Sow behaviour and piglet weight gain after late cross-fostering in farrowing crates and pens.

Determining best practices for managing free farrowing systems is crucial for uptake. Cross-fostering, the exchange of piglets between litters, is routinely performed amongst crate-housed sows. However, cross-fostering can increase fighting amongst the litter and may be more challenging within free farrowing systems as sows have more freedom to respond to cross-fostered piglets. This study compared the effect of either cross-fostering (FOS), or a control of sham-fostering (CON), of four focal piglets per litter on Day 6 postpartum in crates (CRATE) and free farrowing pens (PEN). The post-treatment behavioural responses of sows were recorded (Day 6 = 60 min; Day 7 = 300 min; n = 48), as were the average daily gain (ADG; g/day), total weight gain (TWG; kg) and body lesion scores of focal piglets and their littermates throughout lactation (Day 6, Day 8, Day 11 and Day 26; n = 539) and the post-weaning period (Day 29, Day 32 and Day 60; n = 108). On Day 6, though post-reunion latency to nursing did not differ, latency to successful nursing was longer amongst FOS than CON litters (P < 0.001), more so amongst CRATE FOS than PEN FOS (P < 0.01). On Day 7, PEN FOS sows had fewer successful nursing bouts (P < 0.05) and exhibited decreased lateral (P < 0.01) and increased ventral lying frequencies (P < 0.01) compared to all other housing and treatment combinations. Focal piglet ADG was lower for FOS than CON in the CRATE during Day 6 to Day 8 (P < 0.01) and lower in the PEN during Day 6 to Day 8 (P < 0.001), Day 8 to Day 11 (P < 0.01) and Day 11 to Day 26 (P < 0.05). The TWG of pre-weaned focal piglets (Day 6 to Day 26) was higher amongst CON than FOS litters (P = 0.01). Post-weaning, piglet ADG was higher for PEN than CRATE during Day 26 to Day 29 (P < 0.01) and higher for FOS than CON during Day 26 to Day 29 (P < 0.05), Day 29 to Day 32 (P < 0.001) and Day 32 to Day 60 (P < 0.01); thus, TWG was higher for FOS than CON during the weaner (P = 0.001) and the combined lactation and weaner periods (P = 0.09). In conclusion, sow behaviour was disrupted by cross-fostering in the crates and pens and continued to be disturbed on the following day amongst penned sows. FOS piglets exhibited reduced ADG after cross-fostering, which extended throughout lactation in the pens. However, the increased post-weaning weight gain of FOS piglets meant that their TWG was higher than CON piglets, irrespective of the farrowing system used.

Temporary crate opening procedure affects immediate post-opening piglet mortality and sow behaviour.

Producers are interested in utilising farrowing systems with reduced confinement to improve sow welfare. However, concerns of increased mortality may limit commercial uptake. Temporary confinement systems utilise a standard crate which is opened 3 to 7 days postpartum, providing protection for neonatal piglets at their most vulnerable age and later increased freedom of movement for sows. However, there is anecdotal evidence that piglet mortality increases immediately after the temporary crate is opened. The current study aims were to determine if piglet mortality increases post-opening, to trial different opening techniques to reduce post-opening piglet mortality and to identify how the different opening techniques influence sow behaviour. Three opening treatments were implemented across 416 sows: two involved opening crates individually within each farrowing house when each litter reached 7 days of age, in either the morning or afternoon (AM or PM), with a control of the standard method used on the farm to open all crates in each farrowing house simultaneously once the average litter age reached 7 days (ALL). Behavioural observations were performed on five sows from each treatment during the 6 h after crate opening, and during the same 6 h period on the previous and subsequent days. Across all treatments, piglet mortality was significantly higher in the post-opening than pre-opening period (P<0.0005). Between opening treatments, there were significant differences in piglet mortality during the 2 days after crate opening (P<0.05), whilst piglet mortality also tended to differ from crate opening until weaning (P=0.052), being highest in ALL and lowest in PM. Only sows in the PM treatment showed no increase in standing behaviour but did show an increased number of potentially dangerous posture changes after crate opening (P=0.01), which may be partly attributed to the temporal difference in observation periods. Sow behaviour only differed between AM and ALL on the day before crate opening, suggesting the AM treatment disrupted behaviour pre-opening. Sows in AM and PM treatments showed more sitting behaviour than ALL, and therefore may have been more alert. In conclusion, increases in piglet mortality after crate opening can be reduced by opening crates individually, more so in the afternoon. Sow habituation to disturbance before crate opening may have reduced post-opening piglet mortality, perhaps by reducing the difference in pre- and post-opening sow behaviour patterns.

Consistency is key: interactions of current and previous farrowing system on litter size and piglet mortality.

Global interest in alternative indoor farrowing systems is increasing, leading to a growing number of farms utilising such systems alongside standard crates. There is evidence that interchanging sows between different farrowing systems affects maternal behaviour, whilst the subsequent effect of this on piglet mortality is unknown. The current study hypothesised that second parity piglet mortality would be higher if a sow farrowed in a different farrowing system to that of her first parity. Retrospective farm performance records were used from 753 sows during their first and second parities. Sows farrowed in either standard crates (crates), temporary crates (360s) or straw-bedded pens (pens), with mortality recorded as occurring either pre- or post-processing. Inter- and intra-parity sow consistency in performance were also investigated. Overall, total piglet mortality reduced from the first to the second parity, being significantly higher in the crates and higher in the 360s during the first or second parity, respectively. In the second parity, an interaction of the current and previous farrowing systems resulted in the lowest incidence of crushing for sows housed in the same system as their first parity for the crates and pens, but not the 360s. Post-processing mortality was significantly higher in the crates if a sow previously farrowed in the 360s and vice versa. Sows which previously farrowed in a pen had a significantly larger litter size and lower pre-processing mortality from crushing in their second parity than sows previously housed in the crates or the 360s. No inter-parity consistency of sow performance was found, whilst intra-parity consistency was found in the first but not second parity. In conclusion, returning sows to the same farrowing system appears to reduce piglet mortality, whilst farrowing in a pen during the first parity significantly increased second parity litter size without increasing piglet mortality.

Lenalidomide plus R-CHOP21 in newly diagnosed diffuse large B-cell lymphoma (DLBCL): long-term follow-up results from a combined analysis from two phase 2 trials.

Lenalidomide-RCHOP (R2-CHOP21) has been shown to be safe and effective in patients with untreated diffuse large B-cell lymphoma (DLBCL). The aim of this analysis is to report long-term outcome and toxicities in newly diagnosed DLBCL patients who received R2-CHOP21 in two independent phase 2 trials, conducted by Mayo Clinic (MC) and Fondazione Italiana Linfomi (FIL). All patients received R-CHOP21 plus lenalidomide. Long-term progression-free survival (PFS), time to progression (TTP), overall survival (OS) and late toxicities and second tumors were analyzed. Hundred and twelve patients (63 MC, 49 FIL) were included. Median age was 69 years, 88% were stage III-IV. At a median follow-up of 5.1 years, 5y-PFS was 63.5%, 5y-TTP 70.1% and 5y-OS 75.4%; according to cell of origin (COO): 5y-PFS 52.8% vs 64.5%, 5y-TTP 61.6% vs 69.6% and 5y-OS 68.6% vs 74.1% in germinal center (GCB) vs non-GCB respectively. Four patients experienced grade 4-5 late toxicities. Grade ≤ 3 toxicities were infections (N = 4), thrombosis (N = 1) and neuropathy (N = 3). Seven seconds tumors were observed. Long-term follow-up demonstrates that R2-CHOP21 efficacy was maintained with high rates of PFS, TTP, and OS. Lenalidomide appears to mitigate the negative prognosis of non-GCB phenotype. Incidence of therapy-related secondary malignancies and late toxicities were low.

Preliminary results using ultrasound transmission for image-guided thermal therapy.

The feasibility of using an acoustic camera as a real-time imaging device for thermal surgery was investigated. The study compares camera images of tissue samples taken before, during and after a volume of tissue was thermally coagulated using focused ultrasound (US). This apparatus has analogous acoustic counterparts to an optical charge couple device (CCD) camera. The setup was operated in transmission mode, with a tissue sample placed between the camera and a 10-MHz illuminating transducer. A high-intensity continuous-wave US signal from a therapeutic transducer was focused inside the sample tissue. A reversible, time-dependent variation in image intensity was observed in the region of the therapeutic sonications in all tissues tested: bovine fat and porcine and rabbit livers. Correlations between image intensities and temperatures were shown; rabbit liver resulted in a correlation coefficient (R(2)) of 0.6694 and bovine fat resulted in an R(2) of 0.9455. When temperatures high enough to coagulate tissue were reached, permanent changes in the images were observed. Lesion locations and dimensions from the images were found to be comparable to the sectioned tissue samples. An R(2) of 0.919 resulted when lesion size detected from the camera was compared to the actual lesion size. Preliminary results may indicate that the camera has an application for monitoring thermal surgery.

Usefulness of MR imaging-derived thermometry and dosimetry in determining the threshold for tissue damage induced by thermal surgery in rabbits.

PURPOSE: To investigate in vivo the feasibility of using magnetic resonance (MR) imaging-derived temperature and thermal dose measurements to find the threshold of thermal tissue damage. MATERIALS AND METHODS: Sonications were delivered in rabbit thigh muscles at varying powers. Temperature-sensitive MR images obtained during the sonications were used to estimate the temperature and thermal dose. The temperature, thermal dose, and applied power were then correlated to the occurrence of tissue damage observed on postsonication images. An eight-element phased-array transducer was used to produce spatially flat temperature profiles that allowed for averaging to reduce the effects of noise and the voxel size. RESULTS: The occurrence of tissue damage correlated well with the MR imaging-derived temperature and thermal dose measurements but not with the applied power. Tissue damage occurred at all locations with temperatures greater than 50.4 degrees C and thermal doses greater than 31.2 equivalent minutes at 43.0 degrees C. No tissue damage occurred when these values were less than 47.2 degrees C and 4.3 equivalent minutes. CONCLUSION: MR imaging thermometry and dosimetry provide an index to predict the threshold for tissue damage in vivo. This index offers improved online control over minimally invasive thermal treatments and should allow for more accurate target volume coagulation.

Early human T cell activation events with engagement of surface MHC class II.

Major histocompatibility complex (MHC) class II are expressed on most activated human lymphocytes. They direct antigen presentation events in dendritic cells and B cells (collectively called antigen presenting cells), but the role for MHC class II in human T cells is not well understood. To understand the role of surface MHC class II and to identify the molecules involved in signaling, we have defined the early activation sequence in T cells when MHC class II are engaged by a specific antibody. Specifically, we have characterized the involvement of phosphotyrosine kinases, phospholipase C (PLC), and Ca2+ mobilization. With the engagement by either whole anti-class II antibody or its Fab fragments, the enzymatic activity of p56lck and ZAP-70 increased, but there was no increase in p59fyn activity. In addition, the intracellular free Ca2+ increased, which was due to enhanced influx and not to the mobilization of intracytoplasmic Ca2+. These events did not require cross-linking because they were not significantly augmented by the addition of antispecies antibody. The coimmunoprecipitation of tyrosine phosphorylated PLC-gamma1 with surface MHC class II suggested that PLC-gamma1 could be recruited to MHC class II after engagement. These results show the complexities of the early signals transduced by the engagement of surface MHC class II on T cells.

Brefeldin A-induced alterations in processing of MHC class II-Ii complex depend upon microtubular function.

The role of microtubules in the brefeldin A (BFA)-associated relocation of major histocompatibility complex (MHC) class II alphabeta chains (alphabeta) and the invariant chain (Ii) was characterized in Raji cells by the use of nocodazole (ND). BFA blocked the transport of alphabeta Ii proteins through the Golgi and redistributed them to the endoplasmic reticulum (ER) along with Golgi-resident enzymes. The result of the colocalization of processing enzymes and newly synthesized proteins was a downshift of alphabeta Ii molecular weight (MW) of 2 kDa, and their resistance to endoglycosidase H (endo H) after 6 hr of chase. ND by itself had no effect on the processing and transport of alphabeta to the cell surface. The addition of ND to BFA-treated cells downshifted alphabeta Ii by 4 kDa. Additionally, alphabeta Ii proteins remained sensitive to neuraminidase after 16 hr of chase. In vitro alpha-mannosidase treatment of immunoprecipitated alphabeta Ii generated a similar 4-kDa downshift of MW. Either 1-deoxymannojirimycin (DJN) or swainsonine (SWN) blocked the MW downshift caused by BFA + ND treatment. These observations indicated that in Raji cells, most of the BFA-associated relocations of cis-, medial Golgi proteins, and the addition of sialic acid from the trans-Golgi were microtubule-independent. The retrograde transport of the medial Golgi enzyme N-acetylglucosamine transferase, however, required microtubular function. Microtubule disrupters could affect BFA treatment of viral infections by further disrupting viral protein processing.

An analysis of exam room utilization in U.S. medical schools.

Examination room utilization in U.S. academic practices has not generally included clinical space used in the teaching of medicine. The lack of planning guidelines at some medical schools for examination room space may have them operating inefficiently by as much as 50 percent or 60 percent. Not having guidelines may be causing medical schools to commit valuable resources to develop unnecessary space. A survey of 126 U.S. medical schools determined their estimated maximum annual examination room visit capacity at 40 percent to 50 percent of their EMAERVC during the study period yet planned to add examination room capacity.

Effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion in pylorus-ligated rat.

The effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion were evaluated in a pylorus-ligated rat model. Oral administration of salicylate (50 mg/kg), aspirin (50 mg/kg), and indomethacin (3.5 mg/kg) significantly increased ulcerogenesis over the basal value by six- to sevenfold, but ibuprofen's (10 mg/kg) fourfold increase was not significant. Aspirin in conjunction with histamine (0.5 mg/kg subcutaneously) significantly increased ulcerogenesis by 2.7-fold compared to histamine alone. Basal acid secretion was increased significantly by 156% after indomethacin, but not by other nonsteroidal antiinflammatory drugs. In contrast, all nonsteroidal antiinflammatory drugs, except indomethacin, significantly decreased histamine-stimulated acid secretion. Non-steroidal antiinflammatory drugs had no effect on pepsinogen secretion. Ranitidine pretreatment (25 mg/kg intraperitoneally) significantly decreased basal acid and pepsinogen secretion in all treatment groups by > 85% and > 40%, respectively, and ulcerations induced by salicylate, aspirin, and indomethacin were also inhibited by 90%, 60%, and 60%, respectively. The observed inhibition of prostaglandin E2 generation by nonsteroidal antiinflammatory drugs under basal secretory conditions appeared to correlate with the extent of ulcerogenesis. Our data support the concept that acid, in addition to inhibition of prostaglandin E2 synthesis, plays an important role in the pathogenesis of nonsteroidal antiinflammatory drug-induced gastropathy.

Prohibitin expression during cellular senescence of human diploid fibroblasts.

Prohibitin is an evolutionarily conserved gene postulated to possess tumor suppressor activity and to contribute to the limited lifespan of human diploid fibroblast-like cells. Prohibitin mRNA and protein expression and its ability to become post-translationally modified were determined in human diploid fibroblast-like cells of different in vitro ages. The expression of prohibitin mRNA and protein changes little with increasing in vitro age; however, its protein product is post-synthetically modified in younger but not older cells. These results suggest that prohibitin is similar to the retinoblastoma gene product whose anti-proliferative activity remains active in older cells because it is not post-synthetically modified.

Nonsalicylate nonsteroidal antiinflammatory drugs augment prestimulated acid secretion in rabbit parietal cells. Investigation of the mechanisms of action.

The effects of nonsalicylate nonsteroidal antiinflammatory drugs on acid secretion were studied in isolated rabbit parietal cells. Indomethacin, naproxen, and carprofen (10(-6)-10(-4) mol/L) potentiated histamine-, forskolin-, 3-isobutyl-1-methylxanthine-, and dibutyryl cyclic adenosine monophosphate-stimulated acid secretion without affecting basal acid secretion. This augmentation of secretagogue-stimulated acid secretion was dependent on extracellular calcium because potentiation was abolished by calcium depletion of the medium or in the presence of the calcium antagonist lanthanum chloride. Potentiation was independent of the H2 and muscarinic receptors and did not appear to involve guanine nucleotide regulatory proteins. Proton pump activity was unaffected by indomethacin. Furthermore, nonsteroidal antiinflammatory drugs increased calcium efflux through the plasma membrane, as measured by calcium 45, and decreased endogenous prostaglandin E2 content. Exogenous dimethyl prostaglandin E2 inhibited the potentiating effect of these drugs on histamine-stimulated but apparently not on dibutyryl cyclic adenosine monophosphate-stimulated acid secretion. The data indicate that nonsalicylate nonsteroidal antiinflammatory drugs interacted at a postreceptor site between adenylate cyclase and the proton pump. The potentiating effects of these drugs were regulated by calcium and possibly modulated by prostanoids.

Aspirin potentiates prestimulated acid secretion and mobilizes intracellular calcium in rabbit parietal cells.

The effects of aspirin on gastric acid secretion were studied in isolated rabbit parietal cells (PC). Aspirin (10(-5) M) potentiated histamine-, dibutyryl cyclic AMP (dbcAMP)-, forskolin- and 3-isobutyl-1-methylxanthine-stimulated acid secretion without affecting basal acid secretion. Augmentation of secretagogue-stimulated acid secretion by aspirin was dependent on calcium (Ca2+) since potentiation was blocked by removal of extracellular Ca2+ ([Ca2+]o) or addition of the calcium antagonist lanthanum chloride. Using the Ca2+ probe fura-2, aspirin (10(-6) - 2 X 10(-5) M) rapidly increased intracellular free Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The source of released Ca2+ was intracellular as demonstrated by depletion of intracellular Ca2+ and [Ca2+]o with EGTA washing. Aspirin did not affect several other signal transduction sites involved in stimulus-secretion coupling, including the H2 receptor, intracellular cyclic AMP (cAMP), inositol 1,4,5, triphosphate (IP3) and H+,K(+)-ATPase. Aspirin decreased PC prostaglandin E2 (PGE2) content by 98%. Exogenous dimethyl PGE2 (dmPGE2) inhibited both histamine-stimulated acid secretion and its enhancement by aspirin. In contrast, dmPGE2 abolished aspirin-induced potentiation of dbcAMP-stimulated acid secretion by augmenting the dbcAMP-stimulated response. These results indicate that aspirin acts at a site beyond the adenylate cyclase/cAMP system and before the proton pump, presumably by releasing Ca2+ from an IP3-independent intracellular storage pool and by inhibiting PGE2 generation.

Mechanisms of gastric proton pump inhibition by calcium channel antagonists.

The inhibitory effects of Ca channel antagonists on gastric acid secretion [[14C]-aminopyrine (AP) uptake ratio] have been analyzed in isolated rabbit parletal cells (PC). Secretagogue-stimulated AP uptake was inhibited by verapamil and diltiazem in a dose-dependent manner with IC50 values of 15 and 100 microM, respectively, both in the presence and absence of extracellular Ca. In contrast, nifedipine had no effect on AP accumulation. Verapamil decreased histamine-stimulated respiration with the same IC50 as observed for AP uptake. Imidazole, a weak base, by buffering the acid spaces in PC, reversed the inhibitory effect of verapamil on respiration. In the bullfrog gastric mucosa, forskolin-stimulated proton transport was inhibited by verapamil (10(-4) M) from the luminal but not the serosal side. This inhibitory effect was reversed by either elevating KCl concentration in, or removing the drug from, the secretory solution. Verapamil inhibited gastric microsomal H+,K(+)-adenosine triphosphatase (H+,K(+)-ATPase) and PC K(+)-stimulated p-nitrophenyl phosphatase activities with a higher potency than diltiazem. Inhibition of these enzymes by verapamil and diltiazem was pH dependent. The drugs competed with K+ in both H+,K(+)-ATPase and K(+)-stimulated p-nitrophenyl phosphatase reactions. Our data suggest that inhibition of the gastric proton pump by verapamil or diltiazem is not due to their Ca channel antagonism but to their interaction with the luminal high affinity K(+)-site of the H+,K(+)-ATPase under acidic conditions.

Stimulation of mono (ADP-ribosyl)ation by reduced extracellular calcium levels in human fibroblasts.

Lowering extracellular calcium in cultures of human diploid fibroblast-like cells caused a rapid depletion of NAD pools. This loss of NAD was reversed by restoring extracellular Ca2+ and was inhibited by 3-aminobenzamide, an inhibitor of ADP-ribosyl transfer reactions. The concentrations of 3-aminobenzamide needed to inhibit the loss of NAD were consistent with those required to inhibit cellular mono(ADP-ribosyl) rather than poly(ADP-ribosyl) reactions. Calcium depletion did not inhibit the biosynthesis of NAD. These results suggest that mono(ADP-ribosyl)ation is involved in the regulation of cellular Ca2+ levels.

Effectiveness of publicity campaign encouraging earlier referral of hearing loss in adults.

During 16,070 consultations in general practice 70 adults complained of difficulty with hearing. A simple poster displayed in the waiting areas together with an accompanying leaflet almost doubled the incidence of presentation of loss of hearing. Nevertheless, more than half of those complaining had failed to notice the prominently displayed personally relevant message, and the beneficial effect was lost almost as soon as the poster was removed.

Fluorescent color factor calculation using dBASE-II.

A software system utilizing dBASE-II operating on a dual-drive Apple II+ computer is described. Color factors and retention times for 15 amino acids and epsilon-(gamma-glutamyl)lysine dipeptide are calculated following high performance liquid chromatography. The software package produces a listing of acceptable limits for these parameters calculated as plus and minus 2 standard deviations of the mean. The code is distributed in source form.

Use of videotape and phone teleconference in statewide extension program on milk quality and mastitis control.

Extension specialists used a 3-h videotape and phone teleconferences to teach dairy farmers how to produce quality milk and control mastitis. This 5-d effort reached approximately 20% of the state's commercial dairy farms in 22 meetings at 22 locations. A survey of approximately 170 dairy producers indicated those attending the program had less education, were younger, and more were enrolled in Dairy Herd Improvement program as compared with the average Maryland dairy farmer. Eighty percent reported they would like to see additional videotaped programs; 5% indicated no interest in viewing other topics on videotape. Scores on knowledge pretests and posttests were 66 and 76%, respectively. Only 1.7% were using all 13 mastitis management practices recommended in the educational program, and 11.2% said they would use all 13 practices after participating in the program.