Postpartum dysgalactia syndrome in sows: effects on behavior of sows and piglets.

BACKGROUND: To investigate if specific sow and piglet behavioral characteristics could be used diagnostically, this case-cohort study of the behavior of sows and piglets during the periparturient period (from 24 h before the birth of first piglet to 24 h after the birth of last piglet) was conducted. Data included 32 sows diagnosed with PDS (PDS+) vs. 37 healthy matched controls (PDS-) and their litters. RESULTS: A significant change from active behavior with many postural changes to a more passive behavior was noted in connection with parturition. Sow nesting behavior was less frequent in PDS+ sows compared to PDS- sows during (p = 0.04) and after parturition (p = 0.0004). No difference was found between PDS+ and PDS- in the number of postural changes, interval from last time standing to the birth of the first piglet, interval from last time eating/drinking to the birth of the first piglet, interval from the birth of the first piglet to the sow standing after farrowing, interval from the birth of the last piglet until eating/drinking, occurrence of bar biting, or frequency or duration of eating/drinking during the observation period. Piglets of PDS+ sows stayed outside the creep areas more often than piglets of PDS- sows (p < 0.0001), but there was no difference in the mean number of piglets observed massaging the udder every 10 min. CONCLUSION: These results confirm that sow behavior changes from active before parturition to more passive after parturition. Being diagnosed with PDS affected the periparturient behavior of sows as well as their piglets. The observed reduction in nesting behavior in PDS+ sows may suggest that a highly motivated piglet-oriented behavior was affected. However, classical sickness behaviors like lethargy and passivity seem to be poor markers for PDS.

Gross and histopathological evaluation of umbilical outpouchings in pigs.

Clinical presentations of umbilical outpouchings (UOs) in pigs cover a variety of pathological manifestations. Pigs with UOs often do not reach the abattoir as they die due to complications or are euthanized for welfare concerns. The primary objective was to characterize the gross appearance of UOs in pigs with respect to the different types of pathological manifestations. Also the association between the pathological manifestation and presence of a wound on the UO was evaluated. Pigs (in different age groups, n = 444) with an UO were sampled in Denmark from different locations (two herds and at an abattoir) and examined post mortem. Tissue samples from animals with an enterocystoma or internal umbilical proliferations were collected for histological and immunohistochemical characterization. Hernia umbilicalis was the most frequent cause (72%, n = 320) of the UOs. It was the only diagnosis in 57% (n = 254) of the pigs, and in 15% (n = 66) of the pigs the hernia appeared in combination with other manifestations. Thus, 28% (n = 124) of the pigs were diagnosed with an enterocystoma, internal umbilical proliferations, subcutaneous abscess/ fibrosis or another diagnosis, presented alone or in combination. The distribution of diagnoses varied in the different age groups. Overall, 38% (110/291) of the pigs presented a wound on the UOs post mortem. The age of the pigs confounded the relation between the pathological manifestation and the presence of a wound. The odds that an UO had a wound were lower among pigs with a subcutaneous abscess/ fibrosis compared to pigs diagnosed with an umbilical hernia or enterocystoma (OR, 0.3; 95% Cl, 0.1-0.7). The odds of wounds were higher among weaners (OR, 4.3; 95% Cl 2.3-8.3) and finishers (OR, 6.5; 95% Cl, 3.4-12.7) compared with piglets from the farrowing unit. The area of wounds ranged from 0.03 to 78.5 cm2 and increased with age (P < 0.001). Histologically and immunohistochemically the enterocystomas and internal umbilical proliferations seemed to be lined with mesothelial cells and both had a content comparable with mesenchymal embryonic connective tissue. However, only the cavities of the enterocystomas were also lined with mesothelial cells. In conclusion, UOs in pigs are caused by complex pathological conditions with hernia umbilicalis as the dominating diagnosis. Knowledge clarifying the different pathological manifestations causing an UO and the presence of wounds on the UOs is essential for future prevention strategies.

Survival of pigs with different characteristics of umbilical outpouching in a prospective cohort study of Danish pigs.

Umbilical hernia and other conditions clinically evident as umbilical outpouchings (UOs) affect the welfare and economy in Danish pig production. The objectives of the current study were to characterize the associations between 1) time of detection of the UOs and the odds of dying before scheduled slaughter; 2) time of death, irrespective of the cause, and clinical signs of the UOs, i.e. general condition, size, reducibility, form and skin-color of the UOs; and 3) occurrence of wounds on the UOs and clinical signs: general condition, size, reducibility, form and skin-color. A cohort of Danish conventional pigs with UOs (n = 255) were followed from the detection of an UO until spontaneous death, euthanization or slaughter of the pig. The pigs were clinically examined once a month, and when pigs with an UO died spontaneously, were euthanized or slaughtered, the causes and date of death were recorded. The effects of the clinical manifestations on overall survival were assessed using a Cox proportional hazards model. In total 57 % of the pigs died spontaneously or were euthanized before slaughter. The median age of spontaneous death or euthanasia was 85 days. The UOs were detected at different ages, with half of the pigs (52 %) detected in the farrowing section. No significant association was found between death before scheduled slaughter and the time of detection. Three different clinical manifestations were found to have a prognostic value for overall survival until slaughter, i.e. skin-color of the UO, a general condition of the pig and the size of the UO. An interaction was present between the size and the skin-color of the UO. Wounds on the UO were the most frequent complication resulting in euthanasia (37 %). The odds for developing a wound on the UO were higher for pigs in a general bad condition compared to pigs in a good condition (OR, 5.4; 95 % CL 2.5-11.3), and for pigs with an UO large in size compared to pigs with a small UO (OR, 4.8; 95 % CL 3.0-7.5). The identification of prognostic clinical signs in pigs with an UO is useful in the assessment and decision-making in relation to the future prospects of pigs with UOs.

Effect of two methods and two anaesthetics for local anaesthesia of piglets during castration.

BACKGROUND: Since January 2019, surgical castration of male piglets must be performed using local anaesthesia, if farmers deliver pigs to the primary exporting slaughterhouses according to the "Danish quality scheme"; a voluntary initiative taken by the Danish pig industry. The approved procedure for local anaesthesia in Denmark is a three-step injection method with procaine. A comparison of lidocaine and procaine with the same concentration and injection methods of local anaesthetics has not previously been studied. The purpose of this study was to investigate the effect of two injection methods and two local anaesthetics on piglets' avoidance behaviour (vocalisation and resistance movements) as well as the time spent on the procedures. The study included 203 male piglets that were randomly assigned to one of five treatments: 1. CONTROL: Sham-handling without injection of local anaesthesia, 2. Pro3: Procaine injection using a three-step method, 3. Pro2: Procaine injection using a two-step method, 4. Lid3: Lidocaine injection using a three-step method, 5. Lid2: Lidocaine injection using a two-step method. During injection of local anaesthesia and castration, vocalisation was measured using a decibel meter and resistance movements were registrated by video recordings. RESULTS: During castration, piglets treated with local anaesthesia showed significantly reduced vocalisation and resistance movements and time spent on castration was also significantly reduced compared to the control group. During injection of the local anaesthesia, the piglets had significantly increased vocalisation and resistance movements compared to the control group. Piglets injected with lidocaine had a significantly reduced resistance movement score and a tendency to reduced vocalisation compared to piglets injected with procaine. No differences in avoidance behaviour were found between the injection methods. CONCLUSIONS: The use of local anaesthesia, irrespective of the method and local anaesthetic, was effective in reducing vocalisation and resistance movements during surgery as well as the time spent on castration.

A Novel Mutation of the Calcium-Sensing Receptor Gene Causing Familial Hypocalciuric Hypercalcemia Complicates Medical Followup after Roux-en-Y Gastric Bypass: A Case Report and a Summary of Mutations Found in the Same Hospital Laboratory.

Heterozygous inactivating mutations in the calcium-sensing receptor (CaSR) gene are known to cause familial hypocalciuric hypercalcemia (FHH), usually a benign form of hypercalcemia without symptoms of a disrupted calcium homeostasis. FHH can be mistaken for the more common primary hyperparathyroidism (PHPT), for which surgical treatment may be needed. We describe a case of a 36-year-old woman with hypercalcemia and elevated PTH, initially suspected of having PHPT. Sequencing of the CaSR-gene revealed a mutation in nucleotide 437, changing the amino acid in position 146 from Glycine to Aspartate. The mutation was previously undescribed in the literature, but a very low calcium:creatinine clearance ratio supported the diagnosis FHH. A few years later, the patient's two daughters were tested and the association between mutation and hypercalcemia could be confirmed. The patient was gastric bypass-operated and therefore, due to malabsorption and increased risk of fracture, was in need of adequate calcium supplementation. The chronically elevated calcium levels challenged medical followup, as calcium sufficiency could not be monitored in a traditional manner. Eventually the patient developed elevated alkaline phosphatase, a further increased PTH and a decreased DXA T-score indicating calcium deficiency and bone resorption. As a supplement, all CaSR-mutations found at our hospital, 2005-2018.

Duroc boars have lower progeny mortality and lower fertility than Pietrain boars.

In pig production, Pietrain and Duroc lines are often used as terminal sire lines to produce crossbred slaughter pigs. The objective of this study was to identify the differences in paternal fertility and mortality during the suckling period of crossbred progeny from Pietrain and Duroc terminal sire lines. In total, 87 purebred Duroc boars and 68 purebred Pietrain boars were used as terminal sires to produce 1,823 crossbred Duroc litters (D-litters) and 1,705 crossbred Pietrain litters (P-litters) in two production herds. The sows were crosses between DanBred Landrace and Yorkshire (F1). All boars were kept at the same artificial insemination (AI) station, and all semen doses were produced in the same laboratory. The experiment was balanced according to herd, boars, and time, with approximately 13 sows from each herd mated to each boar within each breed. The results showed higher fertility expressed as litter size at birth in P-litters compared with D-litters led to 0.5 higher total number born (TNB) for P-litters (P = 0.0076). However, piglet mortality including number of stillborn piglets was lower in D-litters compared with P-litters (P < 0.0001), and 5 d after farrowing, the average litter size in P-litters ranged 0.4 below the litter size in D-litters (P < 0.027). At 21 d after birth, mean litter size in P- and D-litters were 14.5 and 14.9 piglets per litter, respectively (P < 0.015). This indicated that Pietrain progenies were weaker than Duroc progenies, and it was concluded that use of Duroc boars as the terminal sire line led to lower piglet mortality. In the two herds, the mean piglet mortality rate including still born piglets ranged from 19.5% to 23.6% and from 17.6% to 19.1% in P- and D-litters, respectively.

TAILOR - tapered discontinuation versus maintenance therapy of antipsychotic medication in patients with newly diagnosed schizophrenia or persistent delusional disorder in remission of psychotic symptoms: study protocol for a randomized clinical trial.

BACKGROUND: The aim of the TAILOR trial is to investigate the effect of closely monitored tapering/discontinuation versus maintenance therapy with antipsychotic medication in patients with newly diagnosed schizophrenia or persistent delusional disorder and with minimum 3 months' remission of psychotic symptoms. METHODS AND DESIGN: Two hundred and fifty patients will be included from the psychiatric early intervention program, OPUS, in two regions in Denmark. Inclusion criteria are: ICD-10 diagnoses schizophrenia (F20, except F20.6) or persistent delusional disorder (F22), minimum 3 months' remission of psychotic symptoms and in treatment with antipsychotic medication (except clozapine). The patients will be randomized to maintenance therapy or tapering/discontinuation with antipsychotic medication in a 1-year intervention. The tapering/discontinuation group will be using a smartphone application to monitor early warning signs of psychotic relapse. Patients will be assessed at baseline, 1-, 2- and 5-year follow-up regarding psychotic and negative symptoms, side-effects of antipsychotic medication, social functioning, cognitive functioning, perceived health status, patient satisfaction, substance and alcohol use, sexual functioning and quality of life. The primary outcome will be remission of psychotic symptoms and no antipsychotic medication after 1 year. Secondary outcome measures will include: co-occurrence of remission of psychotic symptoms and 0-1-mg haloperidol equivalents of antipsychotic medication after 1-year intervention; antipsychotic dose; antipsychotic side effects; negative symptoms; social functioning; cognitive functioning; and patient satisfaction. Exploratory outcomes will include remission, clinical recovery, substance and alcohol use, sexual functioning, quality of life, self-beliefs of coping and user experience of support from health workers. Safety measures will include death, admissions to psychiatric hospital, severe self-harm and psychotic relapses. DISCUSSION: The TAILOR trial will contribute knowledge about the effect of tapering/discontinuation of antipsychotic medication in the early phases of schizophrenia and related disorders and the results may guide future clinical treatment regimens of antipsychotic treatment. TRIAL REGISTRATION: EU Clinical Trials Register - EudraCT number: 2016-000565-23 . Registered on 5 February 2016.

Computer tomographic investigation of subcutaneous adipose tissue as an indicator of body composition.

BACKGROUND: Modern computer tomography (CT) equipment can be used to acquire whole-body data from large animals such as pigs in minutes or less. In some circumstances, computer assisted analysis of the resulting image data can identify and measure anatomical features. The thickness of subcutaneous adipose tissue at a specific site measured by ultrasound, is used in the pig industry to assess adiposity and inform management decisions that have an impact on reproduction, food conversion performance and sow longevity. The measurement site, called "P2", is used throughout the industry. We propose that CT can be used to measure subcutaneous adipose tissue thickness and identify novel measurement sites that can be used as predictors of general adiposity. METHODS: Growing pigs (N = 12), were each CT scanned on three occasions. From these data the total volume of adipose tissue was determined and expressed as a proportion of total volume (fat-index). A computer algorithm was used to determined 10,201 subcutaneous adipose thickness measurements in each pig for each scan. From these data, sites were selected where correlation with fat-index was optimal. RESULTS: Image analysis correctly identified the limits of the relevant tissues and automated measurements were successfully generated. Two sites on the animal were identified where there was optimal correlation with fat-index. The first of these was located 4 intercostal spaces cranial to the caudal extremity of the last rib, the other, a further 5 intercostal spaces cranially. CONCLUSION: The approach to image analysis reported permits the creation of various maps showing adipose thickness or correlation of thickness with other variables by location on the surface of the pig. The method identified novel adipose thickness measurement positions that are superior (as predictors of adiposity) to the site which is in current use. A similar approach could be used in other situations to quantify potential links between subcutaneous adiposity and disease or production traits.

Erythropoietin improves spatial delayed alternation in a T-maze in rats subjected to ablation of the prefrontal cortex.

Systemically administered human recombinant erythropoietin (EPO) may have the potential to reduce the cognitive and behavioural symptoms of mechanical brain injury. In a series of studies we address this possibility. Previously, we studied the effects of EPO given to fimbria-fornix transected rats at the moment of injury. We have found that such treatment improves substantially the posttraumatic acquisition of allocentric place learning tasks administered in a water maze and in an 8-arm radial maze as well as a spatial delayed alternation task administered in a T-maze. It is, however, essential also to evaluate this clinically important ability of EPO after other types of mechanical brain injury. Consequently, we presently studied the effects of similarly administered EPO in rats subjected to bilateral subpial aspiration of the anteromedial prefrontal cortex as well as control operated rats, respectively. We evaluated the posttraumatic behavioural/cognitive abilities of these animals in a spatial delayed alternation task performed in a T-maze. Administration of EPO to the prefrontally ablated rats was associated with a reduction of the lesion-associated behavioural impairment--while such an impairment was clearly seen in the saline injected prefrontally ablated group. In sham operated rats administration of EPO did not influence the task acquisition significantly. The results of the present study confirm our previous demonstrations that EPO is able to reduce the behavioural/cognitive consequences of mechanical brain injury. This ability is emphasized by its relative independence on the type of lesion as well as the neural structure affected.

The selective activation of the glutamate receptor GluR5 by ATPA is controlled by serine 741.

Only a few agonists exhibit selectivity between the AMPA and the kainate subtypes of the glutamate receptor. The most commonly used kainate receptor preferring agonist, (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid [(S)-ATPA], is an (R,S)-2-amino-3-(5-methyl-3-hydroxy-4-isoxazolyl)propionic acid (AMPA) derivative in which the methyl group at the 5-position of the isoxazole ring has been replaced by a tert-butyl group. When characterized by the two-electrode voltage clamp method in Xenopus laevis oocytes, ATPA exhibits at least 50-fold higher potency on the kainate receptor subtype, GluR5, compared with the AMPA receptors. Through mutagenesis studies of GluR5 and the AMPA receptor subtype, GluR1, we demonstrate that this pronounced selectivity for ATPA can be ascribed to Ser741 in GluR5 and Met722 in GluR1. Examination of other aliphatic substitutions at the 5-position of the isoxazole ring revealed that (R,S)-2-amino-3-(5-isopropyl-3-hydroxy-4-isoxazolyl)propionic acid (isopropyl-AMPA) displayed a 6-fold higher potency for GluR5 than for GluR1, whereas the analogs, propyl-AMPA and isobutyl-AMPA, did not exhibit significantly different potencies. Our study suggests that the GluR5 selectivity was a result not only of steric interference between the bulky tert-butyl group in ATPA and the methionine (Met722) in GluR1 but also a serine-dependent stabilization of the active conformation of GluR5 induced by ATPA. The stabilization was agonist-dependent and observed only for ATPA and isopropyl-AMPA, not for other AMPA analogs with bulky substitutions at the 5-position of the isoxazole ring.

Frequency of MART-1/MelanA and gp100/PMel17-specific T cells in tumor metastases and cultured tumor-infiltrating lymphocytes.

Melanoma differentiation antigens, such as MART-1/MelanA and gp100/PMel17, frequently are observed as targets of tumor infiltrating lymphocytes (TIL) originated from HLA-A*0201-expressing patients with melanoma. Furthermore, particular clinical relevance was attributed to gp100/pMel17 based on the impression that the adoptive transfer of gp100-recognizing TIL was associated with clinical responses in a small group of patients. However, the actual frequency of specific T cells for these melanoma differentiation antigens has never been directly enumerated in ex vivo or in vitro expanded TIL cultures. Here, we enumerated melanoma differentiation antigen-specific T-cell precursor frequency in TIL using tetrameric HLA/epitope complexes, functionally characterizing their responsiveness to cognate epitope by cytokine release assay. T-cell precursor frequencies were enumerated in 11 fresh-tumor preparations and 17 TIL adoptively transferred into patients bearing HLA-A*0201. MART-1 or gp100-specific T cells could be detected respectively in 5 and 2 of the 11 fresh preparations and in 5 and 2 of the 17 adoptively transferred TIL. With one exception, melanoma differentiation antigen-specific T-cell precursor frequency in fresh material and TIL ranged between 5,000 to 21,000/10(6) CD8+ T cells. T-cell precursor frequency was not significantly higher in TIL whose administration was associated with clinical response. These data provide direct enumeration of MART-1/MelanA and gp100/pMel17 reactivity ex vivo and in vitro in the context of HLA-A*0201.