate search motifs comprising principal T cell contacts plus HLA class II binding motifs may suffice to identify most mimicry peptides.

Fingertip loading and carpal tunnel pressure: differences between a pinching and a pressing task.

Carpal tunnel syndrome may be caused by repeated or sustained elevated carpal tunnel pressure. This study examined the relationship between carpal tunnel pressure, posture, and fingertip load. In 20 healthy individuals, carpal tunnel pressure was measured with a catheter inserted into the carpal tunnel of the dominant hand and connected to a pressure transducer. With the wrist in a pressure-neutral position, the subjects pressed on a force transducer with the index finger to levels of 0, 5, 10, and 15 N. They then pinched the transducer at the same levels of force. For both fingertip-loading postures, the carpal tunnel pressure increased with increasing fingertip load. Carpal tunnel pressures were significantly greater (p < 0.015) for the pinching task (14.2, 29.9, 41.9, and 49.7 mm Hg [1.89, 3.99, 5.59, and 6.63 kPa] for 0, 5, 10, and 15 N force levels, respectively) than for simple finger pressing (7.8, 14.1, 20.0, and 33.8 mm Hg [1.04, 1.88, 2.67, and 4.51 kPa]). This study indicates that although the external load on the finger remained constant between the two tasks, the internal loading, as measured by carpal tunnel pressure, experienced a near 2-fold increase by using a pinch grip. These findings should be given consideration in designing work tasks and tools because relatively low fingertip forces, especially in a pinch grip, elevate carpal tunnel pressures to levels that, if prolonged, may lead to the development or exacerbation of carpal tunnel syndrome.

Effects of forearm pronation/supination on carpal tunnel pressure.

The effects of forearm rotation and metacarpophalangeal (MP) flexion on carpal tunnel pressure were investigated in 17 healthy adults who had no evidence of carpal tunnel syndrome (CTS). Pressure was continuously recorded with a saline-filled catheter inserted into the carpal tunnel and connected to a pressure transducer while test subjects slowly rotated the forearm from full pronation to full supination. Forearm rotation was repeated with MP flexion of 0 degrees, 45 degrees, and 90 degrees. Both forearm rotation and MP flexion, and their interaction term, significantly affected carpal tunnel pressure and accounted for most of the variability in the data. Highest mean pressures (55 mmHg) were recorded in full supination and 90 degrees MP flexion and lowest pressures (12 mmHg) were recorded at 45 degrees pronation and 45 degrees MP flexion. These data may be useful in the design of tasks and hand tools in the management and prevention of CTS.

Strain inhomogeneity in the anterior cruciate ligament under application of external and muscular loads.

To determine whether mathematical relations between strains in different bundles and loads would be needed to predict injury of the anterior cruciate ligament (ACL), this work tested the hypothesis that strains developed in two bundles of the ACL were significantly different under the application of a number of loads important to injury etiology of the ACL. To provide the data for testing this hypothesis, liquid mercury strain gages were installed on both the anteromedial (AMB) and posterolateral (PLB) bundles of the ACL of ten specimens, which were then subjected to passive flexion/extension, hyperextension moment, anterior force, internal and external axial moments, quadriceps, and hamstrings forces. Various combinations of these loads were also applied. Flexion angles ranged from 8 deg of hyperextension through 120 deg of flexion. The data were analyzed using a repeated measures analysis of variance. The analyses indicated that significant strain differences existed between the two bundles only for passive flexion/extension. However, the analyses did not support the hypothesis that AMB and PLB strains are significantly different from each other under the application of external and muscular loads. Because noticeable differences (> 3 percent) between bundle strains did exist in some load cases for limited ranges of flexion and the PLB strain was consistently higher than the AMB strain, it may be sufficient to consider strain in only the PLB when predicting ligament damage based on strain-load relations.